Early developmental intervention programmes provided post hospital discharge to prevent motor and cognitive impairment in preterm infants

Abstract

Background

Infants born preterm are at increased risk of cognitive and motor impairments compared with infants born at term. Early developmental interventions for preterm infants are targeted at the infant or the parent‐infant relationship, or both, and may focus on different aspects of early development. They aim to improve developmental outcomes for these infants, but the long‐term benefits remain unclear. This is an update of a Cochrane review first published in 2007 and updated in 2012 and 2015.

Objectives

Primary objective

To assess the effect of early developmental interventions compared with standard care in prevention of motor or cognitive impairment for preterm infants in infancy (zero to < three years), preschool age (three to < five years), and school age (five to < 18 years).

Secondary objective

To assess the effect of early developmental interventions compared with standard care on motor or cognitive impairment for subgroups of preterm infants, including groups based on gestational age, birthweight, brain injury, timing or focus of intervention and study quality.

Search methods

We searched CENTRAL, MEDLINE, Embase, CINAHL, PsycINFO and trial registries in July 2023. We cross‐referenced relevant literature, including identified trials and existing review articles.

Selection criteria

Studies included randomised, quasi‐randomised controlled trials (RCTs) or cluster‐randomised trials of early developmental intervention programmes that began within the first 12 months of life for infants born before 37 weeks' gestational age (GA). Interventions could commence as an inpatient but had to include a post discharge component for inclusion in this review. Outcome measures were not prespecified, other than that they had to assess cognitive outcomes, motor outcomes or both. The control groups in the studies could receive standard care that would normally be provided.

Data collection and analysis

Data were extracted from the included studies regarding study and participant characteristics, timing and focus of interventions and cognitive and motor outcomes. Meta‐analysis using RevMan was carried out to determine the effects of early developmental interventions at each age range: infancy (zero to < three years), preschool age (three to < five years) and school age (five to < 18 years) on cognitive and motor outcomes. Subgroup analyses focused on GA, birthweight, brain injury, time of commencement of the intervention, focus of the intervention and study quality. We used standard methodological procedures expected by Cochrane to collect data and evaluate bias. We used the GRADE approach to assess the certainty of evidence.

Main results

Forty‐four studies met the inclusion criteria (5051 randomly assigned participants). There were 19 new studies identified in this update (600 participants) and a further 17 studies awaiting outcomes. Three previously included studies had new data. There was variability in the focus and intensity of the interventions, participant characteristics, and length of follow‐up. All included studies were either single or multicentre trials and the number of participants varied from fewer than 20 to up to 915 in one study. The trials included in this review were mainly undertaken in middle‐ or high‐income countries. The majority of studies commenced in the hospital, with fewer commencing once the infant was home. The focus of the intervention programmes for new included studies was increasingly targeted at both the infant and the parent‐infant relationship. The intensity and dosages of interventions varied between studies, which is important when considering the applicability of any programme in a clinical setting.

Meta‐analysis demonstrated that early developmental intervention may improve cognitive outcomes in infancy (developmental quotient (DQ): standardised mean difference (SMD) 0.27 standard deviations (SDs), 95% confidence interval (CI) 0.15 to 0.40; P < 0.001; 25 studies; 3132 participants, low‐certainty evidence), and improves cognitive outcomes at preschool age (intelligence quotient (IQ); SMD 0.39 SD, 95% CI 0.29 to 0.50; P < 0.001; 9 studies; 1524 participants, high‐certainty evidence). However, early developmental intervention may not improve cognitive outcomes at school age (IQ: SMD 0.16 SD, 95% CI ‐0.06 to 0.38; P = 0.15; 6 studies; 1453 participants, low‐certainty evidence). Heterogeneity between studies for cognitive outcomes in infancy and preschool age was moderate and at school age was substantial. Regarding motor function, meta‐analysis of 23 studies showed that early developmental interventions may improve motor outcomes in infancy (motor scale DQ: SMD 0.12 SD, 95% CI 0.04 to 0.19; P = 0.003; 23 studies; 2737 participants, low‐certainty evidence). At preschool age, the intervention probably did not improve motor outcomes (motor scale: SMD 0.08 SD, 95% CI ‐0.16 to 0.32; P = 0.53; 3 studies; 264 participants, moderate‐certainty evidence). The evidence at school age for both continuous (motor scale: SMD ‐0.06 SD, 95% CI ‐0.31 to 0.18; P = 0.61; three studies; 265 participants, low‐certainty evidence) and dichotomous outcome measures (low score on Movement Assessment Battery for Children (ABC) : RR 1.04, 95% CI 0.82 to 1.32; P = 0.74; 3 studies; 413 participants, low‐certainty evidence) suggests that intervention may not improve motor outcome.

The main source of bias was performance bias, where there was a lack of blinding of participants and personnel, which was unavoidable in this type of intervention study. Other biases in some studies included attrition bias where the outcome data were incomplete, and inadequate allocation concealment or selection bias. The GRADE assessment identified a lower certainty of evidence in the cognitive and motor outcomes at school age. Cognitive outcomes at preschool age demonstrated a high certainty due to more consistency and a larger treatment effect.

Authors' conclusions

Early developmental intervention programmes for preterm infants probably improve cognitive and motor outcomes during infancy (low‐certainty evidence) while, at preschool age, intervention is shown to improve cognitive outcomes (high‐certainty evidence). Considerable heterogeneity exists between studies due to variations in aspects of the intervention programmes, the population and outcome measures utilised. Further research is needed to determine which types of early developmental interventions are most effective in improving cognitive and motor outcomes, and in particular to discern whether there is a longer‐term benefit from these programmes.

Plain language summary

Do early intervention programmes improve physical and mental development in babies born too early?

Key messages

Early intervention programmes given to babies born too early may improve mental and physical development in infancy (zero to three years) and do improve mental development at preschool age (three to five years).

There is a lack of good‐quality evidence for mental and physical development at school age (five to less than 18 years).

Future research in this area should focus on whether interventions in the first year of life are of benefit as children grow older.

Why do babies born early need interventions?

Babies born too early (before 37 weeks of pregnancy) are more likely to have developmental problems, such as delays in thinking and learning abilities (mental development), or delays in sitting, walking and/or using their hands (physical development).

What are early intervention programmes?

Early developmental interventions aim to reduce mental and physical developmental problems in babies born too early by providing activities to support and improve development. Interventions may focus on the baby, the parent‐baby relationship, or a combination of these, and can include different forms of physical and psychological therapy, as well as education.

What did we want to find out?

We wanted to find out if giving early developmental interventions to babies born too early improved their mental and physical abilities throughout childhood.

We also wanted to find out if different types of intervention were better than others. For example:

‐ when the intervention started, in the hospital or at home;

‐ what the intervention focused on: the parent, the baby, the parent‐baby relationship or a combination;

‐ whether having a brain injury influenced the effects of early intervention;

‐ whether the age and weight of the baby at birth influenced the effects of early intervention.

What did we do? 
This review was an update from a previous review completed in 2015.

We searched for studies where babies born too early (less than 37 weeks of age) were assigned randomly into a treatment group that provided early developmental intervention, or a control group that received standard follow‐up care, which is the typical medical follow‐up for preterm babies, and where there was sometimes some more information about caring for babies born early. The intervention could start while the baby was in hospital, but there also had to be intervention that continued at home. The study had to measure the babies’ mental or physical development, or both, after the intervention, and we grouped the age of measurement into three groups: infancy (zero to three years), preschool age (three to five years) and school age (five to less than 18 years).

We compared and summarised the results of the studies and rated our confidence in the evidence based on factors such as the study method, the number of babies in each study, and how many were assessed after the intervention.

What did we find?

We found that aspects of the studies varied a lot regarding the duration of the intervention, the ages of the babies in the study, the length of follow‐up, and what the intervention focused on.

There were 44 studies in this review involving 5051 babies who were born too early. There were 19 new studies included in this update and three studies we previously included that had new data.

We found that most of the interventions were focused on both the baby and the parent‐baby relationship.

We also found that early developmental interventions improve mental development at preschool age, while they probably did not improve motor outcomes at preschool age. At infant age, our study showed that interventions may improve mental and physical development. They do not, however, benefit mental and physical development at school age.

What are the limitations of the evidence?

There was a lot of variation in aspects of the studies, in particular, how long the interventions lasted and how much intervention infants were given. There was also a range of different measurement tools used to measure development in each age group, particularly for physical development. We have limited confidence in the results at school age follow‐up because of concerns about the small number of studies with data.

How up to date is this evidence?

This review updates our previous review from 2015. The evidence is up to date until July 2023.

Summary of findings

Summary of findings 1. Summary of findings table ‐ Early developmental intervention programmes compared to standard follow‐up in preterm infants.

Early developmental intervention programmes compared to standard follow‐up in preterm infants
Patient or population: preterm infants Setting: post hospital discharge Intervention: early developmental intervention programmes Comparison: standard follow‐up
Outcomes	Anticipated absolute effects* (95% CI)		Relative effect (95% CI)	№ of participants (studies)	Certainty of the evidence (GRADE)	Comments
	Risk with standard follow‐up	Risk with early developmental intervention programmes
Cognitive outcome in infancy ‐ DQ (Bayley, Griffiths, Brunet‐Leizine)	‐	SMD 0.27 SD higher (0.15 higher to 0.4 higher)	‐	3132 (25 RCTs)	⊕⊕⊝⊝ Lowa,b,c	In comparison to standard follow‐up, early intervention programmes may improve cognitive outcomes at infancy.
Cognitive outcome at preschool age ‐ IQ (Bayley, Stanford‐Binet, McCarthy, WPPSI‐III)	‐	SMD 0.39 higher (0.29 higher to 0.5 higher)	‐	1524 (9 RCTs)	⊕⊕⊕⊕ Highb,d	In comparison to standard follow‐up, early intervention programmes improve cognitive outcomes at preschool age.
Cognitive outcome at school age ‐ IQ (WISC, Kaufmann, DAS, WASI‐II)	‐	SMD 0.16 SD higher (0.06 lower to 0.38 higher)	‐	1453 (6 RCTs)	⊕⊕⊝⊝ Lowe	In comparison to standard follow‐up, early intervention programmes may not improve cognitive outcomes at school age.
Motor outcome in infancy (Bayley, Griffiths Locomotor)	‐	SMD 0.12 SD higher (0.04 higher to 0.19 higher)	‐	2737 (23 RCTs)	⊕⊕⊝⊝ Lowb,c,f	In comparison to standard follow‐up, early intervention programmes may improve motor outcomes at infancy.
Motor outcome at preschool age (Griffiths Locomotor, McCarthy, MABC)	‐	SMD 0.08 higher (0.16 lower to 0.32 higher)	‐	264 (3 RCTs)	⊕⊕⊕⊝ Moderateg,h	In comparison to standard follow‐up, early intervention programmes will probably not improve motor outcomes at preschool age.
Motor outcome at school age (Griffiths Locomotor, MABC)	‐	SMD 0.06 SD lower (0.31 lower to 0.18 higher)	‐	265 (3 RCTs)	⊕⊕⊝⊝ Lowb,i,j	In comparison to standard follow‐up, early intervention programmes may not improve motor outcomes at school age.
Motor outcome at school age (low score on MABC)	370 per 1000	385 per 1000 (303 to 488)	RR 1.04 (0.82 to 1.32)	413 (3 RCTs)	⊕⊕⊝⊝ Lowb,h,i	In comparison to standard follow‐up, early intervention programmes may not improve motor outcomes at school age.
*The risk in the intervention group (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI). CI: confidence interval; RR: risk ratio; SMD: standardised mean difference
GRADE Working Group grades of evidence High certainty: we are very confident that the true effect lies close to that of the estimate of the effect. Moderate certainty: we are moderately confident in the effect estimate: the true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different. Low certainty: our confidence in the effect estimate is limited: the true effect may be substantially different from the estimate of the effect. Very low certainty: we have very little confidence in the effect estimate: the true effect is likely to be substantially different from the estimate of effect.
See interactive version of this table: https://gdt.gradepro.org/presentations/#/isof/isof_question_revman_web_429953928469989050.

^a Downgraded by two levels due to risk of bias and inconsistency but upgraded by one level due to large treatment effect
^b Due to nature of the intervention, a majority of the studies did not blind the participants or personnel. Further, there were some studies without adequate allocation concealment and some studies with lower than 80% follow‐up.
^c Reduced one level because of publication bias
^d Downgraded by one level due to risk of bias but upgraded by one level due to large treatment effect
^e Downgraded by two levels due to risk of bias and inconsistency
^f Downgraded by one level due to risk of bias
^g Downgraded by one level due to imprecision
^h Due to wide confidence intervals, the clinical outcome is likely to be different if the true effect was at the upper versus the lower end of the confidence interval. 
ⁱ Downgraded by two levels due to risk of bias and imprecision
^j Due to small number of studies the confidence intervals are wide

Background

Description of the condition

Infants born preterm or at low birthweight (LBW) are at increased risk of developing motor, cognitive and behavioural impairment compared with infants born at term (Bhutta 2002; Cheong 2021; Doyle 2004; Pedersen 2000; Spittle 2013). Despite improving rates of survival for extremely low birthweight (ELBW) infants since the 1990s, the rate of disability has remained relatively constant, with up to 50% of these infants later exhibiting developmental disabilities such as motor, cognitive or behavioural impairment (Bhutta 2002; Doyle 2004; Doyle 2021). Five to 15 per cent of children will have cerebral palsy (CP) (Spittle 2007; Tin 1997; Vohr 2005).

These neurosensory impairments are complex and are often subtle, and may affect various aspects of the child's development. At school age, children born preterm experience problems across most educational domains (Pascoe 2021; Spittle 2022). They tend to have difficulty learning, particularly in applying mathematical concepts (Anderson 2003). Attentional problems and hyperactivity are commonly reported in children born prematurely (Horwood 1998). These can substantially affect academic achievement and social integration (Botting 1998; Hoy 1992; Sommerfelt 1996; Spittle 2009b; Spittle 2022). Minor motor impairments, which are similar to those seen in children with developmental co‐ordination disorder (Diagnostic and Statistical Manual of Mental Disorders Fourth Edition (DSM‐IV)), have been found to be more prevalent in very preterm infants (Williams 2010). These motor problems persist into adolescence and can affect school performance and self‐esteem (Powls 1995). In adulthood, very low birthweight (VLBW) infants continue to exhibit higher rates of neurosensory impairment, with lower academic scores and a lower high school graduation rate compared with adults born at normal birthweight (Hack 2002).

Learning, behaviour and motor impairment in preterm children can be associated with medical risk factors e.g. birthweight, gestational age, periventricular leukomalacia (PVL), intraventricular haemorrhage (IVH), respiratory distress syndrome (RDS), and necrotising enterocolitis (NEC); however, such problems account for only a portion of the variance associated with these long‐term outcomes (Olsen 2022; Vohr 2000). Nonmedical factors such as social status, parental education, parenting style, parental mental health, family structure, family functioning, and the home environment are also associated with developmental outcomes of children born preterm (Hogan 2000; Laucht 1997; Spittle 2021b; Treyvaud 2010).

Description of the intervention

Early developmental interventions have been used in the clinical setting with the aim of improving overall functional outcomes for these infants. As a result of the complex biological, medical and environmental elements that contribute to development, early intervention may encompass many components, and services may be provided through a variety of disciplines (Berger 1998; Spittle 2016; Spittle 2021a). Early intervention for preterm infants may focus on different aspects of early development, depending on targeted outcomes.

Developmental care is an intervention that focuses on the environment and the infant, and it is designed to minimise stress for the infant in the neonatal intensive care unit (NICU) (Als 1997; Symington 2003). Several systematic reviews have described variable short‐term benefits of developmental care such as reduced oxygen dependency and improved neurodevelopmental outcomes up to 12 months; however, benefits were not sustained at two years (Cheong 2021; Jacobs 2002; Symington 2003).

How the intervention might work

Early intervention programmes that focus on development post hospital discharge and into the community setting may have a greater impact on long‐term morbidity than developmental care that is applied in hospitals only, as they focus more on family factors and the home environment. Interventions aimed at enhancing the parent‐infant relationship focus on sensitising parents to infant cues and on teaching appropriate and timely responses to infant needs. Evidence suggests that early high‐quality parent‐infant interactions positively influence cognitive and social development in children (Melnyk 2001; Treyvaud 2010; Treyvaud 2016). There is some evidence that suggests effects of early intervention on cognitive outcomes for preterm children do not appear to be specific to the type of therapy received, and receipt of any early intervention for preterm infants is associated with improved cognitive function at between one and two years (McManus 2012). Several types of interventions, such as physiotherapy and infant stimulation programmes, focus on infant development. Physiotherapy trials often aim to optimise motor development but vary in the theoretical rationale underlying the intervention programme. Some physiotherapy interventions are based on principles of neurodevelopmental therapy (NDT), which aims to modify sensory input and/or abnormal movement patterns with the goal of improving motor outcomes through active and/or passive techniques (Blauw‐Hospers 2005; Brown 2001). Systematic reviews of the effects of NDT in children with neurological dysfunction have been inconclusive or shown no benefit (Brown 2001; Morgan 2016; Morgan 2021; Ottenbacher 1986). Environmental and social factors are well recognised as influencing the development of children, especially those at increased biological risk (Cheong 2021; Shonkoff 2003; Treyvaud 2016). It is important to remember the importance of the role of parents in shaping long‐term neurodevelopment of the high‐risk preterm newborn. Increasingly, positive parenting and parents' mental health are shown to have long‐lasting advantages for preterm infants (Cheong 2020). Other styles of intervention for motor development focus on specific tasks to improve an aspect of motor development (Campbell 2012; Guimarães 2015; Nascimento 2019). Increasing evidence supports the implementation of environmental enrichment programmes in which the intervention aims to improve at least one aspect of cognitive or motor outcomes by providing an optimal environment for learning (Cheong 2021; Spittle 2016). Early intervention programmes that include enhancement of parent‐infant interactions; adaptation of the environment to promote motor or cognitive skills; and parent education about supporting skills have been shown to be of benefit for infants with cerebral palsy, but less is known about these interventions for children born preterm (Morgan 2013; Morgan 2021).

Why it is important to do this review

For the purposes of this review, an early developmental intervention is considered to be a programme beginning within the first year of life, with or without an inpatient hospital component, for which the aim is to enhance infant development. Interventions have been grouped to focus on the parent‐infant relationship, development of the infant, or both. Although some interventions may specifically target motor or cognitive development, a strong relationship between these areas has been noted. For example, by influencing motor function, such interventions may improve cognitive outcomes, as they allow infants greater opportunity to interact with their environment (Becker 1999; Thelen 1996). Different models of intervention programmes may have different goals, such as prevention, remediation or treatment of a specific delay or disability (Majnemer 1998). When an intervention is begun at an early age for infants at high risk of neurodevelopmental problems, the intervention has a preventative focus, with strategies aimed at minimising the effects of prematurity and promoting optimal development. However, during the course of an intervention, if a specific dysfunction becomes apparent or a diagnosis is made, strategies may then focus on promoting development with the diagnosis profile influencing the intervention delivered (e.g. cerebral palsy). It is important for the care provider to understand the effectiveness of preventative intervention programmes in the high‐risk preterm infant population.

Objectives

Primary objective

To assess the effect of early developmental interventions compared with standard care in prevention of motor or cognitive impairment in preterm infants at infancy (zero to < three years), preschool age (three to < five years), and school age (five to < 18 years).

Secondary objectives

To assess the effect of early developmental interventions compared with standard care on motor or cognitive impairment for subgroups of preterm infants including groups based on gestational age, birthweight, brain injury, timing or focus of intervention, and study quality.

Methods

Criteria for considering studies for this review

Types of studies

We included all trials using random, quasi‐random or cluster‐randomised allocation that met the inclusion criteria. The randomisation process was assessed for each study when assessing selection bias. We also included randomised trials that used a cross‐over design, but data were only analysed for the first phase of the intervention where there was a clear intervention and control group. We only included studies reported as full text.

Types of participants

We included preterm infants born at less than 37 weeks' gestational age (according to the best obstetrical estimate at the time of delivery). We excluded studies that did not report outcomes for preterm infants separately from those for infants born at term. Studies that included preterm infant subgroups such as those with or without brain injury were included as long as the goal was to assess the effect of intervention between groups.

Types of interventions

We included early developmental intervention programmes that aimed to improve cognitive or motor outcomes. Enrolment in early intervention programmes could occur while the infant was an inpatient during primary hospitalisation or post hospital discharge. Intervention had to begin within the first 12 months of post‐term age and could be provided at home, in hospital, or at a community centre. The intervention must have been carried out by a health professional such as a physiotherapist, a doctor, a psychologist, an occupational therapist, rehabilitation specialist, or a nurse.

Types of interventions could include physiotherapy, occupational therapy, psychological therapy, neurodevelopmental therapy, parent‐infant relationship enhancement, infant stimulation, infant development, developmental care, and early intervention (education). Interventions such as osteopathy were not included. Interventions could focus on the parent‐infant relationship, development of the infant, or both.

Studies that involved only a single training session were not included as they did not meet with the goal of an intervention programme designed to improve a global development construct, e.g. cognitive or motor development. The comparator groups in the included studies were identified and infants could receive standard care that would normally be provided by the institution or community service. This could include a therapy service where an infant was diagnosed with a disability.

Types of outcome measures

We included only standardised objective measures of cognitive and motor outcomes. The following are some of the outcome measures that may have been used to assess cognitive and motor development. The measures listed below are identified according to each age range, as outcome measures are generally specific to a particular age band. The majority of outcome measures are listed as continuous measures. However, the rate of cerebral palsy (CP) is a dichotomous outcome and the Movement Assessment Battery for Children (MABC) scores can be used as a continuous outcome or a dichotomous outcome.

An additional outcome measure called the Brunet‐Lezit Revised Test (Josse 1997) was included in the motor outcome measures in this review.

We did not exclude studies based on non‐reporting of outcomes of interest; however, we excluded studies that did not include outcomes within the scope of our review, i.e. motor and cognitive impairment.

Primary outcomes

We divided outcomes into age bands: infancy (zero to < three years), preschool age (three to < five years) and school age (five to < 18 years). The protocol for this review included outcomes for the age band > 18 years of age (Spittle 2005). This has been excluded in this update as it has yielded very few potential articles and to date there has been only one study with a follow‐up after 18 years of age (I.H.D.P. 1990)(SeeDifferences between protocol and review).

Cognitive outcomes

Continuous

• Infancy (zero to < three years): Bayley Scales of Infant Development ‐ Mental Development Index Edition I (BSID‐MDI‐I; Bayley 1969), Bayley Scales of Infant Development ‐ Mental Development Index Edition II (BSID‐MDI‐II; Bayley 1993), Bayley Scales of Infant and Toddler Development ‐ Edition III Cognitive Scale (BSITD‐III; Bayley 2005), and the Griffiths Mental Development Scale ‐ General Cognitive Index (GCI) (Griffiths 1954; Griffiths 1970)

• Preschool age (three to < five years): Stanford‐Binet Intelligence Scale (3rd Edition, 1972) (Terman 1973), McCarthy Scales of Children's Abilities (McCarthy 1972), Wechsler Preschool and Primary Scale of Intelligence ‐ Revised (WPPSI‐R) (Wechsler 1989), and Differential Abilities Scale Edition II (DAS‐II; Elliot 2007)

• School age (five to < 18 years): WPPSI, Wechsler Intelligence Scale for Children ‐ Full Scale IQ (WISC‐III) (Wechsler 1991), Kaufman Assessment Battery for Children ‐ Mental Processing Composite (Kaufman 1983), Griffiths Mental Development Scale (Griffiths 1970), British Abilities Scale (BAS) (Elliot 1996), Differential Abilities Scale Edition II (DAS‐II; Elliot 2007), and Wechsler Abbreviated Scale of Intelligence ‐ second edition (WASI‐II)(Wechsler 2011)

Motor outcomes

Continuous

• Infancy (zero to < three years): Bayley Scales of Infant Development ‐ Psychomotor Development Index Edition I (BSID‐PDI‐I; Bayley 1969), Bayley Scales of Infant Development ‐ Psychomotor Development Index Edition II (BSID‐PDI‐II; Bayley 1993), Bayley Scales of Infant and Toddler Development ‐ Total Motor Quotient Edition III (BSITD‐III; Bayley 1993), and the Griffiths Locomotor Subscale (Griffiths 1954; Griffiths 1970), Test of Infant Motor Performance (TIMP) (Campbell 1995), Alberta Infant Motor Scale (AIMS) (Piper 1994), Peabody Developmental Motor Scales Editions I and II (Folio 2000), and Brunet‐Lezit Revised Test (Josse 1997)

• Preschool (three to < five years) and school age (five to < 18 years): Movement Assessment Battery for Children (MABC) Editions 1 and 2 (Henderson 1992; Henderson 2007), Bruininks‐Oseretsky Test of Motor Proficiency (BOTMP) (Bruininks 1978), Griffiths Locomotor Subscale (Griffiths 1970), and McCarthy Scales of Children's Abilities (McCarthy 1972), Motor Scales

Secondary outcomes

Dichotomous outcomes

• Rates of Cerebral Palsy (CP)

• Rates of non‐CP motor impairment: MABC scores < 5th centile

Search methods for identification of studies

The Neonatal Group Information Specialist developed search strategies in consultation with the authors. We used methodological filters to limit retrieval to randomised, controlled and quasi‐randomised trials.

Electronic searches

We conducted searches without publication type or language limits in 2021 and, most recently, in July 2023. Searches of CENTRAL, MEDLINE, CINAHL and PsycINFO were conducted from 2015 to 2023. Given the high sensitivity of the search strategy, the Embase search was limited by the most recent year to identify records not yet in CENTRAL. Sources and database coverage dates are as follows:

• Cochrane CENTRAL, Issue 7, 2023, via CRS (search date 13 July 2023);

• Ovid MEDLINE® All (1946 to 13 July 2023);

• Embase via Ovid (1974 ‐); searches 13 August 2021 and 13 July 2023;

• CINAHL via EbscoHost (1986 to 13 July 2023);

• PsycINFO via Proquest (1806 to 13 July 2023).

Our search strategies are available in: Appendix 1; Appendix 2; Appendix 3; Appendix 4; Appendix 5.

Searching other resources

We searched the following trial registries without date limits on 17 July 2023:

• US National Library of Medicine's clinicaltrials.gov (https://classic.clinicaltrials.gov/);

• WHO ICTRP (https://www.who.int/clinical-trials-registry-platform/the-ictrp-search-portal);

• ISRCTN trial registry (https://www.isrctn.com/).

Our search terms are available in Appendix 6.

We cross‐referenced relevant literature, including identified trials and existing review articles.

Data collection and analysis

We collected information regarding the method of randomisation, stratification, blinding, intervention and whether the trial was single or multicentre for each included study. We noted information regarding trial participants with respect to prematurity (gestational age (GA)) or birthweight (BW). We analysed the clinical outcomes noted above in 'Types of outcome measures'.

Where a review author was involved in an included study, this information was gathered by another author who was independent of that study (see Declarations of interest).

Selection of studies

We managed search results in Endnote. We used both Endnote and Covidence to remove duplicates. We assessed titles and abstracts in two ways: using Cochrane's Screen4Me (S4M) system (https://community.cochrane.org/sites/default/files/uploads/S4M_Users_FAQs.pdf), and by author screening.

The S4M system includes three levels of assessment for identifying non‐RCT records. Of these three levels, we used two: Known Assessments and RCT Classifier (Marshall 2018; Noel‐Storr 2020; Thomas 2021). Records remaining after S4M classification were screened independently by two of three authors (AS, JO, TT). These same authors independently screened the full texts of studies remaining after title/abstract assessment. At any point during the screening process, disagreements were resolved by discussion or by another review author. Where a review author was involved in an included study, any decisions regarding inclusion were made by other authors.

We collated multiple reports of the same study so that the study, rather than the reference, was the unit of interest in the review. Information about studies is provided in the following tables: Characteristics of included studies; Characteristics of excluded studies; Characteristics of studies awaiting classification; and Characteristics of ongoing studies.

We reported the study selection process in sufficient detail to generate a PRISMA flow diagram (Liberati 2009).

Data extraction and management

Three review authors independently extracted and entered study data (JO, TT, AS) using the Cochrane statistical software (RevMan Web 2023) for data entry. We used a standard data collection form for study characteristics and outcome data. This was piloted on one study in the review and was then used to extract data from each included study. Where there were disagreements, these were resolved with discussion and consensus or by the inclusion of another author. Where a review author was involved in an included study, data extraction was performed by another author who was independent of that study.

If any queries arose or in cases where additional data were required, we contacted the study authors for clarification or to request data.

We described ongoing studies identified by our search, when available, detailing the primary author, research question(s), methods, and outcome measures, together with an estimate of the reporting date, and reported them in the Characteristics of ongoing studies table.

Data extracted included:

• administrative details ‐ author(s), publication date, when the study was conducted, other published papers from the same study;

• study characteristics ‐ RCT or quasi or cluster‐randomised, number of centres, study setting, randomisation procedures, completeness of follow‐up;

• participants ‐ details of inclusion criteria in the study including gestational age and/or birthweight, brain injury. Numbers randomised and lost to follow‐up or withdrawal;

• intervention ‐ aims, focus of intervention, commencement timing, person delivering intervention, frequency and duration, details of comparison group;

• outcomes ‐ measurement tools used, cognitive and/or motor outcomes assessed, age(s) or time point(s) where outcome assessed, details of blinding of assessors;

• Outcomes as listed in Types of outcome measures.

Assessment of risk of bias in included studies

Three review authors (AS, JO and TT) independently assessed the risk of bias (low, high, or unclear) in all included trials using the original Cochrane Risk of bias tool (RoB1)(Higgins 2011) for the following domains.

• Sequence generation (selection bias)

• Allocation concealment (selection bias)

• Blinding of participants and personnel (performance bias)

• Blinding of outcome assessment (detection bias)

• Incomplete outcome data (attrition bias)

• Selective reporting (reporting bias)

• Any other bias

We resolved any disagreements by discussion, or by using a third assessor. See Appendix 7 for a more detailed description of the risk of bias for each domain. 

Where a review author was involved in an included study, the decisions regarding bias were made by another author who was independent of that study.

Measures of treatment effect

We used Review Manager Web (RevMan Web 2023) software to conduct data management and analysis. We used the standard methods of Cochrane Neonatal to synthesise the data. For data analysis, 'early intervention' refers to infants who were involved in early developmental intervention programmes, and 'standard care' refers to infants who had received standard medical follow‐up. Standard follow‐up varied between studies, as different hospitals/institutions used different standard follow‐up procedures.

For individual trials, when possible, we reported mean values for treatment and control groups (and 95% confidence intervals (CIs)) for continuous variables. For the meta‐analysis of continuous outcomes, we calculated standardised mean differences (SMDs), as a variety of outcome measures (with different standard deviations (SDs)) measured the same outcome. For example, cognitive outcomes in infancy can be measured by Bayley MDI (Edition I, II or III). For dichotomous outcomes, we reported risk ratio (RR) and risk difference (RD) (and 95% CIs) for treatment and follow‐up groups.

We pooled cognitive and motor outcome data into three age groups ‐ infancy (zero to < three years), preschool age (three to < five years) and school age (five to < 18 years). When studies reported data at more than one time point within an age group, we used data from the latest assessment. For example, if a study reported cognitive outcomes at 12 months and 24 months, we used only 24‐month data.

Unit of analysis issues

We performed the primary analyses for each individual randomised to the intervention and control groups for each study. In the meta‐analysis and data synthesis, we only included the first‐phase data from cross‐over trials.

With respect to a cluster‐randomised trial, information on the study design and unit of analysis for each study, indicating whether clustering of observations was present due to allocation to the intervention at the group level or clustering of individually randomised observations (e.g. patients within clinics) was extracted.

Available statistical information needed to account for the implications of clustering on the estimation of outcome variances was extracted, such as design effects or intra‐cluster correlations, and whether the study adjusted results for the correlations in the data. In cases where the study did not account for clustering, we ensured that appropriate adjustments were made to the effective sample size following Cochrane guidance (Higgins 2020). Where possible, we aimed to derive the intra‐cluster correlation (ICC) for these adjustments from the trial itself, or from a similar trial. If an appropriate ICC was unavailable, we conducted sensitivity analyses to investigate the potential effect of clustering by imputing a range of values of ICC. If any trials had multiple arms that were compared against the same control condition that was included in the same meta‐analysis, we combined groups to create a single pair‐wise comparison.

Dealing with missing data

We carried out analysis on an intention‐to‐treat basis for all included outcomes. Whenever possible, we analysed all participants in the treatment group to which they were randomised, regardless of the actual treatment received. If we identified important missing data (in the outcomes) or unclear data, we requested the missing data by contacting the original investigators.

Where data were missing, and could not be derived as described, we approached the analysis as follows:

• we contacted the original study investigators to request the missing data;

• where possible, we imputed missing SDs using the coefficient of variation (CV) or calculated from other available statistics including standard errors, confidence intervals, and P values;

• if the data were assumed to be missing at random, we analysed the data without imputing any missing value;

• we clarified the assumptions of any methods used to deal with missing data;

• we discussed the issue of missing data in the discussion section.

Assessment of heterogeneity

We described the clinical diversity and methodological variability of the evidence in the review text and with study tables describing study characteristics including design features, population characteristics, and intervention details. The Characteristics of included studies table summarises key clinical and methodological characteristics.

We inspected the forest plots and described the direction and the magnitude of effects and the degree of overlap between confidence intervals. We also considered the statistics generated in forest plots that measure statistical heterogeneity. To assess statistical heterogeneity, we used the I² statistic to quantify inconsistencies amongst the trials in each analysis. We also considered the P value from the Chi² test to assess if this heterogeneity was significant (P < 0.1). If we identified substantial heterogeneity, we reported the finding and explored possible explanatory factors using prespecified subgroup analysis (e.g. differences in study quality, participants, intervention timing and outcome assessments). A rough guideline was used to interpret the I² value rather than a simple threshold, and our interpretation took into account an understanding that measures of heterogeneity would be estimated with high uncertainty when the number of studies was small.

We classified the degree of heterogeneity as follows:

• 0% to 40% might not represent important heterogeneity;

• 30% to 60% may represent moderate heterogeneity;

• 50% to 90% may represent substantial heterogeneity;

• more than 75% may represent considerable heterogeneity.

Assessment of reporting biases

We assessed reporting bias by comparing the stated primary and secondary outcomes with reported outcomes. Where study protocols were available, we compared these to the full publications to determine the likelihood of reporting bias. We used funnel plots to screen for publication bias where there were a sufficient number of studies (> 10) reporting the same outcome. If publication bias was suggested by a significant asymmetry of the funnel plot on visual assessment, we incorporated this in our assessment of certainty of evidence (Egger 1997).

Data synthesis

When multiple studies were identified with similar outcome measures, we performed meta‐analysis using Review Manager Web (RevMan Web 2023). For categorical outcomes, we calculated the typical estimates of RR with 95% CI; for continuous outcomes, we calculated the SMD, each with the 95% CI. We used a fixed‐effect model to combine data where it was reasonable to assume that studies were estimating the same underlying treatment effect. When studies were not considered appropriate for meta‐analysis, we reported individual trials separately. When there was evidence of heterogeneity, we reported on different study characteristics and performed subgroup analyses.

Subgroup analysis and investigation of heterogeneity

We explored possible reasons for heterogeneity by scrutinising included studies and, when appropriate, using subgroup analysis. We interpreted tests for subgroup analyses with caution, given the potential for confounding with other study characteristics and the observational nature of the comparisons. In particular, subgroup analyses with fewer than five studies per category are unlikely to be adequate to ascertain valid differences in effects and will not be highlighted in our results. When subgroup comparisons were possible, stratified meta‐analysis and a formal statistical test for interaction were conducted to examine subgroup differences that could account for effect heterogeneity.

The subgroup analyses were chosen based on potential differences in intervention effectiveness related to the list below. Subgroup analysis was conducted as follows for cognitive and motor outcomes in each age bracket, as for the main analyses, when early intervention was compared with standard follow‐up care.

• Gestational age, birthweight and brain injury (periventricular leukomalacia (PVL)/intraventricular haemorrhage (IVH))

  • GA: < 28 weeks, 28 to < 32 weeks, 32 to < 37 weeks;

  • BWt: < 1000 g, 1000 to < 1500 g, 1500 to < 2500 g;

  • Brain injury: absence or presence of grade III or IV IVH or cystic PVL (or both) or an abnormal ultrasound/magnetic resonance image (MRI) before initiation of the intervention.

• Interventions started during inpatient stay with a post discharge component versus those that commenced post hospital discharge.

• Interventions focused on the parent‐infant relationship, infant development, or both.

Sensitivity analysis

We performed a sensitivity analysis comparing high versus low risk of bias. The risk of bias was considered high if the study had selection bias, either with sequence generation or allocation concealment. No other sensitivity analysis was performed for this review.

Summary of findings and assessment of the certainty of the evidence

We used the GRADE approach, as outlined in the GRADE Handbook (Schünemann 2013), to assess the certainty of evidence of the following (clinically relevant) outcomes:

• cognitive outcomes at infant, preschool and school age (continuous outcomes);

• motor outcomes at infant, preschool and school age (continuous outcomes);

• motor outcomes at school age (dichotomous outcome).

Three review authors (AS, JO and TT) independently assessed the certainty of the evidence for each of the outcomes above. We considered evidence from RCTs as high certainty but downgraded the evidence by one level for serious (or two levels for very serious) limitations based upon the following: design (risk of bias), consistency across studies, directness of the evidence, precision of estimates, and presence of publication bias. We used the GRADEpro GDT Guideline Development Tool to create a Table 1 to report the certainty of the evidence.

The GRADE approach results in an assessment of the certainty of a body of evidence as one of four grades.

• High certainty: we are very confident that the true effect lies close to that of the estimate of the effect.

• Moderate certainty: we are moderately confident in the effect estimate: the true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different.

• Low certainty: our confidence in the effect estimate is limited: the true effect may be substantially different from the estimate of effect.

• Very low certainty: we have very little confidence in the effect estimate: the true effect is likely to be substantially different from the estimate of effect.

We justified all decisions to down‐ or upgrade the certainty of the evidence in footnotes, and made comments to aid the reader's understanding of the review, where necessary (Schünemann 2023).

Results

Description of studies

Results of the search

Searches identified 15,201 references. After removing 7570 duplicates, 7631 were available for screening. We rejected 1716 references based on Screen4Me assessments; for details see (Figure 1; Figure 2). We excluded 5744 based on title/abstract screening and reviewed 171 full texts or trial registry records.

1.

Screen4Me 2021

2.

Screen4Me 2023

We included 44 studies (81 references); 19 studies are new and 25 from the previous version of the review. We excluded 62 studies (72 references), and identified 17 ongoing studies (18 references). Details are available in Figure 3.

3.

The 19 new studies are as follows: Alberge 2023; Apaydin 2023; Campbell 2012; Castel 2016; Colditz 2019; Dusing 2018; Fan 2021; Finlayson 2020; Kara 2019; Leucona 2017; Ochandorena‐Acha 2022; Milgrom 2019; Pascoali Rodovanski 2021; Sgandurra 2017; Shafaroodi 2022; Treyvaud 2022; Youn 2021; Zhang 2023; Ziegler 2021.

Included studies

We included 44 studies (19 new; 25 from the original review) and provide information below. Details for each study are provided in the Characteristics of included studies table and a synthesis of characteristics is provided below.

Types of studies

Thirty‐seven of the 44 included studies were RCTs, with the remaining being either quasi‐RCTs (Bao 1999; Goodman 1985; Leucona 2017; Melnyk 2001; Resnick 1988; Sajaniemi 2001), or a cluster‐randomised controlled trial (Johnson 2009). However, randomisation methods for six of the RCTs were not clear (Barrera 1986; Field 1980; Gianni 2006; Nelson 2001; Rice 1979; Yigit 2002).

Types of participants

There was a range of gestational age and birthweight criteria for inclusion in the studies and those that used an age or birthweight cut‐off are shown in Table 2.

1. Summary of gestational age and birthweight cut‐offs for infant inclusion in studies.

Gestational age (weeks)	< 37	< 34	< 33	< 32	< 30	< 29
	Apaydin 2023; Bao 1999; Barrera 1986; Field 1980; I.H.D.P. 1990; Lekskulchai 2001; Melnyk 2001; Nelson 2001; Nurcombe 1984; Rice 1979; Shafaroodi 2022; Teti 2009	Goodman 1985; Resnick 1988*; Dusing 2015; Treyvaud 2022; Yigit 2002*	APIP 1998; Cameron 2005	Colditz 2019, Ziegler 2021; Koldewijn 2009*; Johnson 2009	Alberge 2023; Finlayson 2020; Milgrom 2019; Spittle 2009; Youn 2021*	Dusing 2018#
Birthweight (grams)	< 2500	< 2000	< 1800	< 1500	< 1000
	Ohgi 2004#	Kaaresen 2006; Yigit 2002*	Goodman 1985; Resnick 1988*	Koldewijn 2009*; Wu 2014; Kara 2019#; Youn 2021*	Sajaniemi 2001

* birthweight or gestational age used as inclusion criteria

# study included other criteria such as brain injury

Other studies used an age range for inclusion, such as Kyno 2012, which included infants with gestational age from 30 to < 36 weeks, Castel 2016 from 28 to 35 weeks, Sgandurra 2017 and Ochandorena‐Acha 2022 from 28 to < 34 weeks, Fan 2021 from 28 to < 32 weeks, and Pascoali Rodovanski 2021 and Zhang 2023 from 28 to 37 weeks GA. Campbell 2012 included infants with a GA range from 23 to 32 weeks with brain injury. One study included infants with a birthweight range of 750 g to < 1599 g (Leucona 2017), and Gianni 2006 included infants with birthweight < 1250 g.

Types of comparator groups

Each intervention study includes an intervention group and a comparator/control group. In all cases (except Melnyk 2001), the comparator group was considered standard care. However, the description of standard care varied greatly from no detail to including a well described protocol. For example, in the study by Pascoali Rodovanski 2021, parents in both groups were given a comprehensive handbook for infants up to three months' chronological age (CA) which is described in detail. Table 3 describes the comparison groups identified in the included studies.

2. Description of comparison intervention.

Minimal detail on standard care	Standard care groups received the usual medical follow‐up for the preterm infants and referral to further intervention if required	Standard care groups received the usual medical follow‐up for the preterm infants and referral for further intervention if required, and/or general preterm community support information	Standard care includes a traditional therapy programme
APIP 1998; Bao 1999; Cameron 2005; Field 1980; Johnson 2009; Kyno 2012; Lekskulchai 2001; Leucona 2017; Nurcombe 1984; Teti 2009; Yigit 2002; Youn 2021	Alberge 2023; Castel 2016; Dusing 2015; Dusing 2018; Fan 2021; Gianni 2006; Goodman 1985; I.H.D.P. 1990; Kaaresen 2006; Koldewijn 2009; Ochandorena‐Acha 2022; Ohgi 2004; Resnick 1988; Sajaniemi 2001; Shafaroodi 2022; Spittle 2009; Treyvaud 2022; Wu 2014; Zhang 2023	Barrera 1986; Colditz 2019; Finlayson 2020; Milgrom 2019; Rice 1979; Sgandurra 2017	Apaydin 2023; Campbell 2012; Kara 2019; Nelson 2001; Ziegler 2021

Melnyk 2001 ‐ utilised a placebo group, not a comparison group

Pascoali Rodovanski 2021 ‐ parents in both groups were given a comprehensive handbook for preterm infant care up to 3 months CA.

The amount of therapy an infant may receive in the standard care group is usually unknown and not quantified in the included studies. Two studies gathered information regarding other services received by parent recall at the final assessment (Colditz 2019), or by a system of parent recording and questionnaire (Dusing 2015).

