Relation of climatic exposures with intrahepatic cholestasis of pregnancy in a two-center retrospective cohort.

OBJECTIVE: To investigate relation between climatic exposures and intrahepatic cholestasis of pregnancy (ICP) in Chinese cities Shanghai and Sanya. BACKGROUND: ICP is a pregnancy-specific liver disease associated with adverse fetal outcomes. Although the etiology of ICP remains unclear, climatic exposures are increasingly recognized as one of the critical correlates in ICP onset. METHODS: This is a two-center retrospective cohort study included 48, 081 pregnant women from Shanghai (31°N, temperate) and Sanya (18°N, tropical). Baseline demographic data, pregnancy outcomes and meteorological data were collected. Generalized additive models (GAMs) were employed to analyze non-linear associations between environmental exposures and ICP risk, with statistical comparisons of baseline characteristics and complications between ICP and non-ICP groups. RESULTS: GAM analysis revealed that temperature, sunlight and PM2.5 exhibited positive gestation-age-dependent non-linear correlations with ICP risk in Shanghai, while relative humidity showed an inverse correlation. No meteorological exposures showed significant associations with ICP in Sanya. Sunlight could amplify heat-related exposure signals alongside high temperature. In Shanghai, pregnancies conceived in February and March showed the highest ICP incidence, while Sanya showed no significant seasonal fluctuation and maintained a higher overall ICP incidence than Shanghai under constant warm climate. Thalassemia prevalence was higher in ICP cases compared to controls in both regions (Sanya: 31.8% vs. 17.9%; Shanghai:1.0% vs. 0.4%, all P<0.05). ICP patients in both cohorts demonstrated shortened gestational age, with Shanghai exhibiting a more pronounced gestational age reduction correlated with higher cesarean delivery rates. CONCLUSION: High temperature, intense sunlight exposure, and high PM2.5 concentration across preconception and mid-pregnancy serves as major climatic correlates of ICP incidence.