19-35: Intrahepatic Cholestasis of Pregnancy

Intrahepatic cholestasis of pregnancy is characterized by incomplete clearance of bile acids in genetically susceptible women. The principal symptom is pruritus, which can be generalized but tends to have a predilection for the palms and soles. Presentation is typically in the third trimester, and women with multifetal pregnancies are at increased risk. The finding of an elevated serum bile acid level, ideally performed in the fasting state, confirms the diagnosis. Associated laboratory derangements include modest elevations in hepatic transaminase levels and mild hyperbilirubinemia. Although rare, the bilirubin level may be sufficiently elevated to result in clinical jaundice. The symptoms and laboratory abnormalities resolve quickly after delivery but can recur in subsequent pregnancies or with exposure to combination oral contraceptives.

Adverse fetal outcomes, particularly preterm birth, nonreassuring fetal status, meconium-stained amniotic fluid, and stillbirth, have consistently been reported in women with cholestasis of pregnancy. The risk for adverse perinatal outcomes appears to correlate with disease severity as measured by the degree of bile acid elevation, and women with fasting bile acids greater than 40 mcmol/L have been reported to be at greatest risk. Because of the risks associated with cholestasis of pregnancy, many clinicians recommend antenatal testing in the third trimester, and if cholestasis is present, elective early delivery to reduce the risk of stillbirth. The diagnosis of cholestasis of pregnancy is made when the level of bile salts is 10 mcmol/L or more (not necessarily fasting) with maternal symptoms. The Society for Maternal-Fetal Medicine (SMFM) 2021 recommends early delivery (36 weeks’ gestation) when the patient’s bile acid level is greater than 100 mcmol/L and other fetal tests are normal; in the symptomatic patient whose bile acid level is below 100 mcmol/L, the SMFM suggests delivery between 36 and 39 weeks’ gestation. The ACOG endorses ursodeoxycholic acid as the first-line agent for the treatment of maternal symptoms of intrahepatic cholestasis of pregnancy. A 2019 randomized controlled trial did not find that ursodeoxycholic acid improved perinatal outcomes.