A systematic review and individual participant meta-analysis found evidence for the clinical benefit of antenatal ursodeoxycholic acid treatment in women with intrahepatic cholestasis of pregnancy. The study was published in The Lancet Gastroenterology & Hepatology.
Searches of PubMed, Web of Science, Embase, MEDLINE, CINAHL, Global Health, MIDIRS, and Cochrane since inception to January 1, 2020 returned 85 studies fulfilling the inclusion criteria. These had 30 or more participants and reported on at least 1 individual with intrahepatic cholestasis of pregnancy and bile acid concentrations of 40 μmol/L or more. The primary outcome was prevalence of stillbirth, but insufficient data was expected, so a composite, main secondary outcome of stillbirth and preterm birth was included.
There was no difference in prevalence of stillbirth between women treated with ursodeoxycholic acid (35/5097 fetuses; 0.7%) and those who were not (12/2038 fetuses; 0.6%) (adjusted odds ratio [aOR], 1.04; 95% CI, 0.35–3.07; P =.95). There was also no difference in prevalence of stillbirth when considering singleton pregnancies, randomized controlled trials, or two-arm studies alone.
Treatment with ursodeoxycholic acid did not affect the prevalence of the composite outcome in all studies (aOR, 1.28; 95% CI, 0.86-1.91; P =.22). However, when only randomized controlled trials were considered, it was associated with a reduced composite outcome (aOR, 0.60; 95% CI, 0.39-0.91; P =.016).
This study was limited in terms of analysis. Data was unavailable from multiple other studies, limiting the sample size accessible for comparison with the randomized controlled trials. Additionally, potential selection bias for studies included in the independent participant data meta-analysis also limited the interpretation of the findings.
Investigators noted, “…this meta-analysis suggests that ursodeoxycholic acid treatment in women with intrahepatic cholestasis of pregnancy reduces the risk of preterm birth.” It should be noted that adverse outcomes are associated with higher bile acid concentrations and thus, women with more severe disease will likely benefit the most. The author’s concluded, “…ursodeoxycholic acid should be offered as part of antenatal treatment for intrahepatic cholestasis of pregnancy, and, particularly, to women with a disease onset before 37 gestational weeks and serum bile acid concentrations of 40 μmol/L or more.”
Disclosures: Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures.
Ovadia C, Sajous J, Seed PT, et al. Ursodeoxycholic acid in intrahepatic cholestasis of pregnancy: a systematic review and individual participant data meta-analysis. Lancet Gastroenterol Hepatol. Published online April 26, 2021. doi: 10.1016/S2468-1253(21)00074-1