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. 2018 Jun 20;2018(6):CD012409. doi: 10.1002/14651858.CD012409.pub2
Protocol citation Overview outcomes pre‐specified in protocol
Abiramalatha T, Thomas N, Gupta V, Viswanathan A, McGuire W. High versus standard volumes of enteral feeds for preterm or low birth weight infants (Protocol). Cochrane Database of Systematic Reviews 2016, Issue 10. Secondary outcomes pre‐specified include:

  1. Neurodevelopmental outcomes assessed after 12 months post term: neurological evaluations; developmental scores; and classifications of disability, including auditory and visual disability. We will define neurodevelopmental impairment as the presence of 1 or more of the following: non‐ambulant cerebral palsy; developmental quotient > 2 SD below the population mean; and blindness (VA less than 6/60) or deafness (any hearing impairment requiring — or unimproved by — amplification)
Amari S, Shahrook S, Ota E, Mori R. Branched‐chain amino acid supplementation for improving nutrition in term and preterm neonates (Protocol). Cochrane Database of Systematic Reviews 2016, Issue 7. Primary outcomes pre‐specified include:

  1. Neurological development

    1. Major neurodevelopmental disability after 18 months' post‐term age

    2. Cerebral palsy (yes/no)

    3. Developmental delay (> 2 SD below the mean in a validated mental development test) or intellectual impairment (> 2 SD below the mean in a validated intelligence test) (yes/no)

    4. Blindness (vision < 6/60 in both eyes) (yes/no)

    5. Sensorineural deafness (requiring amplification) (yes/no)
Askie LM, Darlow BA, Davis PG, Finer N, Stenson B, Vento M, Whyte R. Effects of targeting higher versus lower arterial oxygen saturations on death or disability in preterm infants (Protocol). Cochrane Database of Systematic Reviews 2014, Issue 7. Primary outcomes pre‐specified include:

  1. Composite outcome of death or major disability by 18 to 24 months' corrected age (gestational age plus chronological age)


Secondary outcomes pre‐specified include:

  1. Major disability by 18 to 24 months' corrected age (gestational age plus chronological age)

  2. Cerebral palsy with GMFCS level 2 or higher, or MACS level 2 or higher at 18 to 24 months' corrected age (gestational age plus chronological age)
Choo YM, Ahmad Kamar A, Tengku Kamalden TAF, Looi ML, Tan K, Lai NM. Lutein and zeaxanthin for reducing morbidity and mortality in preterm infants (Protocol). Cochrane Database of Systematic Reviews 2016, Issue 5. Secondary outcomes pre‐specified include:

  1. Neurodevelopmental outcome assessed at 18 months to 28 months (Newman 2012). We will accept any of the following outcomes alone or in combination:cerebral palsy, mental retardation (BSID MDI < 70), and hearing deficit (aided or < 60 dB on audiometric testing) or assessment via use of a validated cognitive/language/behavioural/social interaction/adaptive test (Albers 2007)
Dawson JA, Davis PG, Foster JP. Routine oro/nasopharyngeal suction versus no suction in the delivery room (Protocol). Cochrane Database of Systematic Reviews 2013, Issue 1. Secondary outcomes pre‐specified include:

  1. Long‐term neurodevelopmental outcome (rates ofcerebral palsy on physician assessment; developmental delay, i.e. DQ > 2 SD < the mean on validated assessment tools, e.g. BSID MDI)
Foster JP, Buckmaster A, Sinclair L, Lees S, Guaran R. Nasal continuous positive airway pressure (nCPAP) for term neonates with respiratory distress (Protocol). Cochrane Database of Systematic Reviews 2015, Issue 11. Secondary outcomes pre‐specified include:

  1. Neurodevelopmental disability (after at least 18 months' postnatal age) defined as neurological abnormality including cerebral palsy on clinical examination, developmental delay > 2 SD below population mean on a standardised test of development, blindness (VA < 6/60), or deafness (any hearing impairment requiring amplification)
Foster JP, Taylor C, Bredemeyer SL. Topical anaesthesia for needle‐related pain in newborn infants (Protocol). Cochrane Database of Systematic Reviews 2013, Issue 1. Secondary outcomes pre‐specified include:

