Intrahepatic cholestasis of pregnancy: changes in maternal-fetal bile acid balance and improvement by ursodeoxycholic acid

Abstract

Intrahepatic cholestasis of pregnancy (ICP) is a disease characterized by generalized pruritus and biochemical cholestasis that appears typically during the last trimester of gestation. The most predictive and accurate markers for diagnosis and follow-up of ICP are increased total bile acid levels (above 11,0 micromol/L), enhanced cholic acid percentage (above 42%) and decreased glycine/taurine bile acid ratio (below 1.0). Although essentially benign for the mother, evidence associates ICP with fetal poor prognosis resulting from increased transfer of bile acids from mother to fetus, who showed reduced ability to eliminate bile acids across the placenta. Those conditions lead to an accumulation of bile acids in the cord blood serum, meconium and amniotic fluid that may account for a diminished fetal well-being and sudden intra-uterine death by ICP. Ursodeoxycholic acid (UDCA) treatment was shown to reduce the bile acid content in the fetal compartment, while restoring the ability of the placenta to carry out vectorial transfer of these compounds towards the mother, decreasing bile acid levels in maternal serum and its passage to the fetus. In addition, UDCA administered to the mother also lowers the amount of bile acids present in colostrum without either increasing the UDCA concentration or causing major changes in lithocholic acid levels, further supporting the safety of UDCA in late pregnancy. Therefore, it is tempting to indicate UDCA as a first choice therapy for ICP as much as relevant aspects of fetal outcome may also be improved. This review focuses on the altered bile acid profiles in maternal and fetal compartments during ICP and its recovery by UDCA administration. Further elucidation of the precise mechanisms of action of UDCA and its therapeutic potential in improving fetal prognosis could result in the approval of UDCA for ICP treatment.