Types of interventions

Aims and outcomes of interventions

The aims of intervention programmes varied between studies, with most programmes aiming to improve both cognitive and motor outcomes as a primary outcome or as part of a developmental outcome. Table 4 summarises the outcomes: cognitive, motor or both for included studies. The incidence of cerebral palsy is also identified as a motor outcome in some studies.

3. Outcomes assessed for included studies.

Cognitive and motor outcomes	Motor outcomes only	Cognitive outcomes only	Incidence of cerebral palsy
Alberge 2023; Apaydin 2023; APIP 1998; Bao 1999; Barrera 1986; Castel 2016; Colditz 2019; Dusing 2015; Dusing 2018; Field 1980; Finlayson 2020; Goodman 1985; I.H.D.P. 1990; Kaaresen 2006; Koldewijn 2009; Kyno 2012; Johnson 2009; Leucona 2017; Milgrom 2019; Nelson 2001; Nurcombe 1984; Ochandorena‐Acha 2022; Ohgi 2004; Rice 1979; Resnick 1988; Sajaniemi 2001; Shafaroodi 2022; Spittle 2009; Teti 2009; Treyvaud 2022; Wu 2014; Youn 2021; Ziegler 2021; Zhang 2023	Cameron 2005; Campbell 2012; Fan 2021; Kara 2019; Lekskulchai 2001; Pascoali Rodovanski 2021; Sgandurra 2017; Yigit 2002	Gianni 2006; Melnyk 2001	APIP 1998; Cameron 2005; Campbell 2012; Kara 2019; Spittle 2009; Wu 2014

Types of interventions

Although intervention programmes were focused on improving cognitive or motor outcomes, or both, theoretical constructs and components of these programmes varied greatly. Some examples include intervention programmes teaching parents about infant development and milestones or understanding behavioural cues, while others focus on infant stimulation. Enhancement of the parent‐infant relationship continues to be a major focus of many early intervention programmes for preterm infants. The most common utilised method of implementation is parent education and home strategies. A few studies utilise motor training programmes and this latest review identified two studies using internet‐based programmes to implement the intervention. Treyvaud 2022 used an e‐prem website and phone clinician support to implement an age‐dependent module‐based programme, while Zhang 2023 used a WeChat group to provide online consultation and follow‐up from term age to three months' CA. Table 5 outlines the range of professions described as delivering the intervention. Those studies where the clinicians who implemented the intervention are unclear are not included in the table (Field 1980; Melnyk 2001; Nelson 2001; Ohgi 2004; Pascoali Rodovanski 2021; Shafaroodi 2022; Zhang 2023).

4. Professional discipline delivering intervention.

Doctors	Nurses	Physiotherapists	Occupational Therapists	Psychologists	Rehabilitation staff	Educational professionals
Bao 1999	APIP 1998; Johnson 2009; Kaaresen 2006; Kyno 2012; Nurcombe 1984; Resnick 1988; Rice 1979; Youn 2021*	Apaydin 2023; Cameron 2005; Campbell 2012; Dusing 2015; Dusing 2018; Goodman 1985; Kara 2019; Koldewijn 2009; Lekskulchai 2001; Ochandorena‐Acha 2022; Spittle 2009*; Wu 2014; Youn 2021*; Yigit 2002; Ziegler 2021	Barrera 1986;* Finlayson 2020*; Leucona 2017*; Sajaniemi 2001	Barrera 1986*; Castel 2016; Colditz 2019; Finlayson 2020*; Gianni 2006; Leucona 2017*; Sajaniemi 2001; Spittle 2009*	Alberge 2023; Fan 2021; Sgandurra 2017	I.H.D.P. 1990

* more than one discipline implemented intervention

Frequency of interventions

The frequency and duration of intervention programmes ranged from four sessions over approximately one month (Melnyk 2001), to weekly sessions over 12 months, followed by bi‐weekly sessions for another two years (I.H.D.P. 1990).

In the most recent group of included studies, most commenced post discharge from hospital and there are now 23 studies in this group (Alberge 2023; Apaydin 2023; APIP 1998; Bao 1999; Barrera 1986; Campbell 2012; Fan 2021; Field 1980; Gianni 2006; Goodman 1985; I.H.D.P. 1990; Kara 2019; Lekskulchai 2001; Leucona 2017; Pascoali Rodovanski 2021; Rice 1979; Sajaniemi 2001; Sgandurra 2017; Spittle 2009; Treyvaud 2022; Yigit 2002; Youn 2021; Ziegler 2021).

Twenty‐one studies began when the infant was still an inpatient (Cameron 2005; Castel 2016; Colditz 2019; Dusing 2015; Dusing 2018; Finlayson 2020; Johnson 2009; Kaaresen 2006; Koldewijn 2009; Kyno 2012; Melnyk 2001; Milgrom 2019; Nelson 2001; Nurcombe 1984; Ochandorena‐Acha 2022; Ohgi 2004; Resnick 1988; Shafaroodi 2022; Teti 2009; Wu 2014; Zhang 2023).

Types of outcome measures

There is a range of standardised outcome measures used to assess both cognitive and motor development and each assessment tool is specific for both outcome and age group. At infant age, the BSID‐I, BSID‐II and Bayley‐III are versions of the same assessment and have both motor and cognitive scores. For cognitive outcome measures, there is some overlap between ages, with the Griffiths Mental Developmental Scale being used at both infant and preschool age and the WPPSI being used at preschool and school age. The Griffiths Locomotor subscale is also used for motor outcomes for each age group and the movement ABC is used for preschool and school age motor outcomes. The latter assessment is a motor assessment with dichotomous outcomes that uses a cut‐off point to determine delayed development.

Cognitive outcomes

Infancy

At infant age, the outcome measures include standardised measures of development and also a questionnaire (ASQ) to assess cognitive performance.

• Seven studies used BSID‐I MDI (Barrera 1986; Field 1980; I.H.D.P. 1990; Nurcombe 1984; Resnick 1988; Rice 1979; Sajaniemi 2001);

• Eight studies used BSID‐II MDI (Bao 1999; Johnson 2009; Kaaresen 2006; Koldewijn 2009; Melnyk 2001; Nelson 2001; Ohgi 2004; Teti 2009);

• Thirteen studies used the latest version, the Bayley‐III, to assess cognitive outcomes at infant age (Alberge 2023; Apaydin 2023; Colditz 2019; Dusing 2015; Dusing 2018; Finlayson 2020; Leucona 2017; Milgrom 2019; Spittle 2009; Treyvaud 2022; Youn 2021; Wu 2014; Ziegler 2021);

• Three studies used the Griffiths Mental Developmental Scale (APIP 1998; Gianni 2006; Goodman 1985);

• Three studies used the ASQ (Ochandorena‐Acha 2022; Shafaroodi 2022; Zhang 2023);

• One study used the Brunet‐Lezine Revised test (Castel 2016).

Preschool age

The following tests were used to assess cognitive performance at preschool age:

• one study used the Norwegian version of the BSID‐II (Kaaresen 2006);

• one study used the Griffiths Locomotor Subscale (Gianni 2006);

• one study used the Stanford‐Binet Intelligence Scale (I.H.D.P. 1990);

• two studies used the McCarthy Scales of Children's Abilities (Barrera 1986; Nurcombe 1984);

• one study used the Mullen Scales of Early Learning (Kyno 2012);

• two studies used the WPPSI ( Milgrom 2019; Sajaniemi 2001); and

• one study used the Differential Abilities Scale II (Spittle 2009).

School age

The following tests were used to assess cognitive performance at school age:

• three studies used WPPSI and WISC‐III (I.H.D.P. 1990; Kaaresen 2006; Koldewijn 2009);

• one study used the WASI‐II (Spittle 2009);

• one study used the Kaufman Assessment Battery for Children‐Mental Processing Composite (Nurcombe 1984); and

• one study used the British Abilities Scale (APIP 1998).

Motor outcomes

Infancy

At infant age, the following tests were used to assess motor performance:

• seven studies used the BSID‐I MDI (Bao 1999; Barrera 1986; Field 1980; I.H.D.P. 1990; Nurcombe 1984; Resnick 1988; Rice 1979);

• six studies used the BSID‐II MDI (Johnson 2009; Kaaresen 2006; Koldewijn 2009; Nelson 2001; Ohgi 2004; Teti 2009);

• thirteen studies used the Bayley‐III (Alberge 2023; Apaydin 2023; Dusing 2015; Dusing 2018; Finlayson 2020; Kara 2019; Leucona 2017; Milgrom 2019; Spittle 2009;Treyvaud 2022; Wu 2014; Youn 2021;Ziegler 2021);

• two studies used the Griffiths Locomotor Subscale (Gianni 2006; Goodman 1985);

• four studies used the Alberta Infant Motor Scale (Cameron 2005; Campbell 2012; Ochandorena‐Acha 2022; Sgandurra 2017);

• five studies used the Test of Infant Motor Performance (Campbell 2012; Dusing 2015; Fan 2021; Lekskulchai 2001; Pascoali Rodovanski 2021); and

• one study, the Brunet‐Lezine Revised test (Castel 2016).

One study reported on the age of acquisition of motor skills such as sitting and crawling (Yigit 2002). A second study included walking performance at 12 months of age (Campbell 2012).

Preschool age

The following tests were used to assess motor performance at preschool age:

• the Norwegian version of the BSID‐II was used by Kaaresen 2006;

• the Griffiths Locomotor Subscale by Gianni 2006;

• the Movement ABC by Spittle 2009; and

• the PEDI by Koldewijn 2009.

School age

The following tests were used to assess motor outcomes at school age:

• the McCarthy Scales of Children's Abilities was used by Kaaresen 2006;

• the Griffiths Locomotor Subscale by Goodman 1985; and

• three studies used the Movement ABC (APIP 1998; Koldewijn 2009; Spittle 2009).

Other motor measures:

• Nine studies reported rates of CP (APIP 1998; Cameron 2005; Campbell 2012; Goodman 1985; Kara 2019; Koldewijn 2009; Spittle 2009; Wu 2014; Yigit 2002).

• No studies have reported on rates of developmental co‐ordination disorder. However, three studies used different cut‐offs and reported on the number of children classified as having a motor impairment (APIP 1998; Koldewijn 2009; Spittle 2009).

Excluded studies

We excluded 62 studies (72 references) for the reasons presented in the Characteristics of excluded studies table. The main reasons for exclusion included the study methodology, types of participants, the type and timing of intervention not within the scope of the review, and outcomes not measured (i.e. not motor or cognitive).

Ongoing studies

There are 17 ongoing studies (18 references). See the Characteristics of ongoing studies table for information on those studies.

Studies awaiting classification

There are no studies awaiting classification.

Risk of bias in included studies

Aspects of bias were assessed for each study ‐ see Figure 4; Figure 5 and descriptions below.

4.

5.

Allocation

Of the 44 included studies, 22 described adequate concealment of allocation (APIP 1998; Cameron 2005; Castel 2016; Colditz 2019; Finlayson 2020; I.H.D.P. 1990; Kaaresen 2006; Kara 2019; Koldewijn 2009; Kyno 2012; Lekskulchai 2001; Milgrom 2019; Nurcombe 1984; Ochandorena‐Acha 2022;Ohgi 2004; Pascoali Rodovanski 2021;Spittle 2009; Teti 2009; Treyvaud 2022;Wu 2014; Youn 2021;Ziegler 2021). The remaining studies either did not clearly state their method or did not use allocation concealment, as in the case of four studies (Goodman 1985; Johnson 2009; Melnyk 2001; Resnick 1988). Twelve studies did not clearly state randomisation methods (Bao 1999; Barrera 1986Dusing 2015; Dusing 2018; Field 1980; Gianni 2006; Leucona 2017; Nelson 2001; Rice 1979; Sajaniemi 2001; Sgandurra 2017; Yigit 2002).

Blinding

Melnyk 2001 was the only study that included a comparison treatment group; therefore, it is the only study that may have blinded participants to the intervention. APIP 1998 included two intervention groups ‐ one that received a developmental intervention, and one that received parent support only in order to control for the parent support component of an intervention that occurs with any family contact. Barrera 1986 also had two intervention groups which were compared to a standard care group. All other studies involved comparison of the intervention programme versus standard care, which is summarised in the section 'Comparator groups'. In all other studies, the families were not blinded to their group allocation and no studies reported masking of therapists who delivered the interventions. Masking of therapists delivering the interventions is often not feasible unless the programme is designed to do this, as in the case of Melnyk 2001, where the intervention is described on audiotape and in written material.

All studies had at least one blinded outcome measure, except for Castel 2016, Kyno 2012; Pascoali Rodovanski 2021 and Yigit 2002 in which it is unclear whether assessors were blinded to participants' intervention status, and Teti 2009, which did not include blinded assessors.

Incomplete outcome data

Completeness of follow‐up varied greatly both within and between studies. Twenty‐five studies had greater than 80% follow‐up at one point (Apaydin 2023;APIP 1998; Bao 1999; Campbell 2012; Castel 2016; Colditz 2019; Field 1980; Finlayson 2020; I.H.D.P. 1990; Johnson 2009; Kaaresen 2006; Koldewijn 2009; Lekskulchai 2001;Milgrom 2019; Nurcombe 1984; Ochandorena‐Acha 2022;Ohgi 2004; Pascoali Rodovanski 2021; Sgandurra 2017; Shafaroodi 2022; Spittle 2009; Wu 2014; Youn 2021; Zhang 2023; Ziegler 2021). However, some of these studies had less than 80% follow‐up at later time points and therefore have been classified as unclear risk in the completeness of the follow‐up section. Further, assessing the completeness of follow‐up for some studies was difficult because the number of participants included at the start of these trials was not clearly stated (Barrera 1986; Gianni 2006; Resnick 1988; Rice 1979). Studies that began in the NICU can have greater potential for lower follow‐up rates, as survival of infants was not always as apparent as when infants were recruited post hospital discharge. For example, Cameron 2005 began the intervention programme in hospital and reported only 83% follow‐up at four months of age, as 7% (five infants) of infants in the study died before the first outcome assessment was performed at four months. This trend was not found in the new studies included in this review update. Goodman 1985 stopped this study after 20 infants in four subgroups had completed the study, despite enroling 107 infants. Sajaniemi 2001 excluded infants with CP and mental retardation post randomisation; this resulted in low follow‐up rates for children who were initially randomly assigned.

Selective reporting

Included studies were examined for selective reporting bias with respect to when the outcome data were analysed and whether the reported data were fully reported and only analysed for the specified outcome. No studies reported outcomes that were analysed before the interventions were completed. The majority of studies reported the specified outcomes clearly with full disclosure of the participant numbers. Bao 1999 scored high risk for selection bias as it was unclear whether participants were withdrawn from the study, while the group reported on in Barrera 1986 are part of a larger intervention study and only those with complete data were reported on. In the study by Gianni 2006, the number of infants who were assessed for eligibility versus those who consented is unclear and the number of withdrawals was not reported. The recent study by Ziegler 2021 scored a high risk of selection bias as there was missing baseline data for 50 percent of the included infants on the main outcome measure, the Infant Motor Profile. The intervention study by Zhang 2023 did not report the flow of infants through the study process.

Other potential sources of bias

Due to the nature of the intervention studies included in this review, it is not possible to blind the participants or parents to the group allocation. This is the case for all the studies that are included in this review. Where the authors of this review were involved in an included study, the risk of bias was identified as unclear.

Effects of interventions

See: Table 1

The primary objective was to determine the effects of early developmental intervention programmes post hospital discharge for preterm infants on cognitive and motor development compared with standard medical follow‐up during infancy (zero to two years of age), preschool age (three to < five years of age), school age (five to < 18 years of age). The following section describes cognitive and motor outcomes for each age group and subsequent subgroup analyses.

Early developmental intervention versus standard follow‐up

Cognitive outcomes in infancy

Twenty‐five studies reported cognitive outcomes in infancy. Meta‐analysis demonstrated that early intervention may improve cognitive outcomes in infancy compared with standard follow‐up: (standardised mean DQ 0.27 SD; 95% CI 0.15 to 0.40; P < 0.001; 25 studies, 3132 participants, low‐certainty evidence). Of these 25 studies, only five individual studies reported an effect of intervention compared to standard care (P < 0.05), (Apaydin 2023; Bao 1999; Colditz 2019; I.H.D.P. 1990; Wu 2014; (CBIP only)). Heterogeneity between studies was moderate (I² = 56%; Figure 6), and reflected the diversity of the early intervention programmes (Analysis 1.1).

6.

Funnel plot for cognitive outcomes in infancy

1.1. Analysis.

Comparison 1: Early developmental intervention versus standard follow‐up (all studies), Outcome 1: Cognitive outcome in infancy ‐ Developmental Quotient

Eleven studies did not provide adequate data for meta‐analysis. Six of these reported differences in favour of the intervention group (Castel 2016; Field 1980; Resnick 1988; Rice 1979; Shafaroodi 2022; Zhang 2023), and five reported no effect of intervention (Barrera 1986; Fan 2021; Gianni 2006; Leucona 2017; Ochandorena‐Acha 2022). Rice 1979 reported in favour of the intervention group (N = 15) at four months of age (P < 0.05) compared with the control group (N = 15) on the BSID‐I; however, this study did not report means and SDs. Field 1980 reported that the intervention group (N = 27) scored a mean of nine DQ points higher than the control group (N = 25) on the BSID‐I at eight months; however, these study authors did not report SDs (P < 0.001). Resnick 1988 reported an effect of intervention at 12 months (P = 0.04) but not at six months, while Gianni 2006 reported no differences between intervention and control groups at 12 and 24 months but did not include data to support this. Leucona 2017 reported standard scores for the Bayley‐III and found no intervention effect on cognitive scores (P = 0.19) but noted that both groups did improve in this domain. Castel 2016 reported a global score (DQ) using the Brunet‐Leizine Revised Test and found in favour of the intervention group (estimated mean score difference of 7.8 points, P < 0.001). Fan 2021 reported a DQ calculated from the subdomains of the Gesell Developmental Scales and reported no effect of intervention (P > 0.05) after the RCT phase of the study. The Ages and Stages Questionnaire was utilised by three recent studies, two of which reported an intervention effect on problem‐solving section at three months CA (Zhang 2023), and six months CA (Shafaroodi 2022), and one which reported no difference between groups at eight months CA (Ochandorena‐Acha 2022).

Cognitive outcome at preschool age

Nine studies reported cognitive outcomes (Barrera 1986; Gianni 2006; I.H.D.P. 1990; Kaaresen 2006; Kyno 2012; Milgrom 2019; Nurcombe 1984; Sajaniemi 2001; Spittle 2009). These data were pooled for meta‐analysis which demonstrated that early intervention improves cognitive outcomes for children of preschool age compared with standard follow‐up: (standardised mean IQ: 0.39 SD; 95% CI 0.29 to 0.50; P < 0.001; I² = 43%; 9 studies, 1524 participants, high‐certainty evidence; Figure 7; Analysis 1.2).

7.

Funnel plot cognitive outcome at preschool age

1.2. Analysis.

Comparison 1: Early developmental intervention versus standard follow‐up (all studies), Outcome 2: Cognitive outcome at preschool age ‐ Intelligence Quotient

Cognitive outcome at school age

Six studies reported sufficient data for meta‐analysis at school age (APIP 1998; I.H.D.P. 1990; Kaaresen 2006; Koldewijn 2009; Nurcombe 1984; Spittle 2009). At this age, the intervention may not improve cognitive outcomes at school age (IQ: SMD 0.16 SD, 95% CI ‐0.06 to 0.38; P = 0.14; I² = 65%; 6 studies, 1453 participants, low‐certainty evidence; Figure 8; Analysis 1.3).

8.

Funnel plot cognitive outcome at school age

1.3. Analysis.

Comparison 1: Early developmental intervention versus standard follow‐up (all studies), Outcome 3: Cognitive outcome at school age ‐ Intelligence Quotient

Motor outcome in infancy

Twenty‐three studies provided sufficient data for meta‐analysis with the Bayley PDI (Edition I, II or III), the Griffiths Locomotor Subscale or the Brunet‐Leizine Revised test (Alberge 2023; Apaydin 2023; Bao 1999; Castel 2016; Colditz 2019; Dusing 2015; Dusing 2018; Finlayson 2020; Goodman 1985; I.H.D.P. 1990; Johnson 2009; Kaaresen 2006; Koldewijn 2009; Milgrom 2019; Nelson 2001; Nurcombe 1984;Ochandorena‐Acha 2022; Ohgi 2004; Spittle 2009; Treyvaud 2022; Wu 2014;Youn 2021; Ziegler 2021). Meta‐analysis showed that early developmental interventions may improve motor outcomes in infancy compared with standard follow‐up (Developmental Quotient: SMD 0.12 SD, 95% CI 0.04 to 0.19; P = 0.003; I² = 35%; 23 studies, 2737 participants, low‐certainty evidence; Figure 9; Analysis 1.4). Three of these 18 studies individually reported a positive effect of intervention (P < 0.05) (Castel 2016; Colditz 2019; Koldewijn 2009).

9.

Funnel plot motor outcome in infancy

1.4. Analysis.

Comparison 1: Early developmental intervention versus standard follow‐up (all studies), Outcome 4: Motor outcome in infancy ‐ Developmental Quotient

Eighteen studies reported motor outcomes (Barrera 1986; Cameron 2005; Campbell 2012; Fan 2021; Field 1980; Gianni 2006; Kara 2019; Kyno 2012; Lekskulchai 2001; Leucona 2017; Pascoali Rodovanski 2021; Resnick 1988; Rice 1979; Sgandurra 2017; Shafaroodi 2022; Teti 2009; Yigit 2002; Zhang 2023). However, these studies were not appropriate for use in meta‐analysis (because of the type of assessment tool used, the type of data reported, or due to missing data). Lekskulchai 2001 reported a positive effect of intervention (P < 0.001) when the Test of Infant Motor Performance was used at four months of age and where the focus was motor development. Pascoali Rodovanski 2021 reported no impact of intervention using the TIMP assessment. However, their intervention was targeted at visual outcomes and both groups did receive an intervention package. Leucona 2017 reported a positive intervention effect on fine motor development (scaled scores) using the Bayley‐III post intervention (P < 0.01), but there was no effect on gross motor scores. Kyno 2012 found no differences between groups on gross and fine motor subscales of the Mullen Scales of Early Learning at 36 months. Two studies reported motor outcomes using the ASQ and found an effect of intervention compared to standard care (Shafaroodi 2022; Zhang 2023).

Motor outcome at preschool age

Three studies reported motor outcomes that were included in meta‐analysis (Gianni 2006; Kaaresen 2006; Spittle 2009). At preschool age, the intervention probably will not improve motor outcomes (motor scale: SMD 0.08 SD, 95% CI ‐0.16 to 0.32; P = 0.53; 3 studies, 264 participants, moderate‐certainty evidence; Analysis 1.5). Koldewijn 2009 reported data from the PEDI at 44 months with the intervention group scoring higher on mobility skills and mobility assistance subscales. However, this type of assessment tool is not suitable for inclusion in meta analysis.

1.5. Analysis.

Comparison 1: Early developmental intervention versus standard follow‐up (all studies), Outcome 5: Motor outcome at preschool age

Motor outcome at school age (continuous variables)

Two studies reported motor outcomes (Goodman 1985; Koldewijn 2009) using the Griffith Locomotor Subscale or MABC at six years of age, and Spittle 2009 reported motor outcomes at eight years of age using the MABC. The evidence at school age for continuous outcomes suggests that intervention may not improve motor outcome (motor scale: SMD ‐0.06 SD, 95% CI ‐0.31 to 0.18; P = 0.61; 3 studies; 265 participants, low‐certainty evidence; Analysis 1.6). Kaaresen 2006 reported no differences in total motor score using the McCarthy Scales of Children's Ability at five years, but this was not included in the meta‐analysis as summary data were not reported.

1.6. Analysis.

Comparison 1: Early developmental intervention versus standard follow‐up (all studies), Outcome 6: Motor outcome at school age

Motor outcome at school age (dichotomous variables)

Three studies reported motor outcomes at five years of age using assessments using a cut‐off or percentile. The APIP 1998 (using a cut‐off equivalent to the upper quartile of the term reference group); Koldewijn 2009 (using cut‐off ≤15th centile) and Spittle 2009 (using cut‐off ≤ 15th centile) assessed dichotomous outcomes from the MABC. In addition, Spittle 2009 (using cut‐off ≤ 15th centile) assessed dichotomous outcomes from the MABC at 13 years. Meta‐analysis suggests that intervention may not improve motor outcome (low score on Movement‐ABCa: RR 1.04, 95% CI 0.82 to 1.32; P = 0.36; 3 studies; 413 participants, low‐certainty evidence; Analysis 1.7).

1.7. Analysis.

Comparison 1: Early developmental intervention versus standard follow‐up (all studies), Outcome 7: Motor outcome at school age

Rate of cerebral palsy

Nine studies reported rates of CP (APIP 1998; Cameron 2005; Campbell 2012; Goodman 1985; Kara 2019; Koldewijn 2009; Spittle 2009; Wu 2014; Yigit 2002). Overall, there was little evidence for differences in rates of CP between intervention and standard follow‐up groups (typical RR 0.85, 95% CI 0.57 to 1.25; P = 0.40; Analysis 1.8).

1.8. Analysis.

Comparison 1: Early developmental intervention versus standard follow‐up (all studies), Outcome 8: Rate of cerebral palsy

Subgroup analysis: gestational age

Most studies included infants born over a wide range of gestational ages, from which it was not possible to extract data within subgroups of gestational age.

Cognitive outcome in infancy

One study reported data for GA in infancy that was used in meta‐analysis (APIP 1998). Researchers reported that infants born at a gestational age < 28 weeks (DQ; SMD 0.39, 95% CI ‐0.06 to 0.83; P = 0.09, 87 participants) benefited more from the intervention programme than infants born at gestational age ≥ 28 weeks (DQ; SMD 0.09, 95% CI ‐0.25 to 0.43; P = 0.60, 153 participants). Two studies reported no differences in outcomes between infants born at gestational age < 28 weeks and ≥ 28 weeks (Koldewijn 2009; Johnson 2009). These results were not included for use in meta‐analysis as the data were not provided for each subgroup. There were no studies that reported on subgroups between 32 and 37 weeks gestational age.

Cognitive outcome at preschool age

No studies reported outcomes in relation to gestational age.

Cognitive outcome at school age

No studies reported outcomes in relation to gestational age.

Motor outcome in infancy

Two studies reported no differences in outcomes between infants born at gestational age < 28 weeks and ≥ 28 weeks (Johnson 2009; Koldewijn 2009). These results could not be included in the meta‐analysis as the data were not provided for each subgroup.

Motor outcome at preschool age

No studies reported outcomes in relation to gestational age.

Motor outcome at school age (continuous variables)

No studies reported outcomes in relation to gestational age.

Motor outcome at school age (dichotomous variables)

No studies reported outcomes in relation to gestational age.

Rate of cerebral palsy (outcome 2.2)

One study reported rates of CP for the subgroup with infants born 28 to < 32 weeks' GA and found no effect of intervention (typical RR 1.29, 95% CI 0.37 to 4.53; P value = 0.7, 1 study, 16 participants; Analysis 2.2).

2.2. Analysis.

Comparison 2: Early developmental intervention versus standard follow‐up (subgroup analysis: gestational age), Outcome 2: Rate of cerebral palsy

Subgroup analysis: birthweight

Five studies investigated infants with different birthweight groupings and there was variety in the definition of the groupings. As a result, only three were included in the meta‐analysis for cognitive outcomes at infant and preschool age. There is little evidence for the effect of intervention between the subgroups for cognitive and motor outcomes, except for cognitive outcomes at infant age (P = 0.006; I² = 80.7%)

Cognitive outcome in infancy

Four studies investigated the impact of birthweight on effects of early developmental interventions. However, only three of these studies used the birthweight subgroups of LBW (1500 to 2499 g), VLBW (1000 to 1499 g) and ELBW (< 1000 g), (Barrera 1986; Sajaniemi 2001; Teti 2009). Barrera 1986 carried out subgroup analyses of heavier infants (1500 to 1999 g) and lighter infants (< 1500 g) and reported that infants born at lower birthweight in both intervention groups made greater therapeutic gains compared with infants born at higher birthweight. However, investigators did not report means and SDs. Sajaniemi 2001 included only infants who were ELBW (< 1000 g BW) and at 24 months did not report a treatment effect of intervention. Teti 2009 found no differences in cognitive outcomes in infancy when comparing infants born ELBW and VLBW. There was evidence for subgroup differences but, with substantial heterogeneity, limited conclusions can be drawn (P = 0.006; I² = 80.7%; Analysis 3.1).

3.1. Analysis.

Comparison 3: Early developmental intervention versus standard follow‐up (subgroup analysis: birth weight), Outcome 1: Cognitive outcome in infancy ‐ Developmental Quotient

I.H.D.P. 1990 analysed the results of a higher weight subgroup (2001 to 2499 g) and a lower weight subgroup (< 2000 g) and reported that infants born at higher birthweight benefited more from the intervention programme. Heavier infants who received intervention (N = 125) scored 0.75 SD (95% CI 0.52 to 0.98; P < 0.001) higher than heavier infants who received standard follow‐up (N = 197), and investigators reported no differences in outcomes between infants born at lighter birthweight (N = 218) who received intervention and those who received standard follow‐up (N = 355). These data could not be added to the meta‐analysis because the reported weight categories were different. APIP 1998 reported data for infants born at higher birthweight (≥ 1250 g) and at lighter birthweight (< 1250 g). They found that lighter birthweight infants in the 'Portage group' scored 5.3 DQ points higher (95% CI 0.2 to 10.2; P < 0.05, 51 participants) than infants in the control group, whereas they observed no effect of intervention in the heavier subgroup at 12 months.

Cognitive outcome at preschool age

The only study that reported outcomes according to birthweight at preschool age found an intervention effect for higher birthweight infants (0.70 SD; 95% CI 0.47 to 0.93; P < 0.001, 328 participants) (I.H.D.P. 1990). Sajaniemi 2001 included only infants who were ELBW (< 1000 g BW) and at four years of age reported a treatment effect for these lighter birthweight infants compared with standard follow‐up (0.41 SD; 95% CI 0.02 to 0.81; P = 0.04, 100 participants; Analysis 3.2).

3.2. Analysis.

Comparison 3: Early developmental intervention versus standard follow‐up (subgroup analysis: birth weight), Outcome 2: Cognitive outcome at preschool age ‐ Intelligence Quotient

Cognitive outcome at school age

I.H.D.P. 1990 at school age reported that heavier birthweight infants who received intervention scored 4.4 IQ points higher than heavier infants who received standard follow‐up; however, they found no differences in the lighter weight group (SDs were not reported). At age five years, APIP 1998 found no differences related to birthweight between intervention and control groups. No meta‐analysis was performed, and it is not possible to draw conclusions regarding the intervention of different birthweight groups due to the small number of studies and conflicting evidence.

Motor outcome in infancy

I.H.D.P. 1990 reported no differences in motor outcomes between infants in intervention and control groups born at heavier (≥ 2000 g) or lighter (< 2000 g) weight. Barrera 1986 also reported no differences in motor outcomes between infants in intervention and control groups born at heavier (1500 to 1999 g) or lighter (< 1500 g) weight. Data were not used for meta‐analysis.

Motor outcome at preschool age

No studies reported motor outcomes in relation to birthweight.

Motor outcome at school age (continuous variables)

No studies reported motor outcomes in relation to birthweight.

Motor outcome at school age (dichotomous variables)

No studies reported motor outcomes in relation to birthweight.

Rate of cerebral palsy

No studies reported CP outcomes in relation to birthweight.

Subgroup analysis: brain injury

Most of the included studies did not report separate results for infants who had PVL or IVH and meta‐analysis was performed for cognitive and motor outcomes in infancy in three studies. Campbell 2012 reported outcomes for infants with brain injury, but these data were not used in meta‐analysis, and they did not report an effect of intervention on this group of infants.

Cognitive outcome in infancy

Two studies included only infants who were at risk for adverse neurological outcomes due to PVL or IVH, or both (Nelson 2001; Ohgi 2004). These two studies showed no impact of intervention on cognitive outcomes in infancy (DQ; SMD 0.50, 95% CI ‐0.12 to 1.13; P = 0.11, 2 studies, 41 participants; Analysis 4.1). APIP 1998 was the only study that reported cognitive outcomes for infants in intervention and control groups who had abnormal ultrasound results compared with those who had normal ultrasound results. Researchers reported that infants at risk for adverse neurological outcomes derived benefit from early developmental intervention, whereas infants who were not at risk showed no cognitive benefit associated with the intervention programme.

4.1. Analysis.

Comparison 4: Early developmental intervention versus standard follow‐up (subgroup analysis: brain injury), Outcome 1: Cognitive outcome in infancy ‐ Developmental Quotient

Three studies excluded infants with abnormal imaging, PVL or IVH (Fan 2021; Sgandurra 2017; Wu 2014). However, only Wu 2014 had data available for subgroup analysis. There were no differences between subgroups in the presence or absence of brain injury (P = 0.66; Analysis 4.1).

Cognitive outcome at preschool age

No studies reported cognitive outcomes in relation to brain injury.

Cognitive outcome at school age

APIP 1998 was the only study that reported outcomes in relation to normal and abnormal ultrasound findings; they found no differences between groups at school age.

Motor outcome in infancy

Ohgi 2004 and Nelson 2001 included infants at risk for adverse neurological outcomes due to PVL or IVH, or both, and showed no significant differences between intervention and follow‐up groups (DQ; SMD 0.47, 95% CI ‐0.15 to 1.10; P = 0.14, 2 studies, 41 participants; Analysis 4.2).

4.2. Analysis.

Comparison 4: Early developmental intervention versus standard follow‐up (subgroup analysis: brain injury), Outcome 2: Motor outcome in infancy ‐ Developmental Quotient

Motor outcome at preschool age

No studies reported motor outcomes in relation to brain injury.

Motor outcome at school age (continuous variables)

No studies reported motor outcomes in relation to brain injury.

Motor outcome at school age (dichotomous variables)

No studies reported motor outcomes in relation to brain injury.

Rate of cerebral palsy

No studies reported CP outcomes in relation to brain injury.

Subgroup analysis: commencement of intervention programme (inpatient vs post hospital discharge)

The intervention programme could commence while an inpatient and could continue post discharge or commence post discharge during the first year of life. Twenty‐seven studies reported data suitable for meta‐analysis in this subgroup classification, with the majority being at infant age. There is little evidence for the effect of intervention between the subgroups for cognitive and motor outcomes, except for cognitive outcomes at school age (P = 0.02).

Cognitive outcome in infancy

Amongst the 25 studies that reported sufficient data for meta‐analysis, 15 began when infants were in the NICU (Colditz 2019; Dusing 2015; Dusing 2018; Finlayson 2020; Johnson 2009; Kaaresen 2006; Koldewijn 2009; Melnyk 2001; Milgrom 2019; Nelson 2001; Nurcombe 1984; Ohgi 2004; Teti 2009;Treyvaud 2022; Wu 2014). Ten studies began post hospital discharge (Alberge 2023; Apaydin 2023; APIP 1998; Bao 1999; Goodman 1985; I.H.D.P. 1990; Sajaniemi 2001; Spittle 2009; Youn 2021; Ziegler 2021). Programmes that began while infants were inpatients suggest intervention probably had an impact on cognitive outcome in infancy (DQ; SMD 0.26, 95% CI 0.09 to 0.40; P = 0.002, 15 studies, 1304 participants), as did programmes that commenced post hospital discharge compared with standard care (DQ; SMD 0.34, 95% CI 0.10 to 0.58; P = 0.006, 10 studies, 1750 participants). Effects of interventions that commenced in the NICU had moderate heterogeneity (I² = 34%), while for those that commenced post hospital discharge, the heterogeneity was substantial (I² = 76%; Analysis 5.1). There was little evidence for differences in the effect of the intervention between the subgroups (P = 0.56).

5.1. Analysis.

Comparison 5: Early developmental intervention versus standard follow‐up (subgroup analysis: commencement of intervention), Outcome 1: Cognitive outcome in infancy ‐ Developmental Quotient

Cognitive outcome at preschool age

Studies that commenced the intervention in the NICU (Kaaresen 2006; Kyno 2012; Milgrom 2019; Nurcombe 1984) reported an effect in favour of the intervention (IQ; SMD 0.33, 95% CI 0.12 to 0.55; P = 0.003, 4 studies, 332 participants). The five studies that began post discharge also reported an impact of intervention compared to standard care (IQ; SMD 0.41, 95% CI 0.29 to 0.53; P < 0.0001, 5 studies, 1192 participants; Analysis 5.2).

5.2. Analysis.

Comparison 5: Early developmental intervention versus standard follow‐up (subgroup analysis: commencement of intervention), Outcome 2: Cognitive outcome at preschool age ‐ Intelligence Quotient

Cognitive outcome at school age

Nurcombe 1984, Kaaresen 2006 and Koldewijn 2009 are the only studies that began in the NICU and reported outcomes at school age, demonstrating the intervention probably had an effect in favour of the intervention group (IQ; SMD 0.49, 95% CI 0.09 to 0.88; P = 0.02, 3 studies, 322 participants), but there is a substantial level of heterogeneity amongst groups (65%). The three studies that began post hospital discharge showed no impact of intervention (IQ; SMD ‐0.01, 95% CI ‐0.13 to 0.11; P = 0.82, 3 studies, 1137 participants). Sample sizes of studies in which interventions began in the NICU (N = 322) were much smaller than sample sizes of studies in which interventions began post hospital discharge (N = 1137) (Analysis 5.3).

5.3. Analysis.

Comparison 5: Early developmental intervention versus standard follow‐up (subgroup analysis: commencement of intervention), Outcome 3: Cognitive outcome at school age ‐ Intelligence Quotient

Motor outcome in infancy

Amongst the 23 studies that provided sufficient data for meta‐analysis, 14 began when infants were in the NICU (Colditz 2019; Dusing 2015; Dusing 2018; Finlayson 2020; Johnson 2009; Kaaresen 2006; Koldewijn 2009; Milgrom 2019; Nelson 2001; Nurcombe 1984; Ochandorena‐Acha 2022; Ohgi 2004; Treyvaud 2022; Wu 2014). Nine studies began post hospital discharge (Alberge 2023; Apaydin 2023; Bao 1999; Castel 2016; Goodman 1985; I.H.D.P. 1990; Spittle 2009; Youn 2021; Ziegler 2021). Programmes that began in hospital had a greater impact on motor outcomes in infancy (DQ; SMD 0.17, 0.06 to 0.28; P = 0.003, 14 studies, 1293 participants) than programmes that began post hospital discharge (DQ; SMD 0.07, 95% CI ‐0.04 to 0.17; P = 0.20, 9 studies, 1444 participants) (Analysis 5.4).

5.4. Analysis.

Comparison 5: Early developmental intervention versus standard follow‐up (subgroup analysis: commencement of intervention), Outcome 4: Motor outcome in infancy ‐ Developmental Quotient

Motor outcome at preschool age

Three studies reported motor outcome data for preschool age. One study commenced in the NICU and reported data at preschool age showing no differences between groups (Kaaresen 2006). Gianni 2006 and Spittle 2009 commenced post discharge and reported no impact of intervention at this age (Analysis 5.5).

5.5. Analysis.

Comparison 5: Early developmental intervention versus standard follow‐up (subgroup analysis: commencement of intervention), Outcome 5: Motor outcome at preschool age

Koldewijn 2009 commenced intervention in the NICU and reported that the intervention group demonstrated improvements in mobility skills and mobility assistance subscales of the PEDI at 44 months but did not report data suitable for meta‐analysis.

Motor outcome at school age (continuous variables)

Goodman 1985, Koldewijn 2009 and Spittle 2009 commenced interventions post hospital discharge and showed no differences between groups (Analysis 5.6). No subgroup data were available for interventions that commenced as an inpatient.

5.6. Analysis.

Comparison 5: Early developmental intervention versus standard follow‐up (subgroup analysis: commencement of intervention), Outcome 6: Motor outcome at school age

Motor outcome at school age (dichotomous variables)

Three studies that commenced post hospital discharge and reported rates of motor impairment (APIP 1998; Koldewijn 2009; Spittle 2009) found no differences between groups (Analysis 5.7). No subgroup data were available for interventions that commenced as an inpatient.

5.7. Analysis.

Comparison 5: Early developmental intervention versus standard follow‐up (subgroup analysis: commencement of intervention), Outcome 7: Motor outcome at school age (low score on MABC)

Rate of cerebral palsy

Cameron 2005, Koldewijn 2009 and Wu 2014 were the only studies that began in the NICU and reported rates of CP and meta‐analysis show no effect of intervention in this subgroup (P = 0.87). Six studies commenced post hospital discharge (APIP 1998; Campbell 2012; Goodman 1985; Kara 2019; Spittle 2009; Yigit 2002). Again, there was no effect of intervention on rates of CP in this subgroup (P = 0.37; Analysis 5.8).

5.8. Analysis.

Comparison 5: Early developmental intervention versus standard follow‐up (subgroup analysis: commencement of intervention), Outcome 8: Rate of cerebral palsy

Subgroup analysis: focus of intervention (parent‐infant relationship vs infant development vs combination)

Studies were defined as having an intervention focus on the parent‐infant relationship, infant development, or both with the aim of improving cognitive or motor outcomes as part of infant development. Twenty‐nine studies were available for meta‐analysis with the majority focusing on the parent‐infant relationship and infant development. Overall, there was little or weak evidence for differences in the effect of the intervention between the subgroups, with cognitive and motor outcomes at all ages. The exception was cognitive outcome at preschool age where there was evidence for differences in the effect of the intervention between the subgroups (P = 0.008).

Cognitive outcome in infancy

Two studies focused their intervention primarily on the parent‐infant relationship (Melnyk 2001; Milgrom 2019). Infants who received early intervention from this subgroup reported no impact of intervention compared with infants who received standard follow‐up; standardised mean DQ 0.35 SD (95% CI ‐0.30 to 1.00; P = 0.29, 2 studies, 146 participants). Three studies that focused the intervention primarily on infant development (APIP 1998; Bao 1999; Goodman 1985) also reported no impact of intervention; SMD DQ 0.49 SD (95% CI ‐0.16 to 1.14; P = 0.14, 3 studies, 334 participants). There is a high level of heterogeneity (I² = 87) between these studies, reflecting the diversity of early intervention programmes that focus on infant development. The remaining 20 studies focused on both the parent‐infant relationship and infant development (Alberge 2023; Apaydin 2023; Colditz 2019; Dusing 2015; Dusing 2018; Finlayson 2020; I.H.D.P. 1990; Johnson 2009; Kaaresen 2006; Koldewijn 2009; Nelson 2001; Nurcombe 1984; Ohgi 2004; Sajaniemi 2001; Spittle 2009; Teti 2009;Treyvaud 2022; Wu 2014;Youn 2021; Ziegler 2021). Meta‐analysis demonstrates that the intervention probably improves cognitive outcome in this subgroup compared with standard care; standardised mean DQ 0.24 SD (95% CI 0.11 to 0.37; P < 0.001, 20 studies, 2559 participants).

I.H.D.P. 1990 and Colditz 2019 were the only individual studies that reported an effect in favour of the intervention group, whereas most of the other studies reported a trend in favour of intervention. APIP 1998 investigated the effects of parent support on infant development (with parent support) versus standard follow‐up and reported no differences between groups (Analysis 6.1).

6.1. Analysis.

Comparison 6: Early developmental intervention versus standard follow‐up (subgroup analysis: focus of intervention), Outcome 1: Cognitive outcome in infancy ‐ Developmental Quotient

Cognitive outcome at preschool age

One study focused on the parent‐infant relationship alone and reported no difference between groups (Milgrom 2019). There were seven studies that focused on both infant development and the parent‐infant relationship (Gianni 2006; I.H.D.P. 1990; Kaaresen 2006; Kyno 2012; Nurcombe 1984; Sajaniemi 2001; Spittle 2009). They reported a large difference of 0.44 in standardised mean IQ in favour of the intervention (95% CI 0.33 to 0.55; P < 0.0001, 7 studies, 1391 participants; Analysis 6.2). There was substantial heterogeneity (I² = 85.8%) in this subgroup. No subgroup data were available for interventions that focused on the parent‐infant relationship alone.

