Effect of Probiotic Supplementation in Preventing Necrotizing Enterocolitis Sepsis and Mortality Among Preterm and Very Low Birth Weight Infants: A Systematic Review and Meta-Analysis.

Abstract

Preterm and very low birth weight (VLBW) infants are highly vulnerable to gastrointestinal and systemic complications due to immature gut barriers, dysbiosis, and underdeveloped immunity, with necrotizing enterocolitis (NEC) and late-onset sepsis contributing significantly to morbidity and mortality. Probiotic supplementation has been proposed as a strategy to restore gut microbial balance, enhance gastrointestinal maturation, and reduce disease risk. This study systematically reviews the impact of probiotics on NEC, sepsis, mortality, feeding tolerance, hospitalization, and related physiological outcomes in preterm and VLBW infants. Studies were identified through databases in accordance with Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines, including those that examined probiotic interventions in preterm or VLBW populations. Primary outcomes assessed were NEC, sepsis, and mortality, while secondary outcomes included feeding tolerance, hospital stay, and inflammatory or metabolic markers. Data were extracted and synthesized narratively to evaluate clinical trends and strain-specific efficacy. Findings showed that multi-strain probiotic supplementation consistently reduced NEC incidence, improved feeding tolerance, accelerated full oral feeding, and shortened hospitalization. Selected probiotics also lowered C-reactive protein and total serum bilirubin, suggesting systemic anti-inflammatory and metabolic benefits, whereas single-strain probiotics demonstrated variable efficacy. Mortality outcomes, however, were consistently unaffected across studies. Overall, probiotics are safe and provide clinically significant benefits in preterm and VLBW infants, particularly for NEC prevention and improved feeding and hospital outcomes, with multi-strain formulations appearing more effective and underscoring the importance of strain selection for optimizing therapeutic outcomes.