Abstract
BACKGROUND: What kinds of fetal adverse outcomes beyond stillbirth directly correlate to the severity of intrahepatic cholestasis during pregnancy (ICP) remained tangled. Herein, we conducted a retrospective cohort study and a dose-response meta-analysis to speculate the association between the severity of ICP and its adverse outcomes. METHODS: We retrospectively collected a cohort of ICP patients from electronic records from Guangzhou Women and Children's Medical Center between Jan 1st, 2018, and Dec 31st, 2022. Also, we searched PubMed, Cochrane, Embase, Scopus, and Web of Science to extract prior studies for meta-analysis. The Kruskal-Wallis test, a one-way or two-way variants analysis (ANOVA), and multi-variant regression are utilized for cohort study. One stage model, restricted cubic spline analysis, and fixed-effect model are applied for dose-response meta-analysis. The data analysis was performed using the R programme. RESULTS: Our cohort included 1,289 pregnant individuals, including 385 mild ICP cases, 601 low moderate ICP cases, 282 high moderate ICP cases, and 21 severe ICP cases. The high moderate bile acid levels were correlated to preterm birth [RR = 2.14, 95%CI 1.27 to 3.62), P < 0.01], and preterm premature rupture of membranes [RR = 0.34, 95%CI 0.19 to 0.62), P < 0.01]. We added our cases to cases reported by other studies included in the meta-analysis. There were 15,826 patients included in dose-response meta-analysis. The severity of ICP was associated with increased risks of stillbirth, spontaneous preterm birth, iatrogenic preterm birth, preterm birth, admission to neonatal intensive care unit, and meconium-stained fluid (P < 0.05). CONCLUSIONS: Our study shows the correlation between the severity of ICP and the ascending risks of stillbirth, preterm birth, and meconium-stained fluid, providing new threshold TBA levels. PROSPERO REGISTRATION NUMBER: CRD42023472634.