6.2. Analysis.

Comparison 6: Early developmental intervention versus standard follow‐up (subgroup analysis: focus of intervention), Outcome 2: Cognitive outcome at preschool age ‐ Intelligence Quotient

Barrera 1986 reported cognitive outcomes at this age. However, they were not included in the meta‐analysis, as the data from the two treatment groups (one focused on infant development and one focused on the parent‐infant relationship) were pooled for reporting.

Cognitive outcome at school age

At school age, five studies focused on the parent‐infant relationship and infant development (I.H.D.P. 1990; Kaaresen 2006; Koldewijn 2009; Nurcombe 1984; Spittle 2009). The five studies in this subgroup reported different individual results, with I.H.D.P. 1990, Kaaresen 2006 and Spittle 2009 showing no impact of intervention, while Nurcombe 1984 and Koldewijn 2009 demonstrated results in favour of intervention effectiveness. As a group, there is weak evidence for the intervention having an impact on cognitive outcome (IQ; SMD 0.27, 95% CI ‐0.01 to 0.55; P = 0.06, 5 studies, 1273 participants). Heterogeneity (I² = 73%) was substantial because of differences in sample size and in study outcomes. One study focused on infant development (APIP 1998); and reported little evidence for the effects of early intervention (P = 0.49; Analysis 6.3). No subgroup data were available for interventions that focused on the parent‐infant relationship alone.

6.3. Analysis.

Comparison 6: Early developmental intervention versus standard follow‐up (subgroup analysis: focus of intervention), Outcome 3: Cognitive outcome at school age ‐ Intelligence Quotient

Motor outcome in infancy

There are now 23 studies included in the meta‐analysis for this subgroup. Two studies focused on infant development alone (Bao 1999; Goodman 1985), and one study on the parent‐infant relationship (Milgrom 2019). Programmes that focused on both the parent‐infant relationship and infant development demonstrated that intervention probably improves motor outcome (DQ: SMD 0.12 SD, 95% CI 0.04 to 0.20; P = 0.003, 20 studies, 2514 participants). Those that focused on infant development (DQ: SMD 0.26 SD, 95% CI ‐0.05 to 0.58; P = 0.10, 2 studies, 157 participants) or the parent‐infant relationship (DQ: SMD ‐0.15 SD, 95% CI ‐0.54 to 0.23; P = 0.44, 1 study, 104 participants) did not demonstrate an impact of intervention (Analysis 6.4). There was little evidence for differences in the effect of the intervention between the subgroups (P = 0.26).

6.4. Analysis.

Comparison 6: Early developmental intervention versus standard follow‐up (subgroup analysis: focus of intervention), Outcome 4: Motor outcome in infancy

Motor outcome at preschool age

Gianni 2006, Kaaresen 2006 and Spittle 2009 focused on the parent‐infant relationship and infant development and showed no differences between intervention and standard care (Analysis 6.5). No data were available for other subgroups.

6.5. Analysis.

Comparison 6: Early developmental intervention versus standard follow‐up (subgroup analysis: focus of intervention), Outcome 5: Motor outcome at preschool age

Motor outcome at school age (continuous variables)

One study focused on infant development alone (Goodman 1985). Two studies focused on both infant development and the parent‐infant relationship (Koldewijn 2009; Spittle 2009). Both subgroups reported no effect of intervention compared with standard care (Analysis 6.6).

6.6. Analysis.

Comparison 6: Early developmental intervention versus standard follow‐up (subgroup analysis: focus of intervention), Outcome 6: Motor outcome at school age

Motor outcome at school age (dichotomous variables)

APIP 1998 focused on infant development and two other studies focused on both infant development and parent‐infant relationship (Koldewijn 2009; Spittle 2009); with no subgroups reporting differences between intervention and control (Analysis 6.7). No subgroup data were available for interventions that focused on the parent‐infant relationship alone.

6.7. Analysis.

Comparison 6: Early developmental intervention versus standard follow‐up (subgroup analysis: focus of intervention), Outcome 7: Motor outcome at school age (low score on MABC)

Rate of cerebral palsy

The nine studies that reported rates of CP were spread between the subgroups that focused on infant development (Cameron 2005; Campbell 2012; Goodman 1985; Yigit 2002), and both the parent‐infant relationship and infant development (APIP 1998; Kara 2019; Koldewijn 2009; Spittle 2009; Wu 2014). Both groups reported no effect of intervention compared with standard care (Analysis 6.8). No subgroup data were available for interventions that focused on the parent‐infant relationship alone.

6.8. Analysis.

Comparison 6: Early developmental intervention versus standard follow‐up (subgroup analysis: focus of intervention), Outcome 8: Rate of cerebral palsy

Sensitivity analysis: studies with high vs low risk of bias

Sixteen studies were considered to have low risk of selection bias, as they were RCTs with adequate allocation concealment, and they provided sufficient data for meta‐analysis (APIP 1998; Castel 2016; Colditz 2019; Finlayson 2020; I.H.D.P. 1990; Kaaresen 2006; Koldewijn 2009; Milgrom 2019; Nurcombe 1984; Ochandorena‐Acha 2022; Ohgi 2004; Spittle 2009; Treyvaud 2022; Wu 2014; Youn 2021; Ziegler 2021). The remaining 11 studies that were included in the meta‐analysis are considered at high risk of selection bias. There was little evidence for differences in the effect of the intervention between the subgroups in all age groups and outcomes.

Cognitive outcome in infancy

Fourteen of the studies included in this meta‐analysis were of low risk of bias and analysis of this group demonstrate an impact of intervention (DQ; SMD 0.26 SD, 95% CI 0.15 to 0.38; P < 0.001, 14 studies, 2386 participants) compared with standard care. This low risk subgroup also demonstrated a more moderate level of heterogeneity (39%) than is seen with the high risk subgroup (72%), which themselves also demonstrated an impact of intervention compared with standard care (DQ; SMD 0.36 SD, 95% CI 0.05 to 0.66; P = 0.02, 11 studies, 746 participants; Analysis 7.1).

7.1. Analysis.

Comparison 7: Early developmental intervention versus standard follow‐up (sensitivity analysis: risk of bias), Outcome 1: Cognitive outcome in infancy ‐ Developmental Quotient

Cognitive outcome at preschool age

At preschool age, there were eight studies with low risk of bias which demonstrated a significant treatment effect supporting the intervention group (IQ; SMD 0.36 SD, 95% CI 0.25 to 0.46; P < 0.001, 8 studies, 1507 participants). The five high risk of bias studies also demonstrated an impact of intervention compared with standard care (DQ; SMD 0.23 SD, 95% CI 0.00 to 0.45; P = 0.05, 5 studies, 319 participants; Analysis 7.2).

7.2. Analysis.

Comparison 7: Early developmental intervention versus standard follow‐up (sensitivity analysis: risk of bias), Outcome 2: Cognitive outcome at preschool age ‐ Intelligence Quotient

Cognitive outcome at school age

At school age, all six studies were at low risk of bias but showed little evidence of a treatment effect (IQ; SMD 0.16 SD, 95% CI ‐0.06 to 0.38; P = 0.15, 6 studies, 1453 participants; Analysis 7.3). No subgroup data were available for high risk of bias studies.

7.3. Analysis.

Comparison 7: Early developmental intervention versus standard follow‐up (sensitivity analysis: risk of bias), Outcome 3: Cognitive outcome at school age ‐ Intelligence Quotient

Motor outcome in infancy

Both the low and high risk of bias subgroups reported an effect of intervention for motor development at this age. The low risk of bias group of 15 studies (DQ; SMD 0.11 SD, 95% CI 0.03 to 0.20; P = 0.008, 15 studies, 2208 participants) and the high risk of bias subgroup (DQ; SMD 0.18 SD, 95% CI 0.01 to 0.35; P = 0.04, 8 studies, 529 participants; Analysis 7.4) favour intervention compared with standard care.

7.4. Analysis.

Comparison 7: Early developmental intervention versus standard follow‐up (sensitivity analysis: risk of bias), Outcome 4: Motor outcome in infancy ‐ Developmental Quotient

Motor outcome at preschool age

Kaaresen 2006 and Spittle 2009, the only low risk of bias studies to have reported on this outcome, revealed no differences between intervention and standard care. Gianni 2006 was the only high risk of bias study which revealed no differences between intervention and standard care (Analysis 7.5).

7.5. Analysis.

Comparison 7: Early developmental intervention versus standard follow‐up (sensitivity analysis: risk of bias), Outcome 5: Motor outcome at preschool age

Motor outcome at school age (continuous variables)

Two studies were at low risk of bias and showed no difference between intervention and standard care (Koldewijn 2009; Spittle 2009). Goodman 1985 was the only high‐risk study which revealed no differences between intervention and standard care (Analysis 7.6).

7.6. Analysis.

Comparison 7: Early developmental intervention versus standard follow‐up (sensitivity analysis: risk of bias), Outcome 6: Motor outcome at school age

Motor outcome at school age (dichotomous variables)

Three studies were at low risk of bias (APIP 1998; Koldewijn 2009; Spittle 2009). There were no differences between intervention and standard care (Analysis 7.7). No subgroup data were available for high risk of bias studies.

7.7. Analysis.

Comparison 7: Early developmental intervention versus standard follow‐up (sensitivity analysis: risk of bias), Outcome 7: Motor outcome at school age (low score on MABC)

Rate of cerebral palsy

Six studies at low risk of bias reported rates of CP and found no differences between intervention and standard care (APIP 1998, Cameron 2005, Kara 2019; Koldewijn 2009; Spittle 2009; Wu 2014). There were three high risk of bias studies (Campbell 2012; Goodman 1985; Yigit 2002), which revealed no differences between intervention and standard care (Analysis 7.8).

7.8. Analysis.

Comparison 7: Early developmental intervention versus standard follow‐up (sensitivity analysis: risk of bias), Outcome 8: Rate of cerebral palsy

Discussion

Summary of main results

The primary goal of this updated review was to compare the effects of early developmental intervention programmes provided post hospital discharge for preterm infants on cognitive and motor development versus standard medical follow‐up at infancy (zero to < three years), preschool age (three to < five years), school age (five to < 18 years). It is the 4th update of the review following previous versions in 2008, 2012 and 2015. We included in this review 44 randomised or quasi‐RCTs of early developmental interventions for preterm infants, of which there are 19 new trials and three additional studies that report longer‐term outcomes of two trials that were included in previous versions of the review. The evidence suggests that early developmental intervention programmes for preterm infants may improve cognitive and motor outcomes during infancy, while at preschool age the intervention improves cognitive outcomes. At school age, these early developmental intervention programmes may not improve cognitive or motor outcomes compared with standard care. The trials included in this review were mainly undertaken in middle‐ or high‐income countries.

Not all studies provided sufficient data for inclusion in the meta‐analysis, with an additional 12 studies able to be added in this review. Findings from this updated meta‐analysis demonstrated a treatment effect of early intervention on cognitive outcomes in infancy of approximately 1/3 SD on standardised cognitive tests, similar to the previous review. There was a slight decrease in effect size at preschool age on standardised IQ tests from 0.43 SD (2015 review) to 0.39 SD (current review) but this effect is still considered to be of clinical importance. With respect to motor outcomes, the effect size for motor outcomes at infant age increased slightly from 0.10 SD (2015 review) to 0.12 SD (current), demonstrating a small effect of intervention in infancy which was not seen at the later age points, despite the inclusion of three more studies in the meta‐analysis. The focus of the intervention in the more recently included trials is predominantly on both the infant and the parent‐infant relationship.

Subgroup analysis was useful for investigating characteristics of the infants or the trials. However, there were limited data for the school age outcome groups. The characteristics of the infants were analysed to determine whether subgroups of infants may be more responsive to interventions or types of interventions. To account for differences in gestational age and birthweight infants across studies, subgroup analyses were planned for both of these important predictors of outcome. Most studies did not report outcomes according to GA or birthweight and there were none in the latest eleven included studies, thus limiting the conclusions from these subgroup analyses. The I.H.D.P. 1990 reported that infants who were born weighing between 2000 g and 2500 g had greater response to intervention than lighter infants. Barrera 1986 and APIP 1998 found the opposite response, with infants born at VLBW having a greater impact on cognitive outcomes in infancy. Sajaniemi 2001 included only ELBW infants and reported significant effects on cognitive development. No studies reported differences in motor outcomes between intervention and control groups related to GA or birthweight. There is more consistency with the 19 recently included studies, with most including preterm infants based on GA and, while there was some variability, most infants were born before 34 weeks GA. Only two recent studies used birthweight as part of their inclusion criteria (Kara 2019; Leucona 2017).

The presence of brain injury is important to consider when effects of interventions on preterm infants are assessed. Meta‐analysis included three studies only and revealed no difference between subgroups with respect to the presence or absence of brain injury. The three studies that included infants with periventricular leukomalacia (PVL) or intraventricular haemorrhage (IVH) reported no differences in cognitive and motor outcomes between intervention and control groups (Campbell 2012; Nelson 2001; Ohgi 2004). The standard follow‐up group in these studies received physiotherapy as required, which may have affected the motor outcomes of these infants. APIP 1998 reported that infants with abnormal cranial ultrasound findings had a positive cognitive response to intervention, but infants who received intervention or standard follow‐up with normal cranial ultrasound showed no differences in outcomes. Ziegler 2021 included infants born < 32 weeks who demonstrated abnormal neurological signs between 35 weeks' GA and 4 months' CA based on neurological assessment or cranial ultrasound abnormalities. They reported improved outcomes on the Infant Motor Profile at 18 months for the intervention group but no difference between groups with the Bayley‐III at 24 months. Studies that excluded infants with abnormal imaging, PVL or IVH included Fan 2021, Sgandurra 2017, and Wu 2014, however, only Wu had data available for subgroup analysis. The only study to stratify infants with PVL/IVH was Dusing 2018, however, it was not possible to perform subgroup analysis as the groups were small and two infants with brain injury dropped out of the study.

Two types of subgroup analyses were performed in relation to types of intervention programmes. The first subgroup analysis compared interventions that commenced while the infant was still in hospital versus those that were started post hospital discharge. Both types of programmes were found to have an intervention effect on cognitive outcomes at infancy and preschool age. Only interventions commenced in hospital were found to have an effect on motor outcomes in infancy. There was no benefit of intervention for either type of programme for school age outcomes. The model for interventions that began while the infants were inpatients was more homogenous, as all focused on improving the parent‐infant relationship and on enhancing parents' abilities to read and respond appropriately to infants' behavioural cues. The engagement of parents who commence an intervention while their infant is in hospital may be greater and this aspect of the intervention may warrant more investigation. There was greater diversity in the structure of the interventions that occurred post hospital discharge.

The focus of the intervention programme on the parent‐infant relationship, infant development, or both was also analysed. In the current review, there were more studies where the intervention programme includes both the parent‐infant relationship and infant development. Subgroup analysis demonstrates that interventions with a component that focused on both aspects have a greater impact on cognitive outcomes at infancy and preschool age when compared with interventions that focused on infant development or parent support alone. This trend is also seen for school age cognitive outcomes and for motor outcomes in infancy. The importance of the role of the family and the environment in early intervention for infants with higher needs is increasingly well recognised and active participation of the child and parent is more likely to bring about better outcomes for the child (Khurana 2020). Some of the more recent studies included in this review utilised models of intervention that focused on these factors. Two included studies used the Coping with and Caring for Infants with Special Needs programme (COPCA), which is a comprehensive intervention post discharge with a family and educational component and a neurodevelopmental component (Kara 2019; Ziegler 2021). The family were active participants in the goal‐setting and implementation of interventions. Dusing 2015, Dusing 2018 and Finlayson 2020 all undertook the Supporting Play Exploration and Early Developmental Intervention (SPEEDI) programme which commenced in the NICU and continued with a home programme for three months. The goals were to provide an enriched environment and increased opportunities for the infant through collaborative parent, therapist and infant interactions. The Baby Triple P for Preterm Infants was the model used by Colditz 2019 and this is again focused on parent coping strategies, supporting a positive relationship between parent and infant and enhancing parents' ability to understand their infants' needs and promote development. This was a larger high quality study that reported an effect of intervention on motor and cognitive outcomes at two years compared with usual care.

The methodological quality of the included studies was variable, and sensitivity analysis was performed to assess the effects of study quality on cognitive and motor outcomes. When only higher‐quality studies were included in the meta‐analysis, an intervention effect on cognitive outcomes was evident in infancy and at preschool age. However, this was not the case for motor outcomes.

Overall completeness and applicability of evidence

This review update includes 19 new trials and three updated data sets for existing trials. This provides the review with more complete and current data and further understanding of the types of intervention and outcomes that the authors are investigating.

Inclusion criteria for early developmental intervention programmes applied in the current review were very specific in an attempt to limit variability amongst intervention programmes. As Blauw‐Hospers 2005 reported, the term 'early intervention' can be understood in one of two ways: intervention that occurs early in life, or intervention that occurs early in expression of the condition. We have included only intervention programmes that began early in life ‐ within the first 12 months, when the brain is highly plastic (Hadders‐Algra 2001). These intervention programmes are more likely to be targeted at prevention because longer‐term problems may not be apparent and specific diagnoses are less likely.

The new included group of studies that focused only on motor development utilised specific motor training programmes designed to improve motor development through more specific training. Campbell 2012 used a kicking and treadmill training programme while Sgandurra 2017 implemented the CareToy intervention, an intensive, customised, home‐based, family‐centred training programme, provided through remote management of a CareToy system delivered at home. The specific goal‐directed activities were remotely planned by the clinical/rehabilitative staff according to specific infant capabilities. These studies focused only on motor outcomes, and motor assessments such as the Alberta Infant Motor Scale (AIMS) and the Infant Motor Profile (IMP) were used. Training a specific task such as kicking did improve the frequency of kicking, but motor development scores on the AIMS were not improved by the exercise. The CareToy system focused more on visual motor training and, while the IMP score was significantly higher in the exercise group, there was no difference between the groups' scores with the AIMS. The targeting of intervention to the infant's needs and setting appropriate goals are important in achieving improved outcomes, and this has been demonstrated in the study by Morgan 2015, where infants with cerebral palsy participated in an RCT of Goals ‐ Activity ‐ Motor ‐ Enrichment (GAME) and were improved in motor development when compared to standard care.

Contextual factors such as the setting and focus of the intervention may play a role in defining the applicability of the evidence. Preterm infants who began intervention during primary hospitalisation improved more in cognitive outcomes compared to standard follow‐up, rather than those that started post hospital discharge compared with standard care. This effect was also seen in infants who commenced intervention post hospital discharge. However, substantial heterogeneity was observed in studies grouped under this subcategory. When the intervention focused on developing the parent‐infant relationship and infant development, the cognitive and motor benefits were greater in the early years. This focus on enhancing the environment, relationships and infant development is important in designing an intervention programme for these infants in the clinical setting and is demonstrated by Apaydin 2023, which developed a Sensory strategies, Activity‐based motor training, family collaboration and Environmental Enrichment (SAFE) programme where family collaboration and enrichment were the main focus. Methods of implementation are most commonly parent education and home strategies, with this latest review identifying two studies using internet‐based programmes to implement the intervention and provide support (Treyvaud 2022; Zhang 2023). This style may have a greater applicability for families in rural and remote communities.

While subgroup analysis was useful for investigating areas of variation between trials, this systematic review has not investigated which aspect of early developmental interventions has a greater effect on outcome ‐ i.e. what is the optimal duration, timing, frequency or focus of the intervention. Further research is needed to identify components of intervention that are most effective on the basis of cost and benefit. I.H.D.P. 1990 was estimated to cost USD 15,146 per year per child and was an intensive programme provided over three years for the infants in the intervention group. This remains a costly intervention as compared with interventions provided by Nurcombe 1984, which reported better long‐term outcomes and was less costly to implement, with 11 sessions provided over four months. The level of compliance with an intervention programme is also a factor when implementing and assessing effectiveness. The study by Youn 2021, which comprised home visits based on the MITP intervention and group sessions based on the IHDP at a centre provided by physiotherapists, reported no effect of their intervention on cognitive or motor outcomes. The authors hypothesised that this may in part be due to the intervention period lasting until six months' CA or the low compliance that was recorded, particularly for the centre‐based group sessions. Families who participated in the study by Ochandorena‐Acha 2022 reported compliance by completing a daily diary. The authors reported an association between parents' compliance and infant development with infants of mothers with good compliance showing higher scores on the AIMS and the ASQ‐3 compared to those with poorer compliance. Colditz 2019 also recorded compliance and noted that better participation rates may improve outcomes, an important consideration for future research. Dusing 2015 recorded compliance and, in order to control for poor compliance, decided a priori that infants who received less than 70% of the prescribed intervention would be dropped from the outcomes' analysis. There are a range of factors that contribute to the outcome in an intervention study and this demonstrates the importance of assessing compliance when undertaking an intervention study.

The trials included in this review were mainly undertaken in middle‐ or high‐income countries. Thus, it is less clear how applicable the evidence is in low‐income countries and how other contextual factors such as socioeconomic status (SES), age, and educational background of mothers would impact the applicability of the evidence. Variables such as SES are important to consider when different studies are compared, but this was not included as a subgroup in the protocols. Rice 1979 and Field 1980 included only infants who were born to mothers with low SES. APIP 1998 and Nurcombe 1984 reported significant differences in SES between groups despite randomisation. The control group in the study by APIP 1998 included a higher percentage of mothers who were educated beyond 16 years of age, were in non‐manual occupations, and had use of a car compared with the intervention groups. All three of these variables were independently associated with Griffiths quotients and may explain some variance in outcomes. Nurcombe 1984 reported that results were adjusted to account for differences in SES between groups. Koldewijn 2009 reported both unadjusted and adjusted results for several variables, including SES. When results were adjusted, a significant effect on motor development was noted in infancy, but not when results were unadjusted. Teti 2009 chose to target infants of African‐American mothers for their study because of associated high rates of premature birth and noted that at least half of families were living below the poverty threshold. When adjusted for poverty status, results revealed a greater intervention effect on cognitive outcome (MDI) for infants of mothers living above the poverty threshold. Field 1980 and Rice 1979 included only families with low SES and, while Leucona 2017 did not specify the participants to be of low SES, the study found after recruitment that all 24 participants lived in low SES settings. This does limit the generalisability of these results to the general population.

The meta‐analysis in this review sought to examine motor and cognitive outcomes using standardised assessments. Since the 2000s, a shift has occurred in how disability is measured. Instead of measurement via a medical framework, disability is measured on the basis of functional outcomes, activity limitations, and participation restrictions as part of a social and environmental framework (Simeonsson 2003). The World Health Organisation now uses the International Classification of Functioning, Disability and Health, rather than the old model of International Classification of Impairments, Disabilities and Handicaps (WHO 2001). Early intervention may not be able to change the physical outcomes of a motor disorder such as cerebral palsy (CP); however, it may change how affected individuals function and participate in society. For example, an intervention may affect motor outcomes in a more functional way. Furthermore, early developmental interventions may affect other areas of development, seen in improvements in behaviour, or parents themselves, seen in decreased levels of anxiety and depression; this has been demonstrated by several studies (Kaaresen 2006; Koldewijn 2009; Spittle 2009).

Finally, it is important to acknowledge that there are many factors that influence long‐term outcomes of children born preterm (Cheong 2020). These not only include access to early intervention but also family support, SES, brain injury, to name a few (Spittle 2021b). Whilst we have examined the long‐term effects of interventions that commenced very early in development, it is possible that children would benefit from further intervention throughout childhood, particularly if they are diagnosed with a specific disability or impairment (Morgan 2021).

Quality of the evidence

The certainty of the evidence for cognitive and motor outcomes was assessed with the GRADEpro software. Decisions were made to downgrade certainty where there are unclear methods of allocation concealment, a high rate of attrition bias, or inconsistency as a result of heterogeneity. Due to the nature of early developmental intervention programmes, blinding of the parents and therapists involved in implementing intervention is not possible, so this item was not considered when grading certainty. Where the treatment effect was large, GRADE classification was upgraded by one level. Although the direction of effects in the majority of included trials favoured the intervention group, substantial heterogeneity and risk of bias affected the GRADE classification decisions, as did imprecision in results where the confidence intervals were wide.

The certainty of evidence in infancy was downgraded because of inconsistency in results across studies, with substantial heterogeneity in some outcomes and age groups, but upgraded for cognitive outcomes because of the larger treatment effect. Overall, with a 'low' level of confidence, the evidence supports the findings that early developmental intervention programmes may improve cognitive and motor outcomes in infancy.

At preschool age, the certainty of evidence was graded as 'high' for cognitive outcomes and 'moderate' for motor outcomes. This demonstrates that intervention improves cognitive outcomes and probably does not improve motor outcomes at this age. The reason for downgrading the certainty of evidence for motor outcomes was serious imprecision in estimates of effect because of the small number of participants and wide 95% confidence intervals that included benefit as well as no benefit.

At school age, we rated the certainty of evidence as 'low' because of high attrition bias for both cognitive and motor outcomes, substantial heterogeneity in studies reporting cognitive outcomes, and serious imprecision in motor outcomes, and therefore, intervention may not improve these outcomes.

Potential biases in the review process

Trials of developmental interventions, by their nature, have some limitations. It is not feasible, in the case of a developmental programme, to mask the person implementing the intervention nor the recipient of the intervention (in this case, mother and baby) unless a comparison group providing an alternative intervention is used instead of a control group. Only one study provided a comparison treatment instead of a non‐treatment control (Melnyk 2001), however, this was a quasi‐randomised trial with a high risk of bias. When interventions are delivered, whether they focus on infant development or on the parent‐infant relationship, the component of parental support may affect outcomes. APIP 1998 was the only study to control for parent support by including three groups: one that received an infant development programme, one that received parent support only, and a control group. The assessments for methodological quality used in this review did not take sample size into account, although larger studies included in the meta‐analysis were weighted with respect to the overall effect. Sample size is important when the outcomes of individual programmes are assessed, as some studies may not have had enough power to demonstrate differences between groups. I.H.D.P. 1990 was by far the largest, including 985 infants, followed by APIP 1998, with 308 infants. Significant results reported by I.H.D.P. 1990 and a large sample size influenced the overall results of the meta‐analysis.

Follow‐up rates or attrition bias can be a problem for studies that assess outcomes at different time periods after an intervention. This review found that cognitive and motor outcomes assessed at infancy and preschool age were found to have better follow‐up rates, while those at school age were lower. A number of studies reported reduced follow‐up rates at school age and this attrition bias contributed to a lower certainty of evidence for this age group (APIP 1998; Goodman 1985; Koldewijn 2009; Nurcombe 1984).

Interventions received by 'treatment groups' in this review varied in theoretical content, environmental context, intensity, and duration of follow‐up. These contributed to significant levels of heterogeneity in the pooling of outcomes for some age groups and may limit the conclusions that can be drawn from these results. A wide variety of measurement tools were used in these studies, restricting the ability of review authors to pool data. Fewer measurement tools were utilised to assess cognitive development than were used to assess motor development; this made it possible for review authors to pool cognitive data for meta‐analysis at different ages. Effects of early intervention on motor development could be subjected to meta‐analysis in infancy only when the Bayley (Edition I, II or III) or Griffiths Locomotor Subscale were used. Other motor measurement tools that assess movement quality and motor performance in greater detail, such as the Alberta Infant Motor Scale (AIMS), the Test of Infant Motor Performance (TIMP) and Infant Motor Profile (IMP) were used by some studies. However, pooling these data for meta‐analysis was not appropriate. The diversity of motor assessment tools and lack of data at older ages limit the ability of review authors to compare results between studies. The meta‐analysis of long‐term effects of early developmental interventions on motor and cognitive outcomes was limited by the small number of studies and demonstrated high levels of attrition bias.

Details of standard follow‐up were not always well described. Many of the studies that reported details of follow‐up indicated that infants and families still had access to developmental services such as physiotherapy and social services (Goodman 1985; Nelson 2001; Ohgi 2004; Resnick 1988; Spittle 2009) and received physiotherapy in accordance with institutional policies, which may have influenced motor outcomes of the standard follow‐up group. The majority of studies do acknowledge that there are infants from this high‐risk population that will be referred for further therapy services due to concerns with development, and although evidence for some of these services is limited (Wang 2006), it could be considered unethical to prevent access to them. The amount of therapy an infant received in the standard care group is usually unknown and not quantified in the included studies and may improve outcomes, making a treatment effect more difficult to detect. Studies that gathered information regarding other services included Colditz 2019, where information was gathered by parent recall at the final assessment, and Dusing 2015, which utilised a system of parent recording and questionnaire during the study. Colditz 2019 noted that access to community services did not differ between groups, and Dusing 2015 reported that infants in the SPEEDI group received more therapeutic intervention than those in the standard care group.

The comparison or standard follow‐up group in the included studies is designed to provide a usual care situation with which to compare an intervention. The construct of this group is an important consideration in assessing the effectiveness of an intervention also, as it has the capacity to contaminate the results. It is often described as the medical follow‐up provided by a centre post discharge and received by all infants (both control and experimental). There is a risk, however, of contamination of control and intervention groups with additional treatments or other therapies, as families of preterm infants may seek additional treatment for a child who is perceived to be 'at risk' of developmental delay. They may also be referred if problems arise, and it would be unethical to prevent families from seeking other interventions. This review identified a small number of included studies that aimed to assess a new style of intervention programme with the traditional type that would be received by these infants and, in these cases, the traditional therapy is the comparison (Apaydin 2023; Ziegler 2021).

Some studies choose to compare an intervention that is more traditional and infant‐focused to one which focuses on the parent‐infant relationship, infant and environmental enrichment. This approach is more acceptable where the included preterm infants have a brain injury, but is also being used for lower‐risk preterm infants and the results vary between studies, with Apaydin 2023 reporting a small effect on cognitive function post intervention and Ziegler 2021 reporting a sustained effect of the intervention on motor function for COPCA compared to the NDT approach. In the study by Pascoali Rodovanski 2021, however, both groups received a package of generic activities for preterm infants at home in the first three months and the intervention received visual motor activities as well. There was no effect of intervention on motor outcomes at three months CA, which may in part be due to the standard care and intervention being too similar.

Spittle 2009 involved five of the six authors (JO, AS, RB, PA, LD) of this systematic review. Treyvaud 2022 (AS, PA, LD) involved three of the six authors of this review. One author from Finlayson 2020 (AS), Dusing 2018 (TT) and Colditz 2019 (RB) are also involved in this review. While we have adopted Cochrane review methods in conducting this review, readers must consider that there is the potential for bias as a result of involvement in these studies.

This review does not report any adverse events associated with the implementation of early intervention for preterm infants. The only study to assess adverse reactions to an intervention was Pascoali Rodovanski 2021 and strategies were implemented should this occur. While there have been no particular harms or adverse events identified in these intervention studies, there is the potential for such events particularly with respect to parent stress associated with the burden of intervention or the diagnosis of disability. Further safety in regard to falls or any other injuries that occur during intervention sessions should be documented. This is a limitation of the review and will be considered in the next update.

Agreements and disagreements with other studies or reviews

There continues to be considerable interest and debate about how to best reduce or prevent long‐term impairments and improve cognitive and motor outcomes for children born preterm. There is also increasing debate with respect to which style of intervention is the more effective in improving cognitive and/or motor outcomes. There are a number of RCTs and systematic reviews on this topic, and they continue to add to the body of knowledge in this area. Our first review in 2005 provided the first reported meta‐analysis of early developmental interventions provided post discharge from hospital for preterm infants. Blauw‐Hospers 2005 published a systematic review at a similar time investigating the effects of early intervention on motor outcomes for all infants at risk of, or diagnosed with, developmental motor disorders and included interventions that could have an inpatient‐only component (in contrast to our review which had to have a post discharge component). They reported that NIDCAP had a positive effect on motor outcomes for high‐risk infants. The Blauw‐Hospers 2005 systematic review was broader than the current review in that it included all early intervention programmes that began from birth to 18 months for all infants at risk of, or diagnosed with, developmental motor disorders. Review authors did not include preterm infants at 'low risk' of developmental motor disorders; therefore, many of the studies included in the current review were not included by Blauw‐Hospers 2005. Vanderveen 2009 in their systematic review, focused on early intervention programmes for preterm infants involving parents. This review also included interventions that were based only in the hospital, such as NIDCAP, along with interventions post hospital discharge, and their findings were similar to those reported in our review. They identified 25 studies that used a variety of interventions including parent education, infant stimulation, home visits and individualised developmental care. Meta‐analysis showed early improvement in cognitive and motor performance that was not sustained at school age. A more recent review by Khurana 2020 reviewed the literature on neonatal therapy that commenced in the NICU and continued post discharge on motor, cognitive and behavioural outcomes for preterm infants. Neonatal therapy was defined as being implemented using the synactive theory of development in a family‐centred model of care and was administered by a therapist or parent with therapist support. Fifteen studies were grouped into styles of intervention, such as parent‐delivered motor intervention (PDMI), therapist‐delivered postural control intervention (TDPCI), or developmental care and, while they were not able to use meta‐analysis, data were synthesised and the authors reported that the PDMI intervention, which is more task‐focused, had a positive effect on motor outcomes. There was limited evidence for effectiveness of the TDCPI intervention and developmental care for cognitive and motor outcomes and there were limited data post 12 months of age. Khurana 2020 reported considerable variability in focus of intervention, dosage and timing of interventions and study quality, which is a finding consistent with this current review.

Authors' conclusions

Implications for practice.

Meta‐analysis demonstrated that early developmental interventions post hospital discharge for preterm infants improve cognitive outcomes at preschool age and may improve cognitive and motor outcomes at infant age. At preschool age, the intervention may not improve motor outcomes. By school age, the intervention may not improve cognitive or motor outcomes.

Interventions that focus on both the parent‐infant relationship and infant development are more likely to have an effect on cognitive and motor development over the short to medium term compared with standard care. Heterogeneity between early developmental intervention programmes in regard to content, focus, and intensity limits the conclusions that can be drawn in this review.

Implications for research.

Additional high‐quality RCTs are needed to identify effective components of successful early developmental interventions for preterm infants. In particular, identifying the most effective focus for intervention, the best time to commence intervention and greater selectivity of high‐risk populations may identify the most effective construct and reveal those infants who may benefit the most from an intervention. Targeting an intervention in this way may reduce costs and increase effectiveness.

There is a need for longer‐term follow‐up high‐quality RCTs of interventions focusing on both motor and cognitive outcomes for preterm infants as only limited conclusions can be made from this review. In order to impact longer‐term outcomes, studies that focus on implementing an intervention not only in the early period but at other time points would be providing valuable information about the effectiveness of interventions on an ongoing basis.

Measurement tools for motor outcomes must be sensitive enough to detect changes in motor performance in infancy and older ages and to identify minor neurological problems. This review has not investigated effects on behaviour, parental outcomes (such as depression and anxiety), function, activity levels or participation, all of which may be influenced by early developmental intervention programmes.

What's new

Date	Event	Description
13 February 2024	New search has been performed	This updates the review, "Early developmental intervention programmes post hospital discharge to prevent motor and cognitive impairments in preterm infants", published in the Cochrane Database of Systematic Reviews (Spittle 2015). Searches were conducted up to July 13, 2023. This update includes 19 new studies and three papers with new data from studies already included. There are now 44 included studies in this review with 5051 participants.
13 February 2024	New citation required and conclusions have changed	There is a greater effect of intervention on motor outcomes at infant age in this current review; however, the effect size is still relatively small.

History

Protocol first published: Issue 4, 2005
Review first published: Issue 2, 2007

Date	Event	Description
11 January 2021	Amended	Submission February 2022
6 May 2020	Amended	Review "Early developmental intervention programs post‐hospital discharge to prevent motor and cognitive impairments in preterm infants", update not completed at this date.
21 August 2015	New citation required but conclusions have not changed	This review identified an additional 4 trials, along with 3 additional long‐term outcomes studies for trials that were previously included. A total of 25 trials are included in this review
21 August 2015	New search has been performed	This updates the review, "Early developmental intervention programs post‐hospital discharge to prevent motor and cognitive impairments in preterm infants", published in the Cochrane Database of Systematic Reviews (Spittle 2007)
1 October 2012	New citation required and conclusions have changed	This updated review identified an additional 6 studies, resulting in inclusion of a total of 21 studies in this review
17 September 2008	Amended	Converted to new review format
1 December 2006	New citation required and conclusions have changed	Substantive amendments made

Appendices

Appendix 1. Search strategy: CENTRAL

	CENTRAL via CRS
	July‐13‐2023
1	MESH DESCRIPTOR Adaptation, Psychological EXPLODE ALL AND CENTRAL:TARGET	6390
2	MESH DESCRIPTOR Brain Injuries EXPLODE ALL AND CENTRAL:TARGET	3237
3	MESH DESCRIPTOR Central Nervous System EXPLODE ALL AND CENTRAL:TARGET	14028
4	MESH DESCRIPTOR Cerebral Palsy EXPLODE ALL AND CENTRAL:TARGET	2125
5	MESH DESCRIPTOR Child Behavior EXPLODE ALL AND CENTRAL:TARGET	2813
6	MESH DESCRIPTOR Child Development EXPLODE ALL AND CENTRAL:TARGET	3311
7	MESH DESCRIPTOR cognition EXPLODE ALL AND CENTRAL:TARGET	16541
8	MESH DESCRIPTOR Cognition Disorders EXPLODE ALL AND CENTRAL:TARGET	7186
9	MESH DESCRIPTOR Developmental Disabilities EXPLODE ALL AND CENTRAL:TARGET	757
10	MESH DESCRIPTOR Infant Behavior EXPLODE ALL AND CENTRAL:TARGET	381
11	MESH DESCRIPTOR Intellectual Disability EXPLODE ALL AND CENTRAL:TARGET	1255
12	MESH DESCRIPTOR Social Skills EXPLODE ALL AND CENTRAL:TARGET	367
13	MESH DESCRIPTOR Intelligence EXPLODE ALL AND CENTRAL:TARGET	8296
14	MESH DESCRIPTOR Intelligence Tests EXPLODE ALL AND CENTRAL:TARGET	790
15	MESH DESCRIPTOR Learning Disabilities EXPLODE ALL AND CENTRAL:TARGET	719
16	MESH DESCRIPTOR Mental Processes EXPLODE ALL AND CENTRAL:TARGET	63889
17	MESH DESCRIPTOR Motor Activity EXPLODE ALL AND CENTRAL:TARGET	42059
18	MESH DESCRIPTOR Motor Skills EXPLODE ALL AND CENTRAL:TARGET	2293
19	MESH DESCRIPTOR Movement Disorders EXPLODE ALL AND CENTRAL:TARGET	8631
20	MESH DESCRIPTOR Nervous System EXPLODE ALL AND CENTRAL:TARGET	27027
21	MESH DESCRIPTOR Nervous System Physiological Phenomena EXPLODE ALL AND CENTRAL:TARGET	64622
22	MESH DESCRIPTOR Neurodevelopmental Disorders EXPLODE ALL AND CENTRAL:TARGET	9988
23	MESH DESCRIPTOR Neuropsychological Tests EXPLODE ALL AND CENTRAL:TARGET	18921
24	MESH DESCRIPTOR Psychomotor Disorders EXPLODE ALL AND CENTRAL:TARGET	1297
25	MESH DESCRIPTOR Psychomotor Performance EXPLODE ALL AND CENTRAL:TARGET	10411
26	MESH DESCRIPTOR Wechsler Scales EXPLODE ALL AND CENTRAL:TARGET	274
27	((adaptation and psychological) or ASQ or Bayley Scale* or birth injur* or brain injur* or central nervous system or cerebral injur* or cerebral palsy or child behavior or child behaviour or child development or cognition or cognition disorder* or cognitive delay* or cognitive development or developmental co‐ordination disorder* or developmental coordination disorder* or developmental disabilit* or developmental delay* or Griffiths Mental Development Scale or (infant* ADJ5 (behavior* or behaviour* or development* or temperament)) or intellectual impairment* or intellectual disabilit* or intelligence or intelligence test* or learning disabilit* or mental development* or mental processes or motor activit* or motor skill* or movement disorder* or nervous system or nervous system physiological phenomena or neurodevelopment* or neuropsychological test* or psychomotor delay or psychomotor disorder* or psychomotor performance or social skill* or Wechsler Scale*) AND CENTRAL:TARGET	125318
28	#1 OR #2 OR #3 OR #4 OR #5 OR #6 OR #7 OR #8 OR #9 OR #10 OR #11 OR #12 OR #13 OR #14 OR #15 OR #16 OR #17 OR #18 OR #19 OR #20 OR #21 OR #22 OR #23 OR #24 OR #25 OR #26 OR #27	267767
29	MESH DESCRIPTOR Musculoskeletal Manipulations EXPLODE ALL AND CENTRAL:TARGET	4107
30	MESH DESCRIPTOR Nervous System EXPLODE ALL AND CENTRAL:TARGET	27027
31	MESH DESCRIPTOR Occupational Therapy EXPLODE ALL AND CENTRAL:TARGET	1035
32	MESH DESCRIPTOR Parent‐Child Relations EXPLODE ALL AND CENTRAL:TARGET	2478
33	MESH DESCRIPTOR Parents EXPLODE ALL AND CENTRAL:TARGET	7558
34	MESH DESCRIPTOR Physical Therapy Modalities EXPLODE ALL AND CENTRAL:TARGET	35963
35	MESH DESCRIPTOR Physical Therapy Specialty EXPLODE ALL AND CENTRAL:TARGET	142
36	MESH DESCRIPTOR Play and Playthings EXPLODE ALL AND CENTRAL:TARGET	1527
37	MESH DESCRIPTOR Play Therapy EXPLODE ALL AND CENTRAL:TARGET	96
38	MESH DESCRIPTOR Social Support EXPLODE ALL AND CENTRAL:TARGET	4342
39	MESH DESCRIPTOR Touch EXPLODE ALL AND CENTRAL:TARGET	809
40	MESH DESCRIPTOR Therapeutic Touch EXPLODE ALL AND CENTRAL:TARGET	162
41	MESH DESCRIPTOR Massage EXPLODE ALL AND CENTRAL:TARGET	1691
42	MESH DESCRIPTOR Psychology, Educational EXPLODE ALL AND CENTRAL:TARGET	5941
43	MESH DESCRIPTOR Sensory Art Therapies EXPLODE ALL AND CENTRAL:TARGET	3371
44	MESH DESCRIPTOR Psychology EXPLODE ALL AND CENTRAL:TARGET	1508
45	MESH DESCRIPTOR Rehabilitation EXPLODE ALL AND CENTRAL:TARGET	51307
46	MESH DESCRIPTOR Exercise EXPLODE ALL AND CENTRAL:TARGET	38588
47	MESH DESCRIPTOR Exercise Movement Techniques EXPLODE ALL AND CENTRAL:TARGET	3213
48	(developmental care or (development* ADJ2 (program* or education* or intervention*)) or developmental neurorehabilitation or (early ADJ2 (intervention* or development* or education* or neurodevelopment* or therap* or program*)) or (educational ADJ2 behavioral ADJ2 program*) or (educational ADJ2 behavioural ADJ2 program*) or exercise* or father child relation* or home intervention* or home care service* or infant cue* or infant stimulation* or (intervention* ADJ2 program*) or massage or mother child relations* or ((multisensory or auditory or tactile or visual or vestibular) ADJ2 (intervention* or stimulat*)) or musculoskeletal manipulation* or music therap* or neurodevelopmental therap* or neuro‐developmental therap* or occupational therap* or parent child relation* or parent infant relation* or (parent* ADJ2 (education* or psychology)) or parent‐focused intervention program* or parenting intervention* or physical therap* or physiotherapy* or play* or psycholog* or psychosocial functioning or rehabilitation or sensory therap* or sensorimotor stimulation treatment* or social support* or touch or therapeutic touch) AND CENTRAL:TARGET	401543
49	#29 OR #30 OR #31 OR #32 OR #33 OR #34 OR #35 OR #36 OR #37 OR #38 OR #39 OR #40 OR #41 OR #42 OR #43 OR #44 OR #45 OR #46 OR #47 OR #48	436539
50	MESH DESCRIPTOR Infant, Newborn EXPLODE ALL AND CENTRAL:TARGET	20493
51	( infant or infants or infant's or "infant s" or infantile or infancy or newborn* or "new born" or "new borns" or "newly born" or neonat* or baby* or babies or premature or prematures or prematurity or preterm or preterms or "pre term" or premies or "low birth weight" or "low birthweight" or VLBW or LBW or ELBW or NICU) AND CENTRAL:TARGET	105269
52	#50 OR #51	105272
53	#28 AND #49 AND #52	8924
54	2015 TO 2023:YR AND CENTRAL:TARGET AND #53	4583

