Docosahexaenoic Acid and Bronchopulmonary Dysplasia in Preterm Infants

This was a multicenter randomized trial conducted at 13 centers in Australia, New Zealand, and Singapore. It enrolled very preterm infants born before 29 weeks of gestation who had begun enteral feeding within 3 days after birth; the DHA arm included 631 randomized infants, with 592 in the primary outcome analysis.

Very preterm infants received enteral docosahexaenoic acid (DHA) as a microencapsulated aqueous emulsion of fractionated tuna oil at 60 mg/kg/day, given as 0.17 ml/kg three times daily by nasogastric or orogastric tube. Treatment continued until the primary outcome assessment at 36 weeks postmenstrual age or discharge home, and it was compared with a soy control emulsion.

DHA supplementation did not reduce bronchopulmonary dysplasia and was associated with a higher risk of the primary outcome. Physiological BPD occurred in 291/592 (49.1%) in the DHA group versus 269/613 (43.9%) in control, with an adjusted RR of 1.13 (1.02-1.25; P=0.02). The composite of physiological BPD or death before 36 weeks postmenstrual age was also higher with DHA: 330/631 (52.3%) versus 298/642 (46.4%), adjusted RR 1.11 (1.00-1.23; P=0.045). Clinical BPD was numerically higher as well, 315/592 (53.2%) versus 304/612 (49.7%), adjusted RR 1.09 (1.00-1.18; P=0.06). Overall, the findings do not support routine DHA supplementation for prevention of BPD and raise safety concerns.

The trial tested a single DHA dose and formulation in a specific very preterm population, which limits generalizability to other doses, formulations, or gestational ages. Several outcomes were secondary or exploratory, and no clear benefit was seen across other neonatal outcomes. Interpretation is also constrained by outcome measurement at 36 weeks postmenstrual age or discharge home rather than longer-term follow-up.