Efficacy and Safety of Probiotic Supplementation for Neonatal Jaundice: a Systematic Review and Meta-Analysis

Abstract 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 toward 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 treating NJ. Two reviewers individually completed evidence selection, data extraction, and quality evaluation. Mean differences (MDs) in total serum bilirubin (TSB) levels between two groups were pooled using random-effects model by the DerSimonian and Laird method, and heterogeneity was quantified using I² statistics. Thirty RCTs (2776 neonates) were included. Probiotics supplementation significantly reduced TSB from day 1 (MD:-0.35, 95% confidence interval [CI]:-0.63 to -0.06) to day 10 (MD:-1.74, 95% CI:-2.54 to -0.95) mg/dL. Infants Patients who received probiotics supplementation also showed a significantly shorter duration of phototherapy (MD:-17.09, 95% CI:-24.43 to -9.76) h and hospitalization (MD:-1.17, 95% CI:-1.60 to -0.74) days. Furthermore, probiotics 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 an effective and safe adjuvant treatment for NJ, with potential benefits observed in both preterm and full-term infants.