Appendix 2. Search strategy: MEDLINE

	Ovid MEDLINE(R) All: July‐13‐2023
#	Searches	Results
1	exp Adaptation, Psychological/	139752
2	exp Brain Injuries/pc [Prevention & Control]	2540
3	exp Central Nervous System/gd, in [Growth & Development, Injuries]	54052
4	exp Cerebral Palsy/	23628
5	exp Child Behavior/	27148
6	exp Child Development/	66506
7	exp Cognition/	198417
8	exp Cognition Disorders/	115998
9	exp Developmental Disabilities/	22313
10	exp Infant Behavior/	3807
11	exp Intellectual Disability/	105273
12	exp social skills/	2681
13	exp Intelligence/ or exp Intelligence tests/ or exp learning disabilities/ or exp mental processes/ or exp motor activity/ or exp motor skills/ or exp motor skills disorders/ or exp movement disorders/	1772083
14	exp Nervous System/gd [Growth & Development]	53089
15	exp Nervous System Physiological Phenomena/	1170372
16	exp Neurodevelopmental Disorders/	209353
17	exp Neuropsychological Tests/	192766
18	exp Psychomotor Disorders/	14527
19	exp Psychomotor Performance/	121146
20	exp Wechsler Scales/	6530
21	((adaptation and psychological) or ASQ or Bayley Scale* or birth injur* or brain injur* or central nervous system or cerebral injur* or cerebral palsy or child behavior or child behaviour or child development or cognition or cognition disorder* or cognitive delay* or cognitive development or developmental co‐ordination disorder* or developmental coordination disorder* or developmental disabilit* or developmental delay* or Griffiths Mental Development Scale or (infant* adj5 (behavior* or behaviour* or development* or temperament)) or intellectual impairment* or intellectual disabilit* or intelligence or intelligence test* or learning disabilit* or mental development* or mental processes or motor activit* or motor skill* or movement disorder* or nervous system or nervous system physiological phenomena or neurodevelopment* or neuropsychological test* or psychomotor delay or psychomotor disorder* or psychomotor performance or social skill* or Wechsler Scale*).mp.	1604959
22	or/1‐21 [Conditions]	3754308
23	exp Birth Injuries/rh, th [Rehabilitation, Therapy]	332
24	exp Brain Injuries/rh, th [Rehabilitation, Therapy]	15472
25	exp Early Intervention, Educational/	3515
26	exp Home Care Services/	50855
27	exp Mother‐Child Relations/	22854
28	exp Musculoskeletal Manipulations/	18670
29	exp Nervous System/th [Therapy]	32
30	exp Occupational Therapy/	14858
31	exp parent‐child relations/ or exp father‐child relations/	60846
32	exp Parents/ed, px [Education, Psychology]	66303
33	exp Physical Therapy Modalities/	178461
34	exp Physical Therapy Specialty/	2972
35	exp "Play and Playthings"/	16750
36	exp Play Therapy/	1195
37	exp Social Support/	79798
38	exp Touch/	18126
39	exp Therapeutic Touch/	978
40	exp Massage/	6915
41	exp Psychology, Educational/	121875
42	exp sensory art therapies/	55239
43	exp Psychology/	70496
44	exp Rehabilitation/	352765
45	exp Exercise/	246373
46	exp Exercise Movement Techniques/	10286
47	(developmental care or (development* adj2 (program* or education* or intervention*)) or developmental neurorehabilitation or (early adj2 (intervention* or development* or education* or neurodevelopment* or therap* or program*)) or (educational adj2 behavioral adj2 program*) or (educational adj2 behavioural adj2 program*) or exercise* or father‐child relation* or home intervention* or home care service* or infant cue* or infant stimulation* or (intervention* adj2 program*) or massage or mother‐child relations* or ((multisensory or auditory or tactile or visual or vestibular) adj2 (intervention* or stimulat*)) or musculoskeletal manipulation* or music therap* or neurodevelopmental therap* or neuro‐developmental therap* or occupational therap* or parent‐child relation* or parent‐infant relation* or (parent* adj2 (education* or psychology)) or parent‐focused intervention program* or parenting intervention* or physical therap* or physiotherapy* or play* or psycholog* or psychosocial functioning or rehabilitation or sensory therap* or sensorimotor stimulation treatment* or social support* or touch or therapeutic touch).mp.	4064401
48	or/23‐47 [Interventions]	4340630
49	(randomized controlled trial or controlled clinical trial).pt.	686569
50	(randomi?ed or randomly).ti,ab.	1106383
51	(trial or groups or placebo*).ti,ab.	3226676
52	((single or doubl* or tripl* or treb*) and (blind* or mask*)).ti,ab.	224832
53	or/49‐52	3776763
54	exp animals/ not humans.sh.	5137253
55	53 not 54 [RCT filter‐amended version of Cochrane filter to increase sensitivity]	3264918
56	exp infant, newborn/ or exp Infant/	1251414
57	(newborn* or new born or new borns or newly born or baby* or babies or premature or prematurity or preterm or pre term or low birth weight or low birthweight or VLBW or LBW or infant or infants or 'infant s' or infant's or infantile or infancy or neonat*).ti,ab.	967467
58	or/56‐57 [Neonatal Population Filter]	1697830
59	and/22,48,55,58 [Condition & Intervention & RCT & Neonatal Terms]	13547
60	59 and ("2015" or "2016" or "2017" or "2018" or "2019" or 202*).yr.	5521

Appendix 3. Search strategy: Embase

	Embase (OVID) 1974 to 2023 July 12
	Date limit: 2023
#	Searches	Results
1	coping behavior/	74172
2	exp brain injury/pc [Prevention]	4504
3	central nervous system/	497047
4	exp cerebral palsy/	44669
5	exp child behavior/	56039
6	exp child development/	50033
7	exp cognition/	3003514
8	exp cognitive defect/	617148
9	exp developmental disorder/	60128
10	exp child behavior/	56039
11	exp intellectual impairment/	620098
12	exp social competence/	7688
13	exp intelligence/ or exp mental capacity/	98647
14	exp intelligence test/ or cognitive function test/ or exp wechsler intelligence scale/	24836
15	exp learning disorder/	40523
16	exp mental function/	4555902
17	exp motor activity/	642673
18	exp motor performance/	91726
19	exp psychomotor disorder/	88826
20	exp motor dysfunction/	910897
21	exp nervous system/ and (growth or development or developing).ti,ab,kw.	489964
22	physiological process/	16086
23	brain development/ or nervous system development/ or brain maturation/	108794
24	exp neuropsychological test/ or cognitive function test/ or motor function test/ or perception test/	140930
25	psychomotor disorder/	6369
26	exp psychomotor performance/	211755
27	((adaptation and psychological) or ASQ or Bayley Scale* or birth injur* or brain injur* or central nervous system or cerebral injur* or cerebral palsy or child behavior or child behaviour or child development or cognition or cognition disorder* or cognitive delay* or cognitive development or developmental co‐ordination disorder* or developmental coordination disorder* or developmental disabilit* or developmental delay* or Griffiths Mental Development Scale or (infant* adj5 (behavior* or behaviour* or development* or temperament)) or intellectual impairment* or intellectual disabilit* or intelligence or intelligence test* or learning disabilit* or mental development* or mental processes or motor activit* or motor skill* or movement disorder* or nervous system or nervous system physiological phenomena or neurodevelopment* or neuropsychological test* or psychomotor delay or psychomotor disorder* or psychomotor performance or social skill* or Wechsler Scale*).mp.	2178492
28	or/1‐27 [Conditions]	7153933
29	exp birth injury/	6166
30	exp brain injury/rh, th [Rehabilitation, Therapy]	12585
31	early intervention/	33577
32	early childhood intervention/	3209
33	exp home care/	88361
34	mother child relation/ or child parent relation/	87887
35	exp musculoskeletal manipulation/ or manipulative medicine/	16353
36	exp nervous system/ and (therapy or therapies or therapeutic*).ti,ab,kw.	380078
37	occupational therapy/ or rehabilitation/	121494
38	father child relation/	3745
39	parent/ and (education* or psychology).mp.	27420
40	exp physiotherapy/	107923
41	exp play/ or exp play therapy/	6007
42	exp social support/	116477
43	exp therapeutic touch/ or exp touch/	33405
44	massage/	16763
45	exp *psychology/	200244
46	exp *rehabilitation/	133593
47	exp *exercise/	178046
48	exp *"movement (physiology)"/	146614
49	(developmental care or (development* adj2 (program* or education* or intervention*)) or developmental neurorehabilitation or (early adj2 (intervention* or development* or education* or neurodevelopment* or therap* or program*)) or (educational adj2 behavioral adj2 program*) or (educational adj2 behavioural adj2 program*) or exercise* or father‐child relation* or home intervention* or home care service* or infant cue* or infant stimulation* or (intervention* adj2 program*) or massage or mother‐child relations* or ((multisensory or auditory or tactile or visual or vestibular) adj2 (intervention* or stimulat*)) or musculoskeletal manipulation* or music therap* or neurodevelopmental therap* or neuro‐developmental therap* or occupational therap* or parent‐child relation* or parent‐infant relation* or (parent* adj2 (education* or psychology)) or parent‐focused intervention program* or parenting intervention* or physical therap* or physiotherapy* or play* or psycholog* or psychosocial functioning or rehabilitation or sensory therap* or sensorimotor stimulation treatment* or social support* or touch or therapeutic touch).mp.	4465183
50	or/29‐49 [Interventions]	5061386
51	newborn/ or prematurity/	675589
52	(infant or infants or infant? or infantile or infancy or newborn* or new born or new borns or newly born or neonat* or baby* or babies or premature or prematures or prematurity or preterm or preterms or pre term or preemie or preemies or premies or low birth weight or low birthweight or VLBW or LBW or ELBW or NICU).ti,ab,kw.	1221558
53	or/51‐52 [Cochrane Neonatal standard search terms‐EMBASE]	1445972
54	Randomized controlled trial/ or Controlled clinical study/	986130
55	random$.ti,ab,kw.	1993209
56	Randomization/	99643
57	placebo.ti,ab,kw.	368827
58	((double or single or doubly or singly) adj (blind or blinded or blindly)).ti,ab,kw.	276047
59	double blind procedure/	211964
60	(controlled adj7 (study or design or trial)).ti,ab,kw.	455161
61	parallel group$1.ti,ab.	32493
62	(crossover or cross over).ti,ab.	125361
63	((assign$ or match or matched or allocation) adj5 (alternate or group$1 or intervention$1 or patient$1 or subject$1 or participant$1)).ti,ab.	418554
64	(open adj label).ti,ab.	110172
65	or/54‐64 [ Terms based on Cochrane Central strategy]	2811370
66	(exp animals/ or exp invertebrate/ or animal experiment/ or animal model/ or animal tissue/ or animal cell/ or nonhuman/) and (human/ or normal human/ or human cell/)	25723219
67	exp animals/ or exp invertebrate/ or animal experiment/ or animal model/ or animal tissue/ or animal cell/ or nonhuman/	33004288
68	67 not 66 [Animal Exclusion‐Anne Eisinga, Cochrane UK]	7281069
69	65 not 68 [Filter: RCT‐EMBASE]	2518236
70	and/28,50,53,69 [Conditions & Interventions & Neonate & RCT]	7825
71	70 and 2023.yr.	259

Embase, OVID, 1974 to 2021 August 13

Date limit: 2021

1 coping behavior/ (64348)
2 exp brain injury/pc [Prevention] (4212)
3 central nervous system/ (480072)
4 exp cerebral palsy/ (39189)
5 exp child behavior/ (51353)
6 exp child development/ (46726)
7 exp cognition/ (2463893)
8 exp cognitive defect/ (527236)
9 exp developmental disorder/ (49420)
10 exp child behavior/ (51353)
11 exp intellectual impairment/ (540433)
12 exp social competence/ (5640)
13 exp intelligence/ or exp mental capacity/ (84478)
14 exp intelligence test/ or cognitive function test/ or exp wechsler intelligence scale/ (20718)
15 exp learning disorder/ (36518)
16 exp mental function/ (3994120)
17 exp motor activity/ (572936)
18 exp motor performance/ (79751)
19 exp psychomotor disorder/ (78906)
20 exp motor dysfunction/ (800678)
21 exp nervous system/ and (growth or development or developing).ti,ab,kw. (427648)
22 physiological process/ (12504)
23 brain development/ or nervous system development/ or brain maturation/ (93914)
24 exp neuropsychological test/ or cognitive function test/ or motor function test/ or perception test/ (118668)
25 psychomotor disorder/ (5876)
26 exp psychomotor performance/ (199063)
27 ((adaptation and psychological) or ASQ or Bayley Scale* or birth injur* or brain injur* or central nervous system or cerebral injur* or cerebral palsy or child behavior or child behaviour or child development or cognition or cognition disorder* or cognitive delay* or cognitive development or developmental co‐ordination disorder* or developmental coordination disorder* or developmental disabilit* or developmental delay* or Griffiths Mental Development Scale or (infant* adj5 (behavior* or behaviour* or development* or temperament)) or intellectual impairment* or intellectual disabilit* or intelligence or intelligence test* or learning disabilit* or mental development* or mental processes or motor activit* or motor skill* or movement disorder* or nervous system or nervous system physiological phenomena or neurodevelopment* or neuropsychological test* or psychomotor delay or psychomotor disorder* or psychomotor performance or social skill* or Wechsler Scale*).mp. (1929707)
28 or/1‐27 [Conditions] (6290099)
29 exp birth injury/ (5535)
30 exp brain injury/rh, th [Rehabilitation, Therapy] (11500)
31 early intervention/ (27598)
32 early childhood intervention/ (2943)
33 exp home care/ (78724)
34 mother child relation/ or child parent relation/ (77432)
35 exp musculoskeletal manipulation/ or manipulative medicine/ (14865)
36 exp nervous system/ and (therapy or therapies or therapeutic*).ti,ab,kw. (321507)
37 occupational therapy/ or rehabilitation/ (107417)
38 father child relation/ (3592)
39 parent/ and (education* or psychology).mp. (26305)
40 exp physiotherapy/ (92682)
41 exp play/ or exp play therapy/ (5625)
42 exp social support/ (99146)
43 exp therapeutic touch/ or exp touch/ (28601)
44 massage/ (14936)
45 exp *psychology/ (188170)
46 exp *rehabilitation/ (119152)
47 exp *exercise/ (154120)
48 exp *"movement (physiology)"/ (135003)
49 (developmental care or (development* adj2 (program* or education* or intervention*)) or developmental neurorehabilitation or (early adj2 (intervention* or development* or education* or neurodevelopment* or therap* or program*)) or (educational adj2 behavioral adj2 program*) or (educational adj2 behavioural adj2 program*) or exercise* or father‐child relation* or home intervention* or home care service* or infant cue* or infant stimulation* or (intervention* adj2 program*) or massage or mother‐child relations* or ((multisensory or auditory or tactile or visual or vestibular) adj2 (intervention* or stimulat*)) or musculoskeletal manipulation* or music therap* or neurodevelopmental therap* or neuro‐developmental therap* or occupational therap* or parent‐child relation* or parent‐infant relation* or (parent* adj2 (education* or psychology)) or parent‐focused intervention program* or parenting intervention* or physical therap* or physiotherapy* or play* or psycholog* or psychosocial functioning or rehabilitation or sensory therap* or sensorimotor stimulation treatment* or social support* or touch or therapeutic touch).mp. (3941063)
50 or/29‐49 [Interventions] (4458107)
51 newborn/ or prematurity/ (611328)
52 (infant or infants or infant? or infantile or infancy or newborn* or new born or new borns or newly born or neonat* or baby* or babies or premature or prematures or prematurity or preterm or preterms or pre term or preemie or preemies or premies or low birth weight or low birthweight or VLBW or LBW or ELBW or NICU).ti,ab,kw. (1094057)
53 or/51‐52 [Cochrane Neonatal standard search terms‐EMBASE] (1304232)
54 Randomized controlled trial/ or Controlled clinical study/ (858467)
55 random$.ti,ab,kw. (1698951)
56 Randomization/ (91580)
57 placebo.ti,ab,kw. (328104)
58 ((double or single or doubly or singly) adj (blind or blinded or blindly)).ti,ab,kw. (247366)
59 double blind procedure/ (186476)
60 (controlled adj7 (study or design or trial)).ti,ab,kw. (392589)
61 parallel group$1.ti,ab. (27911)
62 (crossover or cross over).ti,ab. (112038)
63 ((assign$ or match or matched or allocation) adj5 (alternate or group$1 or intervention$1 or patient$1 or subject$1 or participant$1)).ti,ab. (360306)
64 (open adj label).ti,ab. (89765)
65 or/54‐64 [ Terms based on Cochrane Central strategy] (2441629)
66 (exp animals/ or exp invertebrate/ or animal experiment/ or animal model/ or animal tissue/ or animal cell/ or nonhuman/) and (human/ or normal human/ or human cell/) (22610260)
67 exp animals/ or exp invertebrate/ or animal experiment/ or animal model/ or animal tissue/ or animal cell/ or nonhuman/ (29330871)
68 67 not 66 [Animal Exclusion‐Anne Eisinga, Cochrane UK] (6720611)
69 65 not 68 [Filter: RCT‐EMBASE] (2179828)
70 and/28,50,53,69 [Conditions & Interventions & Neonate & RCT] (6709)
71 70 and "2021".yr. [Date restricted; top up search to account for records not yet in CENTRAL] (295)

Appendix 4. Search strategy: CINAHL

	CINAHL Complete, Ebscohost
	July‐13‐2023
	( ((adaptation and psychological) or ASQ or Bayley Scale* or birth injur* or brain injur* or central nervous system or cerebral injur* or cerebral palsy or child behavior or child behaviour or child development or cognition or cognition disorder* or cognitive delay* or cognitive development or developmental co‐ordination disorder* or developmental coordination disorder* or developmental disabilit* or developmental delay* or Griffiths Mental Development Scale or (infant* N5 (behavior* or behaviour* or development* or temperament)) or intellectual impairment* or intellectual disabilit* or intelligence or intelligence test* or learning disabilit* or mental development* or mental processes or motor activit* or motor skill* or movement disorder* or nervous system or nervous system physiological phenomena or neurodevelopment* or neuropsychological test* or psychomotor delay or psychomotor disorder* or psychomotor performance or social skill* or Wechsler Scale*) ) AND ( (developmental care or (development* N2 (program* or education* or intervention*)) or developmental neurorehabilitation or (early N2 (intervention* or development* or education* or neurodevelopment* or therap* or program*)) or (educational N2 behavioral N2 program*) or (educational N2 behavioural N2 program*) or exercise* or father child relation* or home intervention* or home care service* or infant cue* or infant stimulation* or (intervention* N2 program*) or massage or mother child relations* or ((multisensory or auditory or tactile or visual or vestibular) N2 (intervention* or stimulat*)) or musculoskeletal manipulation* or music therap* or neurodevelopmental therap* or neuro‐developmental therap* or occupational therap* or parent child relation* or parent infant relation* or (parent* N2 (education* or psychology)) or parent‐focused intervention program* or parenting intervention* or physical therap* or physiotherapy* or play* or psycholog* or psychosocial functioning or rehabilitation or sensory therap* or sensorimotor stimulation treatment* or social support* or touch or therapeutic touch) ) AND ( (infant or infants or infant’s or infantile or infancy or newborn* or "new born" or "new borns" or "newly born" or neonat* or baby* or babies or premature or prematures or prematurity or preterm or preterms or "pre term" or premies or "low birth weight" or "low birthweight" or VLBW or LBW) ) AND ( (randomized controlled trial OR controlled clinical trial OR randomized OR randomised OR placebo OR clinical trials as topic OR randomly OR trial OR PT clinical trial)	3617
	Publilshed date: 2015‐‐2023	1986

Appendix 5. Search strategy: PsycINFO

	PsycINFO OVID July 13 2023
#	Searches	Results
1	neonatal development/	2166
2	((neonate* or newborn* or new born* or (prematur* adj2 infant*)) adj4 development*).ti,ab,id.	908
3	or/1‐2 [Infant development]	2959
4	exp cognitive development/ or psychological development/ or brain development/	80906
5	cerebral palsy/ or brain disorders/ or exp movement disorders/	42492
6	neural development/ or exp brain development/	18073
7	exp movement disorders/ or intellectual development disorder/	79391
8	neurorehabilitation/ or neuropsychological rehabilitation/	2690
9	adaptive behavior/ or adaptive behavior measures/	4559
10	early childhood development/	16594
11	exp Learning Disabilities/ or exp brain injuries/ or exp central nervous system disorders/	272907
12	((adaptation adj4 psychological) or birth injur* or brain injur* or central nervous system or cerebral injur* or cerebral palsy or child behavior or child behaviour or child development or cognition or cognition disorder* or cognitive delay* or cognitive development or developmental co‐ordination disorder* or developmental coordination disorder* or developmental disabilit* or developmental delay* or (infant* adj5 (behavior* or behaviour* or development* or temperament)) or intellectual impairment* or intellectual disabilit* or intelligence or intelligence test* or learning disabilit* or mental development* or mental processes or (mental* adj2 retard*) or motor activit* or motor skill* or movement disorder* or nervous system or nervous system physiological phenomena or neurodevelopment* or neuropsychological test* or psychomotor delay or psychomotor disorder* or psychomotor performance or social skill*).ab,id,ti.	492663
13	or/4‐12	774083
14	(developmental care or (development* adj2 education*) or developmental neurorehabilitation or (early adj2 (development* or education* or neurodevelopment* or therap*)) or exercise* or father child relation* or home intervention* or home care service* or infant cue* or infant stimulation* or massage or mother child relations* or ((multisensory or auditory or tactile or visual or vestibular) adj2 stimulat*) or musculoskeletal manipulation* or music therap* or neurodevelopmental therap* or neuro‐developmental therap* or occupational therap* or parent child relation* or parent infant relation* or parent‐focused or physical therap* or physiotherapy* or play* or psycholog* or psychosocial functioning or rehabilitation or sensory therap* or sensorimotor stimulation treatment* or social support* or touch).ti,ab,id.	1168500
15	physical therapy/ or massage/	4123
16	(care or program* or intervention*).ti,ab,id.	1109571
17	"bayley scales of infant development"/ or developmental measures/ or intelligence measures/ or wechsler intelligence scale for children/	11331
18	(bayley scale* or ((developmental or intelligenc*) adj3 measur*) or wechsler or Griffith* Mental Development Scale*).ti,ab,id.	21756
19	exp Parent Child Communication/ or exp Parent Training/ or exp Intervention/	153667
20	or/14‐19	2018064
21	neonatal intensive care/	1981
22	(infant or infants or infant or infantile or infancy or newborn* or new born newly born or neonat* or baby* or babies or premature or prematures or prematurity or preterm or preterms or pre term or premies or "low birth weight" or "low birthweight" or VLBW or LBW).ti,ab,id.	144577
23	or/21‐22	144603
24	randomized controlled trials/	996
25	clinical trials/	12206
26	(random* or quasirandom* or quasi‐random*).ti,ab,id.	239911
27	24 or 25 or 26	245220
28	13 and 20 and 23 and 27	1218
29	3 and 27	148
30	or/28‐29	1311
31	limit 30 to human	1211
32	limit 31 to ("0100 journal" or "0110 peer‐reviewed journal" or "0120 non‐peer‐reviewed journal" or "0130 peer‐reviewed status unknown")	1073
33	limit 32 to yr="2021 ‐Current"	96

	PsycINFO via ProQuest:
	Search date: August 16, 2021
	NOFT= any fiield except full‐text
1	noft ((adaptation and psychological) or ASQ or Bayley Scale* or birth injur* or brain injur* or central nervous system or cerebral injur* or cerebral palsy or child behavior or child behaviour or child development or cognition or cognition disorder* or cognitive delay* or cognitive development or developmental co‐ordination disorder* or developmental coordination disorder* or developmental disabilit* or developmental delay* or Griffiths Mental Development Scale or (infant* N5 (behavior* or behaviour* or development* or temperament)) or intellectual impairment* or intellectual disabilit* or intelligence or intelligence test* or learning disabilit* or mental development* or mental processes or motor activit* or motor skill* or movement disorder* or nervous system or nervous system physiological phenomena or neurodevelopment* or neuropsychological test* or psychomotor delay or psychomotor disorder* or psychomotor performance or social skill* or Wechsler Scale*)	75,806
2	noft (developmental care or (development* N2 (program* or education* or intervention*)) or developmental neurorehabilitation or (early N2 (intervention* or development* or education* or neurodevelopment* or therap* or program*)) or (educational N2 behavioral N2 program*) or (educational N2 behavioural N2 program*) or exercise* or father child relation* or home intervention* or home care service* or infant cue* or infant stimulation* or (intervention* N2 program*) or massage or mother child relations* or ((multisensory or auditory or tactile or visual or vestibular) N2 (intervention* or stimulat*)) or musculoskeletal manipulation* or music therap* or neurodevelopmental therap* or neuro‐developmental therap* or occupational therap* or parent child relation* or parent infant relation* or (parent* N2 (education* or psychology)) or parent‐focused intervention program* or parenting intervention* or physical therap* or physiotherapy* or play* or psycholog* or psychosocial functioning or rehabilitation or sensory therap* or sensorimotor stimulation treatment* or social support* or touch or therapeutic touch)	166,426
3	noft (infant or infants or infant’s or infantile or infancy or newborn* or "new born" or "new borns" or "newly born" or neonat* or baby* or babies or premature or prematures or prematurity or preterm or preterms or "pre term" or premies or "low birth weight" or "low birthweight" or VLBW or LBW)
4	noft (randomized controlled trial OR controlled clinical trial OR randomized OR randomised OR placebo OR clinical trials as topic OR randomly OR trial)
5	Date: 2015‐2021	1324

Appendix 6. Search strategy: ISRCTN

Date	Site	Terms	Results
July‐17‐2023	clinicaltrials.gov	development cognitive neonate [Other terms]	237
July‐17‐2023	clinicaltrials.gov	development neonate early [Other terms]	132
July‐17‐2023	clinicaltrials.gov	development neonate neuro [Other terms]	47
July‐17‐2023	clinicaltrials.gov	development neonate motor [Other terms]	279
July‐17‐2023	clinicaltrials.gov	development neonate cerebral palsy [Other terms]	101
July‐17‐2023	clinicaltrials.gov	development neonate brain program [Other terms]	43
July‐17‐2023	clinicaltrials.gov	development neonate brain community [Other terms]	11
July‐17‐2023	clinicaltrials.gov	development neonate brain parent [Other terms]	85
July‐17‐2023	clinicaltrials.gov	development neonate brain home [Other terms]	45
July‐17‐2023	clinicaltrials.gov	development neonate brain and child (birth‐17 years) [Other terms]	5
July‐17‐2023	clinicaltrials.gov	development neonate brain family [Other terms]	49
July‐17‐2023	ICTRP	cognitive and neonate [homepage search box]	0
July‐17‐2023	ICTRP	brain development AND neonate [homepage search box]	0
July‐17‐2023	ICTRP	cognition AND neonate [homepage search box]	0
July‐17‐2023	ICTRP	developmental AND neonate [homepage search box]	4
July‐17‐2023	ICTRP	Early development AND neonate [homepage search box]	1
July‐17‐2023	ICTRP	Note: Tried other combinations as for the clinicaltrials.gov searches and retrieved 0 results consistently.
July‐17‐2023	ISRCTN	early developmental interventions within Participant age range: Neonate ‐ 3 unique results	10
July‐17‐2023	ISRCTN	developmental care within Participant age range: Neonate ‐ 0 unique results	20
July‐17‐2023	ISRCTN	early developmental care AND infant* within Participant age range: Child ‐ 1 unique result	6
July‐17‐2023	ISRCTN	early developmental interventions; within Participant age range: Neonate	4
			1079

Appendix 7. Risk of bias tool

1. Sequence generation (checking for possible selection bias). Was the allocation sequence adequately generated?

For each included study, we categorised the method used to generate the allocation sequence as:

1. low risk (any truly random process e.g. random number table; computer random number generator);

2. high risk (any non‐random process e.g. odd or even date of birth; hospital or clinic record number); or

3. unclear risk.

2. Allocation concealment (checking for possible selection bias). Was allocation adequately concealed?

For each included study, we categorised the method used to conceal the allocation sequence as:

1. low risk (e.g. telephone or central randomisation; consecutively numbered sealed opaque envelopes);

2. high risk (open random allocation; unsealed or non‐opaque envelopes, alternation; date of birth); or

3. unclear risk.

3. Blinding (performance bias and detection bias). Was knowledge of the allocated intervention adequately prevented during the study?

For each included study, we categorised the methods used to blind study participants and personnel from knowledge of which intervention a participant received. Blinding was assessed separately for different outcomes or class of outcomes. We categorised the methods as:

1. low risk, high risk or unclear risk for participants; and

2. low risk, high risk or unclear risk for personnel.

4. Blinding of outcome assessment (checking for possible detection bias). Was knowledge of the allocated intervention adequately prevented at the time of outcome assessment?

For each included study, we categorised the methods used to blind outcome assessment. Blinding was assessed separately for different outcomes or class of outcomes. We categorised the methods as:

1. low risk for outcome assessors;

2. high risk for outcome assessors; or

3. unclear risk for outcome assessors.

5. Incomplete outcome data (checking for possible attrition bias through withdrawals, dropouts, protocol deviations). Were incomplete outcome data adequately addressed?

For each included study and for each outcome, we described the completeness of data including attrition and exclusions from the analysis. We noted whether attrition and exclusions were reported, the numbers included in the analysis at each stage (compared with the total randomised participants), reasons for attrition or exclusion where reported, and whether missing data were balanced across groups or were related to outcomes. Where sufficient information was reported or supplied by the trial authors, we re‐included missing data in the analyses. We categorised the methods as:

1. low risk (< 20% missing data);

2. high risk (≥ 20% missing data); or

3. unclear risk.

6. Selective reporting bias. Are reports of the study free of suggestion of selective outcome reporting?

For each included study, we described how we investigated the possibility of selective outcome reporting bias and what we found. For studies in which study protocols were published in advance, we compared prespecified outcomes versus outcomes eventually reported in the published results. If the study protocol was not published in advance, we contacted study authors to gain access to the study protocol. We assessed the methods as:

1. low risk (where it is clear that all of the study's prespecified outcomes and all expected outcomes of interest to the review have been reported);

2. high risk (where not all the study's prespecified outcomes have been reported; one or more reported primary outcomes were not prespecified outcomes of interest and are reported incompletely and so cannot be used; study fails to include results of a key outcome that would have been expected to have been reported); or

3. unclear risk.

7. Other sources of bias. Was the study apparently free of other problems that could put it at a high risk of bias?

For each included study, we described any important concerns we had about other possible sources of bias (for example, whether there was a potential source of bias related to the specific study design or whether the trial was stopped early due to some data‐dependent process). We assessed whether each study was free of other problems that could put it at risk of bias as:

1. low risk;

2. high risk; or

3. unclear risk.

If needed, we explored the impact of the level of bias through undertaking sensitivity analyses.

Data and analyses

Comparison 1. Early developmental intervention versus standard follow‐up (all studies).

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1.1 Cognitive outcome in infancy ‐ Developmental Quotient	25	3132	Std. Mean Difference (IV, Random, 95% CI)	0.27 [0.15, 0.40]
1.2 Cognitive outcome at preschool age ‐ Intelligence Quotient	9	1524	Std. Mean Difference (IV, Fixed, 95% CI)	0.39 [0.29, 0.50]
1.3 Cognitive outcome at school age ‐ Intelligence Quotient	6	1453	Std. Mean Difference (IV, Random, 95% CI)	0.16 [‐0.06, 0.38]
1.4 Motor outcome in infancy ‐ Developmental Quotient	23	2737	Std. Mean Difference (IV, Fixed, 95% CI)	0.12 [0.04, 0.19]
1.5 Motor outcome at preschool age	3	264	Std. Mean Difference (IV, Fixed, 95% CI)	0.08 [‐0.16, 0.32]
1.6 Motor outcome at school age	3	265	Std. Mean Difference (IV, Fixed, 95% CI)	‐0.06 [‐0.31, 0.18]
1.7 Motor outcome at school age	3	413	Risk Ratio (M‐H, Fixed, 95% CI)	1.04 [0.82, 1.32]
1.8 Rate of cerebral palsy	9	1033	Risk Ratio (M‐H, Fixed, 95% CI)	0.85 [0.57, 1.25]

Comparison 2. Early developmental intervention versus standard follow‐up (subgroup analysis: gestational age).

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
2.1 Cognitive outcome in infancy ‐ Developmental Quotient	1		Std. Mean Difference (IV, Fixed, 95% CI)	Subtotals only
2.1.1 28 to < 32 weeks	1	153	Std. Mean Difference (IV, Fixed, 95% CI)	0.09 [‐0.25, 0.43]
2.1.2 < 28 weeks	1	87	Std. Mean Difference (IV, Fixed, 95% CI)	0.39 [‐0.06, 0.83]
2.2 Rate of cerebral palsy	1	16	Risk Ratio (M‐H, Fixed, 95% CI)	1.29 [0.37, 4.53]
2.2.1 28 to < 32 weeks	1	16	Risk Ratio (M‐H, Fixed, 95% CI)	1.29 [0.37, 4.53]

2.1. Analysis.

Comparison 2: Early developmental intervention versus standard follow‐up (subgroup analysis: gestational age), Outcome 1: Cognitive outcome in infancy ‐ Developmental Quotient

Comparison 3. Early developmental intervention versus standard follow‐up (subgroup analysis: birth weight).

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
3.1 Cognitive outcome in infancy ‐ Developmental Quotient	3		Std. Mean Difference (IV, Fixed, 95% CI)	Subtotals only
3.1.1 1500 to < 2500 grams birthweight	2	381	Std. Mean Difference (IV, Fixed, 95% CI)	0.59 [0.38, 0.80]
3.1.2 1000 to < 1500 grams birthweight	1	38	Std. Mean Difference (IV, Fixed, 95% CI)	‐0.31 [‐0.95, 0.33]
3.1.3 < 1000 grams birthweight	2	137	Std. Mean Difference (IV, Fixed, 95% CI)	0.13 [‐0.22, 0.47]
3.2 Cognitive outcome at preschool age ‐ Intelligence Quotient	2		Std. Mean Difference (IV, Fixed, 95% CI)	Subtotals only
3.2.1 1500 to < 2500 grams birthweight	1	328	Std. Mean Difference (IV, Fixed, 95% CI)	0.70 [0.47, 0.93]
3.2.2 < 1000 grams birthweight	1	100	Std. Mean Difference (IV, Fixed, 95% CI)	0.41 [0.02, 0.81]

Comparison 4. Early developmental intervention versus standard follow‐up (subgroup analysis: brain injury).

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
4.1 Cognitive outcome in infancy ‐ Developmental Quotient	3		Std. Mean Difference (IV, Fixed, 95% CI)	Subtotals only
4.1.1 Absence of PVL/IVH	1	143	Std. Mean Difference (IV, Fixed, 95% CI)	0.34 [‐0.01, 0.70]
4.1.2 Presence of PVL/IVH	2	41	Std. Mean Difference (IV, Fixed, 95% CI)	0.50 [‐0.12, 1.13]
4.2 Motor outcome in infancy ‐ Developmental Quotient	3		Std. Mean Difference (IV, Fixed, 95% CI)	Subtotals only
4.2.1 Absence of PVL/IVH	1	143	Std. Mean Difference (IV, Fixed, 95% CI)	0.11 [‐0.24, 0.47]
4.2.2 Presence of PVL/IVH	2	41	Std. Mean Difference (IV, Fixed, 95% CI)	0.47 [‐0.15, 1.10]

Comparison 5. Early developmental intervention versus standard follow‐up (subgroup analysis: commencement of intervention).

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
5.1 Cognitive outcome in infancy ‐ Developmental Quotient	25		Std. Mean Difference (IV, Random, 95% CI)	Subtotals only
5.1.1 Inpatient	15	1304	Std. Mean Difference (IV, Random, 95% CI)	0.26 [0.09, 0.42]
5.1.2 Post hospital discharge	10	1750	Std. Mean Difference (IV, Random, 95% CI)	0.34 [0.10, 0.58]
5.2 Cognitive outcome at preschool age ‐ Intelligence Quotient	9		Std. Mean Difference (IV, Fixed, 95% CI)	Subtotals only
5.2.1 Inpatient	4	332	Std. Mean Difference (IV, Fixed, 95% CI)	0.33 [0.12, 0.55]
5.2.2 Post hospital discharge	5	1192	Std. Mean Difference (IV, Fixed, 95% CI)	0.41 [0.29, 0.53]
5.3 Cognitive outcome at school age ‐ Intelligence Quotient	6		Std. Mean Difference (IV, Random, 95% CI)	Subtotals only
5.3.1 Inpatient	3	322	Std. Mean Difference (IV, Random, 95% CI)	0.49 [0.09, 0.88]
5.3.2 Post hospital discharge	3	1137	Std. Mean Difference (IV, Random, 95% CI)	‐0.01 [‐0.13, 0.11]
5.4 Motor outcome in infancy ‐ Developmental Quotient	23		Std. Mean Difference (IV, Fixed, 95% CI)	Subtotals only
5.4.1 Inpatient	14	1293	Std. Mean Difference (IV, Fixed, 95% CI)	0.17 [0.06, 0.28]
5.4.2 Post hospital discharge	9	1444	Std. Mean Difference (IV, Fixed, 95% CI)	0.07 [‐0.04, 0.17]
5.5 Motor outcome at preschool age	3		Std. Mean Difference (IV, Fixed, 95% CI)	Subtotals only
5.5.1 Inpatient	1	132	Std. Mean Difference (IV, Fixed, 95% CI)	0.06 [‐0.28, 0.40]
5.5.2 Post hospital discharge	2	132	Std. Mean Difference (IV, Fixed, 95% CI)	0.09 [‐0.25, 0.43]
5.6 Motor outcome at school age	3		Std. Mean Difference (IV, Fixed, 95% CI)	Subtotals only
5.6.1 Post hospital discharge	3	265	Std. Mean Difference (IV, Fixed, 95% CI)	‐0.06 [‐0.31, 0.18]
5.7 Motor outcome at school age (low score on MABC)	3		Risk Ratio (M‐H, Fixed, 95% CI)	Subtotals only
5.7.1 Post hospital discharge	3	413	Risk Ratio (M‐H, Fixed, 95% CI)	1.04 [0.82, 1.32]
5.8 Rate of cerebral palsy	9		Risk Ratio (M‐H, Fixed, 95% CI)	Subtotals only
5.8.1 Inpatient	3	354	Risk Ratio (M‐H, Fixed, 95% CI)	0.94 [0.46, 1.93]
5.8.2 Post hospital discharge	6	679	Risk Ratio (M‐H, Fixed, 95% CI)	0.81 [0.51, 1.29]

Comparison 6. Early developmental intervention versus standard follow‐up (subgroup analysis: focus of intervention).

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
6.1 Cognitive outcome in infancy ‐ Developmental Quotient	25		Std. Mean Difference (IV, Random, 95% CI)	Subtotals only
6.1.1 Parent‐infant relationship	2	146	Std. Mean Difference (IV, Random, 95% CI)	0.35 [‐0.30, 1.00]
6.1.2 Infant development	3	334	Std. Mean Difference (IV, Random, 95% CI)	0.49 [‐0.16, 1.14]
6.1.3 Parent‐infant relationship and Infant development	20	2559	Std. Mean Difference (IV, Random, 95% CI)	0.24 [0.11, 0.37]
6.2 Cognitive outcome at preschool age ‐ Intelligence Quotient	8		Std. Mean Difference (IV, Fixed, 95% CI)	Subtotals only
6.2.1 Parent‐infant relationship	1	88	Std. Mean Difference (IV, Fixed, 95% CI)	‐0.14 [‐0.56, 0.28]
6.2.2 Parent‐infant relationship and Infant development	7	1391	Std. Mean Difference (IV, Fixed, 95% CI)	0.44 [0.33, 0.55]
6.3 Cognitive outcome at school age ‐ Intelligence Quotient	6		Std. Mean Difference (IV, Random, 95% CI)	Subtotals only
6.3.1 Infant development	1	126	Std. Mean Difference (IV, Random, 95% CI)	‐0.12 [‐0.47, 0.23]
6.3.2 Parent‐infant relationship and infant development	5	1273	Std. Mean Difference (IV, Random, 95% CI)	0.27 [‐0.01, 0.55]
6.4 Motor outcome in infancy	23		Std. Mean Difference (IV, Fixed, 95% CI)	Subtotals only
6.4.1 Parent‐infant relationship	1	104	Std. Mean Difference (IV, Fixed, 95% CI)	‐0.15 [‐0.54, 0.23]
6.4.2 Infant development	2	157	Std. Mean Difference (IV, Fixed, 95% CI)	0.26 [‐0.05, 0.58]
6.4.3 Parent‐infant relationship and infant development	20	2514	Std. Mean Difference (IV, Fixed, 95% CI)	0.12 [0.04, 0.20]
6.5 Motor outcome at preschool age	3		Std. Mean Difference (IV, Fixed, 95% CI)	Subtotals only
6.5.1 Parent‐infant relationship and infant development	3	264	Std. Mean Difference (IV, Fixed, 95% CI)	0.08 [‐0.16, 0.32]
6.6 Motor outcome at school age	3	265	Mean Difference (IV, Fixed, 95% CI)	‐0.04 [‐1.02, 0.95]
6.6.1 Infant development	1	49	Mean Difference (IV, Fixed, 95% CI)	‐5.31 [‐13.74, 3.12]
6.6.2 Parent‐infant relationship and infant development	2	216	Mean Difference (IV, Fixed, 95% CI)	0.04 [‐0.95, 1.02]
6.7 Motor outcome at school age (low score on MABC)	3	413	Odds Ratio (M‐H, Fixed, 95% CI)	1.07 [0.71, 1.63]
6.7.1 Infant development	1	197	Odds Ratio (M‐H, Fixed, 95% CI)	1.08 [0.60, 1.95]
6.7.2 Parent‐infant and infant development	2	216	Odds Ratio (M‐H, Fixed, 95% CI)	1.06 [0.59, 1.91]
6.8 Rate of cerebral palsy	9		Risk Ratio (M‐H, Fixed, 95% CI)	Subtotals only
6.8.1 Parent‐infant relationship and infant development	5	748	Risk Ratio (M‐H, Fixed, 95% CI)	0.70 [0.42, 1.15]
6.8.2 Infant development	4	285	Risk Ratio (M‐H, Fixed, 95% CI)	1.20 [0.63, 2.27]

Comparison 7. Early developmental intervention versus standard follow‐up (sensitivity analysis: risk of bias).

