The maternal hair metabolome is capable of discriminating intrahepatic cholestasis of pregnancy from uncomplicated pregnancy

Front Endocrinol (Lausanne). 2024 Jan 8:14:1280833. doi: 10.3389/fendo.2023.1280833. eCollection 2023.

Abstract

Introduction: Intrahepatic cholestasis of pregnancy (ICP) is a pregnancy-specific liver disease associated with elevated bile acids in the blood. Diagnosis typically only occurs after the manifestation of clinical symptoms and the metabolic mechanisms underlying its development remain unclear. The aim of this study was to investigate potential specific metabolites and the underlying metabolic changes occurring during the development of ICP in the maternal plasma and hair metabolomes of women diagnosed with either ICP or having a healthy pregnancy.

Methods: A total of 35 Chinese women with ICP and 42 healthy pregnancies were enrolled in our study. Plasma and hair samples, total bile acid levels (TBA), alanine transaminase levels (ALT), aspartate aminotransferase levels (AST), and additional clinical information were collected during the third trimester. Metabolites from maternal plasma and hair segments collected pre-conception and analyzed using gas chromatography-mass spectrometry (GC-MS).

Results: Three plasma metabolites (p < 0.05, q < 0.38) and 21 hair metabolites (p < 0.05, q < 0.05) were significantly different between ICP and healthy pregnancies. A combination of the eight most significant hair metabolites in a multivariate receiver operating characteristic curve model showed the best area under the curve (AUC) was 0.885, whereas the highest AUC using metabolites from plasma samples was only 0.74. Metabolic pathway analysis revealed 32 pathways were significantly (p and q values < 0.05) affected in the hair samples of patients with ICP. Pathways associated with glutathione metabolism and ABC transporters were affected. No metabolic pathways were significantly affected in plasma.

Discussion: Overall, this study showed that the hair metabolome could be more useful than the plasma metabolome for distinguishing ICP from normal pregnancy.

Keywords: cholestasis of pregnancy; gas chromatography-mass spectrometry; hair; metabolomics; plasma.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cholestasis, Intrahepatic* / diagnosis
  • Female
  • Hair
  • Humans
  • Metabolome*
  • Pregnancy
  • Pregnancy Complications*

Supplementary concepts

  • Intrahepatic Cholestasis of Pregnancy

Grants and funding

The author(s) declare financial support was received for the research, authorship, and/or publication of this article. This work was supported by National Key Research and Development Program of China (2022YFC2704702),the Key Research Program of Chongqing Science and Technology Bureau (No. CSTB2022TIAD-KPX0156, CSTC2021JCYJ-MSXMX0213), Chongqing Medical Scientific Research Project (Joint Project of Chongqing Health Commission and Science and Technology Bureau) (2023GGXM005), the Chongqing Municipal Education Commission (KJZD-K202100407), Joint Funds of the National Natural Science Foundation of China (No. U21A20346), General Program of National Natural Science Foundation of China(No. 82171662), and National Base for Innovation and Talent Introduction in Maternal and Fetal Medicine supporting by the Programme of Introducing Talents of Discipline to Universities [(2016)404].