title: Optimising nutrition to improve growth and reduce neurodisabilities in neonates at risk of neurological impairment, and children with suspected or confirmed cerebral palsy.
abstract: BACKGROUND
  Neurological impairment is a common sequelae of perinatal brain injury. Plasticity of the developing brain is due to a rich substrate of developing neurones, synaptic elements and extracellular matrix. Interventions supporting this inherent capacity for plasticity may improve the developmental outcome of infants following brain injury. Nutritional supplementation with combination docosahexaenoic acid, uridine and choline has been shown to increase synaptic elements, dendritic density and neurotransmitter release in rodents, improving performance on cognitive tests. It remains elusive whether such specific 'neurotrophic' supplementation enhances brain plasticity and repair after perinatal brain injury.
  
  
  METHODS
  This is a two year double-blind, randomised placebo controlled study with two cohorts to investigate whether nutritional intervention with a neurotrophic dietary supplement improves growth and neurodevelopmental outcomes in neonates at significant risk of neurological impairment (the D1 cohort), and infants with suspected or confirmed cerebral palsy (the D2 cohort). 120 children will be randomised to receive dietetic and nutritional intervention, and either active supplement or placebo. Eligible D1 neonates are those born <30(+6) weeks gestation with weight <9(th) centile, ≤ 30(+6) weeks gestation and Grade II, III or IV Intra-Ventricular Haemorrhage or periventricular white matter injury, or those born at 31-40(+28) weeks gestation, with Sarnat grade I or II or III Hypoxic Ischaemic Encephalopathy or neuroimaging changes compatible with perinatal brain injury. Eligible D2 infants are those aged 1-18 months with a suspected or confirmed clinical diagnosis of cerebral palsy. The primary outcome measure is composite cognitive score on the Bayley Scales of Infant and Toddler Development III at 24 months. Secondary outcomes include visuobehavioural and visual neurophysiological assessments, and growth parameters including weight, height, and head circumference.
  
  
  CONCLUSIONS
  This is the first study to supplement neonates and infants with perinatal brain injury with the combination of factors required for healthy brain development, throughout the period of maximal brain growth. A further study strength is the comprehensive range of outcome measures employed. If beneficial, supplementation with brain phosphatide precursors could improve the quality of life of thousands of children with perinatal brain injury.
  
  
  BACKGROUND
  Current Controlled trials: ISRCTN39264076 (registration assigned 09/11/2012), ISRCTN15239951 (registration assigned 23/04/2010).
authors.affiliation: Department of Paediatrics, Oxford University, Level 2, Oxford Children's Hospital, Oxford, OX3 9DU, UK. morag.andrew@paediatrics.ox.ac.uk.
authors.forename: Morag J
authors.initials: MJ
authors.lastname: Andrew
authors.affiliation: Institute of Neuroscience, Newcastle University, Sir James Spence Institute, Royal Victoria Infirmary, Newcastle Upon Tyne, NE1 4LP, UK. Jeremy.parr@ncl.ac.uk.
authors.forename: Jeremy R
authors.initials: JR
authors.lastname: Parr
authors.affiliation: Department of Paediatrics, Oxford University, Level 2, Oxford Children's Hospital, Oxford, OX3 9DU, UK. christine.montague-johnson@paediatrics.ox.ac.uk.
authors.forename: Chris
authors.initials: C
authors.lastname: Montague-Johnson
authors.affiliation: Department Experimental Psychology, University of Oxford, South Parks Road, Oxford, OX1 3UD, UK. oliver.braddick@psy.ox.ac.uk.
authors.forename: Oliver
authors.initials: O
authors.lastname: Braddick
authors.affiliation: Department of Paediatrics, Oxford University, Level 2, Oxford Children's Hospital, Oxford, OX3 9DU, UK. karen.laler@paediatrics.ox.ac.uk.
authors.forename: Karen
authors.initials: K
authors.lastname: Laler
authors.affiliation: Centre for Statistics in Medicine, University of Oxford, Botnar Research centre, Windmill Road, Oxford, OX3 7LD, UK. Nicola.williams@csm.ox.ac.uk.
authors.forename: Nicola
authors.initials: N
authors.lastname: Williams
authors.affiliation: Department of Paediatrics, Oxford University, Level 2, Oxford Children's Hospital, Oxford, OX3 9DU, UK. bonny.baker@paediatrics.ox.ac.uk.
authors.forename: Bonny
authors.initials: B
authors.lastname: Baker
authors.affiliation: Department of Paediatrics, Oxford University, Level 2, Oxford Children's Hospital, Oxford, OX3 9DU, UK. peter.sullivan@paediatrics.ox.ac.uk.
authors.forename: Peter B
authors.initials: PB
authors.lastname: Sullivan
mesh_terms: D001720:Birth Injuries / Q000178:diet therapy* / Q000503:physiopathology; D001925:Brain Damage, Chronic / Q000178:diet therapy* / Q000503:physiopathology; D002547:Cerebral Palsy / Q000178:diet therapy* / Q000503:physiopathology; D002794:Choline / Q000627:therapeutic use*; D004281:Docosahexaenoic Acids / Q000627:therapeutic use*; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D007234:Infant, Premature; D008297:Male; D009473:Neuronal Plasticity; D018697:Nootropic Agents / Q000627:therapeutic use*; D012307:Risk Factors; D014529:Uridine / Q000627:therapeutic use*; D014785:Vision, Ocular
chemical_list: D018697:Nootropic Agents; D004281:Docosahexaenoic Acids; D002794:Choline; D014529:Uridine