Probiotic mediated modulation of neonatal health: a meta-analysis of prematurity-related morbidity, jaundice, and respiratory distress.

Introduction: Prematurity remains a major contributor to neonatal morbidity and mortality worldwide, with neonatal jaundice and respiratory distress syndrome (RDS) representing two of the most common complications associated with immature hepatic and pulmonary development. Increasing evidence suggests that probiotic supplementation may improve neonatal outcomes through modulation of the gut microbiome, gut-liver axis, and gut-lung axis; however, published findings remain inconsistent. The meta-analysis evaluated the effects of probiotic supplementation on prematurity-related morbidity, with particular emphasis on neonatal jaundice and RDS. Methods: The study was conducted according to PRISMA 2020 guidelines, and a comprehensive literature search of PubMed, Scopus, Web of Science, and the Cochrane Library identified 18 eligible studies comprising 2,587 preterm infants. Methodological quality was assessed using the Cochrane Risk of Bias 2 tool and Newcastle-Ottawa Scale, and pooled effect estimates were calculated using random-effects models. Results: Probiotic supplementation significantly reduced the incidence of neonatal jaundice (RR = 0.72, 95% CI: 0.61-0.84; p < 0.001), peak total serum bilirubin levels (MD = -1.84 mg/dL, 95% CI: -2.47 to -1.21), and phototherapy requirements (RR = 0.68, 95% CI: 0.55-0.82; p < 0.001). The incidence of RDS was significantly reduced (RR = 0.79, 95% CI: 0.66-0.95; p = 0.012), accompanied by a shorter duration of respiratory support (MD = -1.9 days, 95% CI: -2.8 to -1.0). Moderate heterogeneity was observed across pooled analyses (I² = 42-57%). Exploratory meta-regression suggested that probiotic formulation, early initiation (<72 h), and gestational age contributed to between-study variability. Discussion: Probiotic supplementation was associated with favorable clinical outcomes in preterm infants. The moderate between-study heterogeneity, variability in probiotic strains, formulations, dosages, and treatment protocols, together with limited long-term safety data, warrant cautious interpretation. Future adequately powered multicenter randomized controlled trials, standardized probiotic interventions, individual-patient-data meta-analyses, and long-term follow-up studies are required before routine clinical implementation and standardized probiotic treatment recommendations can be established.