Probiotics Reduce the Risk of Necrotizing Enterocolitis in Preterm Infants: A Meta-Analysis

Abstract

Background: Necrotizing enterocolitis (NEC) is the most common serious acquired disease of the gastrointestinal tract in preterm infants. Probiotic bacteria are live microbial supplements that colonize the gastrointestinal tract and potentially provide benefit to the host. Objective: To compare the efficacy and safety of prophylactic enteral probiotics administration versus placebo or no treatment in the prevention of severe NEC and other morbidities in preterm infants. Methods: A meta-analysis was performed in accordance with the Cochrane Neonatal Review Group methods. Preterm infants <37 weeks’ gestational age and/or <2,500 g birth weight were included. Literature searches were made of MEDLINE, EMBASE, Cochrane Library Controlled Trials Register (CENTRAL), and abstracts of annual meetings of the Society for Pediatric Research and the European Society of Pediatric Research. Results: Nine eligible trials randomizing 1,425 infants were included. Included trials were highly variable with regard to enrollment criteria, baseline risk of NEC in the control groups, timing, dose, formulation of the probiotics, and feeding regimens. In a meta-analysis, enteral probiotics supplementation significantly reduced the incidence of severe NEC [typical RR 0.32 (95% CI 0.17, 0.60)] and mortality [typical RR 0.43 (95% CI 0.25, 0.75)]. There was no evidence of significant reduction of nosocomial sepsis [typical RR 0.93 (95% CI 0.73, 1.19)] or days on total parenteral nutrition [weighted mean difference –1.9 (95% CI –4.6, 0.77)]. The statistical test of heterogeneity for NEC, mortality and sepsis was insignificant. Data regarding extremely low birth weight infants (ELBW) could not be extrapolated. The included trials reported no systemic infection with the probiotics supplemental organism. Conclusion: Enteral supplementation of probiotics reduces the risk of severe NEC and mortality in preterm infants. A large randomized controlled trial is required to investigate the benefit and safety profile of probiotics supplementation in ELBW infants.