Vaginal progesterone treatment for the prevention of preterm birth and intrahepatic cholestasis of pregnancy: A case-control study

Introduction: Intrahepatic cholestasis of pregnancy (ICP) is associated with a distinctive maternal pruritus, abnormal liver function tests, raised serum total bile acids, and increased rates of adverse fetal outcomes, including intrauterine fetal death. Progesterone has been implicated in the pathogenesis of ICP. We aimed to evaluate whether the incidence of ICP is altered in women receiving long-term daily vaginal progesterone, indicated for a short cervical length.

Study design: A matched 1:3 case-control study of pregnant women between January 2014 and January 2019. Study cases included pregnant women with the diagnosis of ICP. Control cases were women without ICP. The primary outcome was the rate of vaginal progesterone treatment among the groups.

Results: The use of vaginal progesterone throughout pregnancy was higher in the ICP group compared with the control group (8/174 [4.6 %] versus 6/522 [1.1 %], respectively, P = 0.03, odds ratio 4 [95 % confidence interval 1.4-11.7]).

Conclusions: Pregnant women treated with long-term vaginal progesterone preparations for the prevention of preterm birth are at increased risk of developing ICP. In the presence of pruritus during pregnancy, we recommend an early consultation and diagnostic test to confirm or rule-out ICP.