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Meta-Analysis
. 2025 Apr 11;25(1):245.
doi: 10.1186/s12876-025-03788-0.

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

Jiaju Han  1 , Yufeng Ren  2 , Peini Zhang  1 , Chengfeng Fang  1 , Leilei Yang  1 , Shenkang Zhou  1 , Zhiqing Ji  1
Affiliations
Meta-Analysis

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

Jiaju Han et al. BMC Gastroenterol. .

Abstract

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 (ESRR: 0.51; 95% CI: 0.46, 0.55, p < 0.001, and ESOR: 0.59; 95%CI: 0.48, 0.72, P < 0.001), and mortality rate (ESRR: 0.72; 95% CI: 0.68, 0.76, P < 0.001, and ESOR: 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.

Keywords: Mortality; Necrotizing enterocolitis; Probiotics; Umbrella meta-analysis.

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Conflict of interest statement

Declarations. Ethics approval and consent to participate: Not applicable. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests.

Figures

Fig. 1
Fig. 1
PRISMA flow chart indicating the study selection process
Fig. 2
Fig. 2
A The Forest plot of the efficacy of probiotics supplementation in prevention of NEC according to relative risk (RR) analysis. B The Forest plot of the efficacy of probiotics supplementation in prevention of NEC according to odds ratio (OR) analysis
Fig. 3
Fig. 3
A The Forest plot of the efficacy of probiotics supplementation on mortality related to NEC according to relative risk (RR) analysis. B The Forest plot of the efficacy of probiotics supplementation on mortality related to NEC according to odds ratio (OR) analysis
See this image and copyright information in PMC

References

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