title: Neurodevelopmental outcomes at 7 years' corrected age in preterm infants who were fed high-dose docosahexaenoic acid to term equivalent: a follow-up of a randomised controlled trial.
abstract: OBJECTIVE
  To determine if improvements in cognitive outcome detected at 18 months' corrected age (CA) in infants born <33 weeks' gestation receiving a high-docosahexaenoic acid (DHA) compared with standard-DHA diet were sustained in early childhood.
  
  
  METHODS
  Follow-up of a multicentre randomised controlled trial. Randomisation was stratified for sex, birth weight (<1250 vs ≥1250 g) and hospital.
  
  
  METHODS
  Five Australian tertiary hospitals from 2008 to 2013.
  
  
  METHODS
  626 of the 657 participants randomised between 2001 and 2005 were eligible to participate.
  
  
  METHODS
  High-DHA (≈1% total fatty acids) enteral feeds compared with standard-DHA (≈0.3% total fatty acids) from age 2-4 days until term CA.
  
  
  METHODS
  Full Scale IQ of the Wechsler Abbreviated Scale of Intelligence (WASI) at 7 years CA. Prespecified subgroup analyses based on the randomisation strata (sex, birth weight) were conducted.
  
  
  RESULTS
  604 (92% of the 657 originally randomised) consented to participate (291 high-DHA, 313 standard-DHA). To address missing data in the 604 consenting participants (22 for primary outcome), multiple imputation was performed. The Full Scale IQ was not significantly different between groups (high-DHA 98.3, SD 14.0, standard-DHA 98.5, SD 14.9; mean difference adjusted for sex, birthweight strata and hospital -0.3, 95% CI -2.9 to 2.2; p=0.79). There were no significant differences in any secondary outcomes. In prespecified subgroup analyses, there was a significant sex by treatment interaction on measures of parent-reported executive function and behaviour. Scores were within the normal range but girls receiving the high-DHA diet scored significantly higher (poorer outcome) compared with girls receiving the standard-DHA diet.
  
  
  CONCLUSIONS
  Supplementing the diets of preterm infants with a DHA dose of approximately 1% total fatty acids from days 2-4 until term CA showed no evidence of benefit at 7 years' CA.
  
  
  BACKGROUND
  Australian New Zealand Clinical Trials Registry: ACTRN12606000327583.
authors: Women's and Children's Health Research Institute, North Adelaide, South Australia, Australia Healthy Mothers, Babies and Children, South Australian Health and Medical Research Institute, Adelaide, South Australia, Australia School of Paediatrics and Reproductive Health, The University of Adelaide, Adelaide, South Australia, Australia FOODplus Research Centre, The University of Adelaide, Adelaide, South Australia, Australia.
authors: Carmel T
authors: http://orcid.org/0000-0003-3308-9948
authors: CT
authors: Collins
authors: Women's and Children's Health Research Institute, North Adelaide, South Australia, Australia Healthy Mothers, Babies and Children, South Australian Health and Medical Research Institute, Adelaide, South Australia, Australia FOODplus Research Centre, The University of Adelaide, Adelaide, South Australia, Australia.
authors: Robert A
authors: RA
authors: Gibson
authors: Clinical Sciences, The Murdoch Children's Research Institute, Parkville, Victoria, Australia Department of Paediatrics, The University of Melbourne, Royal Children's Hospital, Parkville, Victoria, Australia.
authors: Peter J
authors: PJ
authors: Anderson
authors: Healthy Mothers, Babies and Children, South Australian Health and Medical Research Institute, Adelaide, South Australia, Australia School of Paediatrics and Reproductive Health, The University of Adelaide, Adelaide, South Australia, Australia Department of Neonatal Medicine, Women's and Children's Hospital, North Adelaide, South Australia, Australia.
authors: Andrew J
authors: AJ
authors: McPhee
authors: School of Population Health, The University of Adelaide, Adelaide, South Australia, Australia.
authors: Thomas R
authors: TR
authors: Sullivan
authors: Women's and Children's Health Research Institute, North Adelaide, South Australia, Australia FOODplus Research Centre, The University of Adelaide, Adelaide, South Australia, Australia.
authors: Jacqueline F
authors: JF
authors: Gould
authors: School of Population Health, The University of Adelaide, Adelaide, South Australia, Australia.
authors: Philip
authors: P
authors: Ryan
authors: Clinical Sciences, The Murdoch Children's Research Institute, Parkville, Victoria, Australia Department of Paediatrics, The University of Melbourne, Royal Children's Hospital, Parkville, Victoria, Australia Department of Obstetrics and Gynaecology, The Royal Women's Hospital, Parkville, Victoria, Australia.
authors: Lex W
authors: LW
authors: Doyle
authors: Clinical Sciences, The Murdoch Children's Research Institute, Parkville, Victoria, Australia Department of Obstetrics and Gynaecology, The Royal Women's Hospital, Parkville, Victoria, Australia.
authors: Peter G
authors: PG
authors: Davis
authors: Centre of Neonatal Research and Education, The University of Western Australia, Perth, Western Australia, Australia King Edward Memorial Hospital and Princess Margaret Hospital for Children, Subiaco, Western Australia, Australia.
authors: Judy E
authors: JE
authors: McMichael
authors: Centre of Neonatal Research and Education, The University of Western Australia, Perth, Western Australia, Australia King Edward Memorial Hospital and Princess Margaret Hospital for Children, Subiaco, Western Australia, Australia.
authors: Noel P
authors: NP
authors: French
authors: Perinatal Research Centre, University of Queensland Centre for Clinical Research, The University of Queensland, Royal Brisbane and Women's Hospital, Brisbane, Queensland, Australia.
authors: Paul B
authors: PB
authors: Colditz
authors: Centre of Neonatal Research and Education, The University of Western Australia, Perth, Western Australia, Australia King Edward Memorial Hospital and Princess Margaret Hospital for Children, Subiaco, Western Australia, Australia.
authors: Karen
authors: K
authors: Simmer
authors: Centre for Perinatal Medicine, Flinders Medical Centre and School of Medicine, Flinders University, Adelaide, South Australia, Australia.
authors: Scott A
authors: SA
authors: Morris
authors: Women's and Children's Health Research Institute, North Adelaide, South Australia, Australia Healthy Mothers, Babies and Children, South Australian Health and Medical Research Institute, Adelaide, South Australia, Australia School of Paediatrics and Reproductive Health, The University of Adelaide, Adelaide, South Australia, Australia FOODplus Research Centre, The University of Adelaide, Adelaide, South Australia, Australia.
authors: Maria
authors: M
authors: Makrides
mesh_terms: D002648:Child; D002652:Child Behavior / Q000187:drug effects; D002657:Child Development / Q000187:drug effects*; D019587:Dietary Supplements; D004281:Docosahexaenoic Acids / Q000008:administration & dosage*; D056344:Executive Function / Q000187:drug effects; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D007234:Infant, Premature / Q000523:psychology*; D007360:Intelligence / Q000187:drug effects; D008297:Male; D047928:Premature Birth / Q000188:drug therapy* / Q000523:psychology*; D012737:Sex Factors; D014888:Wechsler Scales
chemical_list: D004281:Docosahexaenoic Acids
keywords: NEONATOLOGY; NUTRITION & DIETETICS; PUBLIC HEALTH