Three-Day Omega-3 Course Fails to Significantly Cut Necrotizing Enterocolitis in Preterm Infants

Enteral supplementation with the omega-3 fatty acid docosahexaenoic acid (DHA) did not significantly reduce the incidence of definite necrotizing enterocolitis (NEC) in preterm infants, according to an open-label, single-centre, parallel-group randomized trial published in BMC Pediatrics. The finding tempers hopes that a short course of DHA could prevent one of the most dangerous bowel diseases of premature infancy, though the trial’s small size leaves the true effect uncertain.

NEC is a major cause of death in preterm infants, and the trial was designed to test whether enteral omega-3 supplementation could prevent it. The researchers enrolled 62 preterm infants and allocated them to either enteral omega-3 supplementation (29 infants) or standard care alone (33 infants). The supplement, given at a dose of 60 milligrams of DHA per kilogram of body weight once daily, was administered 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 infants in the control group (45.5%) compared with 7 of 29 infants in the omega-3 group (24.1%). This corresponds to a risk ratio of 0.53 with a 95% confidence interval of 0.25 to 1.12 and a p value of 0.112, which did not reach statistical significance. When the analysis was adjusted for gestational age and delivery-room resuscitation, the odds ratio was 0.41 (95% CI 0.12 to 1.30; p = 0.135), again not statistically significant. Although the point estimates suggest a possible reduction in risk, the confidence intervals include the possibility of no effect, and no secondary outcome retained significance after Benjamini-Hochberg correction for multiple comparisons.

The trial also raised a safety signal. Neutropenia occurred in no control infant but in 6 of the 29 omega-3 infants (20.7%), a risk difference of 20.7 percentage points (95% CI 5.9 to 35.4; p = 0.008). All episodes were reported as mild. The authors describe this excess of mild neutropenia under omega-3 allocation as unexplained and note that it warrants confirmation in future trials with pre-specified haematological safety monitoring.

Mortality was 5 of 33 infants in the control group versus 1 of 29 in the omega-3 group, a difference that was not statistically significant (p = 0.201). No infant in the trial required NEC-related surgery. The trial was registered with the Iranian Registry of Clinical Trials (IRCT20250625066253N1) on 10 January 2026, and the article was published open access on 29 October 2026.

The authors conclude that a three-day course of enteral omega-3 supplementation did not significantly reduce definite NEC in this population. Because the study was open-label and conducted at a single centre with a modest sample size, the estimates of both benefit and harm carry wide uncertainty. The observed neutropenia signal, in particular, is based on a small number of events and requires independent replication before any conclusions about the haematological safety of short-course DHA supplementation in preterm infants can be drawn. Future trials, the authors suggest, should pre-specify haematological safety monitoring to clarify whether the finding is real or a chance result of the small sample.

Subject of Research: A randomized trial of enteral docosahexaenoic acid supplementation for preventing necrotizing enterocolitis in preterm infants

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

Article References: Sabzevari, F., Parvaz, A., Rezaei, M., Bijari, B. B., Jamali, Z., Nikvarz, M., Eslamian, M., & Hajializadeh, A. (2026). Docosahexaenoic acid in preventing necrotizing enterocolitis in preterm infants: a randomized clinical trial. BMC Pediatrics. https://doi.org/10.1186/s12887-026-07968-z

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DOI: 10.1186/s12887-026-07968-z

Keywords: docosahexaenoic acid, omega-3, necrotizing enterocolitis, preterm infants, randomized clinical trial, neutropenia, neonatology, BMC Pediatrics, clinical trial safety, DHA supplementation, Docosahexaenoic, acid