Neurodevelopmental Outcomes of Preterm Infants Fed High-Dose Docosahexaenoic Acid: A Randomized Controlled Trial

Infants born before 33 weeks' gestation are at high risk of developmental disorders and learning disabilities. An inadequate endogenous supply of docosahexaenoic acid (DHA), a major brain lipid, may contribute to this poor developmental outcome. Trials evaluating the possible benefit of dietary DHA on the neurodevelopment of preterm infants have been inconclusive. This randomized, double-blind, controlled trial was designed to evaluate the long-term efficacy of a high-dose DHA enteral feed on the neurodevelopment of preterm infants born at less than 33 weeks' gestation. A total of 657 infants were randomized to receive an enteral feed containing 1% total fatty acids (high-DHA group, n = 322) or a standard feed containing 0.3% total fatty acids (standard-DHA group, n = 335) from day 2 to 4 of life until term corrected age. The data were stratified by birth weight (<1250 vs. >1250 g) and infant gender. At 18 months follow-up, neurodevelopment was assessed using the Bayley Mental Development Index (MDI). In the whole study group, no difference was found in the unadjusted MDI scores of the children receiving high versus standard DHA feeds (mean difference: 1.9, 95% CI: -1.0-4.7), or among boys in the high versus standard feed groups. Adjustment for confounding variables did not change these results. However, girls receiving high-DHA feeds had significantly higher MDI scores than those receiving standard-DHA feeds (unadjusted mean difference: 4.7; 95% CI: 0.5-8.8, P = 0.03; adjusted mean difference: 4.5; 95% CI: 0.5-8.5, P = 0.03). Although ingestion of a high-DHA dose does not increase the MDI scores of all preterm infants born before 33 weeks, it was associated with an increase of MDI scores among girls. These data suggest that future trials with higher doses should be considered.