Introduction: Intrahepatic cholestasis of pregnancy (ICP) is characterised by maternal pruritus and raised serum bile acids, and is associated with adverse fetal outcomes (e.g. preterm birth, neonatal unit admission and stillbirth). Maternal metabolic impacts include higher rates of gestational diabetes mellitus, hypertriglyceridaemia and hypercholesterolaemia. Glucose and lipid metabolism are influenced by gut incretin release, and bile acids are commonly ligands for receptors whose activation results in these hormones being released. We sought to assess the effects of pregnancy and cholestasis upon lipid, glucose and incretin levels, and whether these can be reversed by treatment with ursodeoxycholic acid (UDCA), the most commonly-used treatment for ICP.
Methods: 100 women were given a standardised diet for 24 hours, during which serial blood sampling was performed at 9 timepoints. Participants were pregnant women with ICP or non-pregnant women with a history of ICP, with matched controls for each group. Bile acids, lipids, glucose, GLP-1, PYY, FGF19 and C4 were measured, and results compared using multiple measures of ANOVA and students T tests.
Results: The gestational increases in serum triglycerides, total and LDL cholesterol were exacerbated by ICP. The GLP-1 response to a meal was lower for women with ICP, and was improved with UDCA treatment. Basal PYY was higher for women with ICP, and peaked at a higher level post prandially than for women with normal pregnancies, or non-pregnant controls. Normal pregnancy resulted in lower peak serum FGF19; this was unchanged in non-UDCA treated ICP, but serum concentrations increased with UDCA treatment. UDCA treatment also caused increased faecal lithocholic acid concentrations.
Conclusions: The metabolic disturbances of ICP are contributed to by altered intestinal responses to food. These can be ameliorated by treatment with UDCA, a new indication for the drug in treatment of ICP.