The effectiveness of treatment with probiotics in preventing necrotizing enterocolitis and related mortality: results from an umbrella meta-analysis on meta-analyses of randomized controlled trials.

Introduction: Probiotic supplementation has been proposed as a preventive measure for necrotizing enterocolitis (NEC) in preterm infants. This umbrella meta-analysis assesses the effects of probiotics, including single-strain and multi-strain formulations, on NEC and related mortality.

Methods: A comprehensive search was conducted in PubMed, Scopus, ISI Web of Science, and Embase for studies up to August 2024. The AMSTAR2 tool assessed the quality of included studies. Meta-analysis studies were selected based on the PICOS framework, focusing on preterm neonates (< 37-week gestation), probiotic supplementation (single-strain or multi-strain), placebo or standard care comparison, and outcomes of NEC and mortality. Pooled relative risks (RR) and odds ratios (OR) with 95% confidence intervals (CI) were calculated using random-effects models.

Results: Overall, 35 eligible studies were included into the study. Twenty-six and 32 probiotic intervention arms used single- and multi-strain probiotics, respectively. The findings revealed that probiotics decreased NEC significantly (ES: 0.51; 95% CI: 0.46, 0.55, p < 0.001, and ES: 0.59; 95%CI: 0.48, 0.72, P < 0.001), and mortality rate (ES: 0.72; 95% CI: 0.68, 0.76, P < 0.001, and ES: 0.77; 95%CI: 0.70, 0.84, p < 0.001).

Conclusion: The present review suggests that supplementation with probiotics reduced NEC and related mortality. Probiotic supplementation can be recognized as a NEC-preventing approach in preterm and very preterm infants, particularly Multi-strain probiotics.