Metabolic characteristics of plasma bile acids in patients with intrahepatic cholestasis of pregnancy-mass spectrometric study

Intrahepatic cholestasis of pregnancy (ICP) is one of the more common complications in the middle and late stages of pregnancy, which requires early detection and intervention. The aim of the study is to investigate the changes in the metabolic profile of bile acids (BAs) in plasma of pregnant women with ICP and to look biomarkers for the diagnosis and grading of ICP, and to explore the disease mechanism. The targeted metabolomics based on high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) was used to analyze plasma BAs. Twenty-seven BAs can be quantified in all participants. Among them, 22 BAs were identified as differential BAs between ICP and control groups. Five BAs include 3β-CA, 3β-DCA, CDCA-3Gln, NCA, and Tβ-MCA, were found to be associated with ICP for the first time. Nine BAs include NCA, GCA, GCDCA, GHCA, GUDCA, HCA, TCA, TCDCA and THCA, can be used as possible ICP diagnostic biomarkers. Four BAs, i.e., GLCA, THCA, GHCA and TLCA-3S may be used as potential biomarkers for ICP grading. There were significant differences in plasma BA profiles between ICP patients and the control. The BA profiles of mild ICP group and severe ICP group partially overlapped. Potential diagnostic and grading BA markers were identified. A significant characteristic of ICP group was the increase of conjugated BAs. A mechanism to sustain the equilibrium of BA metabolism and adaptive response has been developed in ICP patients to accelerate excretion and detoxification.