Table 1_Integrated untargeted and targeted metabolomics identifies and validates urinary bile acid biomarkers for the diagnosis of intrahepatic cholestasis of pregnancy.docx

Seven co-DEMs were detected in both sample types, five of which were bile acid species. Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis highlighted primary bile acid biosynthesis as a key pathway associated with ICP. Targeted metabolomics showed marked increases in urinary glycocholic acid (GCA) and taurocholic acid (TCA), both of which remained significant after false discovery rate (FDR) correction, whereas cholic acid (CA) showed a more modest difference in the candidate-focused analysis.

Urinary concentrations of these metabolites were positively correlated with serum total bile acid levels. Receiver operating characteristic (ROC) curve analysis showed strong diagnostic performance for GCA (AUC = 0.95) and TCA (AUC = 0.86), whereas CA showed modest performance (AUC = 0.65).</p>Conclusion<p>Primary bile acid biosynthesis is closely associated with ICP. Urinary GCA and TCA may serve as promising non-invasive biomarkers for the diagnosis of ICP.

These findings require confirmation in larger, independent multicenter cohorts before clinical implementation.</p>