Untargeted lipidomics analysis in women with intrahepatic cholestasis of pregnancy: a cross-sectional study.

OBJECTIVE To compare the plasma lipid profiles in women with normal pregnancies and those with mild or severe intrahepatic cholestasis of pregnancy (ICP). Our goal was to reveal lipidome-wide alterations in ICP and delve into the pathogenesis of ICP from a lipid metabolism perspective. DESIGN Cross-sectional study: normal pregnancies, mild ICP, and severe ICP. SETTING AND POPULATION Women with ICP were recruited from October 2019 to March 2020 in Gansu, China. METHODS Untargeted lipidomics was used to analyze differentially expressed plasma lipids in controls, mild ICP, and severe ICP (n = 30 per group). For lipidomics, liquid chromatography and Q-Exactive Plus Orbitrap mass spectrometry were performed. RESULTS Thirty-three lipids were differentially expressed in the severe and mild ICP groups compared with the control group, and 20 of those were sphingolipids (ceramide: 6 species; sphingomyelin: 14 species). All differentially expressed sphingolipids in women with mild ICP were also differentially expressed in women with severe ICP; the fold change and significance of the differential expression were positively correlated with disease severity. CONCLUSION We systematically characterized the lipidome-wide alterations in mild and severe ICP groups. The results indicated a link between ICP and disordered sphingolipid homeostasis.