Table 1.

Characteristics of included studies in systematic review

Author, year Country	Sample and participants (size, WGA and/or birthweight)	Study Design	Intervention Description	Intervention (who delivered, duration, dose, frequency)	Comparator group	Outcome measurement	Timing of assessment	Main Findings
Als, 2003 [24] USA	N = 92 < 28 WGA <  1250 g BW	RCT 2 parallel groups from 3 different centers.	Developmental Care - NIDCAP emphasizes the behavioral individuality of each infant. It seeks to diminish the infant’s experiences of stress and to enhance the infant’s strengths.	Delivered daily (7 days per wk) by two professionals (a NICU nurse and a developmental professional).	Standard care - some degree of shielding of incubators, sound containment, use of breast milk, and referral to occupational and physical therapy and to community early intervention. Kangaroo care (skin-to-skin holding) was used in one study center.	Neurobehavioral: Assessment of Preterm Infant’s Behavior (APIB). Measurements: Autonomic (respiration, digestion, color), motor (tone, movement, postures), state organization (range, robustness, transition patterns), attention and self-regulation.	At 2 weeks’ CA Infant’s behaviors were recorded every 2 min for approximately 1 h during a medical, nursing, or parent caregiving activity.	Infants of the experimental group had enhanced neuro-behavioral development (for all APIB system scores) compared to infants of the comparator group.
Als, 2004 [32] USA	N = 30 28 to 33 WGA BW between 5 and 95%	RCT 2 parallel groups.	Developmental care - NIDCAP Developmental care emphasizes the behavioral individuality of each infant. Each infant is seen as an active participant in all care.	Initiated within 72 h of admission and continued to the age of 2 weeks CA. Delivered daily (7 days/wk) by two certified NIDCAP professionals, psychologist, and infant developmentalist.	Standard care - shielding incubators, early use of dressing in T-shirts, and side and foot rolls; liberal provision of pacifiers; and inconsistent nurse-dependent encouragement of skin-to-skin holding and breastfeeding.	Neurobehavioral: APIB. Neurological: Precthl Neurological Examination of the Full-term Newborn.	At 2 weeks’ CA.	Infants of the experimental group had enhanced neurobehavioral and neurological development (for all APIB system scores and Precthl variables) compared to infants of the comparator group.
Kanagasabai, 2013 [33] India	N = 50 28 to 36 WGA 1000-2000 g BW	RCT 2 parallel groups.	Sensory Stmulation Multisensory - ATVV stimulation program: Auditory - Soft lullaby between (30–40 dB) for 3 min using a miniature speaker and an mp3 player; Tactile - Gentle stroking massage for 3 min in a sequence of chest, upper limbs and lower limbs in supine position; Visual - Black and white visual stimulation card hung at a distance of 8–10 in. from the neonate for 3 min; Vestibular - Gentle horizontal and vertical rocking for 3 min.	Initiated when infants reached 33 weeks of GA and within 48 h of birth for infants born at 33–36 wk. Delivered five days per wk. ×  12 min daily and until discharge from the hospital.	Usual care: Kangaroo mother care and exclusive breastfeeding.	Neuromotor development: Infant Neurological International Battery (INFANIB) Measurements: Spasticity, head and trunk, vestibular function, legs, French angles (scarf sign, heel to ear, popliteal angle, abductor’s angle).	At term age (between 38 to 40 weeks GA).	Infants in the experimental group had significantly improved neuromotor development compared to infants of the comparator group.
Madlinger-Lewis, 2014 [27] USA	N = 92 ≤ 32 WGA	RCT 2 parallel groups.	Developmental Care - Alternative positioning: Structured blanket (Dandle Roo) made of stretchable cotton with adjustable straps for the upper extremities, a pouch for the lower extremities, and a head boundary designed to hold the legs in a weight-bearing, flexed position, while allowing for movement with recoil back to flexion.	Delivered continuously by nurses and parents whenever in bed and not being held or fed until discharge.	Traditional positioning consisted of any positioning devices or adaptations without the use Dandle Roo (swaddling, use of blankets and cloth rolls).	Neurobehavioral: NICU Network Neurobehavioral Scale (NNNS). Measurements: habituation (not evaluated), orientation, tolerance of handling, quality of movement, self regulation, non-optimal reflexes, stress signs, arousal, hypertonia, hypotonia, asymmetry, excitability, and lethargy.	Between 35 to 40 weeks PMA.	Infants in the experimental group showed significantly less asymmetry of reflex and motor responses than those in the comparator group. No significant effect was found between groups for the other NNNS subscales.
Maguire, 2008 [25] Netherlands	N = 192 <32 WGA	RCT 2 parallel groups.	Developmental care – Positioning and incubators covers reduction of light and sound through use of incubator covers and using positioning aids to optimize physiologic stability and motor development and promote nesting.	Delivered continuously within 48 h of life until discharge.	Usual care consisted of no covers or nesting.	Neurological: Precthl Neurological Assessment of the Full-Term Newborn.	At 40 weeks PMA.	No significant effect between the groups was found for infants’ neurological development.
McAnulty, 2009 [34] USA	N = 107 < 29 weeks WGA < 1250 g BW	RCT 2 parallel groups.	Developmental Care – NIDCAP	Initiated upon NICU admission and continued to the age of 2 weeks CA. Delivered daily (7 days per wk) by two certified NIDCAP professionals, an nurse and a psychologist.	Control group received standard NICU care.	Neurobehavioral: APIB. Neurological: Precthl Neurological Assessment of the Full-Term Newborn.	Weekly observations throughout hospital stay to 2 weeks CA.	Infants of the experimental group had enhanced neurobehavioral development (for 5 APIB scores) and a trend towards better performance on the neurological assessement (Precthl) compared to infants of the comparator group.
