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

Carmel T Collins; Robert A Gibson; Peter J Anderson; Andrew J McPhee; Thomas R Sullivan; Jacqueline F Gould; Philip Ryan; Lex W Doyle; Peter G Davis; Judy E McMichael; Noel P French; Paul B Colditz; Karen Simmer; Scott A Morris; Maria Makrides

doi:10.1136/bmjopen-2014-007314

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

BMJ Open. 2015 Mar 18;5(3):e007314. doi: 10.1136/bmjopen-2014-007314.

Authors

Affiliations

¹ 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.
² 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.
³ 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.
⁴ 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.
⁵ School of Population Health, The University of Adelaide, Adelaide, South Australia, Australia.
⁶ Women's and Children's Health Research Institute, North Adelaide, South Australia, Australia FOODplus Research Centre, The University of Adelaide, Adelaide, South Australia, Australia.
⁷ 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.
⁸ Clinical Sciences, The Murdoch Children's Research Institute, Parkville, Victoria, Australia Department of Obstetrics and Gynaecology, The Royal Women's Hospital, Parkville, Victoria, Australia.
⁹ 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.
¹⁰ Perinatal Research Centre, University of Queensland Centre for Clinical Research, The University of Queensland, Royal Brisbane and Women's Hospital, Brisbane, Queensland, Australia.
¹¹ Centre for Perinatal Medicine, Flinders Medical Centre and School of Medicine, Flinders University, Adelaide, South Australia, Australia.

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.

Design: Follow-up of a multicentre randomised controlled trial. Randomisation was stratified for sex, birth weight (<1250 vs ≥1250 g) and hospital.

Setting: Five Australian tertiary hospitals from 2008 to 2013.

Participants: 626 of the 657 participants randomised between 2001 and 2005 were eligible to participate.

Interventions: 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.

Primary outcome: 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.

Trial registration number: Australian New Zealand Clinical Trials Registry: ACTRN12606000327583.

Keywords: NEONATOLOGY; NUTRITION & DIETETICS; PUBLIC HEALTH.

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Publication types

Multicenter Study
Randomized Controlled Trial
Research Support, Non-U.S. Gov't

MeSH terms

Child
Child Behavior / drug effects
Child Development / drug effects*
Dietary Supplements*
Docosahexaenoic Acids / administration & dosage*
Executive Function / drug effects
Female
Follow-Up Studies
Humans
Infant
Infant, Newborn
Infant, Premature / psychology*
Intelligence / drug effects
Male
Premature Birth / drug therapy*
Premature Birth / psychology*
Sex Factors
Wechsler Scales

Substances

Docosahexaenoic Acids