Abstract
<title>Abstract</title> <p>Background Intrahepatic cholestasis of pregnancy (ICP) is a gestation-specific hepatic complication predominantly occurring in the second and third trimesters, which confers an increased risk of adverse maternal and neonatal outcomes. Nevertheless, the underlying impacts of ICP on neonatal metabolic phenotypes remain poorly elucidated. Aims This study aimed to characterize the alterations in neonatal amino acid and acylcarnitine profiles attributable to maternal ICP, and to further clarify the associations between maternal gestational bile acid dynamic trajectories and offspring metabolic disorders stratified by clinical characteristics. Methods A total of 1,273 women with singleton pregnancies who delivered at Fujian Maternity and Child Health Hospital from April 2022 to January 2026 were retrospectively enrolled in this study. Participants were categorized into the ICP case group (n = 582) and the gestationally healthy control group (n = 691) with matched delivery timelines. All enrolled neonates underwent routine newborn screening covering 11 amino acids and 31 acylcarnitines via tandem mass spectrometry. Results Significant intergroup disparities were observed in maternal serum total cholesterol, triglycerides, alanine transaminase and aspartate transaminase between the two groups, suggestive of progressive hepatic impairment and disrupted lipid metabolism among ICP pregnant women. For neonates delivered by ICP mothers, circulating levels of multiple conditionally essential amino acids and branched-chain amino acids were substantially downregulated. Additionally, ICP led to specific perturbations in short- and medium-chain acylcarnitines: decreased concentrations of C0, C5 and C6DC, accompanied by elevated C14:2 levels. Following bile acid trajectory stratification and adjustment for potential confounding factors, independent discrepancies in neonatal amino acid and acylcarnitine dysmetabolism were detected across distinct trajectory subgroups. Arginine, valine, C5, C6DC and C14:2 were finally identified as pivotal differential metabolic biomarkers. Conclusion The characteristic metabolic biomarkers and bile acid stratification patterns determined in this study provide rigorous evidence for precision clinical management, including individualized surveillance, stratified intervention for ICP parturients, and long-term metabolic follow-up of high-risk neonates.</p>