Diagnostic and therapeutic profiles of serum bile acids in women with intrahepatic cholestasis of pregnancy-a pseudo-targeted metabolomics study

Abstract

Background: Intrahepatic cholestasis of pregnancy (ICP), as a pregnancy-specific liver disorder, obtains increasing recognition due to a series of adverse outcomes. ICP is generally characterized by pruritus and jaundice, and closely related to abnormalities in the metabolism and disposition of bile acids composition. Because of its elusive pathogenesis, ICP has become an intractable issue to be diagnosed and managed for obstetricians. Analysis of metabolic profile could reveal the state of small-molecule metabolites systematically and provide comprehensively metabolic information for diseases. We developed a pseudo-targeted approach to perform metabolomic analysis of bile acids in serum using an ultra-performance liquid chromatography-triple quadrupole time-of-flight tandem mass spectrometry (UPLC-Triple TOF-MS/MS) method.

Methods: We investigated the metabolites of bile acids in 55 healthy pregnant women, 42 women with ICP and 11 women with ICP who persisted to accept ursodeoxycholic acid (UDCA) therapy.

Results: The metabolic profiles of serum bile acids were significantly altered in ICP group compared with the control group. A screened potential combination biomarker, with a high diagnostic efficiency (area under the curve = 0.996, Youden index = 0.940), was superior to total bile acids for the diagnosis of ICP.

Conclusions: The profiles of serum bile acids in women with ICP became more clear under the UDCA therapy, and were fully recovered after the delivery.

Keywords: Diagnostic and therapeutic profiles; Intrahepatic cholestasis of pregnancy; Metabolomics; Pseudo-targeted method; Serum bile acid; UPLC-triple TOF-MS/MS.