Nakwa, 2017 [35] India	N = 36 33 WGA (mean)	RCT 2 parallel groups.	Music: Lullaby (30 to 40 dB during 30 min. Preterm infants received the developmental program as a standard of care.	Delivered three times a week × 30 min for a total of 3 weeks.	Developmental program (as a standard of care) including a tactile, visual, auditory and vistubural stimulation.	Neuromotor development: Test of Infant Motor Performance (TIMP) (posture and movements). Neurological devlopment: INFANIB.	First and last day of intervention during hospitalization.	Infants in the experimental group had significantly improved neuromotor and neurological development compared to infants of the comparator group.
Namprom, 2018 [26] Thailand	N = 50 28 to 32 WGA <  2500 g BW	RCT 2 parallel groups.	Parental participation program (maternal): Three key components: 1- Psychosocial support for mothers to participate in their infant’s care 2-Parent education: teaching the content of developmental care practices for preterm infants 3-Therapeutic developmental interventions pertaining to performance of care practices.	Delivered by a nurse and mothers. Activities were four 1-h teaching sessions and 4 1-h practice sessions over 4 weeks.	Standard care (no description mentioned).	Neurobehavioral development: Neonatal Neurobehavioral Examination (NNE). Measurements: Tone and motor patterns, primitive reflexes, and behavioral responses.	At day 14 and 28 after infants’ birth.	Infants in the experimental group had significantly better neuro-behavioral development (tone and motor pattern, behavioral responses and total score) compared to infants of the comparator group.
Smith, 2014 [36] USA	N = 20 <  30 WGA <  1000 g BW	Pilot RCT 2 parallel groups.	Sensory Stimulation – Tactile (Relaxation (M technique) Structured touch of 8 distinctive patterns, stroking preterm infant’s back on each side of the spine (with the pads of the third and fourth fingers of both hands).	Initiated when the infant reached 30 weeks of GA. Delivered by a nurse or a another research team member. A 7 min of the M technique, 6 times per week for a total of 5 weeks.	Standard care in the two groups (family-centered care and neurodevelopmental strategies including parental presence, skin-to-skin contact, adequate positioning, environment supporting sleep).	Neurobehavioral development: NNNS Habituation (not evaluated in study), orientation, tolerance of handling, quality of movement, self-regulation, nonoptimal reflexes, stress signs, arousal, hypertonia, hypotonia, asymmetry, excitability, and lethargy.	At 35 weeks PMA at the end of the 5 weeks of intervention.	No significant difference between groups was found for any of the NNNS subscales.
Valizadeh, 2017 [37] Iran	N = 76 25 to 30 WGA 1000 g to 2000 g BW	RCT, 4 parallel groups Containement group, combination group, hydrotherapy group, physical activity group.	Three interventions 1. Hydrotherapy group Preterm infant placed in water. Head, neck and pelvis supported (Sweeney and Vignochi method). 2. Physical activity group: Extension and flexion: wrist, elbow, shoulder, ankle, knee and hip joints (Moyer-Mileur protocol). 3. Combination group Hydrotherapy and physical activity.	Initiated at 32 weeks GA. Delivered by a nurse. For each 3 interventions delivered 10 min daily (30 min or 1 h before feeding) for 14 days.	Containment group: Preterm infants placed in a fetal position (lateral) with one hand on the preterm infant’s head (at the top) and one hand over the trunk and hip area,	Neuromotor development: TIMP. Neuromuscular development: New Ballard Score and 2 items from Dubowitz examination. Measurements: New Ballard Score: Posture, Arm Recoil, Popliteal Angle, Scarf Sign, Heel to Ear, Square window. Items from Dubowitz examination: Leg recoil and ankle dorsiflexion.	At 34 weeks PMA (post-intervention).	No significant effect between groups was found for’ neuromotor and neuromuscu-lar development. Infants of the physical therapy and hydrotherapy groups had significantly better leg recoil from Dubowitz examination compared to infants of the comparator group.
Yu, [38] 2019 Taiwan	N = 76 32 to 36 WGA <  1500 g BW	RCT, 2 parallel groups.	Parental Participation Program: interventions on parental participation, feeding, massage, activities, parental support, home transition.	Delivered by physical therapists, parents and nurses. During the NICU stay 5 sessions of interventions of one hour.	Standard care: 5 interventions in the NICU (according to the synactive theory of development) and 7 phone calls after discharge.	Neurobehavioral development: NNE (Chinese version).	Around 40 weeks PMA (between 38 to 44 weeks).	Infants in the experimental group had significantly better neuro-behavioral development (tone and motor patterns and total score) than infants of the comparator group.
Zeraati, [39] 2018 Iran	N = 80 32 to 36 WGA	RCT, 2 parallel groups.	Sensory Stimulation - Multisensory Auditory stimulation (lullaby, 30 to 40 dB for 3 min), tactile stimulation (3 min massage), visual stimulation (3 min black an white card), vestibular stimulation (gentle rockin for 3 min).	Initiated 48 h after birth. Delivered 12 min/session and 5 sessions per week until NICU discharge.	Standard care.	Neuromuscular development: New Ballard Score.	At discharge.	Infants of the experimental group had significantly better neuromuscu-lar development after the intervention compared to infants of the comparator group.