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
7.1 Cognitive outcome in infancy ‐ Developmental Quotient	25		Std. Mean Difference (IV, Random, 95% CI)	Subtotals only
7.1.1 Low risk of selection bias	14	2386	Std. Mean Difference (IV, Random, 95% CI)	0.26 [0.14, 0.38]
7.1.2 High risk of selection bias	11	746	Std. Mean Difference (IV, Random, 95% CI)	0.36 [0.05, 0.66]
7.2 Cognitive outcome at preschool age ‐ Intelligence Quotient	13		Std. Mean Difference (IV, Fixed, 95% CI)	Subtotals only
7.2.1 Low risk of selection bias	8	1507	Std. Mean Difference (IV, Fixed, 95% CI)	0.36 [0.25, 0.46]
7.2.2 High risk of selection bias	5	319	Std. Mean Difference (IV, Fixed, 95% CI)	0.23 [0.00, 0.45]
7.3 Cognitive outcome at school age ‐ Intelligence Quotient	6		Std. Mean Difference (IV, Random, 95% CI)	Subtotals only
7.3.1 Low risk of selection bias	6	1453	Std. Mean Difference (IV, Random, 95% CI)	0.16 [‐0.06, 0.38]
7.4 Motor outcome in infancy ‐ Developmental Quotient	23		Std. Mean Difference (IV, Fixed, 95% CI)	Subtotals only
7.4.1 Low risk of selection bias	15	2208	Std. Mean Difference (IV, Fixed, 95% CI)	0.11 [0.03, 0.20]
7.4.2 High risk of selection bias	8	529	Std. Mean Difference (IV, Fixed, 95% CI)	0.18 [0.01, 0.35]
7.5 Motor outcome at preschool age	3		Std. Mean Difference (IV, Fixed, 95% CI)	Subtotals only
7.5.1 Low risk of selection bias	2	228	Std. Mean Difference (IV, Fixed, 95% CI)	0.02 [‐0.24, 0.28]
7.5.2 High risk of selection bias	1	36	Std. Mean Difference (IV, Fixed, 95% CI)	0.43 [‐0.23, 1.09]
7.6 Motor outcome at school age	3		Std. Mean Difference (IV, Fixed, 95% CI)	Subtotals only
7.6.1 Low risk of selection bias	2	216	Std. Mean Difference (IV, Fixed, 95% CI)	‐0.00 [‐0.27, 0.26]
7.6.2 High risk of selection bias	1	49	Std. Mean Difference (IV, Fixed, 95% CI)	‐0.34 [‐0.91, 0.23]
7.7 Motor outcome at school age (low score on MABC)	3		Risk Ratio (M‐H, Fixed, 95% CI)	Subtotals only
7.7.1 Low risk of selection bias	3	413	Risk Ratio (M‐H, Fixed, 95% CI)	1.04 [0.82, 1.32]
7.8 Rate of cerebral palsy	9		Risk Ratio (M‐H, Fixed, 95% CI)	Subtotals only
7.8.1 Low risk of selection bias	6	808	Risk Ratio (M‐H, Fixed, 95% CI)	0.88 [0.56, 1.39]
7.8.2 High risk of selection bias	3	225	Risk Ratio (M‐H, Fixed, 95% CI)	0.79 [0.34, 1.83]

Characteristics of studies

Characteristics of included studies [ordered by study ID]

Alberge 2023.

Study characteristics
Methods	Fun Prospective parallel‐group open‐label randomised controlled trial assessing the impact of early post‐hospital psychomotor therapy on the development of very preterm infants at 24 months corrected age vs standard care. Single‐centre trial
Participants	N = 161 Intervention group: N = 77 Standard care group: N = 84 Inclusion criteria: preterm infants 24 ≤ 30 weeks GA Exclusion criteria: congential malformation, genetic disease, grade III‐IV intraventricular haemorrhage, cystic PVL, mothers with mental illness, families not speaking French Characteristics: mean GAs for treatment and standard follow‐up groups: 27.6 (SD 1.3) and 27.4 (SD 1.4) weeks, respectively
Interventions	Intervention group: parent and infant focus. Psychomotor therapy is based on the concept of intentionality relating to cognitive, or motor actions. 20 x 1‐hour sessions of psychomotor therapy between 2 and 9 months of age post discharge, once a week for 4 months, then once every 15 days for 4 months. Psychomotor therapy focused on parental support, parent‐infant skills and identifying and treating atypical development. Implemented by a psychomotor therapist Standard care group: follow‐up based on the Amiel‐Tison framework and GMs assessment. Few details reported of standard care Physiotherapy was offered to all infants at paediatrician visit at 2 and 3 months and throughout the study.
Outcomes	Cognitive Infant age Bayley‐III 24 months Motor Infant age Bayley‐III 24 months
Notes	Intention‐to‐treat analysis performed Funding source: this research was funded by the French Health Ministry and National Hospital Clinical Research Project. Declaration of interest: the authors have no conflicts of interest to declare.
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Randomisation lists were created by an independent statistician who was not involved in the study. For each stratum, the sequence of randomisation was generated with the Stata 11 software (StataCorp), using permuted blocks of varying size, with a minimum block size of two.
Allocation concealment (selection bias)	Unclear risk	No information on allocation concealment
Blinding of participants and personnel (performance bias) All outcomes	High risk	Performance bias due to knowledge of allocated interventions by personnel delivering interventions during the study
Blinding of outcome assessment (detection bias) All outcomes	Low risk	Development was evaluated using the BSID‐III at 24 months of age by 2 psychomotor therapists, blinded for group assignment.
Incomplete outcome data (attrition bias) All outcomes	High risk	Completeness of follow up at 24 months: cognitive outcome 70% and motor outcome 71%. The attrition rate was same across the 2 groups and the authors have specified reasons for missing data.
Selective reporting (reporting bias)	Low risk	Results fully reported with intention‐to‐treat analysis
Other bias	Low risk	No other source of bias detected

Apaydin 2023.

Study characteristics
Methods	SIngle‐blind randomised controlled design to investigate the effect of the SAFE early intervention approach for preterm infants vs standard care Study conducted at the Pediatric Rehabilitation Unit in Faculty of Health Sciences at Gazi University
Participants	N = 30 Intervention group: N = 15 Standard care group: N = 15 Inclusion criteria: infants born < 37 weeks' GA, a history of a NICU stay or 15 days or more, CA of 9–10 months and a willingness to participate in study Exclusion criteria: history of congenital disease, medical condition that would impact participation in intervention, living out of reach of research team for home visits Characteristics: mean GA for intervention and standard follow‐up groups: 29.2 (SD 2.2) weeks and 31.1 (SD 2.3) weeks, respectively
Interventions	Intervention group: parent‐infant and infant‐focused. Sensory strategies, Activity‐based motor training, Family collaboration and Environmental Enrichment (SAFE) intervention is a family‐centred intervention in the child's home environment. Collaboration between physiotherapist and family collaborate in developing activities and 2 home visits occur during the intervention period (10 weeks). Standard care group: (N = 15) traditional physiotherapy is standard care in Turkey for preterm infants. 2 home visits from a physiotherapist and neurodevelopmental approach used with infant according to needs Adherence to both programmes was monitored by phone calls. All families complete a logbook to record the intervention dosage given.
Outcomes	Cognitive Bayley‐III infant age (post treatment period) Motor Bayley‐III infant age (post treatment period)
Notes	Assessment done pre‐ and post intervention Funding source: this research did not receive any specific grant from funding agencies in the public, commercial, or not‐for‐profit sectors. Declaration of interest: no conflict of interest reported
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Random allocation software used
Allocation concealment (selection bias)	High risk	No details of allocation concealment reported
Blinding of participants and personnel (performance bias) All outcomes	High risk	Performance bias due to knowledge of allocated interventions by participants and personnel during the study
Blinding of outcome assessment (detection bias) All outcomes	Low risk	2 researchers blinded to group allocation assessed infants at baseline and post intervention.
Incomplete outcome data (attrition bias) All outcomes	Low risk	Follow‐up rates of 80% for intervention and control groups
Selective reporting (reporting bias)	Low risk	Results were fully reported.
Other bias	Low risk	No other source of bias detected

APIP 1998.

Study characteristics
Methods	A multicentre randomised controlled trial (RCT) comparing 2 interventions vs standard follow‐up. All eligible infants born over a 2.5‐year period were randomly assigned to 1 of the 3 groups at 7 to 10 days after birth (Portage, Parent advisor, Follow‐up).
Participants	N = 309 infants randomised. Post randomisation N = 284 consented Intervention ‐ Portage group: N = 111 Intervention ‐ Parent advisor group: N = 99 Standard care group: N = 99 Inclusion criteria: GA < 33 weeks Exclusion criteria: English was not the first language, patient did not live within the study area. Characteristics: mean GAs for the 2 treatment groups (Portage and Parent advisor) and the standard follow‐up group: 31, 30 and 31 weeks, respectively
Interventions	Two intervention programmes were used ‐ 'Portage' and 'Parent advisor' Portage group: Portage group's focus was developmental progress of the child and was implemented via a home visiting educational service for children with additional support needs and their families. Visits were weekly for the first 2 months, then reduced to 1‐2 per month for the next 12 months and then 1 per month until 2 years CA. Parent support was also offered. Parent advisor group: parents received supportive counselling but no advice on infant development. This intervention was used to control for the parent support aspect of the Portage group. Standard care group: details of standard follow‐up for the control group were not reported For data analysis, Portage and Parent advisor groups were included together as the intervention group.
Outcomes	Cognitive Infant age: Griffiths GCI (24 months) Preschool age: none School age: British Abilities Scales Edition II (5 years) Motor Infant age: incidence of cerebral palsy (5 years) Preschool age: none School age: Movement ABC (5 years)
Notes	Standard care group had a higher percentage of mothers who were educated beyond 16 years of age, were in non‐manual occupations and had the use of a car compared with both intervention groups. Consent to participate in the study was obtained post randomisation. Funding source: a five‐year project grant from Action Research. Supplementary funding from Crookes Health Care, Nutricia and Milupsa (UK) Ltd Declarations of interest: not stated
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Randomisation arranged in blocks of 6 with random number table for each stratum
Allocation concealment (selection bias)	Low risk	Opaque envelopes
Blinding of participants and personnel (performance bias) All outcomes	High risk	Performance bias due to knowledge of allocated interventions by personnel delivering interventions during the study. Unclear whether participants were aware of group allocation, and whether personnel or participants were biased towards 1 intervention as superior to the other intervention
Blinding of outcome assessment (detection bias) All outcomes	Low risk	All assessments performed by assessors masked to group allocation
Incomplete outcome data (attrition bias) All outcomes	Unclear risk	Low risk at 24 months (94%) but high risk at 5 years (66%) for cognitive outcomes
Selective reporting (reporting bias)	Low risk	Results were fully reported.
Other bias	High risk	Consent to participate in the study was obtained post randomisation to evaluate acceptability and impact of interventions in population terms. To account for potential bias, families of infants who did not consent to the intervention were invited to participate in outcome assessments and outcome data at 2 years (but not at 5 years), and results were reported on an intention‐to‐treat basis.

Bao 1999.

Study characteristics
Methods	A multicentre quasi‐randomised controlled trial of an intervention package that focused on infant development vs standard follow‐up
Participants	N = 103 infants Intervention group: N = 52 Standard care group: N = 51 Inclusion criteria: GA 28 to 37 weeks Exclusion criteria: not reported Characteristics: mean GA for intervention and standard follow‐up groups: 33.9 (SD 1.8) weeks and 34.2 (SD 2.1) weeks, respectively
Interventions	Intervention group: focus on infant development ‐ aimed to enhance motor, cognitive and speech development, and to improve social behaviours by assessing the development of the infant, then instructing parents on how to carry out a home programme until the next examination. The home programme included exercise and suggestions of toys, books and pictorials appropriate to the child's age and was delivered by a paediatrician. Standard care group: details not described
Outcomes	Cognitive Infant age: BSID‐I MDI (18 and 24 months) Motor Infant age: BSID‐I PDI (18 and 24 months)
Notes	Funding source and declarations of interest: not stated
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	High risk	Randomly assigned according to order of admission to hospital ‐ odd numbers to intervention and even numbers to conventional care
Allocation concealment (selection bias)	High risk	Personnel may have been aware of group allocation as a result of the randomisation procedure.
Blinding of participants and personnel (performance bias) All outcomes	High risk	Performance bias due to knowledge of allocated interventions by personnel delivering interventions during the study
Blinding of outcome assessment (detection bias) All outcomes	Low risk	Assessors were blinded to group allocation.
Incomplete outcome data (attrition bias) All outcomes	Unclear risk	Not stated whether any infants were withdrawn from the study; 100% follow‐up apparent but unclear
Selective reporting (reporting bias)	High risk	Not clear whether participants were withdrawn from the study; few details of inclusion criteria and few population characteristics reported
Other bias	Low risk	No other source of bias identified

Barrera 1986.

Study characteristics
Methods	A multicentre randomised controlled trial comparing 2 types of intervention programmes vs standard follow‐up
Participants	N = 80 infants Intervention groups N = 22* and N = 16* Standard care group: N = 21* Inclusion criteria: BW < 2000 grams or GA ≤ 37 weeks and discharged from hospital with good prognosis for survival Exclusion criteria: life‐threatening illnesses, family did not live within the study area Characteristics: mean GA 33 weeks for all groups
Interventions	Two intervention programmes: Parent‐infant intervention: focus on parent‐infant relationship and aims at improving the quality of the interaction between parent and child by enhancing parents' observational skills and teaching them to be mutually responsive to their infant Developmental programme: focus on infant development. Developmental programme aimed to improve infants' cognition, communication, gross and fine motor development, socio‐emotional skills and self‐help skills. Parents work with therapists to plan and implement developmental activities aimed to improve infant cognition, communication and motor development. Interventions were implemented by therapists or childhood educators, weekly sessions for 3–4 months, bi‐weekly for the next 6 months, monthly for 3 months. Standard care group: home visits for assessment purposes only. During these visits, the examiner answered questions from parents related to their child's development, reading material or community resources. For data analysis, both the parent‐infant and developmental groups were included together as the 'intervention group'.
Outcomes	Cognitive Infant age: BSID‐I MDI (4, 8, 12 and 16 months) Preschool age: McCarthy Scales of Children's Abilities ‐ general cognitive index (4.5 to 5 years) Motor Infant age: BSID‐I PDI (4, 8, 12 and 16 months)
Notes	*21 infants did not complete the study. The number of infants in each group listed includes infants who completed the 1‐year programme, as the number of infants randomly assigned to each group at the beginning of the study was not stated. It is reported that no differences between groups in reasons for withdrawal from the study were noted. Funding source: Ministry of Community and Social Services Grant through the Ontario Mental Health Foundation Declarations of interest: not stated
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Infants were randomly assigned in blocks according to sex, BW, SES and antenatal/postnatal complications.
Allocation concealment (selection bias)	Unclear risk	Unclear what measures were taken to ensure concealment of allocation
Blinding of participants and personnel (performance bias) All outcomes	High risk	Two intervention groups were included; therefore, participants may have been blinded to group allocation. However, it is not clear whether personnel or participants would have had a bias towards the different intervention groups.
Blinding of outcome assessment (detection bias) All outcomes	Low risk	Assessors blinded to group allocation
Incomplete outcome data (attrition bias) All outcomes	High risk	Completeness of follow‐up: high risk at 4, 8, 12 and 16 months (73%) and at 5 years (56%)
Selective reporting (reporting bias)	High risk	Number of infants in each group reported only for infants who completed the programme
Other bias	Low risk	No other source of bias identified

Cameron 2005.

Study characteristics
Methods	Single‐centre randomised controlled trial to investigate the effects of a physiotherapy early intervention programme vs standard follow‐up
Participants	N = 72 infants Intervention group: N = 34 Standard care group: N = 38 Inclusion criteria: BW < 1500 grams and GA < 32 weeks Exclusion criteria: requirement for oxygen at 4 months' corrected age, severe hydrocephalus requiring a shunt, demonstrated signs of drug withdrawal, history of social problems Characteristics: mean GAs for treatment and standard follow‐up groups: 28.7 (SD 2.4) and 29.6 (SD 2.0) weeks, respectively
Interventions	Intervention group: focus on infant development. A physiotherapy programme aimed at improving motor development and promoting symmetry, muscle balance and movement while an inpatient. Post discharge intervention provided on an as‐needs basis until 4 months corrected age and included play activities to encourage development Standard care group: no physiotherapy intervention nor other placebo intervention given
Outcomes	Cognitive None Motor Infant age: Alberta Infant Motor Scale (4 months) Incidence of cerebral palsy (18 months)
Notes	Funding sources and declarations of interest: not stated
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Toss of a coin
Allocation concealment (selection bias)	Low risk	Toss of a coin
Blinding of participants and personnel (performance bias) All outcomes	High risk	Performance bias due to knowledge of allocated interventions by participants and personnel during the study
Blinding of outcome assessment (detection bias) All outcomes	Low risk	Assessors blinded to group allocation
Incomplete outcome data (attrition bias) All outcomes	Low risk	Completeness of follow‐up: 4 months (83%)
Selective reporting (reporting bias)	Low risk	Results fully reported
Other bias	Unclear risk	No other source of bias identified

Campbell 2012.

Study characteristics
Methods	A multicentre randomised controlled pilot study to investigate the effects of a home‐based exercise intervention on the age of independent walking and motor development at 12 months CA on preterm children with brain injury
Participants	N = 16 infants Intervention group: N = 7 Standard care group: N = 9 Inclusion criteria: GA 23–32 weeks and a diagnosis of grade III or IV IVH or PVL as found on an ultrasound scan. Must be healthy at home to participate in exercise programme from 2 months CA Exclusion criteria: genetic syndrome, musculoskeletal deformity Characteristics: range of GA was 23–34 weeks with an overall mean of 27 (SD 2.9). Group characteristics not reported
Interventions	Intervention: infant‐focused ‐ included a kicking and treadmill stepping intervention on top of usual intervention. Commenced at 2 months CA and aimed to promote self‐initiated movement of the legs. The treadmill training commenced at 4 months CA where a parent holds the infant on the treadmill. Control group: infants received usual physical therapy as per their individual needs.
Outcomes	Cognitive none Motor AIMS (2, 4, 6, 10 and 12 months' CA) TIMP at 2 and 4 mos CA, and AIMS at 12 months' CA (data as per Campbell 2012) Incidence of cerebral palsy at 12 months' CA Video footage ‐ used to analyse kicking behaviour, head control and visual attention at 2 and 4 months CA and then at 12 months CA
Notes	AIMS and TIMP data not included in the meta‐analysis Rate of CP included in meta‐analysis Funding source: this project was supported by the University of Illinois at Chicago Center for Clinical and Translational Science, Award Number UL1RR029879 from the National Center for Research Resources (NCRR). Declaration of interest: no conflicts of interest to declare
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Random number table
Allocation concealment (selection bias)	Unclear risk	No information provided on how allocation was concealed
Blinding of participants and personnel (performance bias) All outcomes	High risk	Performance bias due to knowledge of allocated interventions by participants and personnel during the study
Blinding of outcome assessment (detection bias) All outcomes	Low risk	Assessors blinded to group allocation
Incomplete outcome data (attrition bias) All outcomes	Low risk	Completeness of follow up ‐ 89%
Selective reporting (reporting bias)	Low risk	Results were fully reported.
Other bias	Low risk	No other source of bias identified

Castel 2016.

Study characteristics
Methods	Single‐centre, prospective randomised controlled trial assessed the impact of the Triadic parent‐infant Relationship Therapy (TRT) on parent psychological health and infant development.
Participants	N = 65 infants Intervention group: N = 33 Standard care group: N = 32 Inclusion criteria: infants born between 28– < 36 weeks GA with no congenital anomalies or disability Exclusion criteria: no congenital anomalies or any other foreseeable disabilities during the neonatal period. Siblings were not excluded from the study. Term control (N = 24) recruited at 12 months of age to match EG at 12 months CA Characteristics: mean GAs for treatment and standard follow‐up groups: 31.7 (SD 2.7) and 32.5 (SD 2.0) weeks, respectively
Interventions	Intervention: Triadic parent–infant relationship therapy (TRT) developed by the authors and based on attachment theory. Designed to facilitate parent‐infant interactions and promote understanding of infant development. Aims to improve infant cognitive, social‐emotional and behavioural development. Intervention commenced post discharge and comprised 22 sessions, including home visits twice a month during the first 4 months, followed by monthly consultations in neonatology ward up to 18 months' CA. Standard care group: included monthly visits to a doctor for 6 months, then every 3 months
Outcomes	Cognitive Brunet‐Leizine Revised test (BLR) at 3, 9 and 18 months of age Motor Brunet‐Leizine Revised test at 3, 9 and 18 months of age Brunet‐Leizine Revised test ‐ 4 subscores, domains of movement and posture, language, socialisation and co‐ordination. The combination of these four subscores provides a global DQ. Term control group assessed with Brunet‐Leizine Revised test at 18 months of age
Notes	Brunet‐Leizine Revised test (motor scores) at 18 mo included in the meta‐analysis Funding source: this study was supported by a grant from the Hospital Program for Clinical Research (DGS: 2006/0215) and the Wyeth Foundation. Declaration of interest: the authors had no conflicts of interest to declare.
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Blocked randomisation list
Allocation concealment (selection bias)	Low risk	Randomisation was undertaken after informed consent by a member of medical staff who was not involved in the patient inclusion and was the only one to access the list.
Blinding of participants and personnel (performance bias) All outcomes	High risk	Performance bias due to knowledge of allocated interventions by participants and personnel during the study
Blinding of outcome assessment (detection bias) All outcomes	High risk	Assessor not blinded at follow‐up assessments
Incomplete outcome data (attrition bias) All outcomes	Low risk	Completeness of follow up = 80% Reasons regarding missing data were similar across both groups. Note that the control group had a higher attrition rate compared to the intervention group.
Selective reporting (reporting bias)	Low risk	Results were fully reported.
Other bias	Low risk	No other source of bias identified

Colditz 2019.

Study characteristics
Methods	Multicentre RCT was conducted to determine the efficacy of Baby Triple P for preterm infants in enhancing child development at 2 years CA compared to usual care. Random block allocation, stratified for site and risk of brain injury
Participants	N = 323 families (384 infants) Intervention group: N = 196 Standard care group: N = 188 Inclusion criteria: preterm infants born < 32 weeks' GA Exclusion criteria: major congential anomalies associated with poor developmental outcome, parents must have English to complete assessments, families who are unwilling to attend for 24‐month assessment Characteristics; there were no significant differences between the groups with respect to GA, sex or presence of IVH grade I or II. The overall mean gestational age was 28.5 weeks (SD = 2.1).
Interventions	Baby Triple P for Preterm infants: The intervention was designed to guide parents to build adaptive coping skills, build a positive parent‐infant relationship and manage behavioural issues and provide a safe, engaging and enriched learning environment for their child. Intervention is parent and parent‐infant focused, commenced in the NICU and continued post discharge. It consists of 8 sessions: 4 x 2‐hour group sessions in hospital, 4 x 30‐min weekly phone call sessions post discharge from hospital from 2 weeks CA From 3 months CA – at 3 monthly intervals, Triple P tip sheets were sent to parents and also phone support provided. Parents encouraged to attend local Triple P support services Standard care group: All families received care‐as‐usual as an inpatient and post discharge at a local area facility. This consists of routine medical surveillance and possible support from other community providers, including some Primary Care Triple P support. Services accessed were measured at 2 years' CA by parent recall.
Outcomes	Cognitive Bayley III at 24 months' CA Motor Bayley III at 24 months' CA
Notes	Funding source: this study was funded by the National Health and Medical Research Council (APP1024345). The Parenting and Family Support Centre is partly funded by royalties stemming from published resources of the Triple P‐Positive Parenting Program, which is developed and owned by the University of Queensland (UQ). Royalties are distributed to the Faculty of Health and Behavioural Sciences at UQ and contributory authors of the published Triple P resources. Triple P International (TPI) Pty Ltd is a private company licenced by UniQuest Pty Ltd on behalf of UQ, to publish and disseminate Triple P worldwide. TPI had no involvement in this project. Matthew R Sanders is the founder of Triple P and receives royalties from TPI. He is a consultant to Triple P International and an employee at UQ. C.S. is an author of Baby Triple P. Declaration of interest: no conflicts of interest to declare
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Allocation sequence generated by staff not associated with the study and comprised computer‐generated random numbers
Allocation concealment (selection bias)	Low risk	Sealed, opaque envelopes
Blinding of participants and personnel (performance bias) All outcomes	High risk	Performance bias due to knowledge of allocated interventions by participants and personnel during the study
Blinding of outcome assessment (detection bias) All outcomes	Low risk	Assessor blinded to group allocation
Incomplete outcome data (attrition bias) All outcomes	Unclear risk	Completeness of follow up at 24 months: cognitive outcome ‐ 82% (low risk) and motor outcome ‐ 78% (high risk). The attrition rate was the same across the two groups and the authors specified reasons for missing data.
Selective reporting (reporting bias)	Low risk	Details were provided on the infants who missed the 24‐month follow‐up assessment.
Other bias	Unclear risk	An author from this Cochrane review (RB) was involved in the RCT.

Dusing 2015.

Study characteristics
Methods	Single‐centre randomised controlled trial. The aim is to determine the feasibility of completing a clinical trial of Supporting Play Exploration and Early Development Intervention (SPEEDI) for preterm infants. This early and intense intervention is blended with family support to assist in the transition from hospital to home.
Participants	N = 10 infants Intervention group: N = 5 Standard care group: N = 5 Inclusion criteria: GA < 34 weeks, medically stable, living within 30 minutes of the hospital. For multiple births, 1 infant was randomly selected to participate. Exclusion criteria: genetic syndrome, musculoskeletal deformity Characteristics: median GA and interquartile range (IQR) were reported for treatment and standard follow‐up groups: 27 (25‐30) and 31 (28‐33) weeks, respectively.
Interventions	Intervention group SPEEDI: focus on infant and parent‐infant relationship Phase 1 ‐ from 35 weeks to term age. This provides infants with daily movement experiences and was performed by the therapist. Each session lasted 20 minutes, and frequency was 5 times a week. Scheduled meetings with parents provided education and demonstrated intervention. Each family received a minimum of 10 study visits with the therapist, including 2 parent‐education sessions. Phase 2 ‐ post‐term age in the community. Involved the therapist teaching the parent how to identify the infant's responses and behaviours while implementing various motor and social activities at home. It assists parents in establishing a routine for developmentally appropriate play after discharge and to teach them to implement these interventions in the home. Standard care group: This group received standard care in the NICU and in the community. This is not described further. Parents reported on other EI services received during the period of the project.
Outcomes	Cognitive Infant age: Bayley‐III (6 months) Motor Infant age: Bayley‐III (6 months) Test of Infant Motor Performance (0, 3 and 4 months CA)
Notes	Numbers were small. Bayley 6‐month data used in meta‐analysis Funding source: the work was funded by a grant from the Virginia Commonwealth University School of Allied Health Professions Promotion of Research Program. Declarations of interest: not stated
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Infants randomly assigned to intervention or control, but method of randomisation not described
Allocation concealment (selection bias)	Unclear risk	Unclear what measures were taken to ensure concealment of allocation
Blinding of participants and personnel (performance bias) All outcomes	High risk	Performance bias due to knowledge of allocated interventions by participants and personnel during the study
Blinding of outcome assessment (detection bias) All outcomes	Low risk	Assessor and physical therapist blinded to group assignment
Incomplete outcome data (attrition bias) All outcomes	High risk	Completeness of follow‐up: 4 months (70%), 6 months (70%)
Selective reporting (reporting bias)	Low risk	Study authors reported on numbers of infants not available for assessment at various time points.
Other bias	Low risk	No other source of bias identified

Dusing 2018.

Study characteristics
Methods	SIngle‐centre, pilot randomised control trial examining the efficacy of SPEEDI (Supporting Play Exploration and Early Developmental Intervention) to improve reaching and exploratory problem‐solving behaviours
Participants	N = 14 infants Intervention group: N = 7 Standard care group: N = 7 Inclusion criteria: infants born < 29 weeks with or without brain injury. Brain injury includes IVH grade 3 or 4 or periventricular white matter injury, HIE or hydrocephalus requiring shunt. Information was provided to parents of eligible infants between 35 and 40 weeks of gestation if the infant was off ventilator support by 40 weeks of gestation. Exclusion criteria: a diagnosis of a genetic syndrome (e.g. trisomy 21) or musculoskeletal deformity Characteristics: median GA and interquartile range (IQR) were reported for treatment and standard follow‐up groups: 25 (24‐27) and 26 (25‐28) weeks, respectively.
Interventions	Intervention group: SPEEDI programme previously described in Dusing 2015. Focus on infant and parent‐infant relationship Phase 1 ‐ Physical therapists who were experienced in NICU care and early intervention and trained in the SPEEDI programme performed intervention comprising 5 sessions with infant and parent. Phase 2 – 12 weeks, home interventions by parent with five regular follow‐up sessions by SPEEDI PT Standard care group: as described in Dusing 2015
Outcomes	Cognitive Infant age ‐ Bayley‐III at final follow‐up visit and at 3 months post intervention. Bayley‐III data from 12‐mo CA hospital follow‐up programme retrieved from medical records Motor Infant age ‐ Bayley‐III as for cognitive Infant age ‐ TIMP: at end phase 1 (21 days after baseline), end phase 2 (12 weeks after end phase 1) and follow‐up 1 (1 month after end phase 1)
Notes	Author contacted for 12 months Bayley‐III data. Motor and cognitive data at 12 mo CA included in meta‐analysis Funding source: funding provided by the Foundation for Physical Therapy and the Children’s Hospital of Richmond Foundation. The funding sources had no influence on the study design, implementation, analysis, or publication of the results. Declaration of interest: no conflicts of interest to declare
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Infants randomly assigned to intervention or control, but method of randomisation not described
Allocation concealment (selection bias)	Unclear risk	Unclear what measures were taken to ensure concealment of allocation
Blinding of participants and personnel (performance bias) All outcomes	High risk	Performance bias due to knowledge of allocated interventions by participants and personnel during the study
Blinding of outcome assessment (detection bias) All outcomes	Low risk	Assessor and physical therapist blinded to group assignment
Incomplete outcome data (attrition bias) All outcomes	High risk	Completeness of follow up at 12 mo CA ‐ 43%
Selective reporting (reporting bias)	Low risk	Results were fully reported.
Other bias	Unclear risk	An author from this Cochrane review (TT) was involved in the RCT.

Fan 2021.

Study characteristics
Methods	Single‐centre randomised controlled trial with a cross‐over design. Aim to evaluate the effect of an early intervention program on neurodevelopment and physical growth of preterm infants
Participants	N = 73 infants Intervention group: N = 37 Standard care group: N = 36 Preterm reference group recruited retrospectively: N = 33 Inclusion criteria: infants born 28‐ < 32 weeks GA and aged between 36‐ < 40 weeks at recruitment. Included infants must be medically stable and have parents available at home. Exclusion criteria: language barrier or disability and receiving other interventions Characteristics: mean GAs for treatment and standard follow‐up groups: 30.13 (SD 1.56) and 30.35 (SD 1.92) weeks, respectively
Interventions	Intervention group: Researcher with rehabilitation training taught parents and supervised during the intervention period. Parents trained using lecture and simulation. Post discharge, they commence intervention with infants and send videos to researchers. Construct – 3 parts to be implemented separately; 1) hearing and vision‐induced training, 2) physical section involving a whole body massage, 3) social section including kangaroo care and hearing‐vision integrated training Daily intervention for 30 days and assessment on day 60 (post RCT phase). After this, the groups swap and intervention is received by SC group ‐ reassessment on day 120 Standard care group: all infants in the study received standard care consisting of feeding guidance, immunisation and general medical follow‐up.
Outcomes	Cognitive none Motor: Infant age ‐ TIMP at day 60 and day 120 post baseline Other Infant age ‐ Gesell developmental schedule ‐ motor and behaviour
Notes	Funding source: this work was supported by the Chongqing Science and Technology Commission (No. cstc2018jscx‐msybX0071) and joint scientific research project of Chongqing Science and Technology Commission and Health Commission (2021MSXM119). The funder did not play a role in any aspect of the study, including design, data collection, analysis or manuscript writing. Declaration of interest: no conflicts of interest to declare
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Computer‐generated sequence
Allocation concealment (selection bias)	Unclear risk	No information provided on allocation concealment
Blinding of participants and personnel (performance bias) All outcomes	High risk	Performance bias due to knowledge of allocated interventions by participants and personnel during the study
Blinding of outcome assessment (detection bias) All outcomes	Low risk	All assessments were blinded to the assessors.
Incomplete outcome data (attrition bias) All outcomes	Unclear risk	Lack of clarity on infants screened, eligible and enroled in the study
Selective reporting (reporting bias)	Low risk	Results were fully reported.
Other bias	Low risk	No other source of bias identified

Field 1980.

Study characteristics
Methods	Randomised controlled study to assess the effects of the combined risks of being born preterm to a teenage mother and to evaluate the effects of an intervention programme
Participants	N = 60 infants Intervention group: N = 30 Standard care group: N = 30 Inclusion criteria: BW < 2500 grams and GA < 37 weeks. All infants were born to African‐American teenage mothers with low sociodemographic status. Exclusion criteria: serious neonatal complications that would require long periods of intensive care and early separation Characteristics: mean GAs of intervention and standard follow‐up groups: 35.5 and 35.3 weeks, respectively
Interventions	Intervention group: Focus on infant development and parent‐infant relationship. The aim of the intervention was to educate the mother regarding developmental milestones and child‐rearing practices, to teach the mother age‐appropriate stimulation to facilitate cognitive and social interaction and communication skills and to facilitate mother‐infant relationships. The intervention involved home visits by an interventionist and a teenage, black, female work/study student. Standard care group: no details on standard follow‐up given
Outcomes	Cognitive Infant age: BSID‐I MDI (8 months) Motor Infant age: BSID‐I PDI (8 months)
Notes	Funding source: this research was funded by grants OHD90C1358 and OHD90C176471 to Tiffany M. Field. Declarations of interest: not stated
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Unclear (reported that mothers volunteered for intervention, then were randomly assigned to control or intervention)
Allocation concealment (selection bias)	Unclear risk	Unclear
Blinding of participants and personnel (performance bias) All outcomes	High risk	Performance bias due to knowledge of allocated interventions by participants and personnel during the study
Blinding of outcome assessment (detection bias) All outcomes	Unclear risk	Assessors blinded to group allocation
Incomplete outcome data (attrition bias) All outcomes	Low risk	Completeness of follow‐up: 8 months (85.5%)
Selective reporting (reporting bias)	Unclear risk	Results were fully reported.
Other bias	Low risk	No other source of bias identified

Finlayson 2020.

Study characteristics
Methods	Single‐centre, pilot randomised controlled trial assessing the feasibility of SPEEDI for very preterm infants in an Australian context
Participants	N = 17 infants Intervention group: N = 8 Standard care group: N = 9 Inclusion criteria: being born ≤ 30 weeks' gestation, one English‐speaking parent, living within 30 km of the hospital, and medically stable and off ventilator support at enrolment Exclusion criteria: genetic syndrome or musculoskeletal deformity that would affect development Characteristics: mean GAs for treatment and standard follow‐up groups: 26.05 (SD 1.05) and 27.19 (SD 1.58) weeks, respectively
Interventions	Intervention group (SPEEDI): infants were randomly assigned to SPEEDI or usual care between 34–38 weeks of GA Phase 1 takes place from 35 weeks to term age. This provides infants with daily movement experiences and was performed by the therapist. Each session lasted 20 minutes, and frequency was 5 times a week. Scheduled meetings with parents provided education and demonstrated intervention. Each family received a minimum of 10 study visits with the OT or PT, including 2 parent‐education sessions. Phase 2 takes place post‐term age in the community and involved the therapist teaching the parent how to identify the infant's responses and behaviours while implementing various motor and social activities at home. It assists parents in establishing a routine for developmentally appropriate play after discharge and to teach them to implement these interventions in the home. Parents were asked to provide the daily activities for 3 months. Standard care group: included allied health support and parent education for all infants born less than 28 weeks GA using parent education and neurobehavioural assessment to guide therapists. Referral to developmental community services as required
Outcomes	Cognitive Early Problem‐Solving Indicator (EPSI) Bayley‐III at 4 mo CA Motor TIMP at baseline and 3 mo CA General Movement Assessment (GMA) at baseline and 3 mo CA Bayley ‐III at 4 mo CA
Notes	Funding source: this work was supported by the Australian National Health and Medical Council (Centre for Research Excellence 1060733); Career Development Fellowships (APP1159533 to AJS); the University of Melbourne School of Health Sciences; the Murdoch Children's Research Institute; and the Victorian Government's Operational Infrastructure. Declaration of interest: no conflicts of interest to declare
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Computer‐generated allocation sequence
Allocation concealment (selection bias)	Low risk	Sequentially numbered opaque envelopes
Blinding of participants and personnel (performance bias) All outcomes	High risk	Performance bias due to knowledge of allocated interventions by participants and personnel during the study
Blinding of outcome assessment (detection bias) All outcomes	Low risk	All assessments were blinded to the assessors.
Incomplete outcome data (attrition bias) All outcomes	Low risk	Completeness of follow‐up ‐ 100%
Selective reporting (reporting bias)	Low risk	Results were fully reported.
Other bias	Unclear risk	An author from this Cochrane review (AS) was involved in the RCT.

Gianni 2006.

Study characteristics
Methods	Pilot randomised controlled trial of an early post discharge developmental intervention on neurodevelopmental outcomes for preterm infants
Participants	N = 36 infants Intervention group: N = 18 Standard care group: N = 18 Inclusion criteria: BW < 1250 grams, singleton, infant‐fed preterm formula Exclusion criteria: congenital heart disease, chromosomal abnormality, brain abnormality or combination seen on MRI; death during inpatient stay Characteristics: mean GAs of intervention and standard care groups: 28.3 (SD 2.8) and 27.5 (SD 1.8) weeks, respectively
Interventions	Intervention group: infant development and parent‐infant relationship. Psychologists provided intervention related to supporting parent mental health issues associated with preterm birth and mother/child interaction. Standard care group: included visits to paediatrician at 40 weeks and 3, 6, 12, 24 and 36 months of age. No other intervention was provided.
Outcomes	Cognitive Griffiths Mental Developmental Scale (DS) and related subscales at 12, 24 and 36 months Motor none
Notes	Funding sources and declarations of interest: not stated
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Unclear: infants randomly assigned into 2 groups matched for GA; no other information given
Allocation concealment (selection bias)	Unclear risk	Unclear as randomisation methods not stated
Blinding of participants and personnel (performance bias) All outcomes	High risk	Performance bias due to knowledge of allocated interventions by participants and personnel during the study
Blinding of outcome assessment (detection bias) All outcomes	Low risk	Assessors blinded to group allocation
Incomplete outcome data (attrition bias) All outcomes	Unclear risk	Completeness of follow‐up: 100% at 36 months, no information for 12 and 24 months
Selective reporting (reporting bias)	High risk	Unclear how many infants were assessed for eligibility vs consented to the study and whether any withdrawals occurred
Other bias	Low risk	No other source of bias identified

Goodman 1985.

Study characteristics
Methods	Quasi‐randomised controlled trial to investigate effects of early neurodevelopmental therapy vs standard follow‐up on preterm infants
Participants	N =107 infants* Intervention group: N = 40 Standard care group: N = 40 Inclusion criteria: BW < 1700 grams or GA < 34 weeks Exclusion criteria: infants considered neurologically impaired were excluded from the study, as all were given intervention. Characteristics: mean GAs of intervention and standard follow‐up groups: 30.9 (SD 1.9) and 31 (SD 1.8) weeks, respectively
Interventions	Intervention group (N = 40): intervention focused on infant development and included monthly outpatient neurodevelopmental therapy provided by a physiotherapist for 12 months. Parents were shown home exercises which were to be performed daily. Standard care group (N = 40): received by all infants and included attendance at a follow‐up clinic at 6 weeks and at 3, 6, 9 and 12 months' corrected age. This clinic was staffed by a neonatologist, physiotherapists, a speech and hearing therapist, ophthalmologists, public health nurses and a social worker. It is not clear how much 'intervention' was provided to infants in the control group during these visits.
Outcomes	Cognitive Infant age: Griffiths Mental Development Scale (12 months) School age: Griffiths Mental Development Scale 2 (6 years) Motor Infant age: Griffiths Developmental Quotient (locomotor subscale) (12 months) School age: Griffiths Development Quotient (locomotor subscale), neurological examination to assess incidence of cerebral palsy and clumsiness/co‐ordination problems (6 years)
Notes	Funding source: *Prior to commencing study, study authors stated that intention was to study 40 infants in each group. To allow for attrition, 107 infants were enrolled into the study at 3 months. However, the formal study ceased when 80 infants were followed up to 3 months. This study was supported by grants from the South African Medical Research Council and the Leo and Gretta Gillis Fund for Paediatric Research. Declarations of interest: not stated
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Infants assessed as 'normal' or 'at‐risk' on the basis of a neurodevelopmental score and then alternatively assigned to intervention or control groups
Allocation concealment (selection bias)	High risk	Unclear whether study personnel would be aware of group allocation given that children were then alternatively assigned to intervention or control groups
Blinding of participants and personnel (performance bias) All outcomes	High risk	Performance bias due to knowledge of allocated interventions by participants and personnel during the study
Blinding of outcome assessment (detection bias) All outcomes	Low risk	Assessors blinded to group allocation
Incomplete outcome data (attrition bias) All outcomes	High risk	Before beginning the study, study authors stated that their intention was to study 40 infants in the intervention and follow‐up groups. However, they recruited 107 children to allow for withdrawal of infants from the study. They ceased follow‐up when 80 children were assessed and did not report data for remaining 27 children. At 6 years, there was 61% follow‐up.
Selective reporting (reporting bias)	Low risk	Outcomes reported as planned
Other bias	Low risk	No other source of bias identified

I.H.D.P. 1990.

Study characteristics
Methods	A large multicentre randomised trial that investigated the effects of early intervention vs standard follow‐up for preterm infants To minimise the cost of the study, one‐third of participants were randomly assigned to intervention (N = 377) and two‐thirds were randomly assigned to standard follow‐up (N = 608).
Participants	N = 985 infants Intervention group: N = 377 Standard care group: N = 608 Inclusion criteria: BW ≤ 2500 grams or GA < 37 weeks Exclusion criteria: congenital abnormalities, genetic disorders, illness, still hospitalised, neurological impairment of severity that precluded participation in the programme at term Characteristics: mean GA for intervention and standard follow‐up groups: 33 weeks
Interventions	Intervention group: focus on infant development and parent‐infant relationship The intervention group received home visits, attended a child development centre and attended parent group meetings. Home visits were made weekly for the first year and biweekly for the second and third years. Home visits emphasised cognitive, linguistic and social development via a programme of games for the parent to use with the child, and aimed to help parents manage self‐identified problems. Children in the intervention group attended child development centres 5 days per week, from 12 to 36 months' corrected age. Standard care group: Both groups received standard care which included medical, developmental and social assessments, with referral to other services as indicated.
Outcomes	Cognitive Infant age: BSID‐I MDI (12 and 24 months) Preschool age: Stanford‐Binet Intelligence Scale (36 months) School age: WPPSI (5 years) and WISC‐III (8 years) Adult: WASI and PPVT (18 years) Motor Infant age: BSID‐I PDI (12 and 24 months)
Notes	Additional data (means and SDs for 12 and 24 months for MDI and PDI) were obtained from study authors for meta‐analysis. Funding source: the Infant Health and Development Program was funded by grants from the Robert Wood Johnson Foundation to the Department of Pediatrics, Stanford University, Stanford, Calif; the Prank Porter Graham Child Development Center, University of North Carolina at Chapel Hill; and the eight participating universities. Additional support for the National Study Office was provided to the Department of Pediatrics, Stanford University, from the Pew Charitable Trusts; the Bureau of Maternal and Child Health and Resources Developmeant and the National Institute of Child Health and Human Development, Health Resources and Services Administration, Public Health Service, US Dept of Health and Human Services (grant MCJ‐ 060515); and the Stanford Center for the Study of Families, Children, and Youth. Declarations of Interest: not stated
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Computerised adaptive randomisation method to ensure 2:1 ratio of standard follow‐up to intervention; stratified by study site and BW
Allocation concealment (selection bias)	Low risk	Adequate
Blinding of participants and personnel (performance bias) All outcomes	High risk	Performance bias due to knowledge of allocated interventions by participants and personnel during the study
Blinding of outcome assessment (detection bias) All outcomes	Low risk	Assessors blinded to group allocation
Incomplete outcome data (attrition bias) All outcomes	Low risk	Completeness of follow‐up: low risk at 12 months = 90%, 24 months = 89%, 36 months = 93%, 5 years = 82% and 8 years = 89%; high risk at 18 years = 65%
Selective reporting (reporting bias)	Low risk	Results were fully reported.
Other bias	Low risk	No other source of bias identified

Johnson 2009.

