Docosahexaenoic acid in preventing necrotizing enterocolitis in preterm infants: a randomized clinical trial

Necrotising enterocolitis (NEC) is a major cause of death in preterm infants. This trial evaluated enteral omega-3 supplementation for preventing NEC. In this open-label, single-centre, parallel-group randomised trial, 62 preterm infants were allocated to enteral omega-3 supplementation ( n = 29) or standard care alone ( n = 33). The supplement (60 mg docosahexaenoic acid per kilogram, once daily) was given for three days, beginning on the third day of tolerated oral feeding. The primary outcome was definite NEC, defined as modified Bell stage II or higher with radiographic confirmation. Definite NEC occurred in 15 of 33 Control infants (45.5%) and 7 of 29 Omega-3 infants (24.1%) (risk ratio 0.53, 95% CI 0.25 to 1.12; p = 0.112). Adjusted for gestational age and delivery-room resuscitation, the odds ratio was 0.41 (95% CI 0.12 to 1.30; p = 0.135). No secondary outcome retained significance after Benjamini-Hochberg correction. Neutropenia occurred in no Control infant and in 6 Omega-3 infants (20.7%) (risk difference 20.7% points, 95% CI 5.9 to 35.4; p = 0.008); all episodes were mild. Mortality was 5 of 33 Control versus 1 of 29 Omega-3 infants ( p = 0.201); no infant required NEC-related surgery. A three-day course of enteral omega-3 supplementation did not significantly reduce definite NEC. An unexplained excess of mild neutropenia under Omega-3 allocation warrants confirmation in future trials with pre-specified haematological safety monitoring. Iranian Registry of Clinical Trials IRCT20250625066253N1, registered on 10 January 2026. IRCT20250625066253N1 (Iranian Registry of Clinical Trials), registered on 10 January2026.