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

Abstract

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.

Effect of Ursodeoxycholic Acid in Unconjugated Hyperbilirubinemia in the Term Neonates Treated with Phototherapy: A Systematic Review

“…Although, another systematic review conducted by Kuitunen et al 35 showed that usage of the UDCA as adjuvant to PT resulted in shorter PT duration and faster TSB level decline, although, the concerns were related to the high heterogeneities among the included studies. Instead, a recent meta-analysis by Lazarus et al concluded that UDCA with PT was effective in reducing the Pt duration and reducing the TSB levels.…”

Ursodeoxycholic acid and phototherapy versus phototherapy and placebo on neonatal indirect hyperbilirubinemia

“…It may be due to different sample sizes or genetic backgrounds. In a previous metaanalysis by Kuitunen et al (11), they found low-quality evidence that UDCA as an adjuvant to phototherapy decreases the indirect bilirubin. Furthermore, the dose of UDCA was different between studies (11).…”

“…In a previous metaanalysis by Kuitunen et al (11), they found low-quality evidence that UDCA as an adjuvant to phototherapy decreases the indirect bilirubin. Furthermore, the dose of UDCA was different between studies (11). Most of the studies published were conducted in Middle East region (6,11), therefore larger studies from different geographical region and more sample size are recommended.…”

“…Furthermore, the dose of UDCA was different between studies (11). Most of the studies published were conducted in Middle East region (6,11), therefore larger studies from different geographical region and more sample size are recommended.…”

Comparison of the effect of ursodeoxycholic acid and multistrain synbiotic on indirect hyperbilirubinemia among neonates treated with phototherapy: A double-blind, randomized, placebo-controlled clinical trial study

“…It protects the liver against oxidative stress, prevents cell apoptosis, stimulates blood flow to bile, and suppresses destructive factors in immunological mechanisms. [ 9 ] Multiple mechanisms are thought to be involved in the entry of bilirubin into the brain. These include the following: (i) excessive production of bilirubin surpasses the blood and tissues’ normal buffering capacity; (ii) altered bilirubin binding potential, resulting in unconjugated bilirubin in circulation; (iii) permeability of the central nervous system due to disruption of the blood–brain barrier and (iv) other factors that affect or act independently.…”