Probiotic Supplementation for Necrotizing Enterocolitis Prevention in Preterm Neonates: A Systematic Review

Abstract

Introduction: Necrotizing enterocolitis (NEC) remains a leading cause of mortality and morbidity in very low birth weight (VLBW) preterm infants. Despite advances in neonatal intensive care, effective preventive strategies are limited. Probiotics have been proposed as a potential intervention to modulate gut microbiota and reduce NEC risk. This review synthesizes current evidence on probiotic efficacy for NEC prevention.

Methods: A systematic literature search was conducted in PubMed, Cochrane Library, and Scopus for randomized controlled trials (RCTs) published from 2015–2025. Inclusion criteria: preterm infants <34 weeks gestation or birth weight <1500g; probiotic supplementation initiated within first 7 days of life; comparator placebo or no treatment; outcome NEC Bell stage ≥2. Two reviewers independently extracted data and assessed bias using Cochrane RoB2. Meta-analysis used random-effects models.

Results: Fifteen RCTs (n=5,842 infants) were included. Probiotic supplementation significantly reduced NEC incidence compared to control (RR 0.54, 95% CI 0.43–0.68, p<0.001). Number needed to treat was 25. No significant difference in all-cause mortality (RR 0.80, 95% CI 0.62–1.04). Multi-strain probiotics (Lactobacillus + Bifidobacterium) showed greater effect (RR 0.42) than single strain (RR 0.71). No probiotic-attributed systemic infections were reported.

Discussion: Findings support probiotic efficacy for NEC prevention, consistent with prior meta-analyses. Effect size was moderate but clinically meaningful. Heterogeneity across strains and dosing regimens limits generalization. The absence of safety signals is reassuring but underpowered for rare adverse events.

Conclusions: Probiotic supplementation reduces NEC risk in preterm neonates without significant safety concerns. Routine use in high-risk populations is justified, though strain-specific recommendations require further head-to-head trials.