Study characteristics
Methods	Multicentre cluster‐randomised controlled trial with a cross‐over design investigating the effect of a neonatal parenting intervention for very preterm infants on motor and cognitive outcomes. Recruitment across 6 sites in the UK
Participants	N = 233 infants (6 neonatal units) Intervention group: N = 112 Standard care group: N = 121 Inclusion criteria: GA < 32 weeks Exclusion criteria: illness incompatible with life, residing outside the study catchment area Characteristics: mean GAs for intervention and standard follow‐up groups: 28.5 and 29.0 weeks, respectively
Interventions	Intervention group: received the 'Parent Baby Interaction Program' aimed at parent‐infant relationship and infant development. The intervention commenced in the first weeks after birth and the programme consisted of weekly 1‐hour sessions, up to a maximum of 6 sessions. Most sessions were in hospital with a median of 2 sessions post discharge. This included strategies to enhance parent‐infant interaction, facilitate attachment, sensitise parents to their baby's cues and provide education about developmental care principles. Standard care group: received standard care but no details provided
Outcomes	Cognitive Infant age: BSID‐II MDI (24 months) Motor Infant age: BSID‐II PDI (24 months)
Notes	Funding source: supported by the Health Foundation, London, United Kingdom Declaration of interest: no conflicts of interest to declare
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	High risk	Cluster‐randomisation with cross‐over design
Allocation concealment (selection bias)	High risk	Research nurse and parents not blinded to group allocation before recruitment because of cross‐over study design
Blinding of participants and personnel (performance bias) All outcomes	High risk	Performance bias due to possible knowledge of allocated interventions by participants and personnel during the study
Blinding of outcome assessment (detection bias) All outcomes	Low risk	Assessors blinded to group allocation
Incomplete outcome data (attrition bias) All outcomes	Low risk	Completeness of follow‐up: 84% follow‐up (195/233 infants assessed at 24 months)
Selective reporting (reporting bias)	Low risk	Results were fully reported.
Other bias	Low risk	No other source of bias identified

Kaaresen 2006.

Study characteristics
Methods	Randomised controlled trial of a modified version of the Mother Infant Transaction Program (MITP), originally described by Nurcombe 1984, for preterm infants
Participants	N =146 infants Intervention group: N = 72 Standard care group: N = 74 Inclusion criteria: BW < 2000 grams, Norwegian‐speaking, outborn infants who were transferred to the Tromso NICU within 1 week of birth Exclusion criteria: congenital abnormalities, non‐Norwegian speakers, triplets Characteristics: mean GAs for intervention and standard follow‐up groups: 30.3 (SD 3.) and 30.1 (SD 3.5) weeks, respectively
Interventions	Intervention group: focus on infant development and parent‐infant relationship. The intervention included an initial briefing session, followed by daily 1‐hour sessions with both parents and their infants on 7 consecutive days, starting 1 week before discharge, and 4 home visits at 3, 14, 30 and 90 days after discharge. The programme was implemented by a team of nurses and included education on behavioural cues, parent‐infant interaction and appropriate stimulation of the infant. Standard care group: included examination by a physiotherapist and doctor at discharge. Included an offer of training in infant massage by a physiotherapist and a clinical examination of hearing and vision by the doctor
Outcomes	Cognitive Infant age: BSID‐II MDI (24 months) Preschool age: BSID‐II MDI (3 years) School age: WPPSI (9 years) Motor Infant age: BSID‐II PDI (24 months) Preschool age: BSID‐II PDI (3 years) School age: McCarthy Scales of Children's Abilities ‐ Parts 9 and 11 (9 years)
Notes	Funding source: this study was funded by grants from the Norwegian Research Council, Norwegian Council for Mental Health, Norwegian Foundation for Health and Rehabilitation, and Northern Norway Regional Health Authority. Declarations of interest: not stated
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Random assignment arranged in blocks using computer‐generated random numbers and stratified for gestation (< 28 weeks and ≥ 28 weeks)
Allocation concealment (selection bias)	Low risk	Allocation performed using opaque envelopes
Blinding of participants and personnel (performance bias) All outcomes	High risk	Performance bias due to knowledge of allocated interventions by participants and personnel during the study
Blinding of outcome assessment (detection bias) All outcomes	Low risk	Assessors blinded to group allocation
Incomplete outcome data (attrition bias) All outcomes	Low risk	Completeness of follow‐up: 93% follow‐up at 2 years, 92% follow‐up at 3 years, 90% follow‐up at 5 years
Selective reporting (reporting bias)	Low risk	Results fully reported
Other bias	Low risk	No other source of bias identified

Kara 2019.

Study characteristics
Methods	Randomised controlled trial comparing the effects of a family‐based intervention, Coping and Caring for Infants with Special Needs (COPCA) with a Traditional Early Intervention program (TEIP) program on fine and gross motor functions of preterm infants
Participants	N = 42 infants Intervention group COPCA: N = 21 Standard care group TEIP: N =21 Inclusion criteria: BW < 1500 g, CA of 3 months with abnormal general movements at this age Exclusion criteria: major congential abnormalities, no abnormal GMs Characteristics: Median (min‐max) GA for treatment and standard follow‐up groups: 28.85 (26.43‐32)and 29 (27‐32) weeks, respectively
Interventions	Intervention group: focus on infant and parent‐infant relationship. The family‐based COPCA programme had two components: 1) an educational component focusing on family, and 2) a motor component based on neuronal group selection theory. Home‐based and performed by mothers coached by a physiotherapist Standard care group: TEIP was an integrated traditional physiotherapy approach aimed at improving functionality and independence in children based on a neurodevelopmental approach. The focus was on infant development, and it was performed by a physiotherapist. The setting was not specified. Both interventions started at 3 months CA (post NICU discharge) and continued until 12 mo CA for 2 times/week; 60 mins per session over a period of 36 weeks (total 72 sessions)
Outcomes	Cognitive None Motor Infant age: Bayley‐III at 3, 6, 9, 12 and 24 months Incidence of cerebral palsy (24 months)
Notes	Bayley‐III motor domain data at 24 months is not included in the meta‐analysis because scaled scores and median values were used to report data. Declarations of interest and funding sources: not stated
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Simple randomisation technique
Allocation concealment (selection bias)	Low risk	Opaque, sealed envelopes
Blinding of participants and personnel (performance bias) All outcomes	High risk	Performance bias due to knowledge of allocated interventions by participants and personnel during the study
Blinding of outcome assessment (detection bias) All outcomes	Low risk	Assessors blinded to group allocation
Incomplete outcome data (attrition bias) All outcomes	High risk	Completeness of follow = 76 %
Selective reporting (reporting bias)	Low risk	Results were fully reported.
Other bias	Low risk	No other source of bias identified

Koldewijn 2009.

Study characteristics
Methods	Multicentre randomised controlled trial of effects of the 'Infant Behavioural Assessment and Intervention Program' (IBAIP) vs standard follow‐up for preterm infants. Recruitment across 7 sites in Amsterdam
Participants	N = 176 infants Intervention group: N = 86 Standard care group: N = 90 Inclusion criteria: BW < 1500 grams or GA < 32 weeks, or both Exclusion criteria: congenital abnormality, non‐Dutch speakers, mothers with a history of drug use or severe physical or mental illness or participating in another post discharge trial Characteristics: mean GAs for intervention and standard follow‐up groups: 29.6 (SD 2.2) and 30.0 (SD 2.2) weeks, respectively
Interventions	Intervention group: focus on infant development and parent‐infant relationship. The intervention group received 1‐hour sessions, with the first session just before discharge, followed by 6 to 8 home visits up to 6 months' corrected age. Intervention was part of a commercially available training package, which aims to enhance parents' ability to read and respond to their infants' cues throughout everyday life. Standard care group: included regular outpatient visits with a paediatrician and neurobehavioural and developmental assessment at term, 3 months and 6 months
Outcomes	Cognitive Infant age: BSID‐II MDI (6 and 24 months) School age: WPPSI‐III Dutch version (5.5 years) Motor Infant age: BSID‐II PDI (6 months and 24 months) Preschool age: PEDI‐NL and cerebral palsy (44 months), Beery‐Buktenica Developmental Test of Visual‐Motor Integration ‐ Motor Co‐ordination subtest School age: Movment ABC 2nd edition, Visual Motor Integration (5.5 years)
Notes	*Data used in meta‐analysis have been adjusted for gestation, sex, ultrasound, oxygen > 28 days and maternal education. Funding source: supported by grants from the Innovatiefonds Zorgverzekeraars (project 576, supporting the implementation of the intervention programme) and Zorg Onderzoek Nederland (project 62200032, supporting the first author, who wrote the first draft of the manuscript). Declaration of interest: no conflicts of interest to declare
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Random assignment, computer‐generated, stratified for GA (< 30 weeks and ≥ 30 weeks) and recruitment site
Allocation concealment (selection bias)	Low risk	Adequate
Blinding of participants and personnel (performance bias) All outcomes	High risk	Performance bias due to knowledge of allocated interventions by participants and personnel during the study
Blinding of outcome assessment (detection bias) All outcomes	Low risk	Assessors blinded to group allocation
Incomplete outcome data (attrition bias) All outcomes	Unclear risk	Completeness of follow‐up: 44 months = 86% (low risk), 5 years = 77% (high risk)
Selective reporting (reporting bias)	Low risk	Results fully reported
Other bias	Low risk	No other source of bias identified

Kyno 2012.

Study characteristics
Methods	Single‐centre randomised controlled trial of the Mother‐Infant Transaction Program (MITP) vs standard care for infants born at 30 to 36 weeks' GA
Participants	N = 118 infants Intervention group: N = 61 Standard care group: N = 57 Inclusion criteria: GA ≥ 30 to < 36 weeks, admitted to NICU at Oslo University Hospital. Mothers must speak, write and read in Norwegian and have no history of psychiatric disorders or drug abuse. Exclusion criteria: congenital abnormality, hearing loss, chromosomal disorder with expected hospitalisation > 8 days Characteristics: mean GAs for intervention and standard follow‐up groups: 33.6 (SD 1.3) and 33.1 (SD 1.4) weeks, respectively
Interventions	Intervention group: focus on infant development and parent‐infant relationship. Intervention commenced 1 week before discharge and involved 7 sessions during that week. Infants were seen 4 times at home, at 7, 14, 30 and 90 days after discharge by a nurse trained in the programme. Standard care group: not described
Outcomes	Cognitive Preschool age: Mullen Scales of Early Learning (36 months), Early Learning Composite Score Motor Preschool age: Mullen Scales of Early Learning (36 months), Gross Motor and Fine Motor subscales
Notes	Funding source: this project has been financed with the aid of EXTRA funds from the Norwegian Foundation for Health and Rehabilitation, through the organisation Adults for Children. Declarations of interest: not stated
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Computer‐generated random numbers used to allocate groups. Twins randomly assigned to the same group
Allocation concealment (selection bias)	Low risk	Sealed envelopes
Blinding of participants and personnel (performance bias) All outcomes	High risk	Performance bias due to knowledge of allocated interventions by participants and personnel during the study
Blinding of outcome assessment (detection bias) All outcomes	High risk	Researchers non‐blinded. However, reliability between 10 test situations from each group randomly selected to be filmed, then scored by a blinded tester with low disagreement
Incomplete outcome data (attrition bias) All outcomes	High risk	Completeness of follow‐up: 52% at 36 months
Selective reporting (reporting bias)	Low risk	Results fully reported during process to 36 months
Other bias	Low risk	No other source of bias identified

Lekskulchai 2001.

Study characteristics
Methods	Randomised controlled trial to evaluate the effects of a physiotherapy motor developmental programme on improving motor performance for preterm infants vs standard follow‐up
Participants	N = 84 infants Intervention group: N = 43 Standard care group: N = 41 Inclusion criteria: BW and GA < 37 weeks, considered to be 'at‐risk' of adverse neurological sequelae, assessed with TIMP at 40 weeks' post conceptional age Exclusion criteria: congenital abnormality, genetic disorder, surgery or serious illness including hydrocephalus and PVH (grade III) excluded before randomisation Characteristics: mean GA for intervention and standard follow‐up groups: 31.9 (SD 2.4) and 32.3 (SD 2.2) weeks, respectively
Interventions	Intervention group: infant development focus. Motor developmental programme began at 40 weeks' postmenstrual age, with a further 3 visits at 1, 2 and 3 months' corrected age. Physiotherapist instructed primary carer on how to perform 3 activities with the infant during each session, which were to be carried out at home. Before the next visit, the principal researcher evaluated previous month's programme with the carer through an interview and demonstration of activities by the carer. Standard care group: all families were assessed using the TIMP by a research assistant at 1, 2, 3 and 4 months. This standard care group were able to use these time points to discuss any concerns with the principal researcher.
Outcomes	Cognitive None Motor Infant age: TIMP 1, 2, 3 and 4 months
Notes	Unable to use data in meta‐analysis as outcome measure (TIMP) was not appropriate for pooling with other outcome measures. Funding sources and declarations of interest: not stated
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Initial TIMP assessment identified infants with higher risk profile ‐ this group was randomly assigned to intervention or control. The remaining participants were placed in the comparison group.
Allocation concealment (selection bias)	Low risk	Intervention or control slip taken blindly from a container
Blinding of participants and personnel (performance bias) All outcomes	High risk	Performance bias due to knowledge of allocated interventions by participants and personnel during the study
Blinding of outcome assessment (detection bias) All outcomes	Low risk	Assessors blinded to group allocation
Incomplete outcome data (attrition bias) All outcomes	Low risk	Completeness of follow‐up: 1, 2, 3 and 4 months = 86%
Selective reporting (reporting bias)	Unclear risk	Results fully reported
Other bias	Low risk	No other source of bias identified

Leucona 2017.

Study characteristics
Methods	Randomised controlled trial with pre‐test/post‐test experimental design to investigate the effect of Ayres Sensory Integration (ASI) intervention on the developmental progress of ELBW to VLBW premature infants from low socioeconomic settings
Participants	N = 24 Infants were stratified according to corrected age and gender into: Intervention group: N = 12 Standard care group: N = 12 Inclusion criteria: BW 750‐1499 g, GA 26–36 weeks. Recruited in the age range of 4–10 months CA Exclusion criteria: no previous occupational therapy or sensory integration therapy. No additional conditions or neurological abnormalities Characteristics: mean GAs for treatment and standard follow‐up groups: 30.3 and 30.7 weeks respectively (SD not reported)
Interventions	Intervention group: Focus on infant and parent‐infant relationship. Intervention commenced post discharge in preterm infants between 4‐10 mo CA and was implemented by the parent with guidance from an occupational therapist (OT). It consisted of 10 weekly sessions of 45 mins duration. ASI techniques are integrated within the context of parent guidance and child‐centred activity, to normalise the child’s responses to sensory experiences, modulate arousal and promote organised adaptive responses during play and everyday activities. A maximum of two appropriate play/handling recommendations were demonstrated to parents after each session. The model of infant behaviour based on SI and self‐regulation provided a framework within which intervention planning was organised in terms of: (i) helping parents to understand their infant and his/her developmental progress; (ii) facilitating goodness of fit between infants and their sensory environment; and (iii) addressing the underlying sensory processing and self‐regulation problems and/or their behavioural expression in terms of arousal, attention, affect and action. Standard care group: details of standard care not specified
Outcomes	Cognitive Infant age: Bayley ‐III Motor Infant age: Bayley ‐III
Notes	Funding source: this research was mainly self‐funded as part of EL’s M (Occupational Therapy) studies. A financial contribution was made by the South African Institute for Sensory Integration (SAISI) as well as the Research Committee of the School for Allied Health Professions of the University of the Free State(UFS). Declaration of interest: no conflicts of interest to declare
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	No information given on generation of randomised sequence
Allocation concealment (selection bias)	Unclear risk	No information given on how allocation was concealed
Blinding of participants and personnel (performance bias) All outcomes	High risk	Performance bias due to knowledge of allocated interventions by participants and personnel during the study
Blinding of outcome assessment (detection bias) All outcomes	Low risk	Assessors blinded to group allocation
Incomplete outcome data (attrition bias) All outcomes	Low risk	Completeness of follow up = 100%
Selective reporting (reporting bias)	Low risk	Results were fully reported.
Other bias	Low risk	No other source of bias identified

Melnyk 2001.

Study characteristics
Methods	A quasi‐randomised pilot project comparing the Creating Opportunities for Parent Empowerment (COPE) programme and placebo intervention
Participants	N = 55 infants Intervention group: N = 26 Standard care group: N = 29 Inclusion criteria: BW < 2000 grams and GA < 34 weeks Exclusion criteria: perinatal hypoxia or abnormal ultrasound with no congenital or chromosomal abnormalities or metabolic disease Characteristics: mean GAs for intervention and standard follow‐up groups: 31.3 (SD 2.2) and 32.0 (SD 1.6) weeks, respectively
Interventions	Intervention group: focus on the parent‐infant relationship. COPE was a 4‐phase programme that consisted of audiotaped and written information and workbooks on infant behaviour and parental roles. The first 3 sessions occurred 2 to 4 days after admission to hospital, and the last session occurred approximately 1 week after discharge. Standard care group: placebo intervention was delivered at the same 4 time points and involved audiotaped and written information about hospital services, routine discharge information and education about immunisations.
Outcomes	Cognitive Infant age: Bayley Scales of Infant Development‐II MDI (3 and 6 months) Motor None
Notes	This was the only study that included a comparison group receiving a placebo intervention. Funding sources and conflicts of interest: not stated
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	High risk	Quasi‐randomisation with intervention provided in blocks according to the date admitted to hospital
Allocation concealment (selection bias)	High risk	Infants randomly assigned according to date admitted to hospital
Blinding of participants and personnel (performance bias) All outcomes	Low risk	Placebo intervention used; both participants and staff blinded to group allocation
Blinding of outcome assessment (detection bias) All outcomes	Low risk	Assessors blinded to group allocation
Incomplete outcome data (attrition bias) All outcomes	High risk	Completeness of follow‐up: 3 and 6 months = 76%
Selective reporting (reporting bias)	Low risk	Results fully reported
Other bias	Low risk	No other source of bias identified

Milgrom 2019.

Study characteristics
Methods	A randomised controlled trial involving two centres assessing the effects of PremieStart intervention on neurobehavioral development of preterm infants at preschool age and child development at infant age
Participants	N = 123 Intervention group: N = 60 Standard care group: N = 63 Inclusion criteria: GA < 30 weeks Exclusion criteria: insufficient English, triplets, congential abnormalities, maternal drug or alcohol abuse, parent or infant too medically unwell, reside > 100 km from Melbourne Characteristics: mean GAs for treatment and standard follow‐up groups: 27.4 (SD 1.5) and 27.8 (SD 1.7) weeks, respectively
Interventions	Intervention group: focus parent‐infant. The PremieStart programme aims to support parents in developing skills to interact with their infant. The programme was delivered by a psychologist and is based on the Mother‐Infant Transaction Programme. It involves intensive training of parents, specifically mothers, to recognise signs of infant stress, physiological, motor or behavioural. It supports sensitive interactions and graded stimulation between parent and infant. It provides practical support with handling the infant and emotional support for parenting a preterm infant. Nine sessions were delivered in NICU (one per week) and one session at home at 1 month post discharge. Infants in the PremieStart group also received standard care. Standard care group: included individualised care plans and parent attendance at group educational classes in the NICU. The psychologist provided a single session on cognitive strategies to handle stress and anxiety and a 10‐minute non‐therapeutic contact with psychologist every week for the remainder of the intervention period.
Outcomes	Motor Infant age: Bayley‐III Cognitive Preschool age: WPPSI‐III and NEPSY‐II
Notes	Infant age ‐ Bayley‐III motor data and preschool age WPPSI‐III cognitive data were included in the meta‐analysis. Funding source: the work was supported by grants from the National Health & Medical Research Council, Australia. Declaration of interest: no conflicts of interest to declare
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Pre‐generated, permutated blocks schedule
Allocation concealment (selection bias)	Low risk	Group allocation was done by an independent study administrator.
Blinding of participants and personnel (performance bias) All outcomes	High risk	Performance bias due to knowledge of allocated interventions by participants and personnel during the study
Blinding of outcome assessment (detection bias) All outcomes	Low risk	Assessors were blinded to group assignment.
Incomplete outcome data (attrition bias) All outcomes	Unclear risk	Completeness of follow‐up: 2 years = 87% (low risk), 4.5 years = 78% (high risk)
Selective reporting (reporting bias)	Low risk	Study authors reported on number of infants not available for assessment at various time points.
Other bias	Unclear risk	An author from this Cochrane review (PJA) was involved in the RCT.

Nelson 2001.

Study characteristics
Methods	Randomised controlled study to investigate effects of an infant stimulation programme vs standard follow‐up for preterm infants
Participants	N = 37 infants Intervention group: N = 21 Standard care group: N = 16 Inclusion criteria: BW < 1500 grams and GA 23 to 26 weeks (group 1), diagnosed with PVL or grade III IVH (group 2) Exclusion criteria: not medically stable, required mechanical ventilation or was not feeding at commencement of the study (commenced while infants were in the NICU), intrauterine growth restriction, chromosome disorders and NEC Characteristics: mean GAs for intervention and control groups, group 1: 25.6 (SD 1.1) and 25.6 (SD 1.5) weeks; group 2: 27.2 (SD 2.9) and 27.3 (SD 2.4) weeks, respectively
Interventions	Intervention group: focus on infant development and parent‐infant relationship. The intervention group received a multisensory stimulation programme including auditory, tactile, visual and vestibular stimuli in response to infant behavioural and physiological cues. Intervention was provided by a research assistant at the hospital twice daily, 5 days per week until discharge. Mothers were taught the intervention, which they continued to administer at home until infants reached 2 months' corrected age. Standard care group: : All infants received developmental care as inpatients, along with a physiotherapy programme post hospital discharge.
Outcomes	Cognitive Infant age: BSID‐II MDI (12 months) Motor Infant age: BSID‐II PDI (12 months)
Notes	Funding source: this research was supported by the National Institutes of Health, National Institute of Nursing Research, Grant #1RO1 NR2328‐01A2; the Hewlett‐Packard Company, Grant #13580; the Alcoa Foundation; the Harris Foundation; Gould Instruments; and the Campus Research Board, the University of Illinois at Chicago. Declarations of interest: not stated
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Unclear
Allocation concealment (selection bias)	Unclear risk	Unclear
Blinding of participants and personnel (performance bias) All outcomes	High risk	Performance bias due to knowledge of allocated interventions by participants and personnel during the study
Blinding of outcome assessment (detection bias) All outcomes	Low risk	Assessors blinded to group allocation
Incomplete outcome data (attrition bias) All outcomes	High risk	Completeness of follow‐up: 12 months = 70%
Selective reporting (reporting bias)	Low risk	Outcomes fully reported
Other bias	Low risk	No other source of bias identified

Nurcombe 1984.

Study characteristics
Methods	Randomised controlled trial of the Mother‐Infant Transaction Program (MITP), also known as the Vermont Intervention Program, vs standard follow‐up
Participants	N = 78 infants Intervention group: N = 38 Standard care group: N = 40 Inclusion criteria: BW < 2250 grams and GA < 37 weeks Exclusion criteria: congenital abnormality, severe neurological defect, multiple birth, single mother Characteristics: mean GAs for treatment and standard follow‐up groups: 32.3 (SD 2.4) and 31.9 (SD 2.4) weeks, respectively. Significant difference in SES of intervention and standard follow‐up groups despite randomisation
Interventions	Intervention group: focus on infant development and parent‐infant relationship. Intervention was designed to enhance mother‐infant interaction and infant development by teaching mothers to be more sensitive and responsive to their baby's physiological, behavioural and social cues. Intervention consisted of a total of 11 sessions delivered by a trained neonatal intensive care nurse: 7 sessions were conducted in hospital before discharge and 4 at home during the first 3 months following discharge; focused on the infant's motor system, state regulation, social interaction, daily care, preparations for home, mutual enjoyment through play and understanding of temperamental patterns Standard care group: no details reported
Outcomes	Cognitive Infant age: BSID‐I MDI (6, 12 and 24 months) Preschool age: McCarthy Scales (3 and 4 years) School age: Kaufman Assessment Battery for Children (7 and 9 years) Motor Infant age: BSID‐I PDI (6, 12 and 24 months)
Notes	Reported data have been adjusted to control for SES of families. Funding source: the Vermont Infant Studies Project was funded by NIMH Grant 1‐ROI‐MH‐32924. Declarations of interest: not stated
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Toss of a coin
Allocation concealment (selection bias)	Low risk	Toss of a coin
Blinding of participants and personnel (performance bias) All outcomes	High risk	Performance bias due to knowledge of allocated interventions by participants and personnel during the study
Blinding of outcome assessment (detection bias) All outcomes	Low risk	Assessors blinded to group allocation
Incomplete outcome data (attrition bias) All outcomes	Unclear risk	Completeness of follow‐up: low risk at 12 months = 95%; however, longer‐term follow‐up not adequate at 24, 36 and 48 months (68%) and at 7 and 9 years (71%)
Selective reporting (reporting bias)	Low risk	Results fully reported
Other bias	Low risk	No other source of bias identified

Ochandorena‐Acha 2022.

Study characteristics
Methods	Randomised single‐blind clinical trial aiming to evaluate the effectiveness of an early physiotherapy intervention on preterm infants’ motor and global development vs standard care Single‐centre trial
Participants	N = 48 Intervention group: N = 24 Standard care group: N = 24 Inclusion criteria: Infants 28‐34 weeks' GA, parents stay at the hospital for more than 6 hours per day, recruited after 32 weeks' GA or when medically stable Exclusion criteria: preterm triplets, major central nervous system injury (grade III/IV IVH or PVL), severe musculoskeletal or congenital abnormalities, bronchopulmonary dysplasia, major surgery, sepsis or NEC during the neonatal period, hearing impairment or retinopathy of prematurity, and infants born of mothers with a documented history of social problems or mental illness Characteristics: mean GA (weeks) and BW (grams) for intervention and control groups: 31.8 (SD 1.8), 1462.5(SD 437.3) and 32.1 (SD 1.6), 1590.1 (SD 331.2), respectively
Interventions	Intervention group: Focus on infant development and parent‐infant relationship. As well as NIDCAP, the intervention group received an early physiotherapy intervention programme commencing at 32 weeks' CA until 2 months' CA. During hospital stay, sessions involve a tactile/kinaesthetic approach and post discharge, it takes a preventative approach aiming to improve preterm infants’ motor development, enhance the parent–infant relationship, and teach parents about preterm infants’ cues and management strategies. Standard care group: NIDCAP during hospital stay. Prior to discharge, may attend a going‐home session about preterm infant care. A routine physiotherapy visit while in hospital and, if the infant is considered high‐risk, sporadic sessions with a PT for individual assistance are arranged. In those cases, the number and type of activities were recorded.
Outcomes	Cognitive Infant age: ASQ 8 months Motor Infant age: AIMS 8 months
Notes	Funding source: funding from the Catalan Board of Physical Therapists Funding source: the authors declared no conflict of interest.
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	The random assignment of each preterm infant with his/her parents was stratified according to the gestational age at birth (between 28 + 0 and 31 + 6 and between 32 + 0 and 34 + 0 gestational age). The stratification was accomplished using 2 computer‐generated lists at a 1:1 ratio. Twins were assigned to the same group.
Allocation concealment (selection bias)	Low risk	The allocation was made through sealed opaque envelopes (identified according to stratification group and numbered consecutively), which were opened by the first author before parents were given oral and written information.
Blinding of participants and personnel (performance bias) All outcomes	High risk	Performance bias due to knowledge of allocated interventions by participants and personnel during the study
Blinding of outcome assessment (detection bias) All outcomes	Low risk	Both the PTs administering the post intervention assessments and nurses at the neonatal unit were blinded to the participants’ assigned group.
Incomplete outcome data (attrition bias) All outcomes	Low risk	Follow‐up rate of 85%. Details of reasons for failure to continue in study or attend assessment were provided by authors.
Selective reporting (reporting bias)	Low risk	Results were fully reported.
Other bias	Low risk	No other source of bias identified

Ohgi 2004.

Study characteristics
Methods	Randomised controlled trial to determine the effects of an early intervention programme on preterm infants with high risk of cerebral palsy vs standard follow‐up
Participants	N = 24 infants Intervention group: N = 12 Standard care group: N = 12 Inclusion criteria: BW < 2500 grams and at high risk for neurological problems due to IVH or PVL (as shown by ultrasound) or both Exclusion criteria: multiple births, born in another town and returned there Characteristics: mean GAs for treatment and follow‐up groups: 30.3 (SD 3.3) and 30.3 (SD 2.7) weeks, respectively. No significant differences between groups for infant and maternal factors, social factors, distribution of diagnoses and severity of injury
Interventions	Intervention group: focus on infant development and parent‐infant relationship. The intervention group received a behavioural‐based intervention combined with developmental support designed to enhance infant development and the parent‐infant relationship. Intervention began in the NICU and lasted until 6 months' corrected age. Standard care group: All infants in control and intervention groups attended follow‐up clinics and were referred to developmental services if they presented with signs of neurological dysfunction or developmental delay.
Outcomes	Cognitive Infant age: BSID‐II MDI (6 months) Motor Infant age: BSID‐II PDI (6 months)
Notes	Funding source: this study was supported by a grant from Japan Society for the Promotion of Science, No 14922171. Declarations of interest: not stated
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Randomly assigned using method of minimisation
Allocation concealment (selection bias)	Low risk	Adequate
Blinding of participants and personnel (performance bias) All outcomes	High risk	Performance bias due to knowledge of allocated interventions by participants and personnel during the study
Blinding of outcome assessment (detection bias) All outcomes	Low risk	Assessors blinded to group allocation
Incomplete outcome data (attrition bias) All outcomes	Low risk	Completeness of follow‐up: 12 months = 96%
Selective reporting (reporting bias)	Low risk	Results fully reported
Other bias	Low risk	No other source of bias identified

Pascoali Rodovanski 2021.

Study characteristics
Methods	A feasibility study of a two‐arm parallel‐group randomised controlled trial aiming to assess the effect of a home‐based early stimulation program on visual and motor development in preterm infants
Participants	N = 36 Intervention group: N = 18 Standard care group: N = 18 Inclusion criteria: low‐risk preterm infant, 28‐37 week GA, 1–2 months' CA at enrolment, infants with immature visual tracking, no other visual impairments Exclusion criteria: neurological or respiratory impairment, extreme prematurity (< 28 weeks GA or < 1000 g), congenital diseases, medically unstable, participating in any physical or occupational therapy or early intervention service Characteristics: median GA for infants in both groups was 36 weeks.
Interventions	Intervention group: focus on infant development. Early Stimulation Program targeting Visual and Motor Function (ESPVM). This programme is based on the principles of active dependent learning and environmental enrichment and is implemented at home. Caregivers are taught one on one interaction with visual tasks which is then to be done once a day for 28 days. Parents record the details of each daily intervention, including adverse reactions. The intervention group also received the handbook given to the standard care group. Standard care group: caregivers received a handbook with information and activities according to the age range from birth to 3 months. The following information is included in the handbook: a) use songs while the infant is sleeping, b) use toys that make sounds and move, c) present toys close to the infant’s face, d) talk with the infants looking at their eyes during bath time, d) apply soft massage, e) change positions – side‐lying, f) walk with the infant while holding him/her as if he/she was on a chair, g) use the prone position, h) present toys that stimulate the use of both hands at the same time. Investigators read the information together with the caregivers and demonstrated the application of the activities.
Outcomes	Cognitive none Motor Infant age (TIMP) post intervention
Notes	Funding source: this work was supported by the Coordenaç˜ao de Aperfeiçoamento de Pessoal de Nível Superior – Brasil (CAPES) [grant number: Finance code 001, 2016–2018]. Declaration of interest: the authors reported no conflict of interest.
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Infants were consecutively randomised using an electronic allocation system.
Allocation concealment (selection bias)	Low risk	The person responsible for randomisation informed the investigators by phone of group allocation.
Blinding of participants and personnel (performance bias) All outcomes	High risk	Performance bias due to knowledge of allocated interventions by participants and personnel during the study
Blinding of outcome assessment (detection bias) All outcomes	Unclear risk	2 trained investigators applied the assessments and the intervention. The assessments were de‐identified and later analysed by a blinded assessor.
Incomplete outcome data (attrition bias) All outcomes	Low risk	Overall follow‐up rate of 83%. Rates better in intervention group (88.9%) compared to the standard care group (77.8%). 6 infants did not receive the intervention and reasons for this were reported.
Selective reporting (reporting bias)	Low risk	Results were fully reported.
Other bias	Low risk	No other source of bias identified

Resnick 1988.

Study characteristics
Methods	Quasi‐randomised controlled trial to evaluate a programme of hospital and home‐based intervention for preterm infants.
Participants	N = 41 infants Intervention group: N = 21 Standard care group: N = 20 Inclusion criteria: BW < 1800 grams, GA < 37 weeks Exclusion criteria: not specified Characteristics: mean GAs for intervention and control groups: 31.7 (SD 2.9) and 31.0 (SD 2.0) weeks, respectively
Interventions	Intervention group (N = 21): focus on infant development and parent‐infant relationship. While an inpatient, intervention was a stimulation programme and passive movements implemented by early developmental specialist intervention twice a day. Post discharge until 12 months, CA visits by a specialist twice a month for 60–90 mins with the focus on language development, social skills, cognitive and motor development and parenting activities Standard care group (N = 20): families were given access to a full range of social services, physiotherapy and occupational therapy based on the needs of the infant.
Outcomes	Cognitive Infant age: BSID‐I MDI (6 and 12 months) Motor Infant age: BSID‐I PDI (6 and 12 months)
Notes	Funding source: this study was funded in part by the Jessie Ball Dupont Foundation, National Foundation of the March of Dimes, State of Florida's Children's Medical Services, Developmental Services and Developmental Disabilities Council. Declarations of interest: not stated
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	High risk	Infants randomly assigned according to the last digit of hospital number
Allocation concealment (selection bias)	High risk	Infants randomly assigned according to the last digit of hospital number
Blinding of participants and personnel (performance bias) All outcomes	High risk	Performance bias due to knowledge of allocated interventions by participants and personnel during the study
Blinding of outcome assessment (detection bias) All outcomes	Low risk	Assessors blinded to group allocation
Incomplete outcome data (attrition bias) All outcomes	Unclear risk	Completeness of follow‐up: unclear, as it was not stated whether any participants withdrew from the study before the 12‐month assessment.
Selective reporting (reporting bias)	Low risk	Results reported for both intervention and control groups
Other bias	Unclear risk	Exclusion criteria not specified

Rice 1979.

Study characteristics
Methods	Randomised controlled trial of infant stimulation for preterm infants vs standard follow‐up
Participants	N = 30 Intervention group: N = 15 Standard care group: N = 15 Inclusion criteria: born at GA < 37 weeks between 1974 and 1975; born to mothers of low SES Exclusion criteria: not specified Characteristics: mean GAs for intervention and control groups: not stated but reported to be similar between control and intervention groups
Interventions	Intervention group: focus on infant development. Infants received a tactile‐kinaesthetic stimulation programme administered by their mothers that aimed to enhance parent‐infant relationship and to give infants appropriate levels of stimulation. Standard care group: Mothers were given standard discharge information related to caring for their infant. It is reported that mothers were visited regularly by the experimenter and by other public health nurses, who provided social reinforcement for appropriate parenting behaviour.
Outcomes	Cognitive Infant age: BSID‐I MDI (4 months) Motor Infant age: BSID‐I PDI (4 months)
Notes	No funding sources or conflicts of interest: stated
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	No information given on generation of a randomised sequence
Allocation concealment (selection bias)	Unclear risk	No information given on how allocation was concealed
Blinding of participants and personnel (performance bias) All outcomes	High risk	Performance bias due to knowledge of allocated interventions by participants and personnel during the study
Blinding of outcome assessment (detection bias) All outcomes	Low risk	Assessors masked to group allocation
Incomplete outcome data (attrition bias) All outcomes	Unclear risk	Not stated whether any infants withdrew from the study
Selective reporting (reporting bias)	Unclear risk	Included only children born to mothers of low SES
Other bias	Low risk	No other source of bias identified

Sajaniemi 2001.

Study characteristics
Methods	Randomised controlled trial to assess effects of early occupational therapy for preterm infants Infants were matched in pairs in accordance with their perinatal risk scores and then allocated successively to intervention and standard care.
Participants	N = 126 Intervention group: N = 63 Standard care group: N = 63 Inclusion criteria: BW < 1000 grams, born between January 1991 and December 1994 and admitted to Helsinki University Central Hospital Exclusion criteria: cerebral palsy, mental retardation Characteristics: mean GAs for intervention and control group: 27.1 (SD 0.3) and 26.4 (SD 0.3) weeks, respectively
Interventions	Intervention group: focus on infant development. The intervention group received a 1‐hour weekly home‐based intervention from 6 to 12 months aimed at supporting parent‐infant interactions and enhancing motor control. Standard care group: not described; however, children in both groups had access to extra occupational therapy and physiotherapy when required.
Outcomes	Cognitive Infant age: BSID‐I MDI (24 months) Preschool age: WPPSI (4 years) Motor Assessed with Finnish neurodevelopmental assessment ‐ no scores for meta analysis
Notes	Infants were excluded at 2 and 4 years for having cerebral palsy or mental retardation, changing the number of eligible infants at each time point. Follow‐up rates reported in the table are based upon the 126 infants originally allocated. Funding source: this study was supported by the Arvo and Lea Ylppo Foundation. Declarations of interest: not stated
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	High risk	Every second patient was randomly allocated to the control group on a case‐control basis.
Allocation concealment (selection bias)	Unclear risk	Unclear whether participants or personnel were unaware of random assignment during the study
Blinding of participants and personnel (performance bias) All outcomes	High risk	Performance bias due to knowledge of allocated interventions by participants and personnel during the study
Blinding of outcome assessment (detection bias) All outcomes	Low risk	Assessors blinded to group allocation
Incomplete outcome data (attrition bias) All outcomes	High risk	Completeness of follow‐up: 2 years = 79%; 4 years = 76%
Selective reporting (reporting bias)	Low risk	Results fully reported
Other bias	Low risk	No other source of bias identified

Sgandurra 2017.

Study characteristics
Methods	A multicentre randomised controlled trial assessing the short‐term effects of CareToy training on motor and visual development in 3‐9 month‐old preterm infants Random allocation to either CareToy group (n = 19) or standard care (n = 22) group after baseline assessment. Re‐assessed 4 weeks post baseline (T1). This is considered the RCT phase ‐ 4 weeks after this phase, infants in standard care at T1 were switched to a 4‐week CareToy programme (n = 17) and infants that had already completed CareToy training switched over to SC (n = 18).
Participants	N = 41 Intervention group: N = 22 Standard care group: N = 19 Inclusion criteria: infants born between 28 + 0 and 32 + 6 (weeks + days) of GA and aged 3‐9 mo of CA who had achieved a predefined cut‐off score in ASQ‐3 Exclusion criteria: BW < 10th percentile, brain damage, IVH > grade 1, any cystic PVL, seizures, blindness, deafness, severe malformations or participation in other rehabilitation studies Characteristics: mean GAs for intervention and standard care group: 30.7 (SD 1.4) and 30.82 (SD 1.1) weeks, respectively
Interventions	Intervention group: focus on the infant CareToy intervention is an intensive, highly‐customised, home‐based, family‐centred training programme, provided through remote management of a CareToy system delivered at home. It consists of specific goal‐directed activities, remotely planned by the clinical/rehabilitative staff according to specific infant needs and ability. It consists of two phases. Phase 1 ‐ 1 week was devoted to infant and parent habituation to system and identification of main rehabilitation goals. Phase 2 ‐ 3 weeks of continuous planning and customisation of training of daily activities and progress. Automated report to the rehab staff by the CareToy System at the end of each day to monitor progress and accordingly build complex abilities Intervention started post discharge from the NICU, sessions of CareToy 30–45 minutes for 4 weeks (28 days in total) Standard care group: received bimonthly follow‐up checks during which current care advice was provided on early management of preterm infants. Booklets dedicated to home care of preterm infants are given an occasional session with a physical therapist if required.
Outcomes	Three time points ‐ Baseline (T0), 4 weeks post baseline (T1) and 8 weeks post baseline (T2). T1 is the primary endpoint for assessment. Motor Infant age: Infant Motor Profile Infant age: AIMS Cognitive none
Notes	IMP data were not included in the meta‐analysis due to the report of changed scores. Funding source: CareToy (http://www.caretoy.eu) was funded by the European Union under the Seventh Framework Program (https://ec.europa.eu/research/fp7/index_en.cfm), theme Information and Communications Technology (ICT)‐2011.5.1 Personal Health Systems (PHS), Grant ICT‐2011.5.1‐287932. Declaration of interest: no conflicts of interest to declare
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Infants randomly assigned to intervention or control, but method of randomisation not described
Allocation concealment (selection bias)	Unclear risk	Unclear what measures were taken to ensure concealment of allocation
Blinding of participants and personnel (performance bias) All outcomes	High risk	Performance bias due to knowledge of allocated interventions by participants and personnel during the study
Blinding of outcome assessment (detection bias) All outcomes	Low risk	Assessor blinded to group assignment
Incomplete outcome data (attrition bias) All outcomes	Low risk	Completeness of follow up = 100%
Selective reporting (reporting bias)	Low risk	Study authors reported on numbers of infants assessed for eligibility vs consented to the study and whether any withdrawals occurred.
Other bias	Low risk	No other source of bias identified

Shafaroodi 2022.

Study characteristics
Methods	Randomised double‐blind clinical trial aimed at assessing the Creating Opportunities for Parent Empowerment (COPE) program with families of preterm infants vs standard care Infants in intervention and control groups were matched for characteristics such as GA, BW, head circumference, Apgar, new Ballard score.
Participants	N = 40 Intervention group: N = 20 Standard care group: N =20 Inclusion criteria: BW 1000 g‐2500 g or GA < 37 weeks, 5 minutes Apgar 7 or more, hospitalisation for 7–30 days Exclusion criteria: IVH grade III or IV, presence of congenital abnormalities, disease or neonatal death during study, parents excluded their infant for any reason Characteristics: mean GAs and BW for intervention and control groups: 33.05 (SD 1.39), 1847 (SD 350) and 31.8 (SD 2.5), 1602 (459) weeks, respectively
Interventions	Intervention group: Focus on parent‐infant relationship. The COPE programme aims to empower mothers by gradually training them to understand their preterm infant better and establish positive interaction patterns. Performed in 5 steps, step I, 2–4 days following the entrance of the infant to the NICU; step II, 2–4 days after implementing the first step; step III, 1–4 days before the infant leaves the NICU; step IV, about one week after discharge; and step V, about 2 months old of corrected age. Performed by a research therapist Standard care group: Neonates in the control group received routine services and interventions, and the research therapist performed no additional interventions.
Outcomes	Cognitive Infant age: ASQ 6 months Motor Infant age: ASQ 6 months
Notes	Data not suitable for meta analysis Funding source: this study was funded by a project at the Department of Occupational Therapy, School of Rehabilitation Sciences, Iran University of Medical Sciences (No: 5536/105/D/93). Declaration of interest: the authors had no conflict of interest to declare.
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Infants randomly assigned to intervention or control, using a randomised block design
Allocation concealment (selection bias)	Unclear risk	Unclear what measures were taken to ensure concealment of allocation
Blinding of participants and personnel (performance bias) All outcomes	High risk	Performance bias due to knowledge of allocated interventions by participants and personnel during the study
Blinding of outcome assessment (detection bias) All outcomes	Low risk	Assessor (OT) blinded to group allocation
Incomplete outcome data (attrition bias) All outcomes	Low risk	Follow‐up rate of 100% ‐ flow diagram indicated all infants analysed and none lost to follow‐up.
Selective reporting (reporting bias)	High risk	Flow diagram indicated all infants enroled were assessed but results table did not include numbers. Little information available regarding implementation of the intervention ‐ who implemented it, was the post discharge session a home visit, how much was required of the parent between the sessions.
Other bias	Low risk	No other source of bias identified

Spittle 2009.

