Ursodeoxycholic acid as adjuvant treatment to phototherapy for neonatal hyperbilirubinemia: a systematic review and meta-analysis

Background: Neonatal hyperbilirubinemia is observed in most newborns, and 5-15% of neonates require phototherapy. Phototherapy is effective but often prolongs hospitalization and has both short-term and potential long-term harms. The aim of this systematic review and meta-analysis was to evaluate the role of ursodeoxycholic acid (UDCA) combined with phototherapy in neonatal hyperbilirubinemia.

Methods: A literature search was conducted on September 1, 2021; 590 studies were screened, and 17 full texts were assessed by two authors. We included randomized controlled trials with or without placebo intervention. Primary outcomes were changes in total bilirubin levels at 24 hours and phototherapy duration. We calculated mean differences with 95% confidence intervals (CI).

Results: Six studies with 880 neonates were included. Of these studies, only two used a placebo-controlled double-blinded design. The overall risk of bias was high in one and moderate in four of the included studies. The mean decrease in the total bilirubin level during the first 24 hours was 2.06 mg/dL (95% CI 0.82-3.30; six studies) greater in the UDCA treatment group. The phototherapy duration was 19.7 hours (95% CI 10.4-29.1; five studies) shorter in the UDCA treatment group.

Conclusions: We found low-quality evidence that UDCA as an adjuvant to phototherapy seems to decrease total bilirubin faster and shorten phototherapy duration compared to standard treatment. Further studies are needed to confirm the efficacy, acute and long-term outcomes, and safety before implementing UDCA as an adjuvant to phototherapy in neonatal hyperbilirubinemia.