Evaluating the effectiveness and safety of ursodeoxycholic acid in treatment of intrahepatic cholestasis of pregnancy

Background: Intrahepatic cholestasis of pregnancy (ICP) is a specific pregnancy-related disorder without standard medical therapies. Ursodeoxycholic acid (UDCA) is the most used medicine, but the efficacy and safety of UDCA remain uncertain. Several meta-analyses had been made to assess the effects of UDCA in ICP. However, the samples were not large enough to convince obstetricians to use UDCA. We conducted a meta-analysis to evaluate the effects and safety of UDCA in patients with ICP, which included only randomized controlled trials (RCTs). Methods: Six databases were searched. The search terms were “ursodeoxycholicacid,” “therapy,” “management,” “treatment,” “intrahepatic cholestasis of pregnancy,” “obstetric cholestasis,” “recurrent jaundice of pregnancy,” “pruritus gravidarum,” “idiopathic jaundice of pregnancy,” “intrahepatic jaundice of pregnancy,” and “icterus gravidarum.” Randomized controlled trials of UDCA versus control groups (included using other medicines) among patients with ICP were included. The primary outcomes were improved pruritus scores and liver function. Secondary outcomes were the maternal and fetal outcomes in patients with ICP. Data were extracted from included RCTs. The Mantel–Haenzel random-effects model or fixed-effects model was used for meta-analysis. Results: A total of 12 RCTs involving 662 patients were included in the meta-analysis. In pooled analyses that compared UDCA with all controls, UDCA was associated with resolution of pruritus (risk ratio [RR], 1.68; 95% confidence interval [CI],1.12–2.52; P  = 0.01),decrease of serum levels of alanine aminotransferase (ALT) (standardized mean difference (SMD), −1.36; 95% CI, −2.08 to −0.63; P  <0.001), reduced serum levels of bile acid (SMD, −0.68; 95% CI, −1.15 to −0.20; P  <0.001), fewer premature births (RR, 0.56; 95% CI, 0.43–0.72; P  <0.001),reduced fetal distress (RR, 0.68; 95% CI, 0.49–0.94; P  = 0.02), high Apgar scores at 5 minutes (RR, 0.44; 95% CI, 0.24–0.82; P  = 0.009), less frequent respiratory distress syndrome (RDS) (RR, 0.33; 95% CI, 0.13–0.86; P  = 0.02), and fewer neonates in the intensive care unit (NICU) (RR, 0.55; 95% CI, 0.35–0.87; P  <0.05), increased gestational age (SMD,0.44; 95% CI, 0.26–0.63; P  <0.001), and birth weight (SMD, 0.21; 95% CI, 0.02–0.40; P  = 0.03). There were no differences in meconium staining and intrauterine growth retardation (IUGR) between the groups ( P  >0.05). No trials reported adverse effects on mothers and fetuses except nausea and emesis. Conclusion: UDCA is effective and safe to improve pruritus and liver function in ICP. UDCA also reduced adverse maternal and fetal outcomes in pregnant women with ICP.