Efficacy of probiotic supplementation in preventing necrotizing enterocolitis in preterm infants: a systematic review and meta-analysis

Background: Necrotizing enterocolitis (NEC) is a severe condition in preterm infants, involving intestinal inflammation and bacterial invasion, leading to high morbidity and mortality. Probiotics may reduce NEC by promoting beneficial gut bacteria, but the role of Bifidobacterium bifidum G001 (BBG001) is not well understood. This meta-analysis evaluates the effectiveness of BBG001 versus placebo in preventing NEC, late-onset sepsis, and all-cause mortality in preterm infants. Methods: Following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, we conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) from 2014 to 2024. Databases searched included PubMed, Cochrane Central Register, MEDLINE, and EMBASE. Inclusion criteria encompassed RCTs involving preterm infants (<37 weeks gestation and/or <2500 g birth weight) receiving enteral probiotics, including BBG001, compared to placebo. Outcomes assessed were incidence of NEC (>= stage II), late-onset sepsis, and all-cause mortality. Data extraction and quality assessment were independently performed. Results: From 430 identified records, nine studies involving 7180 preterm infants met the inclusion criteria. BBG001 significantly reduced the risk of NEC stage >2 (OR = 0.66; 95% CI [0.47, 0.94], p = .02), mortality and morbidity (OR = 0.74; 95% CI [0.62, 0.89], p = .001), and sepsis (OR = 0.71; 95% CI [0.53, 0.93], p = .01). It also lowered the odds of periventricular leukomalacia (OR = 0.61; 95% CI [0.47, 0.78], p < .0001) and intraventricular hemorrhage (OR = 0.48; 95% CI [0.33, 0.69], p < .0001). Additionally, BBG001 showed a protective effect against infection-related outcomes, reducing the odds of death attributed to infection (OR = 0.80; 95% CI: 0.65, 0.99; p = .04). Conclusions: Probiotic supplementation with BBG001 appears effective in reducing NEC incidence, bloodstream infections, and infection-related deaths in preterm infants. Despite promising results, variability in study designs necessitates further large-scale RCTs to confirm these findings and establish BBG001's role in neonatal care.