High-Dose Docosahexaenoic Acid in Newborns Born at Less Than 29 Weeks’ Gestation and Behavior at Age 5 Years
Authors: Gould Jacqueline F. , Roberts Rachel M. , Anderson Peter J. , Makrides Maria , Sullivan Thomas R. , Gibson Robert A. , McPhee Andrew J. , Doyle Lex W. , Bednarz Jana M. , Best Karen P. , Opie Gillian , Travadi Javeed , Cheong Jeanie L. Y. , Davis Peter G. , Sharp Mary , Simmer Karen , Tan Kenneth , Morris Scott , Lui Kei , Bolisetty Srinivas , Liley Helen , Stack Jacqueline , Collins Carmel T. 
Published: November 2023

Importance

Children born at less than 29 weeks’ gestation are at risk of behavioral difficulties. This may be due in part to the lack of transplacental supply of docosahexaenoic acid (DHA), a key fatty acid with structural and functional roles in the brain.

Objective

To determine whether meeting the neonatal DHA requirement through supplementation is associated with improved behavioral functioning of children born at less than 29 weeks’ gestation.

Design, Setting and Participants

This was a follow-up of children from 10 Australian participating centers in a multi-center, blinded, parallel group randomized clinical trial of infants born at less than 29 weeks’ gestation conducted from June 2012 and September 2015, excluding those with additional fatty acid supplementation or major congenital or chromosomal abnormalities. Follow-up took place from August 2018 to May 2021. Parents of surviving children who had not withdrawn from the original trial were invited to complete questionnaires when the child turned 5 years’ corrected age.

Interventions

Infants were randomized to receive daily enteral emulsions providing 60 mg/kg/d of DHA or a soy-oil emulsion (with no DHA) from within the first 3 days of enteral feeding until 36 weeks’ postmenstrual age or discharge home, whichever occurred first.

Main Outcomes and Measures

The primary outcome of this follow-up was parent-rated behavior and emotional functioning as indicated by the Total Difficulties score of the Strengths and Difficulties Questionnaire. Parents also completed questionnaires about their child’s behavioral manifestations of executive functioning, as well as a range of health outcomes to assess potential longer-term side effects of DHA intervention.

Results

Primary outcome data were available for 731 children (76% of 958 surviving eligible children; 361 in the intervention group and 370 in the control group). Of these 731, 452 (47%) were female, and the mean (SD) corrected age at follow-up was 5.4 (0.5) years. Following imputation for missing data, the mean Total Difficulties score was the same in both groups (intervention group, n = 465; mean [SD], 11.8 [6.3]; control group, n = 493; mean [SD], 11.8 [6.0]; mean difference adjusted for sex, gestational age stratum, and hospital, 0.01; 95% CI, −0.87 to 0.89; P = .98). There was no evidence for differences between the groups in any secondary outcomes of behavior, executive functioning, or health.

Conclusions and Relevance

In this follow-up of a randomized clinical trial, enteral DHA supplementation at the equivalent of the estimated in utero dose for infants born at less than 29 weeks’ gestation did not improve behavioral functioning at age 5 years. There were no indications of adverse effects with DHA supplementation.

Trial Registration

Australian New Zealand Clinical Trial Registry: ACTRN12612000503820