CONTEXT: Uncertainty exists about the benefit of dietary docosahexaenoic acid (DHA) on the neurodevelopment of preterm infants.

OBJECTIVE: To determine the effect of meeting the estimated DHA requirement of preterm infants on neurodevelopment at 18 months' corrected age.

DESIGN, SETTING, AND PARTICIPANTS: 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.

INTERVENTION: 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.

MAIN OUTCOME MEASURES: 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).

RESULTS: 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.

CONCLUSION: 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.