Phototherapy Alone or Combined with Adjuvant Drugs for Neonatal Hyperbilirubinemia: A Systematic Review and Network Meta-Analysis.

Objectives

Neonatal hyperbilirubinemia is a common disease in the neonatal period. In this meta-analysis, we aim to evaluate the efficacy of adjuvant drugs combined with phototherapy in the treatment of neonatal hyperbilirubinemia.

Methods

Randomized controlled trials (RCTs) published before September 2025 were searched from PubMed, Embase, Web of Science, and the Cochrane Library. A Bayesian random-effects network meta-analysis was performed to calculate mean differences and 95% confidence intervals. Interventions were ranked using the surface under the cumulative ranking curve (SUCRA) and probability of being the best treatment (PbBT).

Results

Thirty-five RCTs involving 4060 neonates were included. Compared with phototherapy alone, clofibrate, ursodeoxycholic acid, fenofibrate, and calcium phosphate significantly reduced bilirubin levels and shortened admission duration. Clofibrate showed the greatest efficacy in bilirubin reduction within 48 h (SUCRA = 0.91, PbBT = 60.9%) and in shortening hospitalization (SUCRA = 0.84, PbBT = 40.83%). Probiotics, zinc, and agar exhibited relatively modest effects, while phenobarbital showed no significant benefit.

Conclusions

Adjunctive therapies were associated with greater reductions in bilirubin levels compared with phototherapy alone. Future high-quality RCTs are needed to confirm the long-term efficacy and safety of these adjuvant therapies.