Association between dynamic exposure to total bile acids and fetal myocardial performance index with perinatal outcomes in intrahepatic cholestasis of pregnancy

Risk stratification in intrahepatic cholestasis of pregnancy (ICP) often uses a single or peak total bile acid (TBA), potentially overlooking cumulative exposure. We evaluated whether dynamic TBA metrics relate to fetal myocardial function and perinatal outcomes. We conducted a prospective single‑center cohort from Jan 2023 to Aug 2024 of singleton ICP. Non‑fasting TBA and fetal modified myocardial performance index (Mod‑MPI) were measured serially. Exposures were time‑weighted mean TBA (TW‑TBA), AUC, time ≥ 40/≥100 µmol/L, peak, and last. Primary outcome was Mod‑MPI, and secondary was a composite adverse perinatal outcome (CAPO). Linear mixed‑effects, logistic, and mediation models adjusted for covariates. Of 262 screened, 248 (94.7%) were analyzed, contributing 1,042 TBA draws and 728 Mod‑MPI scans. Mean TW‑TBA was 36.0 ± 17.2 µmol/L; peak was < 40 in 48.4%, 40–99 in 37.9%, ≥ 100 in 13.7%. Each 1‑SD (17.2 µmol/L) higher TW‑TBA was associated with higher (worse) Mod‑MPI (β=+0.022; 95% CI 0.011–0.033; p < 0.001), with nonlinearity at ≥ 100 µmol/L ( p = 0.03). CAPO occurred in 76/248 (30.6%). TW‑TBA was associated with CAPO (adjusted OR 1.47; 95% CI 1.16–1.86; p = 0.001; AUC 0.77), whereas peak TBA was weaker (OR 1.22; 95% CI 1.01–1.48). Mod‑MPI mediated 21% of the TW‑TBA–CAPO association (95% CI 8–39%; p = 0.004). Dynamic bile‑acid exposure, especially TW‑TBA, was linked to impaired fetal myocardial performance and higher odds of adverse perinatal outcomes. Serial TBA testing with Mod‑MPI may enhance ICP risk stratification while multicenter validation is warranted.