Study characteristics
Methods	Single‐centre randomised controlled trial of a preventive care programme vs standard follow‐up for preterm infants
Participants	N = 120 infants Intervention group: N = 61 Standard care group: N = 59 Inclusion criteria: born at GA < 30 weeks Exclusion criteria: non‐English speaking, living > 100 km from the hospital, with or without congenital abnormalities Characteristics: mean GAs for intervention and control groups: 27.3 (SD 1.6) and 27.4 (SD 1.4) weeks, respectively
Interventions	Intervention group: focus on infant development and relationships. The intervention group received 9 visits post hospital discharge from a team of a physiotherapist and a psychologist at home, with each session lasting 1.5 to 2 hours from 1 week post hospital discharge to 11 months' corrected age. Preventive care programme aimed to improve infant development and to support parents' mental health. Standard care group: not systematic; however, each family had access to maternal child health nurses and could access early intervention if referred by a paediatrician or healthcare team.
Outcomes	Cognitive Infant age: Bayley Scales of Infant and Toddler Development Scale‐III: Cognitive (24 months) Preschool age: Differential Ability Scale (DAS‐II) (4 years) School age: Differential Ability Scale (8 years) School age: WASI‐II (13 years) Motor Infant age: Bayley Scales of Infant and Toddler Development Scale‐III: Cognitive (24 months) Preschool age: Movement Assessment Battery for Children 2nd Edition (MABC‐2) (4 years) School age MABC‐2 (8 years) School age MABC‐2 (13 years) Incidence of cerebral palsy
Notes	Funding source: funding support from the National Health and Medical Council (NHMRC) Australia Project grant (ID 284512), the Cerebral Palsy Foundation, Murdoch Childrens Research Institute, the Myer Foundation, Allens Arthur Robinson, and the Thyne Reid Foundation. Cerebral Palsy Foundation Post Doctoral Fellowship (AS) NHMRC Career Development Award 473840 (RB) Funding source: no conflicts of interest to declare *This study included authors of this Cochrane review.
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Computer‐generated randomisation
Allocation concealment (selection bias)	Low risk	Allocation concealment, randomisation via computer‐generated programme and assigned with opaque envelopes
Blinding of participants and personnel (performance bias) All outcomes	High risk	Performance bias due to knowledge of allocated interventions by participants and personnel during the study
Blinding of outcome assessment (detection bias) All outcomes	Low risk	Assessors blinded to group allocation
Incomplete outcome data (attrition bias) All outcomes	Low risk	Completeness of follow‐up: 2 years = 96%, 4 years = 89%; 8 years = 85%
Selective reporting (reporting bias)	Low risk	Results were fully reported.
Other bias	Unclear risk	All authors of this Cochrane review were involved in this randomised controlled trial.

Teti 2009.

Study characteristics
Methods	Multicentre, randomised controlled trial of an intervention programme targeted at very‐low birth weight children of African American women.
Participants	N = 194 infants included Intervention group: N = 99 Standard care group: N = 95 Inclusion criteria: low birthweight infants of African American women Exclusion criteria: mothers with positive toxicology screens or younger than 18 years of age. Infants were excluded if they had a chromosomal abnormality. Characteristics: mean GAs for intervention and control groups: 30.6 (SD 3.2) and 29.9 (SD 3.6) weeks, respectively
Interventions	Intervention group: focus on parent education and parent infant attachment strategies. The intervention began in the NICU at 32 weeks GA for infants born < 32 weeks and between 32 and 36 weeks for those older infants. It included an infant tactile stimulation component and two psychoeducational components targeting infant behaviour and infant individual abilities to enhance attachment and facilitate social and motor behaviours. It consisted of 8 sessions over 20 weeks and continued until approximately 4 months CA. Standard care group: not described
Outcomes	Cognitive Infant age: BSID‐II MDI: 4 months Motor Infant age: BSID‐II PDI: 4 months
Notes	MDI data used for meta‐analysis included VLBW and ELBW groups only, as the LBW group included 2 term‐age children. PDI was not reported separately for preterm infants. Funding source: this study was supported by a grant from the National Institute of Child Health and Human Development (R01 HD38982) awarded to the first author. Declarations of interest: not stated
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Urn randomisation method
Allocation concealment (selection bias)	Unclear risk	No information given on how allocation was concealed
Blinding of participants and personnel (performance bias) All outcomes	High risk	Performance bias due to knowledge of allocated interventions by participants and personnel during the study
Blinding of outcome assessment (detection bias) All outcomes	Unclear risk	Unclear whether assessors were blinded to group allocation
Incomplete outcome data (attrition bias) All outcomes	High risk	Completeness of follow‐up: 4 months = 78%
Selective reporting (reporting bias)	Low risk	Study authors reported using an intention‐to‐treat approach for the investigation and analyses.
Other bias	Low risk	No other source of bias identified

Treyvaud 2022.

Study characteristics
Methods	Randomised controlled trial with a 2‐arm parallel design of e‐prem intervention vs standard care
Participants	N = 103 Intervention group: N = 50 Standard care group: N = 53 Inclusion criteria: GA < 34 weeks Exclusion criteria: congenital anomalies known to adversely affect infant development, primary caregivers unable to communicate in English Characteristics: mean GAs (weeks) and BW (grams) for intervention and control groups: 29.2 (SD 2.1), 1317 (SD 322) and 28.7 (SD 2.2), 1269 (447) weeks, respectively
Interventions	Intervention group: Web‐based intervention focusing on infant development and parent‐infant relationship. An initial clinician‐parent contact in the NICU was followed by family access to the e‐prem website. The programme consists of 8 age‐dependent modules with 5–10 topics in each. While parents could access all modules, the presentation was designed to focus on age‐appropriate content. They also received phone‐based clinician support and the programme continued until the infant was 12 months old. Standard care group: Families received an information pack at recruitment that included information on support services and widely available information on infant development. This included access to intervention services post discharge if required.
Outcomes	Cognitive Infant age: Bayley‐III 24 months Motor Infant age: Bayley‐III 24 months
Notes	Funding source: this work was supported by the National Health and Medical Research Council (Centre for Research Excellence in Newborn Medicine 1060733 and 1153176; project grants 1024516, 1028822; Career Development Fellowship 1108714 to Dr Spittle and 1127984 to Dr Lee; Senior Research Fellowship 1081288 to Dr Anderson; Investigator Grant 1176077 to Dr Anderson). Murdoch Children’s Research Institute is supported by the Victorian Government’s Operational Infrastructure Support Program. Declaration of interest: the authors have indicated they have no potential conflicts of interest relevant to this article to disclose. *This study included authors of this Cochrane review.
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	After collection of baseline data, families were randomly allocated to the intervention or control (standard care) group in a 1:1 ratio. Random allocation was computer‐generated by an independent statistician using block randomisation with variable block sizes, stratified by multiple births (singleton versus multiple). Because the intervention was delivered to the parent, families rather than infants were the unit of randomisation.
Allocation concealment (selection bias)	Low risk	Group allocation was determined by using concealed envelopes.
Blinding of participants and personnel (performance bias) All outcomes	High risk	Performance bias due to knowledge of allocated interventions by participants and personnel during the study
Blinding of outcome assessment (detection bias) All outcomes	Low risk	Outcome assessors were blinded to group allocation.
Incomplete outcome data (attrition bias) All outcomes	Low risk	Completeness of follow‐up at 24 months: cognitive outcome 79.6% and motor outcome 78.6%. Authors specified reasons for missing data.
Selective reporting (reporting bias)	Low risk	Complete reporting of results. Authors unable to reach desired numbers in study due to funding issues. Intention‐to‐treat analysis performed
Other bias	Low risk	No other source of bias identified

Wu 2014.

Study characteristics
Methods	A randomised controlled trial comparing a clinic‐based intervention programme (CBIP), a home‐based intervention programme (HBIP) and a usual care program from shortly after birth until 12 months' corrected age
Participants	N = 211 Intervention group: N = 57 Standard care group: N = 63 Inclusion criteria: birthweight < 1500 grams, GA < 37 weeks, admission to study hospital within 7 days of birth, singleton birth or first child of multiples Exclusion criteria: congenital abnormalities and neurological abnormalities (e.g. grade III/IV IVH, seizures, hydrocephalus) Characteristics: mean GA (weeks) and BW (grams) for CBIP = 30.0 (SD 2.6) and 1179 (SD 228), for HBIP = 29.9 (SD 3.2) and 1149 (SD 283) and for standard care = 29.3 (SD 2.7) and 1091 (SD 268), respectively
Interventions	Intervention groups CBIP (n = 57) and HBIP (n = 63): both interventions focus on infant, parent and parent‐infant relationships. The location of intervention is different, being either clinic‐based or home‐based and is performed by a physiotherapist. Interventions aimed to improve cognitive, motor and language outcomes by targeting child, parent and dyad. Eight sessions involved environment enrichment, feeding support, massage, interaction activities and parental support of 8 sessions. Standard care group (n = 58): same for all groups and included 5 inpatient sessions and 8 neonatal clinic visits focused on the child's health until 12 months post discharge.
Outcomes	Cognitive Infant age: Bayley Scales of Infant and Toddler Development Scale‐III: Cognitive (24 months) Motor Infant age: Bayley Scales of Infant and Toddler Development Scale‐III: Motor (24 months) Incidence of cerebral palsy
Notes	For purposes of meta‐analysis, outcomes for HBIC and CBIC groups were grouped together for comparison vs standard care. Funding source: all phases of this study were supported by two grants from the National Health Research Institute (NHRI‐EX98‐9519PI, NHRI‐EX102‐10106PI) and a grant from the National Science Council (NSC98‐2314‐B‐002‐010‐MY3) in Taiwan. Declaration of interest: no conflicts of interest to declare
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Randomly assigned using computer‐generated random numbers and stratified by gestational age and hospital
Allocation concealment (selection bias)	Low risk	Reported to be concealed from parents, clinical staff and research assistants; details of how concealment occurred not reported
Blinding of participants and personnel (performance bias) All outcomes	High risk	Performance bias due to knowledge of allocated interventions by participants and personnel during the study
Blinding of outcome assessment (detection bias) All outcomes	Low risk	Blinded outcome assessments
Incomplete outcome data (attrition bias) All outcomes	Low risk	Follow‐up at 24 months: 80% (not including early dropouts and pilot infants)
Selective reporting (reporting bias)	Low risk	Dosage of intervention documented, with intention‐to‐treat analysis
Other bias	Low risk	No other source of bias identified

Yigit 2002.

Study characteristics
Methods	Randomised controlled trial investigating effects of early physiotherapy intervention vs standard follow‐up for low‐risk preterm infants Study authors did not report how many infants were initially randomly assigned to each group; however, they did report that 39 infants were dropped from the study within the first 12 months for lack of participation. This resulted in 80 infants in the physiotherapy intervention group and 80 in the standard follow‐up group at 12 months. Infants were registered for the study before hospital discharge; however, it is unclear at what point the intervention commenced.
Participants	N = 199 infants* Intervention group: N = 80 Standard care group: N = 80 Inclusion criteria: BW < 2000 grams and GA < 34 weeks Exclusion criteria: perinatal hypoxia or abnormal neurosonography Characteristics: mean GAs for intervention and standard follow‐up groups: 31.3 (SD 2.2) and 32.0 (SD 1.6) weeks, respectively
Interventions	Intervention group: focus on infant development. Physiotherapy is home intervention based on infant stimulation and neurodevelopmental therapy. Details of the intervention programme were not described. Standard care group: both groups are seen monthly by the same physiotherapist for the first 9 months, then every 3 months until 18 to 24 months of age. Unclear whether this was done for assessment or for intervention
Outcomes	Cognitive None Motor Infant age only: non‐standardised measures of motor outcome such as age of acquisition of milestones and loss of primitive reflexes (1 month to 18 to 24 months) Incidence of cerebral palsy
Notes	*It is stated that 39 infants dropped out of the study because of lack of participation at 12 months; however, numbers of infants initially randomly assigned to intervention and standard follow‐up not reported. Data could not be used in meta‐analysis, as they were not standardised measures. Funding source and declarations of interest: not stated
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	No description of randomisation techniques used
Allocation concealment (selection bias)	Unclear risk	Unclear whether any methods were used to conceal allocation
Blinding of participants and personnel (performance bias) All outcomes	High risk	Performance bias due to knowledge of allocated interventions by participants and personnel during the study
Blinding of outcome assessment (detection bias) All outcomes	Unclear risk	Unclear whether assessors were blinded to group allocation
Incomplete outcome data (attrition bias) All outcomes	Unclear risk	Completeness of follow‐up: 83% follow‐up at 12 months. Study authors did not report how many infants were initially randomly assigned to each group; however, they did report that 39 infants were dropped from the study within the first 12 months for lack of participation.
Selective reporting (reporting bias)	Low risk	Outcomes reported as planned
Other bias	Low risk	No other source of bias identified

Youn 2021.

Study characteristics
Methods	A multi‐centre randomised controlled trial examining the effects of an early preventive care program on neurodevelopmental and behavioural outcomes for preterm infants Infants who were born at gestational age ≤ 30 weeks or birthweight ≤ 1500 g were enroled and randomised before discharge from the NICU to either the intervention group or a control group. 151 patients were enroled but 12 refused and 1 had a congential anomaly leaving 138 that were randomised.
Participants	N = 138 Intervention group: N = 69 Standard care group: N = 69 Inclusion criteria: GA ≤ 30 weeks, BW ≤ 1500g Exclusion criteria: infants with congenital neuromuscular or cardiac problems or chromosomal anomalies Characteristics: mean GA (weeks) and BW (grams) for intervention and standard care groups: GA 29.0 (SD 2.6), BW 1145.5 (SD 344.5) and GA 29.0 (SD 2.5), BW 1188.9 (SD 340.6), respectively
Interventions	Intervention group: Focus on infant and parent‐infant relationship. Based on the IHDP with a mixture of clinic and home visits and group and individual sessions. Four nurse visits at 5 days, 2 weeks and 1 month post discharge and then at 2 months CA focused on infant behaviour, care of preterm infants and attachment strategies. 12 group sessions between 3 and 6 months by a physiotherapist focused on infant growth and development. Standard care group: infants received no home visits or group interventions. No further explanation of standard care or access to intervention services if required
Outcomes	Cognitive Infant age: 24 months Motor Infant age: 24 months
Notes	Funding source: this research was supported by a grant from the Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI), funded by the Ministry of Public Health & Welfare, Republic of Korea (HI14C3451) (14/04/2015). Declaration of interest: the authors had no conflict of interest relevant to this article to disclose.
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Each infant was randomised sequentially using a computerised system of allocation to either the control or intervention group. Assignment was stratified according to singleton versus twin births and < 28 weeks versus ≥ 28 weeks of gestational age. Children from multiple births were assigned randomly to the same group because the intervention was performed with a family‐based approach.
Allocation concealment (selection bias)	Low risk	A web‐based computerised system of allocation was used.
Blinding of participants and personnel (performance bias) All outcomes	High risk	Performance bias due to knowledge of allocated interventions by participants and personnel during the study
Blinding of outcome assessment (detection bias) All outcomes	Low risk	Examiners blinded to group allocation
Incomplete outcome data (attrition bias) All outcomes	Low risk	Follow‐up rate of 98.5%
Selective reporting (reporting bias)	Low risk	Results fully reported
Other bias	Low risk	No other source of bias identified

Zhang 2023.

Study characteristics
Methods	Prospective pilot study of a randomised controlled trial using a pre and post‐test design. Aim to investigate the effect of the Postdischarge Developmental Support Program (PDSP) on preterm infant development
Participants	N = 44 Intervention group: N = 22 Standard care group: N = 22 Inclusion criteria: GA (weeks) 28 + 1 to 36 + 6, main caregivers lived in Wuhan or surrounds; main caregivers agreed to participate in the entire study process. Exclusion criteria: any inherited metabolic diseases, congenital malformations, IVH grade III or IV; main caregivers had cognitive or communication issues or drug use. Characteristics: mean GA (weeks) for intervention and standard care groups: 34.13 (SD 1.91) and 34.22 (1.77), respectively
Interventions	Intervention group: Focus on infant development and parent‐infant relationship. PDSP includes information about care for preterm, breastfeeding, kangaroo mother care, infant massage, mother‐infant interaction, neurodevelopmental education, psychosocial support for caregivers. At discharge, families are invited to online classes via WeChat. Sessions commenced at discharge and continued until 3 months' CA Infants also received routine neonatal healthcare and neonatal clinic visits. Standard care group: routine neonatal healthcare, neonatal clinic visits
Outcomes	Cognitive Infant age: ASQ Chinese version Motor Infant age: ASQ Chinese version
Notes	The actual age of assessment for ASQ was not reported. It is assumed to be after the intervention which finished at 3 months CA and therefore the outcomes are defined as infant age. Funding source: research reported in this publication was supported by the Natural Science Foundation of Hubei Province in China under award number 2018CFB598. Declaration of interest: the authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Eligible infants were numbered from 1 to 44 and matched with the random numbers generated by the computer. They were randomly assigned to either the intervention group (PDSP group) or the control group (usual care group) on a 1:1 ratio.
Allocation concealment (selection bias)	Unclear risk	Allocation concealment methods not reported
Blinding of participants and personnel (performance bias) All outcomes	High risk	Performance bias due to knowledge of allocated interventions by participants and personnel during the study
Blinding of outcome assessment (detection bias) All outcomes	High risk	No reporting of who performed assessments and whether they were blinded to group allocation
Incomplete outcome data (attrition bias) All outcomes	Low risk	Follow‐up rate of 90.1%
Selective reporting (reporting bias)	High risk	There was no flow diagram to demonstrate the flow of participants through the study. Information regarding the assessment process was lacking.
Other bias	Unclear risk	The researchers conducted online education via Rain Classroom, a WeChat‐imbedded software, which was an intelligent free network teaching terminal developed by XuetangX & Tsinghua University. It is unclear whether this access was limited only to the intervention group. Control group participants could potentially access this information and impact results. The intervention was performed only online due to Covid lockdown ‐ this was noted by authors to perhaps have impacted the effect of the infant development section of the intervention.

Ziegler 2021.

Study characteristics
Methods	Randomised controlled trial of a family centred programme, COPCA, on motor outcomes compared with standard physiotherapy
Participants	N = 16 infants recruited Intervention group N = 8 Standard care group N = 8 Inclusion criteria: preterm infants born < 32 weeks gestation recruited between the age of 35 weeks GA and 4 months CA. Included infants were identified as having a moderate‐to‐high risk of cerebral palsy but without significant brain lesions. Exclusion criteria: congenital heart disorder, cystic fibrosis diagnosis, infants participating in a specified study Characteristics: median (range) GA (weeks) for intervention and standard care groups 27 (25‐30) and 29.5 (26‐31), respectively. Median (range) BW (weeks) 850 (570‐1450) and 1025 (690‐1400) for intervention and standard care groups and 29.5 (26‐31), respectively
Interventions	Intervention group: focus on infants and parent‐infant relationship. Families receive the Coping with and Caring for Infants with Special Needs (COPCA) programme at home for a 6‐month period. They receive a weekly face‐to‐face session for 30–45 mins implemented by a physiotherapist. The focus is to build caregiver's competencies in understanding infant behaviour and encourage the family to stimulate their infant's development during daily care. The goal is to increase motor repertoire. Standard care group: traditional infant therapy (TIP) is described as usual physiotherapy which can be variable. This could be at a centre or home and may involve parent training or hands‐on therapy.
Outcomes	Infant Motor Profile at baseline, 3, 6 months post baseline and at 18 months corrected age Cognitive Infant age: Bayley‐III at 24 months Motor Infant age: Bayley‐III at 24 months
Notes	Authors contacted for Bayley‐III data for meta‐analysis. Funding source: this study was supported by the Schweizerische Stiftung für das cerebral gelähmte Kind, the Anna Mueller Grocholski Foundation, the Jubiläumsstiftung der Schweizerischen Mobiliar Genossenschaft and the research fund of the Swiss Association of Physiotherapy. Declaration of interest: authors had no conflicts of interest to declare.
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Computer‐generated sequence
Allocation concealment (selection bias)	Low risk	Random allocation sequences were sent to a study‐specific mail account, from which the neonatologist retrieved the infant's study group allocation.
Blinding of participants and personnel (performance bias) All outcomes	High risk	Performance bias due to knowledge of allocated interventions by participants and personnel during the study
Blinding of outcome assessment (detection bias) All outcomes	Low risk	All assessments were blinded to the assessors.
Incomplete outcome data (attrition bias) All outcomes	Low risk	Follow‐up rates of 94% at 18 months
Selective reporting (reporting bias)	High risk	50% of infants had missing data from the Infant Motor Profile (primary outcome) at baseline assessment.
Other bias	Unclear risk	Lack of clarity on the inclusion criteria in selection of infants with respect to amount of risk of developmental disorders

AIMS: Alberta Infant Motor Scale; ASI: Ayres Sensory Integration; ASQ: Ages & Stages Questionnaire; BLR: Brunet‐Leizine Revised test; BSID‐I: Bayley Scales of Infant Development Edition I; BSID‐II: Bayley Scales of Infant Development Edition II; BSID MDI: Bayley Scales of Infant Development ‐ Mental Development Index; BSID PDI: Bayley Scales of Infant Development ‐ Psychomotor Development Index; BW: birthweight; CA: corrected age; CBIP: clinic‐based intervention programme; CI: confidence interval; COPCA: Coping and Caring for Infants with Special Needs; COPE: Creating Opportunities for Parent Empowerment; CP: Cerebral Palsy; DAS: Differential Abilities Scale; DQ: developmental quotient; DS: developmental scale; EG: experimental group; EI: early intervention; ELBW: extremely low birthweight; EPSI: Early Problem Solving Indicator; ESPVM: Early Stimulation Program targeting Visual and Motor Function; GA: gestational age; GCI: General Cognitive Index; GMs: General Movements; GMA: General Movement Assessment; HBIP: home‐based intervention programme; HIE: Hypoxic Ischaemic Encephalopthy; IQR: interquartile range; IVH: intraventricular haemorrhage; IBAIP: Infant Behavioural Assessment and Intervention Program; IHDP: Infant Health and Development Program; IVH: intraventricular haemorrhage; LBW: low birthweight; Movement ABC: Movement Assessment Battery for Children; MITP: Mother‐Infant Transaction Program; MRI: Magnetic Resonance Imaging; NEC: necrotising enterocolitis; NEPSY: Neuropsychological Assessment; NICU: neonatal intensive care unit; NIDCAP: Newborn Individualised Developmental Care and Assessment Program; OT: Occupational Therapist; PDI: Psychomotor Index; PDSP: Postdischarge Developmental Support Program; PEDI‐NL: Pediatric Evaluation of Disability Inventory; PPVT: Peabody Picture Vocabulary Test; PT: Physiotherapist; PVH: periventricular haemorrhage; PVL: periventricular leukomalacia; RCT: Randomised controlled trial; SAFE: Sensory strategies, Activity‐based motor training, Family collaboration and Environmental Enrichment; SC: Standard Care; SD: standard deviation; SES: socioeconomic status; SI: sensory integration; SPEEDI: Supporting Play Exploration and Early Development Intervention; TEIP: Traditional Early Intervention Program; TIMP: Test of Infant Motor Performance; TIP: Traditional Infant Physiotherapy; TRT:Triadic parent‐infant Relationship Therapy; VLBW: very‐low birthweight; WASI: Wechsler Abbreviated Scale of Intelligence; WISC‐III: Wechsler Intelligence Scale for Children ‐ Full Scale IQ test; WPPSI: Wechsler Preschool and Primary Scale of Intelligence; WASI‐II Wechsler Abbreviated Scale of Intelligence‐ second edition.

Characteristics of excluded studies [ordered by study ID]

Study	Reason for exclusion
Adiguzel 2023	Population not within scope of review
Badr 2006	Population not within scope of review
Barbu‐Roth 2022	Intervention not within scope of review
Beckwith 1988	Intervention not within scope of review
Beeghly 1995	Population not within scope of review
Benzies 2017	Intervention not within scope of review
Britain 1995	Study type not within scope of review
Chen 2001	Study type not within scope of review
Culp 1989	Intervention not within scope of review
Dumuids‐Vernet 2023	Intervention not within scope of review
Fjortoft 2017	Intervention not within scope of review
Flierman 2016	Intervention not within scope of review
Fucile 2012	Outcomes not measured
Ghetti 2019	Intervention not within scope of review
Girolami 1994	Intervention not within scope of review
Guimarães 2015	Intervention not within scope of review
Guzzetta 2011	Intervention not within scope of review
Hane 2015	Setting not within scope of review
Hielkema 2010	Population not within scope of review
Jeba 2022	Setting not within scope of review
Kaaresen 2006b	Outcomes not measured
Kachoosangy 2020	Outcomes not measured
Kanda 2004	Study type not within scope of review
Kang 1995	Outcomes not measured
Kendrick 2000	Study type not within scope of review
Kiechl‐Kohlendoefer 2015	Intervention not within scope of review
Kleberg 2000	Intervention not within scope of review
Kleberg 2002	Intervention not within scope of review
Lai 2016	Intervention not within scope of review
Landsem 2014	Outcomes not measured
Leyener 2021	Setting not within scope of review
Liu 2015	Outcomes not measured
Ma 2015	Outcomes not measured
Matsuishi 1998	Study type not within scope of review
McCarton 2006	Outcomes not measured
Meijssen 2010	Outcomes not measured
Nair 2009	Population not within scope of review
Nascimento 2019	Outcomes not measured
Neel 2019	Intervention not within scope of review
Newnham 2009	Outcomes not measured
Oberg 2012	Intervention not within scope of review
Pelc 2017	Study type not within scope of review
Piper 1986	Population not within scope of review
Romera‐Galisteo 2019	Intervention not within scope of review
Ross 1984	Study type not within scope of review
Scott 1989	Study type not within scope of review
Sgandurra 2014	Study design not within scope of review
Sgandurra 2018	Study type not within scope of review
Silveira 2018	Study type not within scope of review
Slater 1987	Study type not within scope of review
Van Hus 2016	Intervention not within scope of review
Walker 2010	Population not within scope of review
Wasik 1990	Population not within scope of review
Weerasinghe 2023	Outcomes not measured
Welch 2015	Intervention not within scope of review
Welch 2016	Outcomes not measured
Widmayer 1981	Intervention not within scope of review
Williams 2015	Intervention not within scope of review
Winter 2018	Outcomes not measured
Wu 2016	Not cognitive or motor outcomes
Yu 2017	Intervention not within scope of review
Zanelli 2019	Setting not within the scope of review

Characteristics of ongoing studies [ordered by study ID]

ACTRN12621000364875.

Study name	The effect of telehealth for early intervention on neurodevelopmental outcomes of infants born very preterm and their parent’s well‐being: a randomised controlled trial (TEDI‐Prem)
Methods	This study is a randomised controlled trial comparing the effectiveness of the Telehealth for Early Developmental Intervention in babies born very preterm (TEDI‐Prem) intervention in improving motor development in infants born < 32 weeks of gestation compared to standard care.
Participants	466 infants admitted to the nurseries at The Royal Women’s, Royal Children’s, Monash Children’s, Joan Kirner Women’s and Children’s and Northern Hospitals, Victoria, Australia who are born < 32 weeks’ gestational age will be eligible to participate in the study. These infants should be medically stable and not ventilator‐dependent at recruitment (minimum age for enrolment 34 weeks' and maximum 40 weeks’ postmenstrual age), have 1 caregiver who speaks and can read English (as the web content and intervention materials are in English), and able to participate in early intervention programme for a 12‐month period. There is no age limit for parents/caregivers who are eligible for participation. Infants with a diagnosis of a congenital abnormality known to affect neurodevelopment, those who require specific intervention (such as infants with Trisomy 21), those planning to move overseas or interstate before the primary outcome assessment at 12 months' corrected age, or parents who do not wish to engage in telehealth intervention will be excluded from the study.
Interventions	The proposed study will test the efficacy of a programme coined TEDI‐Prem. Infants in the intervention group will be treated through collaboration between a physiotherapist/occupational therapist and one (or both, if available) parent. The principles and goals of the intervention are related to the deficits commonly seen in infants born preterm, with large doses of practice to support postural control and learning, visual, motor, and object interactions. TEDI‐Prem is designed to facilitate parents to promote sensorimotor exploration during play, following training and support over the first year of life beginning in the NICU and extending into the home based upon successful interventions. The intervention will be delivered in 3 phases: Phase 1: 4 face‐to‐face, 1‐on‐1 sessions in hospital for 30‐45 minutes. Topics will centre around understanding and responding to infant behaviour, promoting development through enhanced parent‐child interaction and demonstrating intervention activities. Toys will be used to facilitate motor, cognitive and language development with parents coached on appropriate interactions. If the infant is transferred to another hospital during the intervention, sessions will be delivered at the new hospital (if a participating study site) via telehealth or face‐to‐face. If the infant is discharged home or transferred to a non‐participating hospital prior to completion of Phase 1, it will be delivered by telehealth. Phase 2: 6 sessions, at home via telehealth, 1‐on‐1, for 45‐60 min up to 6 months’ corrected age (CA) (0.25, 1, 2, 3, 4, 6 months’ CA). During these sessions, the therapist will coach the parent to deliver intervention activities with their infant for a minimum of 20 minutes per day, 5 times per week. Parents will be coached to establish a routine for developmental play, including recognising when their child is ready to interact socially and their child’s responses to interactions. Sessions will focus on advancing the parent‐provided interventions with a focus on gross motor skills. Phase 3: 3 sessions, at home via telehealth, 1‐on‐1, for 45‐60 minutes, up to 12 months’ CA (8, 10, 11.5 months’ CA). Sessions will focus on integration into local services depending on the needs of the infant and family. Parents will be coached to establish a routine for developmental play, including different types of play (e.g. fine motor, language and cognitive). All phases include psychosocial education and content to promote parental well‐being and support parental mental health, and have been developed by a multidisciplinary team including psychologists. Further, parent/s will have access to a website (purpose‐built) which will contain study specific content on intervention activities and supplemental content to facilitate the sessions. The website will include short videos, information handouts and their home programme. The website can be accessed at anytime throughout the programme, with parents encouraged to view content during each TEDI‐Prem session. The time needed to complete online content will be dependent on the family, with a minimum of 10 minutes for each session across all phases. Telehealth will include video‐consults so that the therapist can see the infant and coach the parent/s on appropriate early intervention based upon the infant and family’s goals and needs. Physiotherapist/occupational therapist who has completed training specific to delivering TEDI‐Prem (which includes online modules and face‐face training). These therapists will have > 2 years experience in paediatrics. The intervention has core principles which are individualised to the infant and family needs. To measure parent compliance with TEDI‐Prem, at the beginning of each session the parent will be asked what has been successful since the last visit and whether there have been any challenges with delivering the intervention. Parents of infants in both groups will complete questionnaires on play positions to monitor whether they are implementing play throughout the day in a variety of positions as part of their intervention programme for TEDI‐Prem or as part of usual care. Access to other interventions, including discipline and dosage, will be assessed at baseline, 3, 6, 12, 18 and 24 months for both groups. Website analytics, including number of times and duration parents spend on the TEDI‐Prem website will be collected for participants in the intervention group. Fidelity of the therapists delivering TEDI‐Prem will be assessed in a variety of ways. All therapists in this study will complete an on‐line training module. Fidelity will be facilitated through regular staff meetings and audit of home programmes and progression. Adherence of therapists to the intervention outlined in the study protocol will be assessed using three video‐recorded sessions, 1 for Phase 1, 1 for Phase 2 and 1 for Phase 3 for each infant. Adherence will be measured by the frequency with which the intervention therapist demonstrates, talks about, or brainstorms with a parent about the TEDI‐Prem key principles and strategies. Infants enrolled in both groups will receive usual care in the neonatal nursery and community as it is unethical to withhold care. Typical services in the neonatal nursery include on‐site access to paediatric allied health (social work support, physiotherapy, occupational, or speech therapy assessments (as per defining levels of care for Victorian newborn services, 2015, page 13‐15) and access to appropriate follow‐up and referral to local early intervention programmes as deemed necessary by the medical team.
Outcomes	Primary outcome Motor development at 12 months corrected age: The Bayley Scales of Infant and Toddler Development‐ 4th Edition (Bayley‐IV) total motor composite standard score Secondary outcome Cognitive development at 12 and 24 months corrected age: the Bayley‐IV Cognitive composite scores Language development at 12 and 24 months corrected age: the Bayley‐IV language composite score and receptive and expressive scaled scores Motor development at 12 and 24 months corrected age: the Bayley‐IV cognitive composite scores Behaviour development at 12 and 24 months corrected age: the Infant Toddler Social Emotional Assessment (ITSEA) Infant quality of life at 12 and 24 months corrected age: the Toddler and Infant Questionnaire (TANDI) completed by the primary caregiver Primary caregiver depression and anxiety at 12 and 24 months corrected age: the Depression Anxiety Stress Scales (DASS‐21) Parenting self‐efficacy at 12 and 24 months corrected age: the Karitane Parenting Confidence Scale Primary Caregiver Quality of Life at 12 and 24 months corrected age: the Short Form Assessment of Quality of Life (SF‐6D) Parent‐infant interaction at 12 and 24 months corrected age: the Emotional Availability Scale (EAS) Allied Health Utilisation data from birth to 12 and 24 months corrected age will be assessed using a purpose‐built questionnaire on access to allied health services, including discipline and frequency Cost‐effectiveness: the cumulative costs of the TEDI‐Prem programme (training materials, delivering care, overheads) and downstream cost (healthcare, family productivity, and out‐of‐pocket) will be collected over the 24‐month follow‐up period from using a composite of questionnaires on access to allied health therapy and supplemented by Medicare linkage data. Measure of Process of Care at 12 months corrected age: the Measure of processes of care (MPOC) to assess parent’s perceptions of the extent to which specific family‐centred behaviours or actions of healthcare professionals occur. Health Care Utilisation: Medicare linkage data from birth to 12 and 24 months’ CA will be collected.
Starting date	17 January 2022
Contact information	Alicia Spittle; aspittle@unimelb.edu.au
Notes	Estimated study completion date: 31 December 2025

Baraldi 2020.

Study name	Stockholm preterm interaction‐based intervention (SPIBI) ‐ study protocol for an RCT of a 12‐month parallel‐group post discharge program for extremely preterm infants and their parents
Methods	To examine the effect of the Stockholm Preterm Interaction‐Based Intervention (SPIBI) on three overall domains: parent‐child interaction, child development and parental mental health
Participants	Parents of all extremely preterm children residing in Stockholm County who meet the inclusion criteria will be approached by the end of their child’s hospital stay. Inclusion criteria are that the child was born before 28 gestational age, is currently in stable medical condition, and is therefore close to hospital discharge from one of the four neonatal units belonging to the Stockholm Region: Karolinska Hospital Huddinge, Karolinska Hospital Solna, Karolinska Neonatal Unit Danderyd and Sachsska Childhood and Youth Hospital. Exclusion criteria are parents who are not able to communicate in Swedish or English, patients not residing in Stockholm County and acute surgery patients who will spend a substantial amount of time in hospitals far from Stockholm.
Interventions	The Stockholm Preterm Interaction‐Based Intervention (SPIBI) is a strength‐based home‐visit programme focusing on parent‐child interaction, skill in reading children’s cues and the provision of optimal support for children’s next small developmental steps. The aim is to minimise the amount of stress that children experience and to enhance developmentally appropriate parent‐child interaction to achieve mutual enjoyment. Parent behaviour is also a focus of the intervention.
Outcomes	Parent‐child interaction, child development and parental mental health The primary outcome is the Emotional Availability Scales (EAS) The secondary outcome measurements include: For measuring the cognitive, language, and motor development of the children, the Bayley Scales of Infant and Toddler Development, third Edition (BSID‐III), will be used at 24 months corrected age. The child’s executive function at 24 and 36 months corrected age will be measured with the Behaviour Rating of Executive Function, Parental Version (BRIEF‐P). Motor development will be measured by the Alberta Infant Motor Scale (AIMS) at 3 and 12 months corrected age. Parental depression will be measured by the Hospital Anxiety and Depression Scale (HADS). Parental anxiety will be measured by the State‐Trait Anxiety Inventory (STAI) at term age and at 12, 24 and 36 months corrected age. Parental self‐efficacy will be measured by the Parental Self‐Efficacy Scale (PSE) at term age and at 12, 24 and 36 months corrected age. Parental resilience will be measured by the Resilience Scale (RES) for the same ages. The other outcome measurements include: The Hammersmith Neonatal Neurological Outcome (HNNE) is used at term age as a baseline measurement. Post discharge neurological development will be assessed with the Hammersmith Infant Neurological Examination (HINE) at 3 months, 12 months, and 24 months corrected age. Children’s motor development will be measured using Peabody Developmental Motor Scales (PDMS) at 12 months corrected age. Children’s neurological development will be measured using the General Movement Assessment (GMA) scale (normal‐absent fidgety) at 3 months corrected age. Children’s general development will be measured using the Ages and Stages Questionnaire (ASQ) at 12, 24, and 36 months corrected age. Children’s strengths and difficulties will be measured using the Strengths and Difficulties Questionnaire (SDQ) at 24 and 36 months corrected age.
Starting date	September 2018
Contact information	* Correspondence: erika.baraldi@specped.su.se
Notes	Sample size anticipated N = 130 Last day of recruitment: 31st of August 2020 (anticipated), may be later if target is not reached yet Last visit: 31st of August 2021 (anticipated) or 1 year after the last participant has been recruited Data collection completion: 1st of September 2023 (anticipated) No results are published as of 04 November 2023.

CTRI/2022/03/040781.

Study name	A randomised controlled trial to assess the effectiveness of nurse‐led developmental intervention packages on neurodevelopmental outcome of preterm babies in AIIMS, Jodhpur
Methods	This study is a randomised controlled trial comparing the effectiveness of a nurse‐led developmental intervention package in improving motor, cognitive, language and socio‐emotional development of preterm infants compared to standard, neurodevelopmental supportive care during hospitalisation.
Participants	220 infants born at < 36 weeks of gestation will be eligible to participate in the study between 6 and 9 months of age. Eligible infants are admitted to the NICU at AIIMS hospital in Jodhpur for more than 5 days. Infants with congenital anomalies requiring surgical treatment at birth will be excluded from the study. Additionally, infants with a history of TORCH infection or inborn errors of metabolism will not be eligible to participate in the study.
Interventions	The proposed study aims to evaluate the effectiveness of a Nurse‐Led Neurodevelopmental Package, which comprises 2 main components: neurodevelopmental supportive care and multisensory stimulation during the hospitalisation period. Neurodevelopmental supportive care is administered from the day of recruitment until discharge. It encompasses various elements, including nesting, swaddling, containment/tucking, non‐nutritive sucking (NNS), pain prevention using dextrose/sucrose, NNS, and facilitated tucking, family‐centred care, Kangaroo Mother care, breastfeeding/feeding with breast milk, massage therapy with coconut oil, and environmental modifications aimed at minimising noise levels (NICU background noise maintained between 60–70 dB) and reducing exposure to bright light. Multisensory stimulation is introduced starting at 31 weeks of gestation until discharge and involves auditory, tactile, visual, vestibular‐kinaesthetic, gustatory stimulation, massage therapy, and passive exercise. Auditory stimulation includes playing the mother's recorded voice and calming music (Veena, Tabala, recorded lullaby at 30–40 dB) near the baby for 5 minutes, twice a day. Tactile stimulation involves gentle touch by the mother on specific areas of the baby's face and body 3 times a day, and vestibular‐kinaesthetic stimulation is achieved through gentle rocking and swinging of the baby, along with vertical pulling. Visual stimulation comprises the use of dim lighting and presenting black‐and‐white bold patterns with strong contrast for 15 to 20 minutes, twice a day. Massage therapy is performed using coconut oil with gentle, flat‐fingered strokes for 5–10 minutes once a day. Passive exercise is provided once daily during hospitalisation. After hospital discharge, caregivers will continue age‐appropriate multisensory stimulation at home until the infant reaches 6 months of corrected age. Prior to commencing the study, comprehensive training will be provided for nursing officers and mothers of preterm babies. Infants in the control group will only receive neurodevelopmental supportive care during hospitalisation. At home, caregivers will be asked to follow discharge instructions.
Outcomes	Primary outcome To assess the cognitive, motor, language and social –emotional development of preterm infants, Bayley Scales of Infant and Toddler Development Third Edition (Bayley III) will be completed at 9‐months of corrected age. Secondary outcomes Bayley III motor, cognitive, language and social‐emotional scores at 3 months and 6 months of corrected age Assess factors associated with neurodevelopmental outcome of preterm babies at 9 months of corrected age Parental satisfaction with neurodevelopmental supportive care assessed at 9 months of corrected age Knowledge, attitude and skill of nursing officer before and after the training on neurodevelopmental supportive care Effects of different risk factors associated with prematurity on neurodevelopmental outcome are assessed at 9 months of corrected age.
Starting date	02 May 2022
Contact information	Raghu VA; raghuva84@gmail.com
Notes	Date of registration ‐ 03 March 2022 Trial registration last refreshed on 04 April 2022 Proposed date of first enrolment ‐ 02 May 2022 Study completion date ‐ unknown

Dusing 2020.

