Routine probiotic supplementation in preterm infants for necrotizing enterocolitis prevention

Abstract

Background: Necrotizing enterocolitis (NEC) remains one of the most severe gastrointestinal complications in preterm infants, associated with high mortality and long-term morbidity. Probiotic supplementation has been proposed as a preventive strategy through modulation of intestinal microbiota and enhancement of gut barrier function. However, evidence regarding the effectiveness and safety of routine probiotic supplementation in preterm infants remains inconsistent. Methods: A systematic review was conducted according to PRISMA guidelines. Electronic databases including MEDLINE, Embase, the Cochrane Central Register of Controlled Trials, and Web of Science were searched from database inception to the final search date. Studies evaluating routine probiotic supplementation for NEC prevention in preterm infants were included. Randomized controlled trials were analyzed for efficacy outcomes, while observational studies were included to evaluate real-world effectiveness and safety. The primary outcome was severe NEC (Bell stage ≥II). Results: Eleven studies met the inclusion criteria, including nine randomized controlled trials and two observational cohort studies. The studies enrolled several thousand preterm infants across multiple regions. Probiotic preparations varied and included both single-strain and multi-strain formulations containing species of Bifidobacterium, Lactobacillus, and Saccharomyces. Several randomized trials reported reductions in NEC incidence with probiotic supplementation, whereas others showed no significant difference compared with controls. Observational studies suggested potential reductions in mortality but also reported rare cases of probiotic-associated bloodstream infection. Conclusion: Probiotic supplementation may reduce NEC incidence in preterm infants in some settings, but the evidence remains heterogeneous. Further large multicenter trials using standardized probiotic formulations are needed to clarify optimal strains, dosing, and long-term safety.

Keywords: necrotizing enterocolitis, probiotics, preterm infants, very low birth weight, systematic review.