Screening and Validation Serum Potential Biomarkers for Intrahepatic Cholestasis of Pregnancy Comparison to Healthy Controls by ¹H‐NMR and UPLC–MS/MS

The diagnosis of intrahepatic cholestasis of pregnancy (ICP) is indeed a challenging clinical issue due to its complex etiology and the need for accurate diagnostic markers. In this study, proton nuclear magnetic resonance spectroscopy ( 1 H‐NMR) was first performed on serum samples from 20 ICP patients and 20 matched healthy controls to screen for differential metabolites. UPLC–MS/MS was subsequently employed to quantify eight choline pathway metabolites across expanded cohorts, including 40 ICP patients, 17 UDCA‐treated ICP patients, and 40 healthy pregnant women. 1 H‐NMR metabolomics revealed significant perturbations in amino acid metabolism and choline‐related pathways in ICP patients. UPLC–MS/MS validation demonstrated marked elevations in serum choline (+92.0%), betaine (+22.0%), methionine (+37.7%), dimethylglycine (+163.1%), and cystathionine (+13.6%) compared to controls. UDCA intervention significantly reduced choline (−21.0%) and dimethylglycine (−32.5%) levels versus untreated ICP ( p < 0.05). Serum levels of choline and dimethylglycine exhibited exceptional diagnostic performance, with areas under the receiver operating characteristic curve (AUROCs) exceeding 0.84. Furthermore, when these two metabolites were combined using a logistic regression model, an AUROC value of 0.88 was achieved. Our study identifies choline metabolic dysregulation as a characteristic feature of ICP. Serum choline and dimethylglycine as potential biomarkers for ICP screening and treatment monitoring merit further validation.