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

BJOG. 2022 May;129(6):880-888. doi: 10.1111/1471-0528.17026. Epub 2021 Dec 7.

Abstract

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, including women with normal pregnancies, women with mild ICP and women with severe ICP.

Setting: Gansu Provincial Hospital.

Population: Women with ICP were recruited from October 2019 to March 2020 in Gansu, China.

Methods: Untargeted lipidomics was used to analyse differentially expressed plasma lipids in controls, in women with mild ICP and in women with severe ICP (n = 30 per group). For lipidomics, liquid chromatography and Q-Exactive Plus Orbitrap mass spectrometry were performed.

Main outcome measures: Differentially expressed lipids.

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, six 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.

Conclusions: We systematically characterized the lipidome-wide alterations in mild and severe ICP groups. The results indicated a link between ICP and disordered sphingolipid homeostasis.

Tweetable abstract: Abnormal sphingolipid metabolism is involved in the pathogenesis of ICP.

Keywords: Ceramide; intrahepatic cholestasis of pregnancy; lipidomics; sphingolipids; sphingomyelin.

MeSH terms

  • Case-Control Studies
  • Cholestasis, Intrahepatic*
  • Cross-Sectional Studies
  • Female
  • Humans
  • Lipidomics
  • Pregnancy
  • Pregnancy Complications*
  • Sphingolipids

Substances

  • Sphingolipids

Supplementary concepts

  • Intrahepatic Cholestasis of Pregnancy