Efficacy and Safety of Probiotic Supplementation for Neonatal Jaundice: A Systematic Review and Meta-analysis

Neonatal jaundice (NJ) is a common condition in newborns. Probiotics provide health benefits to the host and are widely used to treat various diseases, including neonatal gastrointestinal disorders. However, their efficacy and safety in NJ remain uncertain. Given the relationship of the neonatal bilirubin metabolism to gastrointestinal function, we aimed to synthesize evidence on the effects of probiotics supplementation on NJ. We searched PubMed, EMBASE, Cochrane Library, and China National Knowledge Infrastructure up to January 2025. The eligibility criteria were randomized controlled trials (RCTs) that evaluated the efficacy of probiotics in NJ. Two reviewers independently completed study selection, data extraction, and quality evaluation. Continuous outcomes of interest were pooled as mean differences (MDs) with 95% confidence intervals (CIs) using the inverse variance method with random-effects models. Thirty trials with 2776 neonates were included. Probiotic supplementation significantly reduced total serum bilirubin levels from day 1 (MD - 0.35, 95% CI - 0.63 to - 0.06) to day 10 (MD - 1.74, 95% CI - 2.54 to - 0.95) mg/dL. Infants who received probiotics supplementation also showed a significantly shorter duration of phototherapy (MD - 17.09, 95% CI - 24.43 to - 9.76) hours and hospitalization (MD - 1.17, 95% CI - 1.60 to - 0.74) days. Furthermore, probiotic supplementation was associated with a lower incidence of adverse effects, including diarrhea, rashes, and fevers. These benefits were consistent in both preterm and full-term infants. In conclusion, probiotic supplementation may be a well-tolerated adjunctive therapy with short-term benefits for NJ; however, cautious clinical application is warranted, particularly regarding sustained effects. Future large-scale RCTs are needed to validate our findings, optimize treatment approaches, and evaluate long-term efficacy and safety.