Neurodevelopmental Outcomes of Preterm Infants Fed High-Dose Docosahexaenoic Acid

Abstract

Uncertainty exists about the benefit of dietary docosahexaenoic acid (DHA) on the neurodevelopment of preterm infants. To determine the effect of meeting the estimated DHA requirement of preterm infants on neurodevelopment at 18 months' corrected age. Randomized, double-blind controlled trial enrolling infants born at less than 33 weeks' gestation from April 2001 to October 2005 at 5 Australian tertiary hospitals, with follow-up to 18 months. High-DHA (approximately 1% total fatty acids) enteral feeds compared with standard DHA (approximately 0.3% total fatty acids) from day 2 to 4 of life until term corrected age. Bayley Mental Development Index (MDI) at 18 months' corrected age. A priori subgroup analyses were conducted based on randomization strata (sex and birth weight < 1250 g vs > or = 1250 g). Of the 657 infants enrolled, 93.5% completed the 18-month follow-up. Bayley MDI scores did not differ between the high- and standard-DHA groups (mean difference, 1.9; 95% confidence interval [CI], -1.0 to 4.7). The MDI among girls fed the high-DHA diet was higher than girls fed standard DHA in unadjusted and adjusted analyses (unadjusted mean difference, 4.7; 95% CI, 0.5-8.8; adjusted mean difference, 4.5; 95% CI, 0.5-8.5). The MDI among boys did not differ between groups. For infants born weighing less than 1250 g, the MDI in the high-DHA group was higher than with standard DHA in the unadjusted comparison (mean difference, 4.7; 95% CI, 0.2-9.2) but did not reach statistical significance following adjustment for gestational age, sex, maternal education, and birth order (mean difference, 3.8; 95% CI, -0.5 to 8.0). The MDI among infants born weighing at least 1250 g did not differ between groups. A DHA dose of approximately 1% total fatty acids in early life did not increase MDI scores of preterm infants overall born earlier than 33 weeks but did improve the MDI scores of girls. anzctr.org.au Identifier: ACTRN12606000327583.