Study name	Efficacy of supporting play exploration and early development intervention in the first months of life for infants born very preterm: 3‐arm randomised clinical trial protocol.
Methods	This study is a multisite longitudinal controlled trial comparing developmental outcomes from infants in the Supporting Play, Exploration, and Early Development Intervention (SPEEDI)_Late or SPEEDI_Early group to a usual care group. Following a baseline assessment, each infant will be randomised into 1 of 3 groups: usual care, SPEEDI_Early, or SPEEDI_Later using a block randomisation model. All infants will receive standard care in the NICU and community. The 2 groups who will receive the SPEEDI intervention are divided into SPEEDI_Early and SPEEDI_Late based on their randomisation. Both SPEEDI groups will receive the same intervention, at the same dose, but at different developmental periods.
Participants	Ninety infants born very preterm (< 29 weeks of gestation) and cared for in level IV neonatal intensive care units (NICUs) associated with an academic medical centre will participate in this study. Infants must be medically stable, off ventilator support by 42 weeks of gestation, and live within 60 miles of a participating hospital.
Interventions	The proposed study will assess the efficacy of a programme coined Supporting Play, Exploration, and Early Development Intervention (SPEEDI). SPEEDI intervention is provided using specific intervention strategies that address the key principles. The intervention is delivered in 2 phases with a focus on parent learning and interaction in phase 1 and direct intervention in phase 2. The first 5 sessions (phase 1) occur over 3 weeks in which the therapist uses a guided participation approach to help parents learn to identify ideal times for interaction as well as positive and negative behavioural interaction cues and how to adjust the environment to enhance interaction with the infant in response to the infant's changing abilities. In SPEEDI phase 2, parents are taught a series of daily activities to complete with the infant. The parent uses what they learnt in phase 1 to determine the best time, necessary environmental modifications, and engagement strategies to allow the infant to be as successful as possible with the activities each day. At the core of the protocol, a parent/therapist collaborative is started by building confidence and supporting the parent to enhance parent‐child interactions and develop daily routines that provide developmentally supportive activities earlier than traditional models of EI services.
Outcomes	The Test of Infant Motor Performance will be completed at baseline and at visit 2 to fully describe the sample. The primary outcome measure is the Bayley‐ 3rd edition, Cognitive and Gross Motor Scaled Scores, which will be assessed at visits 2 through 5 with data from visit 3 used to answer the primary study aim. Secondary outcomes Given the high risk of CP in the study population, the Gross Motor Function Measure item set version will be used to assess the infant's motor function. Prechtl's General Movement Assessment (GMA) along with clinical brain imaging will be used during stratification to determine the risk of the infant having CP at baseline. Hammersmith Infant Neurological Exam, a standardised neurological exam, will be administered to support early identification of cerebral palsy. An adaptation of the Early Problem‐Solving Indicator will be used as a measure of play‐based problem‐solving. Given the focus on training parents to provide intervention daily during SPEEDI phase 2, we will assess parent‐child interaction using behavioural coding of a videotape of a 5‐minute natural free play session. These measures will allow us to begin to describe any mediating factors in the efficacy of intervention.
Starting date	Unclear ‐ Submitted: 25 September 2019
Contact information	stacey.dusing@pt.usc.edu
Notes	Project period: 01 August 2018‐31 July 2023

IRCT20220725055554N1.

Study name	The effect of early interventions delivered using telemedicine on the development of premature babies and the self‐efficacy of their parents in the Corona pandemic
Methods	This study is a randomised clinical trial comparing the effectiveness of an early intervention programme delivered through telemedicine on the development of premature infants, in comparison to standard care.
Participants	32 infants, born between 30 and 36 weeks of gestation with a birthweight of over 1500 g, are eligible to participate in the study between 210 and 259 days of age. To participate, parents must be able to read, write, and be proficient in the Persian language, possess a smartphone, and have relative familiarity with virtual systems and social networks. Infants will be excluded from the study if they have a history of severe brain damage or congenital anomalies according to medical records, if they were hospitalised in the NICU for less than a week or more than a month, if their Apgar score was lower than 7, if they had IVH grade 3 or 4, if they lack a guardian or have a single parent, if their mother and baby experience severe malaise, or if the parents are addicted to or alcoholic.
Interventions	The proposed study will evaluate the effectiveness of an early intervention programme delivered via telemedicine. Parents in the intervention group will receive three months of free educational materials, including videos, photos, and images, developed in line with the MITP programme and Hug Care training. These resources will educate parents on caring for and supporting the development of premature infants. The intervention programme will span 3 months and consist of 6 training sessions held every other week. Infants in the control group will only receive routine intervention in the hospital.
Outcomes	Primary outcomes To assess infant development, Bayley, Ages and Stages Questionnaire will be completed at the beginning of the study and 3 months later Parental self‐efficacy will be assessed at the beginning of the study and 3 months later.
Starting date	01 June 2023
Contact information	Zahra Amini; zahra.mini75@gmail.com
Notes	Date of registration ‐ 27 December 2022 Trial registration last refreshed on 07 February 2023 Date of first enrolment ‐ 06 January 2023

Lucas 2023.

Study name	The Best Start trial: ultra‐early parent administered physiotherapy for infants at high risk of cerebral palsy or motor delay – a randomised controlled pilot trial
Methods	This study is a randomised controlled pilot trial comparing the effectiveness of a parent‐delivered physiotherapy intervention commencing early in the NICU in improving motor outcome compared to standard care.
Participants	Thirty infants meeting the criteria of high risk of CP or motor delay will be eligible to participate in this study. Infants will be eligible to participate from 34 weeks of gestational age.
Interventions	Parent‐delivered physiotherapy interventions in Neonatal Intensive Care Unit (NICU), from 34 weeks corrected age (CA)
Outcomes	Primary outcome Alberta Infant Motor Scale (AIMS) total score at 16 weeks' corrected age Secondary outcomes Depression Anxiety and Stress Score (DASS‐21) and Parents Perceptions Survey at 16 weeks' corrected age Bayley Scales of Infant Development (4th edition) at 12 and 24 month's corrected age Neurological examination at 12 and 24 months' corrected age
Starting date	Not available
Contact information	Barbara Lucas; barbara.lucas@health.nsw.gov.au
Notes

NCT01281358.

Study name	Helping our premature infants on to better motor skills (HOP‐ON)
Methods	This study is a randomised controlled trial evaluating the effectiveness of a computer‐based intervention (Helping Our Premature infants ON to better motor skills ‐ HOP‐ON) developed for parents of preterm infants in improving their motor skills compared to those in the control group.
Participants	160 preterm infants born at less than 32 weeks of gestation, who have either recently been discharged from the hospital or are expected to be discharged within the next 2 weeks, will be eligible to participate in the study. Parents should be aged between 16 and 60 years to be included in the study.
Interventions	The proposed study will assess the efficacy of an intervention programme coined as "Helping Our Premature infants ON to better motor skills ‐ HOP‐ON". Participants in this group will receive a CD (or DVD and booklet if there is no access to a computer) highlighting motor skills which could be encouraged with premature infants. The comparator group is called "SMILES". Participants in this group will receive a CD (or DVD and booklet if there is no access to a computer) which contains information on interacting with their premature infant.
Outcomes	Primary outcome The difference in Bayley III motor scale scores at 12 months' corrected age between the experimental and comparator group
Starting date	March 2011
Contact information	Not available
Notes	The study was completed in November 2014. No results are published as of 04 November 2023.

NCT02983513.

Study name	Early intervention in preterm infants: short and long term developmental outcome after a parental training programme
Methods	This study is a randomised controlled trial that evaluates the effectiveness of training parents to reduce early‐life stress and enhance the brain development and long‐term developmental outcomes of preterm infants, in comparison to standard care.
Participants	Seventy infants born between 25 + 0 weeks and 29 + 6 weeks of gestational age will be eligible to participate in the study between 25 and 29 weeks of gestation. Mothers are selected according to the following inclusion criteria: age over 18 years, good comprehension of the Italian language, no obvious cognitive impairments or psychiatric disorders, no drug addiction and no single‐parent families. Infants with a history of major brain lesions as documented by cranial ultrasound (intraventricular haemorrhage > grade 2, cystic periventricular leukomalacia, neurosensorial deficits (retinopathy of prematurity > stage 2), genetic syndromes and/or major congenital malformation, and major neonatal comorbidities) will be excluded from the study.
Interventions	The proposed study will assess the efficacy of an early intervention programme. This intervention will be delivered during the NICU stay, according to the Mother Infant Transaction (MITP) and the PremieStart Protocol. Parents will be trained to recognise signs of infant stress and alert‐available behaviour to promote mother‐infant interaction; adopt principles of graded stimulation; optimise interactions and avoid overwhelming infants through facilitation strategies (for example, engage and support the visual attention of the newborn). The programme will be held in eight main sessions and one additional post‐discharge session. In addition, parents will be trained and invited to promote preterm massage therapy daily according to a detailed protocol. Infants in the standard care group will receive care according to NICU protocols, including Kangaroo Mother Care, nesting and minimal handling.
Outcomes	Primary outcome measures Neonatal Visual Assessment Battery to evaluate visual function at 40 weeks' postmenstrual age. To assess neonatal behaviour, Neonatal Behaviour Assessment Scale at 2 months of corrected age Secondary outcome measures Brain development will be assessed using conventional and advanced MRI techniques at 40 weeks' post menstrual age. Developmental outcome will be assessed using the Bayley‐ 3rd edition at 24 months' corrected age. To assess epigenetic changes, at birth, a cord blood sample (0.5 mL) and at hospital discharge, a peripheral blood sample (0.5 mL) will be collected according to routine clinical procedures. Overall duration of hospitalisation (in days) will be calculated from admission to home discharge from NICU. Weight (in grams) at 40 weeks' post menstrual age Length (in centimetres) at 40 weeks post menstrual age Head circumference (in centimetres) at 40 weeks' post menstrual age Post‐menstrual age at the acquisition of full oral feeding will be recorded. Feeding with human milk at 40 weeks' post menstrual age (yes or no) Children's neurodevelopment will be assessed using the Griffiths Development Scales (GMDS) at 5–6 years of age. Children's behaviour will be assessed using the Child Behaviour Checklist at 5–6 years of age. Children's neuromotor ability is assessed using the Movement Assessment Battery for Children (Movement ABC) at 5–6 years of age. Children's attention abilities will be assessed using the Early Childhood Attention Battery (ECAB) at 5–6 years of age. Epigenetic analysis ‐ L1 promoter methylation (per cent) assessment will be performed on a buccal swab collected during follow‐up assessment at 5–6 years of age.
Starting date	March 2014
Contact information	Not available
Notes	This study was completed in January 2023. Awaiting publication of motor and cognitive outcomes.

NCT03518736.

Study name	Does timing matter? Efficacy of parent‐provided, therapist‐supported, motor and cognitive intervention for infants born very preterm in the first months of life
Methods	This study is a randomised controlled trial comparing the effectiveness of the Supporting Play Exploration and Developmental Intervention (SPEEDI) programme in improving motor outcomes of infants born very preterm compared to standard care.
Participants	Eighty‐five infants born very preterm (˂ 29 weeks of gestation) and cared for in the Neonatal Intensive Care Unit at the Children's Hospital of Richmond at Virginia Commonwealth University or University of Virginia Hospital will be offered an enrolment if they meet the following inclusion criteria. Infants must be medically stable, off ventilator support by 42 weeks of gestation. Live within 60 miles of either hospital (which are 75 miles apart). Early Intervention services in Virginia A parent or a legally responsible adult will also be enroled in the study. Inclusion criteria for the adult is that they speak English and will be a caregiver for the enroled infant. Exclusion criteria include diagnosis of a genetic syndrome or unstable medical condition beyond 42 weeks of gestation. Infants will be randomly assigned to a Usual Care group, SPEEDI_Early, or SPEEDI_Late group.
Interventions	The proposed study aims to assess the efficacy of the Supporting Play Exploration and Developmental Intervention (SPEEDI) programme. Infants randomly assigned to the SPEEDI_Early group will participate in the SPEEDI intervention starting in the hospital and lasting for 4 months. This intervention includes 10 visits with a physical therapist and parent working together to advance an intervention programme and 12 weeks of daily parent intervention. In addition, they will continue with any intervention in the community recommended by their healthcare team. Infants randomly assigned to the SPEEDI_Late group will participate in the SPEEDI intervention starting at 4 months post baseline or approximately 3 months after discharge from the hospital. This intervention includes 10 visits with a physical therapist and parent working together to advance an intervention programme and 12 weeks of daily parent intervention. In addition, they will continue with any intervention in the community recommended by their healthcare team. Infants randomly assigned to the usual care group will not receive any study intervention but will continue with any intervention in the community recommended by their healthcare team.
Outcomes	Primary outcome Bayley Scales of Infant and Toddler Development Cognitive and Gross Motor Scaled Scores collected over a 6‐month time frame starting 15 weeks after visit 1 Secondary outcomes Assessment of Problem‐Solving in Play collected over a 6‐month time frame starting 15 weeks after visit 1 Gross Motor Function Measure (GMFM) collected over a 6‐month time frame starting 15 weeks after visit 1 Test of Infant Motor Performance (TIMP) was collected over a 3‐month time frame starting from visit 1.
Starting date	2 June 2019
Contact information	Stacey Dusing; stacey.dusing@pt.usc.edu
Notes	The study is estimated to be completed by 30 July, 2025.

NCT03668626.

Study name	Family‐centered intervention for preterm children: effects at school age and biosocial mediators
Methods	This study is a randomised controlled trial assessing the impact of a family centred intervention programme (FCIP) on enhancing neurobehavioural and neurophysiological functions in seven‐year‐old, VLBW preterm children in Taiwan, compared to those receiving standard care. The intervention was delivered from birth to 1 year of corrected age in the previous study.
Participants	320 children born at a gestational age of < 37 weeks and birthweight of < 1500 grams will be included in the study at 7 years of age. Eligible children's parents will be of Taiwan nationality, married or together at delivery, and northern family residing in greater Taipei and southern family residing in greater Tainan, Kaohsiung, or Chiayi. Eligible participants in the term infants group include children born in Taiwan with a gestational age > 37 weeks, birthweight > 2000 grams, and parents of Taiwanese nationality at 7 years of age. Children with a history of brain injury(e.g. PVL, stage IV ROP or greater), severe neonatal and perinatal diseases (e.g. seizures, hydrocephalus, meningitis, grade III‐IV IVH and grade II NEC), severe cardiopulmonary disease requiring invasive or non‐invasive ventilator use at hospital discharge, any congenital or chromosome abnormality, hospital discharge beyond 44 weeks' post menstrual age, and born to mothers < 18 years, with mental retardation or history of maternal substance abuse at any time (smoking, alcohol and drug) will not eligible to participate in the study.
Interventions	The proposed study will assess the efficacy of a family‐centred intervention programme (FCIP). This programme included in‐hospital intervention, after‐discharge intervention and neonatal follow‐up. 5 sessions of in‐hospital intervention emphasised modulation of the NICU, teaching of child developmental skills, feeding support, massage, interaction activities and parent support and education. The 7‐session after‐discharge intervention included 4 clinic visits and 3 home visits with specific care in modulation of home environment, teaching of child developmental skills, feeding support, teaching of interactive activities, and parent support and education.
Outcomes	Primary outcome measure The Wechsler Preschool and Primary Scale of Intelligence‐4th Edition Secondary outcome measures Child's past 1‐year medical history recorded by parental interview Child's academic performance will be recorded through parental interviews. Child's neurodevelopment will be assessed using Movement Assessment Battery for Children‐2nd Edition. Child's Electroencephalogram (EEG) measured in the resting state for the participating children at 7 years of age Child's event‐related potential will be measured in the cognitive inhibitory control and working memory procedures and cognition/motor dual tasks with ERP technique for the participating children at 7 years of age. Parenting Stress Index World Health Organization Quality of Life‐Brief Taiwan version to measure parent's quality of life The Child Behaviour Check List completed by parents The Swanson, Nolan, and Pelham Questionnaire to assess children's behaviour Weight, height and head circumference to be measured for up to 2 years
Starting date	17 October, 2018
Contact information
Notes	Study was completed on 31 December, 2021. No results are published as of 04 November 2023.

NCT03714633.

Study name	Stockholm preterm interaction‐based intervention (SPIBI)
Methods	This study is a randomised controlled trial comparing the effectiveness of Stockholm Preterm Interaction‐Based Intervention (SPIBI) in improving parent‐child interaction, child development and parental mental health.
Participants	130 extremely premature infants will be eligible to participate between 32 weeks to 45 weeks of age. These infants will be included in the study close to discharge from their neonatal intensive care unit hospital stay at Stockholm county council. Inclusion criteria are children with parent/parents who do not communicate in Swedish or English, patients not residing in Stockholm county and acute surgery patients who will spend a lot of time in hospitals far from Stockholm.
Interventions	The proposed study is assessing the efficacy of the Stockholm Preterm Interaction‐Based Intervention (SPIBI). This is a home‐based post discharge intervention for extremely premature babies and their parents. The intervention consists of 1 hospital visit, 9 home‐visits and 2 telephone calls during the first year of corrected age, specifically from 1 week before discharge to 12 months of corrected age. The intervention is strength‐based working with infant‐parent interaction, supporting infant development and strengthening the parent in his/her role. Infants randomised in the control group will receive treatment‐as‐usual, which consists of a regular follow‐up programme with neurodevelopmental assessment at term age, 3 months' corrected age, 12 months' corrected age, 24 months' corrected age and 66 months' corrected age. Compared to children not participating in the study, the control group will receive an extended follow‐up programme, with assessment and questionnaires at term age, 3 months corrected age, 12 months' corrected age, 24 months' corrected age and 36 months corrected age. Participants in the control group will be referred to specialised care when needed.
Outcomes	Primary outcome Parent‐child interaction will be assessed at 24 months' corrected age. Secondary outcomes To assess a child's general development, the Bayley Scale of Infant and Toddler Development‐3rd Edition will be assessed at 24 months' corrected age. To assess a child's executive function, Behaviour Rating of Executive Function Parental version (BRIEF‐P) will be administered at 24 and 36 months' corrected age. To assess a child's motor development, the Alberta Infant Motor Scale will be administered at 3 months' and 12 months' corrected age. To assess parental depression, Hospital Anxiety and Depression scale (HADS) will be used at term age, 12, 24 and 36 months' corrected age. To assess parental anxiety, State/Trait Anxiety Inventory (STAI) will be used at term age, 12, 24 and 36 months' corrected age. To assess parental self‐efficacy, parental self‐efficacy scale (PSE) will be used at term age, 12, 24 and 36 months' corrected age. To assess parental resilience, the Resilience scale (RES) will be used at term age, 12, 24 and 36 months' corrected age. Other outcome measures To assess a child's neurological development, the Hammersmith Infant Neurological Examination will be administered at 3 months', 12 and 24 months' corrected age. To assess a child's motor development, Peabody developmental motor scales (PDMS) will be administered at term age & 12 months' corrected age. To assess a child's motor development, General Movement Assessment will be administered at 3 months' corrected age. To assess a child's strength and difficulties, Strengths and Difficulties Questionnaire (SDQ) will be administered at 24 and 36 months' corrected age. To assess a child's autistic symptoms, Modified Checklist for Autism in Toddlers (M‐CHAT) will be used at 24 months' corrected age. To assess an infant's temperament, Infant Behaviour Questionnaire will be used at 12 months' corrected age. To assess parental satisfaction with the intervention, Client Satisfaction Questionnaire (CSQ‐8) & semi‐structured interview will be administered at 12 months' corrected age. To assess preschool educators' view of the child's engagement in preschool, Child Engagement Questionnaire (CEQ) Swedish version will be used at 24 and 26 months' corrected age. To assess preschool educators' view of the child's interaction in preschool, Swedish Questionnaire Ert Barn Vårt Samspel will be used at 24 and 36 months' corrected age. To assess preschool educators' view of the child's playtime in preschool, the Play time/Social Time Teacher Impression Scale will be used at 24 and 36 months' corrected age. To assess preschool educators' view of the child in preschool, semi‐structured preschool teacher interviews will be conducted at 24 and 36 months' corrected age. To assess preschool educators' view of the child's level of function in preschool, ICF‐CY core sets will be administered at 24 and 36 months' corrected age. To assess the long‐term impact on parent‐child interaction, Emotional Availability Scales, EAS will be administered at 24‐months' corrected age.
Starting date	01 September 2018
Contact information	Not available
Notes	Estimated study completion date ‐ 31 December 2024

NCT04685356.

Study name	Effect of the IBAIP in preterm infants neurodevelopment (IBAIP)
Methods	This study is a multisite, randomised controlled trial comparing the effectiveness of the Infant Behavioral Assessment and Intervention Program (IBAIP) in supporting developmental functions of preterm infants compared to standard care.
Participants	240 infants born between 25 weeks + 0 days and 32 weeks + 6 days of gestation, with a normal neurological examination between 36 and 41 weeks of corrected age based on the Amiel‐Tison neurological assessment, will be eligible to participate. Multiple pregnancies will also be eligible. The exclusion criteria include infants with a history of intraventricular haemorrhage of grade III or IV, or periventricular leukomalacia, or brain abnormalities identified in MRI examinations after 36 weeks of corrected age. Additionally, infants with life‐threatening pathologies or severe congenital abnormalities will not be eligible for participation. Maternal health is also taken into account, with exclusion extended to cases of severe maternal physical or mental health issues. Furthermore, parents whose native language is not French are excluded. Lastly, infants currently participating in another interventional study on the management of post hospital neurodevelopment disorders will not be included in this research.
Interventions	The proposed study will assess the efficacy of a programme coined Infant Behavioural Assessment and Intervention Program (IBAIP). The IBAIP intervention programme consists of providing interventions with the child and their family, at home, upon discharge from hospital and up to a corrected age of 6 months. Interventions therefore take place at the early stage of the child's brain development. The intervention is performed by an IBAIP‐trained and certified physiotherapist or psychomotor therapist trained, at the rate of one session per month over a period of approximately 6 to 8 months (6 months of corrected age). The session takes place in the child's usual living environment, at home, in the presence of at least one of the parents. It focusses on the child's behaviours and consists of assisting the family in its interactions with the child so that these are adapted and responsive to the child's development needs over time through repeated interventions. Infants enroled in the standard support group will receive one medical consultation per month. If indicated by the physician providing follow‐up, they may also receive consultations with medical specialists and/or paramedical professionals, such as physiotherapists, speech therapists, and psychomotricity specialists. These consultations may include interventions in the case of developmental delays.
Outcomes	Primary outcome To assess the effect of the IBAIP in very preterm infants (< 33 weeks of gestation) on neurodevelopment, Bayley III scores will be assessed at 24‐months corrected age (CA). Secondary outcomes To assess the effect of IBAIP on the 5 subscores of BSID‐III: cognitive, language, motor, socio‐emotional and behavioural adaptive, Bayley III subscale scores will be analysed at 24‐months CA. To assess the effect of IBAIP on the stress level of mothers and fathers, Parental Stress Index will be used at 24‐months CA. Parent assessment of psychomotor development using Ages and Stages questionnaire at 24‐months CA
Starting date	11 August 2022
Contact information	Jean‐Michel ROUE; jean‐michel.roue@chu‐brest.fr
Notes	Estimated study completion date ‐ 01 August 2026

NCT05261503.

Study name	Investigation of the effectiveness of environmental enrichment‐based intervention in preterm Infants
Methods	This study is a randomised controlled trial comparing the effectiveness of the HEP (Homeostasis‐Enrichment‐Plasticity) approach on motor and sensory functions of preterm infants with developmental delay risk compared to traditional physical therapy.
Participants	32 preterm infants aged 4–10 months, born < 33 weeks and 6 days of gestation with abnormal or suspect results on the Denver Developmental Screening Test II will participate in this study. Additionally, participation requires the absence of any systemic disease and congenital anomaly, and families who are willing to regularly participate in the study process.
Interventions	The proposed study will assess the efficacy of the Homeostasis‐Enrichment‐Plasticity (HEP) approach. Infants in the HEP group will receive 45 minutes of face‐to‐face environmental enrichment‐based intervention 1 day per week and online home support once a week for 12 weeks. The traditional physical therapy group will receive a 45‐minute intervention, 2 days a week for 12 weeks.
Outcomes	All outcomes will be assessed twice, once at the beginning and once at 12 weeks. Primary outcomes 1) Motor Skills assessed using Peabody Developmental Motor Scales 2nd Edition 2) Sensory function assessed using Test of Sensory Functions in Infants Secondary outcome 1) Mental Health of parents evaluated using Beck Anxiety Inventory (BAI)
Starting date	1 March 2022
Contact information	Not available
Notes	Study completed on 5 May 2023 No results were published as of 04 November 2023.

NCT05334550.

Study name	Effectiveness of home based early intervention of extremely premature infant by parent
Methods	This study is a randomised controlled trial assessing the effectiveness of a home‐based early intervention of extremely premature infants primarily delivered by parents on motor development compared to a control group.
Participants	110 infants, with 55 in each group, born between 23 and 28 weeks of gestation, will be enroled in the study at 1 month of corrected age. Participation requires written consent from the parents and, specifically, parents of Korean origin.
Interventions	The proposed study will assess the efficacy of an intervention programme coined Home Based Early Intervention by Parent. Parents of infants in this intervention group will participate through tele‐health using the Zoom platform. Parents will be educated once every two weeks for three months. Parent education consists of a programme developed by the study team's paediatric rehabilitation therapist to help premature infants develop motor skills. Parents will be asked to provide daily exercise training for their children as educated.
Outcomes	Primary outcome measure Change in Test of Infant Motor Performance scores from baseline to 3 months after the start of intervention Secondary outcome measures Change in Edinburgh postnatal depression scale scores from baseline to 3 months after the start of intervention Alberta Infant Motor scale score at 6 months and 12 months after the start of intervention Peabody Development Motor Scale‐2nd Edition score at 12 months after the start of intervention
Starting date	2 June 2022
Contact information	Jeong‐Yi Kwon; jeongyi.kwon@samsung.com
Notes	The study is estimated to be completed by 2 March 2024.

NCT05565287.

Study name	Neonatal neurobehavioral and motor behavior in ultra early physical therapy intervention
Methods	This study is a randomised controlled trial comparing an intervention programme that combines neonatal neurobehaviourism and motor behaviour in the assessment and ultra‐early physical therapy for premature neonates to standard care, with the aim of improving development.
Participants	120 infants born at less than 34 weeks of gestation, who have been hospitalised in the NICU for a minimum of 8 days, will be eligible for participation in the study. Parents must be able to speak and read either Greek or English to be included in the study.
Interventions	The proposed study assesses the efficacy of an intervention programme that combines neonatal neurobehaviourism (Brazelton) and motor behaviour (Prechtl) in parental advice and intervention. The ultra early physiotherapy intervention consists of Neonatal Behavioural Assessment Scale (NBAS)/Newborn Behavioural Observations (NBO) and General Movements (GMs)‐based guidelines for explaining neonatal "signs" in the NICU (lasting 15–30 minutes). These guidelines will also be used to explain neonatal signs to parents at 1st neonatal assessment and intervention upon hospital discharge (lasting 1 hour). These neonatal signs will be explained to parents every 15 to 20 days until the 3rd month of life (corrected age).
Outcomes	Primary outcome measures To assess the neurobehavioural repertoire of the newborn, the Neonatal Behavioural Assessment Scale (NBAS) will be used at birth and 2 months of corrected age. The Newborn Behavioural Observations (NBO) will be completed at birth through the 3rd month of life. To assess the integrity of the CNS of infants, the Qualitative Assessment of General Movements (GMs) will be completed at birth to 20 weeks of corrected age. Karitane Parenting Confidence scale (KPCS) to assess perceived parental confidence at birth to 12 months of age
Starting date	24 March 2021
Contact information	Not available
Notes	The estimated study completion date is 30 March 2025.

NCT05568264.

Study name	Effects of a physical therapy intervention on motor delay in infants admitted to a neonatal intensive care unit
Methods	This study is a randomised controlled trial assessing the effectiveness of an early, evidence‐based, clinical experience‐based therapeutic intervention (from the NICU to 12‐months corrected age) on improving motor function and reducing severity of motor delays in infants at 12‐months corrected age compared to standard care (Aim 1). The study also aims to evaluate the early effects (i.e. before 12 months) of a therapeutic intervention, provided from NICU to 12‐months corrected age, on motor function and severity of motor delay (Aim 2), and evaluate whether an early intervention that focusses on caregiver engagement improves caregiver well‐being (Aim 3).
Participants	192 infants who were admitted to the NICU and qualify for Early Childhood Clinic (NICU high‐risk follow‐up clinic) OR Early Intervention due to birthweight < 1500 grams OR disorders of the central nervous system such as brain injury (including but not limited to extra axial haemorrhage, any grade intraventricular or intraparenchymal haemorrhage, stroke, hypoxic ischaemic encephalopathy (HIE), meningitis hydrocephalus, microcephaly, cortical dysgenesis), and cramped synchronous movements at term PMA. HIE includes mild, moderate, severe exam on the modified Sarnat exam, both cooled and non‐cooled, and also includes "at risk for HIE" with 10‐minute Apgar < 7 plus pH < 7.15 or base deficit ≥ 12. Additionally, infants with bronchopulmonary dysplasia, defined as need for respiratory support at 36 weeks' post menstrual age in an infant born at < 32 weeks of gestation, will also qualify. All infants participating in the study must be medically stable and able to start intervention between 34–48 weeks PMA. The exclusion criteria are related to factors that may hinder the completion of intervention, sensor placement, or clinic assessments. These criteria include individuals with open wounds or skin conditions that prevent the placement of sensors, individuals with immune deficiencies necessitating protective isolation, those with limb reduction defects, and individuals primarily receiving care in another clinic, such as those with meningomyelocele and related conditions or trisomy 21. Additionally, individuals with bleeding disorders or a continuous requirement for anticoagulation, those under palliative or hospice care due to life‐limiting conditions (including trisomy 18 and 13), individuals with known visual impairments at the time of enrolment, those in the custody of the Department of Children and Family Services (DCFS), caregivers who do not speak English, and individuals with any other condition that would impede their participation in the study, as determined by the Principal Investigator (PI), are also excluded. Furthermore, individuals who have previously been enroled in a competing randomised trial with developmental outcome variables are not eligible for participation in this study.
Interventions	The proposed study is assessing the efficacy of a novel physical therapy intervention based on five principles: active learning, caregiver engagement, environmental enrichment, strengths‐based approach, and dose. The intervention will start in the NICU and continue until 12‐months corrected age. Infants in the intervention group will receive up to two therapist visits per week in addition to standard of care physical therapy. Caregivers will be asked to work with their infant on activities provided by the therapist. The therapist will provide resources to support the caregiver in working on these activities with their child, and caregivers will be asked to complete the activities for as much time as possible, throughout the day. Therapists will work with caregivers to identify ways to incorporate activities into their day. Caregiver engagement and caregiver ability to complete sessions and activity recommendations will be monitored. Infants enroled in the control group will receive standard of care.
Outcomes	Primary outcome Bayley‐4 motor score assessed at 12‐months corrected age (CA) Secondary outcomes Movement quality assessed by wearable sensors at each assessment time point, including study enrolment, monthly up to 3‐months CA, 3‐months CA, 6‐months CA, 9‐months CA, 12‐months CA, 18‐months CA (optional), and 24‐months CA (optional) Pediatric Quality of Life Inventory (PedsQL) assessed during NICU stay (up to 45 days post enrolment), at one‐and two‐month intervals after enrolment; at 3‐months CA, 6‐months CA, 9‐months CA, 12‐months CA, 18‐months CA (optional), and 24‐months CA (optional). Bayley‐4 cognitive score assessed at 6‐months CA, 12‐months CA, 18‐months CA (optional), and 24‐months CA (optional). Other outcome measures Pediatric Evaluation of Disability Inventory‐Computer Adaptive Test (PEDI‐CAT) Mobility Domain scores collected at 12‐months corrected age (CA), at 18‐months CA (optional), and at 24‐months CA (optional) Warner Initial Developmental Evaluation of Adaptive and Functional Skills (WIDEA‐FS) scores at 12‐months CA, and at 18‐months CA (optional) and 24‐months CA (optional) Hammersmith Infant Neurological Exam (HINE) scores at 3‐months CA, 6‐months CA, 9‐months CA, and 12‐months CA Motor skills assessed using Alberta Infant Motor Scale (AIMS) at 6‐months CA, 9‐months CA, and 12‐months CA. Neurological, Sensory, Motor, Developmental Assessment (NSMDA) score at 3‐months CA, 9‐months CA, 12‐months CA, 18‐months CA (optional), and 24‐months CA (optional) Optional sensor assessments will be performed if (i) the infant's caregiver is willing to participate. General Movement Assessment, Global and Optimality score at enrolment, at one‐month and two‐months after enrolment, and at 3‐months CA Test of Infant Motor Performance scores at enrolment, at one‐ and two‐months after enrolment, and at 3‐months CA
Starting date	October 2022
Contact information	Sofia Anastasopoulos, DPT; sanastasop@sralab.org
Notes	Estimated study completion date ‐ 31 December 2026

Sandoval‐Cuellar 2022.

Study name	Motor development in premature infants: study protocol for an interdisciplinary hospital‐home intervention
Methods	This study is a randomised controlled trial designed to compare the effectiveness of a hospital‐home interdisciplinary intervention in improving motor development compared with traditional intervention in the NICU.
Participants	Total of 130, with 65 in the experimental group, hospital‐based intervention (HHI) and 65 in the control group to be recruited from neonatal intensive care units in San Rafael Hospital in Tunja and Cundinamarca. Moderate‐to‐late preterm infants (between 34 and 37 weeks of gestation), weighing ≥ 1800 g, being haemodynamically stable, and residing in the cities of Tunja or Bogota will be eligible to participate in the study. Premature infants with haemodynamic alterations, congenital malformations, chromosomal syndromes, oesophageal atresia, cerebral intraventricular haemorrhage, lower Apgar score, HIE and heart disease will be excluded from the study.
Interventions	The proposed study will assess the effectiveness of an intervention programme coined Hospital‐Home Intervention (HHI). HHI is focused on achieving the effective adaptation of the infants to their motor development, according to their corrected ages through parents’ training. The intervention will be performed in 2 settings, i.e. in hospital and at home. The intervention will be performed by personnel other than the evaluators, and the training, calibration, and monitoring of the process will be performed by the researchers. The HHI establishes the training of parents with 2 components: (1) a theoretical part, which covers basic knowledge about motor development and adequate stimulation of premature infants, which will be described and available in a software application; and (2) another practical component, which promotes tactile, auditory, and visual sensory integration, the facilitation of position changes, and muscle balance through ten intervention strategies that include sensory integration, i.e. visual‐auditory fixation exercises, cervico‐ocular coordination and tactile stimulation, through proprioceptive sensory inputs and self‐examination. The intervention includes training parents on the strategies described for stimulating motor development in premature infants. These strategies will be continually performed at home once the premature infants have been discharged from the hospital. It starts at the NICU, with an approximate intervention time of 10 minutes per session, performed twice a day. Subsequently, the strategies should be performed at home with the same frequency and duration and with follow‐up through calls to a mobile device twice‐weekly, together with the use of a software application and WhatsApp instant messaging system. Premature infants should complete 14 sessions per week in the HHI for 4 weeks. During the intervention, the infants should be in an alert state, with eyes open. The duration of each session is adjusted depending on the response and the babies’ condition. Infants in the traditional intervention group will receive conventional strategies used at the NICU and Kangaroo mother care, which are based on the following: manipulation techniques that seek to provide the proper position of the infants and minimise the stress caused by the environment; augmentative techniques that favour containment and maintain the baby in flexion position; breastfeeding, management pain, and sensory techniques, i.e. auditory through songs or parents’ voices; kinaesthetic stimulation, through the passive mobilisation exercises, as well as massages for the infants; tactile stimulation, which will provide relief; and finally visual stimulation through the infants’ facial behaviours, visual fixation, and grading of attention measures while concentrating on a pattern. Premature babies weighing up to 2000 g will also be subjected to the Kangaroo mother method. The basic elements of the Kangaroo method are mainly early hospital discharge for infants in good clinical condition regardless of weight and considering breastfeeding as a source of protection and nutrition in the first months of life, kangaroo position, training of the mothers on care provided for their children, and outpatient consultation to monitor the growth and development of the children.
Outcomes	Test of Infant Motor Performance screening items will be completed pre‐ and post‐intervention, and 1 month later. Questionnaire for assessing parents' or caregivers' degree of knowledge about motor development (CapDMP) will be administered pre‐ and post‐intervention.
Starting date	Not available
Contact information	Adriana Lucía Castellanos‐Garrido; adrianacasga@unisabana.edu.co
Notes	Study completion date ‐ unknown

AIMS: Alberta Infant Motor Scale; ASQ‐3: Ages and Stages Questionnaires, Third Edition; BAI: Beck Anxiety Inventory; BRIEF‐P: Behaviour Rating of Executive Function, Parental Version; BSID‐111: Bayley Scales of Infant Development 3rd edition; CA: Corrected age; CapDMP: Parents' or caregivers' degree of knowledge about motor development; CD: Compact disc; CEQ: Child Engagement Questionnaire; CNS: Central nervous system; CP: Cerebral Palsy; CSQ‐8: Client satisfaction questionnaire; DASS‐21: Depression Anxiety and Stress Scale 21; dB:decibels; DCFS: Department of Children and Family Services; DVD: Digital Optical Disc; EAS: Emotional Availability Scale; ECAB: Early Childhood Attention Battery; EEG: Electroencephalogram; EI: Early Intervention; ERP: Event‐related potential; FCIP: Family‐centred intervention programme; GMs: General movements; GMA: General Movement Assessment; GMDS:Griffiths Mental Development Scales; GMDS: Griffiths Development Scales; GMFM: Gross Motor Function Measure; HADS: Hospital Anxiety and Depression Scale; HEP: Homeostasis‐Enrichment‐Plasticity; HHI: Hospital Home Intervention; HIE: Hypoxic ischaemic encephalopathy; HINE: Hammersmith Infant Neurological Examination; HNNE: Hammersmith Neonatal Neurological Examination; HOP‐ON: Helping Our Premature infants ON to better motor skills; IBAIP: Infant Behavioural Assessment and Intervention Program; ICF‐CY: International Classification of the Child ‐ Children and Youth; ITSEA: Infant Toddler Social Emotional Assessment; IVH: Intraventricular haemorrhage; KPCS: Karitane Parenting Confidence scale; Movement ABC: Movement Assessment Battery for Children; M‐CHAT: Modified Checklist for Autism in Toddlers; MITP: Mother‐Infant Transaction Program; MPOC: Measure of Processes of Care; MRI: Magnetic resonance imaging; NBAS: Neonatal Behavioural Assessment Scale; NBO: Newborn Behavioural Observations; NEC: Necrotising enterocolitis; NICU:Neonatal Intensive Care Unit; NNS: Non‐nutritive sucking; NSMDA: Neurological, Sensory, Motor, Developmental Assessment; PDMS: Peabody Developmental Motor Scales; PEDI‐CAT: Pediatric Evaluation of Disability Inventory Computer Adaptive Test; PedsQL: Pediatric Quality of Life Inventory; PI: Parent Infant; PMA: post menstrual age; PSE: Parental Self‐Efficacy Scale; PVL: Periventricular Leucomalacia; RES: Resilience Scale; ROP: Retinopathy of Prematurity; SDQ: Strengths and Difficulties Questionnaire; SF‐6D: Short Form Assessment of Quality of Life; SPEEDI: Supporting Play, Exploration, and Early Development Intervention; SPIBI: Stockholm preterm interaction‐based intervention; STAI: State‐Trait Anxiety Inventory; TANDI: Toddler and Infant Questionnaire; TEDI‐Prem: Telehealth for Early Developmental Intervention in babies born very preterm; TIMP:Test of Infant Motor Performance; TORCH: Toxoplasmosis, Other Agents, Rubella, Cytomegalovirus, and Herpes Simplex; VLBW: Very‐Low Birthweight; WIDEA‐FS: Warner Initial Developmental Evaluation of Adaptive and Functional Skills

Differences between protocol and review

We made the following changes to the protocol (Spittle 2005).

• There is a change to the inclusion criteria in this updated review ‐ studies that involved a single intervention session only were not included. This type of study utilises a single session aimed at improving a specific task in the short term. This clarification supports the original concept of the review where early intervention is identified as encompassing a range of components to improve the global construct of motor or cognitive development. An additional outcome measure called the Brunet‐Lezit Revised Test (Josse 1997), is included in the outcome measures. The protocol for this review included outcomes for the age band > 18 years of age. This age band has been excluded in this update, as it has yielded very few potential articles and to date there has been only one inclusion (I.H.D.P. 1990).

• Data were included in analyses for each individual in the intervention and control groups for each study. Where an intervention had a pre‐test and post‐test design, only data from the initial RCT phase of the study were included. Where data were missing, authors were contacted. Where possible, we imputed missing standard deviations (SDs) using the coefficient of variation (CV) or calculated the SD from other available statistics including standard errors and confidence intervals. If the data were assumed to be missing at random, we analysed the data without imputing any missing value. Where data were unavailable, analyses were performed on the available data. Cluster‐randomised trials are now identified as being included in this review. Included studies were examined for selective reporting bias with respect to when the outcome data were analysed and whether the reported data were fully reported and only analysed for the specified outcome.

• The GRADE approach is used in this current review as outlined in the GRADE Handbook (Schünemann 2013), to assess the certainty of evidence of the following (clinically relevant) outcomes: cognitive and motor outcomes at infant, preschool and school age. We used the GRADEpro GDT Guideline Development Tool to create a Summary of findings table to report the certainty of the evidence. We have updated the methods to comply with the latest Cochrane methodology.

Contributions of authors

Alicia Spittle and Jane Orton reviewed trials for inclusion, extracted details of study methods and results, entered data into RevMan, wrote the initial synthesis of results, and contributed to all versions of the review.

Tanya Tripathi joined the authorship group for the 2023 update and was involved in reviewing trials for inclusion, extracting details of study methods and results, entering data into RevMan, and contributing to writing of the review.
Ros Boyd extracted details of the results and contributed to all versions of the review.
Lex Doyle and Peter Anderson contributed to synthesis of the results and to all versions of the review.

Sources of support

Internal sources

• Murdoch Childrens Research Institute, Australia

  Top‐up scholarship funding for Alicia Spittle to complete her PhD 2005‐2008

External sources

• NHMRC (National Health and Medical Research Council) Australia ‐ Grant 284512, Australia

  Project grant funding to conduct the trial "VIBeS Plus by Spittle et al 2009".

• Allens Arthur Robinsons Grant, Australia

  Project grant funding to conduct the trial "VIBeS Plus by Spittle et al 2009".

• Cerebral Palsy Alliance, Other

  Alicia Spittle received a post‐doctoral scholarship 2009‐2012

• NHMRC Early Career Fellowship (AJS), Other

  Alicia Spittle received a post‐doctoral scholarship 2012‐2015

• NHMRC Centre of Research Excellence in Newborn Medicine, Other

  Alicia Spittle, Lex Doyle and Peter Anderson are chief investgators on the NHMRC CRE 2015‐2018, 2019‐2023

• NHMRC Career Development Fellowship (RNB), Other

  Alicia Spittle received a post‐doctoral scholarship 2016‐2019; 2019‐2023

• NHMRC Investigator Grant (PJA), Australia

  Salary Support

• Vermont Oxford Network, USA

  Cochrane Neonatal Reviews are produced with support from Vermont Oxford Network, a worldwide collaboration of health professionals dedicated to providing evidence‐based care of the highest quality for newborn infants and their families.

• NHMRC Career Development Fellowship (AJS), Australia

  Salary Support

Declarations of interest

AS: Is an author on three trials included in this review (Finlayson 2020; Spittle 2009; Treyvaud 2022) and works as a health professional (Physiotherapist at the Royal Women's Hospital, Melbourne, Australia). She received a grant from the National Health and Medical Research Council of Australia. She has also published opinions in medical journals on topics related to this review.

RB: Is an author on two trials included in this review (Colditz 2019; Spittle 2009).

JO: Is an author on one trial included in this review (Spittle 2009); works as a health professional (Physiotherapist at the Royal Women's Hospital, Melbourne, Australia). She has also published opinions in medical journals on topics related to this review.

PJA: Is an author on two trials included in this review (Spittle 2009; Treyvaud 2022). He has received funding as an independent contractor/consultant for Pearson Australia and Pearson Clinical Assessment. He received a grant from the National Health and Medical Research Council of Australia. He has also published opinions in medical journals on topics related to this review.

LWD: Is an author on two trials included in this review (Spittle 2009; Treyvaud 2022). He received a grant from the National Health and Medical Research Council of Australia. He has also published opinions in medical journals on topics related to this review.

TT: Is an author on one trial included in this review (Dusing 2018).

None of the authors of the included studies were involved in determining the overall study inclusion and exclusion criteria; and did not make study eligibility decisions about, extract data from, carry out the risk of bias assessment for, or perform GRADE assessments for those studies. TT extracted the data and checked interpretation for Spittle 2009. AS and JO extracted data and checked interpretation for Dusing 2015. TT and JO extracted data and checked interpretation for Finlayson 2020.

New search for studies and content updated (conclusions changed)