Docosahexaenoic Acid in Preventing Necrotizing Enterocolitis in Preterm Infants: A Randomized Clinical Trial

Background and objectives: To evaluate the effect of docosahexaenoic acid (DHA) supplementation on the incidence of NEC in preterm infants. Methods: In a randomized clinical trial, 62 preterm infants (< 34 weeks gestation) were assigned to receive either an oral supplement of docosahexaenoic acid (an omega-3 fatty acid) (n = 29) or standard care (n = 33). The supplement was administered daily at 60 mg/kg of. The primary outcome was the incidence of NEC diagnosed using modified Bell's criteria. Secondary outcomes included gastrointestinal symptoms, laboratory abnormalities, need for surgical intervention, mortality, and length of hospital stay. Results: While the incidence of any NEC (Stage ≥ IA) was not significantly reduced (48.3% vs. 66.7%; p = 0.14), the intervention group had a statistically significant lower incidence of severe NEC (Stage ≥ IIB) compared to the control group (27.6% vs. 57.6%; p = 0.03). This protective effect against severe NEC remained significant in a multivariable logistic regression analysis after adjusting for baseline confounders (OR 0.31, 95% CI [0.10, 0.98]; p = 0.047). Infants receiving DHA also had significantly lower rates of abdominal discoloration (3.4% vs. 45.5%; p < 0.001) and metabolic acidosis (31.0% vs. 57.6%; p = 0.03). Conclusions: In this trial, enteral DHA supplementation did not reduce the overall incidence of any stage NEC but was associated with a significant reduction in severe NEC in preterm infants. Despite baseline differences between groups, this finding suggests a clinically important protective effect. Trial Registration Iranian Registry of Clinical Trials IRCT20250625066253N1, Registered 10 January 2026.