Abstract
Intrahepatic cholestasis of pregnancy (ICP) is a pregnancy-specific liver disorder associated with an increased risk of adverse fetal outcomes. It is characterised by raised maternal serum bile acids, which are believed to cause the adverse outcomes. ICP is commonly treated with ursodeoxycholic acid (UDCA). This study aimed to determine the fetal and maternal bile acid profiles in normal and ICP pregnancies, and to examine the effect of UDCA treatment. Matched maternal and umbilical cord serum samples were collected from untreated ICP (n = 18), UDCA-treated ICP (n = 46) and uncomplicated pregnancy (n = 15) cases at the time of delivery. Nineteen individual bile acids were measured using HPLC-MS/MS. Maternal and fetal serum bile acids are significantly raised in ICP compared with normal pregnancy (p = <0.0001 and <0.05, respectively), predominantly due to increased levels of conjugated cholic and chenodeoxycholic acid. There are no differences between the umbilical cord artery and cord vein levels of the major bile acid species. The feto-maternal gradient of bile acids is reversed in ICP. Treatment with UDCA significantly reduces serum bile acids in the maternal compartment (p = <0.0001), thereby reducing the feto-maternal transplacental gradient. UDCA-treatment does not cause a clinically important increase in lithocholic acid (LCA) concentrations. ICP is associated with significant quantitative and qualitative changes in the maternal and fetal bile acid pools. Treatment with UDCA reduces the level of bile acids in both compartments and reverses the qualitative changes. We have not found evidence to support the suggestion that UDCA treatment increases fetal LCA concentrations to deleterious levels.
Highlights
Intrahepatic cholestasis of pregnancy (ICP) is characterised by maternal pruritus and deranged liver function
We have demonstrated that total serum bile acids are significantly elevated in both maternal and fetal serum from ICP pregnancies, and are reduced by ursodeoxycholic acid (UDCA)-treatment
Elevations were predominantly due to increased conjugated primary bile acids (CA and chenodeoxycholic acid (CDCA))
Summary
Intrahepatic cholestasis of pregnancy (ICP) is characterised by maternal pruritus and deranged liver function. Indirect evidence for the transfer of bile acids from mother to fetus comes from studies involving the concurrent measurement of bile acids in matched maternal and umbilical cord serum [10,11]. These studies identified transplacental gradients that facilitate clearance of these toxic compounds in normal pregnancies, but are reversed in cholestatic pregnancies [12,13], thereby contributing to the accumulation of bile acids in the fetal compartment
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