  1. Neurodevelopmental disability (after at least 18 months' postnatal age) defined as neurological abnormality including cerebral palsy on clinical examination, developmental delay > 2 SD below population mean on a standardised test of development
Good M, Jones LJ, Osborn DA, Abdel‐Latif ME. Transfusion of fresh versus non‐fresh (older) red blood cell in neonates (Protocol). Cochrane Database of Systematic Reviews 2015, Issue 11. Secondary outcomes pre‐specified include:

  1. Neurodevelopmental disability to at least 18 months' postnatal age (defined as neurological abnormality including cerebral palsy on clinical examination, developmental delay > 2 SD below population mean on a standardised test of development, blindness (VA < 6/60), or deafness (any hearing impairment requiring amplification) at any time after term corrected)
Gordon A, Greenhalgh M, McGuire W. Early planned removal versus expectant management of peripherally inserted central catheters to prevent infection in newborn infants (Protocol). Cochrane Database of Systematic Reviews 2016, Issue 4. Secondary outcomes pre‐specified include:

  1. Neurodevelopmental outcomes assessed after 12 months post term using validated tools: neurological evaluations; developmental scores; and classifications of disability, including auditory and visual disability. We will define neurodevelopmental impairment as the presence of 1 or more of the following: non‐ambulant cerebral palsy; DQ > 2 SD below the population mean; and blindness (VA < 6/60) or deafness (any hearing impairment requiring or unimproved by amplification)

  2. Death or neurological impairment assessed after 12 months post term
Gordon A, Greenhalgh M, McGuire W. Early planned removal of umbilical venous catheters to prevent infection in newborn infants (Protocol). Cochrane Database of Systematic Reviews 2016, Issue 4. Secondary outcomes pre‐specified include:

  1. Neurodevelopmental outcomes assessed after 12 months post term using validated tools: neurological evaluations; developmental scores; and classifications of disability, including auditory and visual disability. We will define neurodevelopmental impairment as the presence of 1 or more of the following: non‐ambulant cerebral palsy; DQ > 2 SD below the population mean; and blindness (VA < 6/60) or deafness (any hearing impairment requiring or unimproved by amplification)

  2. Death or neurological impairment assessed after 12 months post term
Green DS, Abdel‐Latif ME, Jones LJ, Osborn DA. Pharmacological interventions for prevention and treatment of upper gastrointestinal bleeding in newborn infants (Protocol). Cochrane Database of Systematic Reviews 2015, Issue 7. Secondary outcomes pre‐specified include:

  1. Neurodevelopmental disability (defined as neurological abnormality including cerebral palsy on clinical examination or global developmental delay (2 or more SD below population mean on BSID or GMDS at any time after term corrected at 1 year, 18 months', 2 years', and 5 years' postnatal age)
Han S, Yu Z, Guo X, Dong X, Chen X, Soll R. Intratracheal instillation of corticosteroids using surfactant as a vehicle for the prevention of chronic lung disease in preterm infants with respiratory distress syndrome (Protocol). Cochrane Database of Systematic Reviews 2011, Issue 4 Secondary outcomes pre‐specified include:

  1. Neurodevelopmental outcome at a later time point (> 1 year post‐conceptional age). Neurodevelopmental impairment is defined as the presence of cerebral palsy and/or mental retardation (BSID MDI < 70) and/or legal blindness (< 20/200 VA) and or deafness (aided or < 60 dB on audiometric testing)
Hegarty JE, Harding JE, Crowther CA, Brown J, Alsweiler J. Oral dextrose gel for the prevention of hypoglycaemia in newborn infants (Protocol). Cochrane Database of Systematic Reviews 2016, Issue 4. Primary outcomes pre‐specified include:

  1. Major neurological disability at 2 years of age or greater (any of legal blindness, sensorineural deafness requiring hearing aids, moderate or severe cerebral palsy, or developmental delay/intellectual impairment (defined as a DQ or IQ lower than 2 SD below the mean))


Secondary outcomes pre‐specified include:

  1. Cerebral palsy and severity at 2 years of age or older
Hyttel‐Sorensen S, Støy Saem L, Greisen G, Als‐Nielsen B, Gluud C. Cerebral near‐infrared spectroscopy monitoring for prevention of brain injury in very preterm infants (Protocol). Cochrane Database of Systematic Reviews 2015, Issue 2. Primary outcomes pre‐specified include:

  1. Major neurodevelopmental disability:

    1. Cerebral palsy

    2. Developmental delay or intellectual impairment:

      1. BSID or GMDS assessment > 2 SD below the mean or intellectual impairment (IQ > 2 SD below mean)

      2. Neuromotor development (BSID ‐ PDI) assessed in survivors

      3. Mental development (BSID ‐ MDI) assessed in survivors

    3. Blindness (vision < 6/60 in both eyes)
Jauncey‐Cooke J, Bogossian F, Hough JL, Schibler A, Davies MW, Grant CA, Gibbons K, East CE. Lung recruitment manoeuvres for reducing respiratory morbidity in mechanically ventilated neonates (Protocol). Cochrane Database of Systematic Reviews 2012, Issue 7. Secondary outcomes pre‐specified include:

  1. Neurodevelopmental impairment: cerebral palsy, sensorineural hearing loss, visual impairment or developmental delay (e.g. GMDS, BSID) assessed at 12 to 24 months' corrected age, 2 years, or 5 years
Kaempfen S, Neumann RP, Jost K, Schulzke SM. Beta‐blockers for prevention and treatment of retinopathy of prematurity in preterm infants (Protocol). Cochrane Database of Systematic Reviews 2015, Issue 9. Secondary outcomes pre‐specified include:

  1. Adverse neurodevelopmental outcomes at 18 to 24 months' corrected age

    1. Cerebral palsy

    2. Moderate to severe developmental delay as assessed by validated neurodevelopmental tests such as BSID
Kent A, Kecskes Z. Magnesium sulfate for term infants following perinatal asphyxia (Protocol). Cochrane Database of Systematic Reviews 2003, Issue 2. Primary outcomes pre‐specified include:

  1. Severe neurodevelopmental disability at or equal to 12 months of age or more. Severe neurodevelopmental disability is defined as cerebral palsy, developmental delay (DQ < 70), or blindness (VA < 6/60 in both eyes), or any combination of these disabilities
Kulasekaran K, Sargent PH, Flenady V. Milrinone for the treatment of cardiac dysfunction in neonates (Protocol). Cochrane Database of Systematic Reviews 2004, Issue 4. Secondary outcomes pre‐specified include:

  1. Neurodevelopmental outcome (neurodevelopmental outcome assessed by a standardised and validated assessment tool and/or a child developmental specialist) at any age reported (outcome data will be grouped at 12, 18, 24 months if available) ‐ cerebral palsy, developmental delay, blindness, sensorineural deafness
Lai NM, Ahmad Kamar A, Choo YM, Kong JY, Ngim CF. Fluid supplementation for neonatal unconjugated hyperbilirubinaemia (Protocol). Cochrane Database of Systematic Reviews 2015, Issue 9. Primary outcomes pre‐specified include:

  1. Proportion of infants with moderate or severe cerebral palsy, defined as a non‐progressive disorder with abnormal muscle tone in at least 1 arm or leg that was associated with abnormal control of movement or posture and a modified GMFCS score (Palisano 2008) ≥ 2 (Rosenbaum 2007), measured at predefined intervals, e.g. at 6, 12, 18, and 24 months


Secondary outcomes pre‐specified include:

  1. Proportion of infants with motor impairment, as indicated by a score of 2 or higher in the modified GMFCS evaluation (Palisano 2008)
Lui K, Foster JP, Davis PG, Ching SK, Oei JL, Osborn DA. Higher versus lower oxygen concentrations titrated to target oxygen saturations during resuscitation of preterm infants at birth (Protocol). Cochrane Database of Systematic Reviews 2012, Issue 11. Primary outcomes pre‐specified include:

  1. Neurodevelopmental disability (after > 18 months' postnatal age):

    1. Neurological abnormality including cerebral palsy on clinical examination, developmental delay > 2 SD below population mean on any standard test of development

    2. Blindness (VA < 6/60)

    3. Deafness (any hearing impairment requiring amplification)
Malhotra A, Veldman A. Recombinant activated Factor VII for prevention and treatment of intraventricular haemorrhage in neonates (Protocol). Cochrane Database of Systematic Reviews 2011, Issue 3. Primary outcomes pre‐specified include:

  1. Severe neurodevelopmental disability as defined by cerebral palsy, low developmental scores (DQ < 2 SD or untestable), blindness, or any combination of these using validated assessment tools at 18 or 24 months: neurological examinations, developmental scores (BSID, etc.)
McCarthy LK, Davis PG, O'Donnell CPF. Nasal airways (single or double prong, long or short) for neonatal resuscitation (Protocol). Cochrane Database of Systematic Reviews 2011, Issue 5. Secondary outcomes pre‐specified include:

  1. Long‐term neurodevelopmental outcome (rates of cerebral palsy on physician assessment; developmental delay, i.e. DQ > 2 SD < the mean on validated assessment tools, e.g. BSID MDI)
Molloy EJ, McCallion N, O'Donnell CPF, Davis PG. Heliox for prevention of morbidity and mortality in ventilated newborn infants (Protocol). Cochrane Database of Systematic Reviews 2008, Issue 3. Secondary outcomes pre‐specified include:

  1. Death or long‐term (< 18 months) major neurodevelopmental disability (cerebral palsy, developmental delay (BSID or GMDS assessment > 2 SD below the mean) or intellectual impairment (IQ > 2 SD below mean), blindness (vision < 6/60 in both eyes), sensorineural deafness requiring amplification)
Neary E, Ni Ainle F, El‐Khuffash A, Cotter M, Kirkham C, McCallion N. Plasma transfusion to prevent intraventricular haemorrhage in very preterm infants (Protocol). Cochrane Database of Systematic Reviews 2016, Issue 9. Primary outcomes pre‐specified include:

  1. Neurodevelopmental disability at 2 years' postnatal age, defined as neurological abnormality on clinical examination, including cerebral palsy, developmental delay > 2 SD below the population mean on any standard test of development, blindness (VA < 6/60), or deafness (any hearing impairment requiring amplification) at any time after 2 years' corrected age
O'Donnell CPF, Davis PG, Morley CJ. Endotracheal intubation versus face mask for newborns resuscitated with positive pressure ventilation at birth (Protocol). Cochrane Database of Systematic Reviews 2004, Issue 4. Secondary outcomes pre‐specified include:

  1. Long‐term neurodevelopmental outcome (rates ofcerebral palsy on physician assessment, developmental delay, i.e. IQ 2 SD < the mean on validated assessment tools, e.g. BSID MDI)
O'Donnell CPF, Davis PG, Morley CJ. Manual ventilation devices for neonatal resuscitation (Protocol). Cochrane Database of Systematic Reviews 2004, Issue 3. Secondary outcomes pre‐specified include:

  1. Long‐term neurodevelopmental outcome (rates of cerebral palsy on physician assessment, developmental delay, i.e. IQ 2 SD < the mean on validated assessment tools, e.g. BSID MDI)
Onland W, De Jaegere APMC, Offringa M, van Kaam A. Systemic corticosteroid regimens for prevention of bronchopulmonary dysplasia in preterm infants (Protocol). Cochrane Database of Systematic Reviews 2014, Issue 1. Secondary outcomes pre‐specified include:

  1. Long‐term neurodevelopmental sequelae, assessed after at least 1 year corrected gestational age and before a corrected gestational age of 4 years, and at the latest reported time point, including cerebral palsy and BSID (MDI)
Onyango AB, Suresh G, Were F. Intermittent phototherapy versus continuous phototherapy for neonatal jaundice (Protocol). Cochrane Database of Systematic Reviews 2009, Issue 4. Primary outcomes pre‐specified include:

  1. Kernicterus defined as either the pathological finding of deep‐yellow staining of neurons and neuronal necrosis of the basal ganglia and brainstem nuclei or acute or chronic neurological deficit including athetoid cerebral palsy, impaired upward gaze and deafness, isolated conditions like auditory neuropathy or dyssynchrony, and subtle bilirubin‐induced neurological dysfunction
Pierro M, Thébaud B, Soll R. Mesenchymal stem cells for the prevention and treatment of bronchopulmonary dysplasia in preterm infants (Protocol). Cochrane Database of Systematic Reviews 2015, Issue 11. Secondary outcomes pre‐specified include:

  1. Cerebral palsy at 18 to 24 months' corrected age

  2. Neurodevelopmental outcome at approximately 2 years' corrected age (acceptable range 18 months to 28 months) including cerebral palsy, delayed neurodevelopment (BSID MDI < 70), legal blindness (< 20/200 VA), and hearing deficit (aided or < 60 dB on audiometric testing). We will define the composite outcome 'neurodevelopmental impairment' as having any 1 of the aforementioned deficits
Rivas‐Fernandez M, Roqué i Figuls M, Tobias A, Balaguer A. Different strains of probiotics for preventing morbidity and mortality in preterm infants: a network meta‐analysis (Protocol). Cochrane Database of Systematic Reviews 2016, Issue 8. Secondary outcomes pre‐specified include:

  1. Neurodevelopment impairment (i.e. rates of cerebral palsy, cognitive delay, deafness, blindness or their composite reported at 18 months' corrected age or later)
Romantsik O, Calevo MG, Bruschettini M. Head midline position for preventing the occurrence or extension of germinal matrix‐intraventricular hemorrhage in preterm infants (Protocol). Cochrane Database of Systematic Reviews 2016, Issue 9. Secondary outcomes pre‐specified include:

  1. Long‐term neurodevelopmental outcomes (yes/no): cerebral palsy on physician assessment, developmental delay (i.e. IQ 2 SD below the mean on validated assessment tools such as BSID MDI) (Bayley 1993; Bayley 2006)

  2. Major neurodevelopmental disability: cerebral palsy, developmental delay (BSID MDI (Bayley 1993; Bayley 2006) or GMDS (Griffiths 1954) assessment > 2 SDs below the mean), intellectual impairment (IQ > 2 SDs below the mean), blindness (vision < 6/60 in both eyes), or sensorineural deafness requiring amplification (Jacobs 2013). We plan to evaluate each of these components as a separate outcome and to extract data on each long‐term outcome from studies that evaluated children after 18 months' chronological age. We will separately assess data on children 18 to 24 months of age and on those 3 to 5 years of age
Seliem W, Bhutta ZA, Soll R, McGuire W. Topical emollient therapy for preventing infection in preterm infants in low‐ or middle‐income countries (Protocol). Cochrane Database of Systematic Reviews 2007, Issue 3. Secondary outcomes pre‐specified include:

  1. Neurodevelopmental outcomes at > 12 months post term (measured using validated assessment tools) and classifications of disability, including auditory and visual disability. The composite outcome "severe neurodevelopmental disability" will be defined as any 1 or combination of the following: non‐ambulant cerebral palsy, severe developmental delay, auditory and visual impairment
Shah D, Tracy M. Cutaneous antisepsis for prevention of intravascular catheter–associated infection in newborn infants (Protocol). Cochrane Database of Systematic Reviews 2014, Issue 3. Secondary outcomes pre‐specified include:

  1. Long‐term neurodevelopmental outcome: neurodevelopmental outcome at approximately 2 years' corrected age (acceptable range 18 months to 28 months) including cerebral palsy, significant mental developmental delay (BSID MDI < 70), legal blindness (< 20/200 VA), and hearing deficit (aided or < 60 dB on audiometric testing). The composite outcome "neurodevelopmental impairment" was defined as having any 1 of the aforementioned deficits
Sinn JKH, Kumar K, Osborn DA, Bolisetty S. Higher versus lower amino acid intake in parenteral nutrition for newborn infants (Protocol). Cochrane Database of Systematic Reviews 2006, Issue 2. Primary outcomes pre‐specified include:

  1. Neurodevelopmental disability at at least 18 months' postnatal age (defined as neurological abnormality including cerebral palsy on clinical examination, developmental delay > 2 SD below population mean on a standardised test of development, blindness (VA < 6/60), or deafness (any hearing impairment requiring amplification) at any time after term corrected)


Secondary outcomes pre‐specified include:

  1. Individual components of neurodevelopment at at least 18 months' postnatal age:

    1. Cerebral palsy on clinical examination

    2. Developmental delay > 2 SD below population mean on a standardised test of development

    3. Blindness (VA < 6/60)

    4. Deafness (any hearing impairment requiring amplification) at any time after term corrected
Van Rostenberghe H, Ho JJ, Quah BS, Noraida R. The effects of thyroxine on end organ damage in asphyxiated neonates (Protocol). Cochrane Database of Systematic Reviews 2009, Issue 4. Primary outcomes pre‐specified include:

  1. Any neurodevelopmental disability assessed at 12 months or more of age:

    1. Presence of no/minor or major disabilities

    2. Presence ofcerebral palsy

    3. Any objective quantitative assessments of neurodevelopmental assessment that are internationally recognised
Xiong T, Chen H, Mu D. Effect of pre‐exchange albumin infusion on neonatal hyperbilirubinaemia and long‐term developmental outcomes (Protocol). Cochrane Database of Systematic Reviews 2014, Issue 2. Primary outcomes pre‐specified include:

  1. Neurological deficits consistent with kernicterus at 2 years of age (including separate analysis of each component): athetoid cerebral palsy, impaired upward gaze and deafness, auditory neuropathy or dys‐synchrony (ABR abnormality), dental dysplasia, and subtle bilirubin‐induced neurological dysfunction
Xiong T, Li H, Zhao J, Dong W, Qu Y, Wu T, Mu D. Hyperbaric oxygen for term newborns with hypoxic ischemic encephalopathy (Protocol). Cochrane Database of Systematic Reviews 2011, Issue 8. Primary outcomes pre‐specified include:

  1. Long‐term (> 18 months) major neurodevelopmental disabilities among all participants or survivors (cerebral palsy, developmental delay (BSID or GMDS assessment > 2 SD below the mean), or intellectual impairment (IQ > 2 SD below mean), blindness (vision < 6/60 in both eyes), sensorineural deafness requiring amplification)
Yu B, Li S, Zhou D, Davis PG. Subcutaneous reservoir drainage versus ventriculoperitoneal shunt for the treatment of posthemorrhagic hydrocephalus in preterm infants (Protocol). Cochrane Database of Systematic Reviews 2009, Issue 3. Primary outcomes pre‐specified include:

  1. The incidence rates of death or neurodevelopmental disability in infancy (> 12 months' postnatal age). Neurodevelopmental disability includes developmental delay (e.g. the score of BSID < 2 SD below the mean indicates developmental delay), cerebral palsy, blindness, deafness, and any other neurodevelopmental abnormalities
Yu Z, Guo X, Han S, Lu J, Sun Q. Erythropoietin for term and late preterm infants with hypoxic ischemic encephalopathy (Protocol). Cochrane Database of Systematic Reviews 2010, Issue 1. Primary outcomes pre‐specified include:

  1. The primary outcome measure will be either death or long‐term (1 year or 18 months) major neurodevelopmental disability (cerebral palsy, developmental delay (BDIS or GMDS assessment > 2 SD below the mean), or intellectual impairment (IQ > 2 SD below mean), blindness (vision < 6/60 in both eyes), sensorineural deafness requiring amplification)


Secondary outcomes pre‐specified include:

  1. Each component of the primary outcome:

    1. Cerebral palsy

    2. Developmental delay or intellectual impairment

    3. Blindness

    4. Sensorineural deafness requiring amplification patient
Yu Z, Sun Q, Han S, Lu J, Ohlsson A, Guo X. Erythropoietin for preterm infants with hypoxic ischaemic encephalopathy (Protocol). Cochrane Database of Systematic Reviews 2012, Issue 12. Primary outcomes pre‐specified include:

  1. Either death (at 28 days and at discharge) or long‐term (1 year or 24 months' corrected age) intellectual impairment (IQ > 2 SD below mean), blindness (vision < 6/60 in both eyes), sensorineural deafness requiring amplification


Secondary outcomes pre‐specified include:

  1. Each component of the primary outcome:

    1. Death at 28 days and at discharge

    2. Cerebral palsy at > 1 year (the criterion for the diagnosis of cerebral palsy was a fixed motor deficit diagnosed by a neurologist)

    3. Developmental delay (BSID or GMDS > 2 SD below the mean) or intellectual impairment (IQ > 2 SD below mean) at 1 year or 24 months' corrected age

    4. Blindness (vision < 6/60 in both eyes) at 1 year or 24 months' corrected age

    5. Sensorineural deafness requiring amplification patient at 1 year or 24 months' corrected age