A Chinese longitudinal maternity cohort study (2013-2021) on intrahepatic cholestasis phenotypes: Risk associations

Haitong Zhe Sun1, Haiyang Tang2, Jing Fang3

  • 1Department of Obstetrics, Women's Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310006, PR China; Department of Paediatrics, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117609, Republic of Singapore; Centre for Sustainable Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117609, Republic of Singapore; Yusuf Hamied Department of Chemistry, University of Cambridge, Cambridge CB2 1EW, UK; Department of Earth Sciences, University of Cambridge, Cambridge CB2 3EQ, UK.

PubMed

Intrahepatic cholestasis of pregnancy (ICP) is an idiopathic disease that occurs during mid-to-late pregnancy and is associated with various adverse pregnancy outcomes, including intrauterine fetal demise. However, since the underlying cause of ICP remains unclear, there is an ongoing debate on the phenotyping criteria used in the diagnostic process. Here, we identified single- and multi-symptomatic ICP (ICP-S and ICP-M) in 104,221 Chinese females from the ZEBRA maternity cohort, with the objective of exploring the risk implications of the two phenotypes on pregnancy outcomes and from environmental exposures. We employed multivariate binary logistic regression to estimate confounder-adjusted odds ratios and found that ICP-M was more strongly associated with preterm birth and low birth weight compared to ICP-S. Throughout pregnancy, incremental exposure to PM2.5, O3, and greenness could alter ICP risks by 17.3%, 12.5%, and -2.3%, respectively, with more substantial associations observed with ICP-M than with ICP-S. The major scientific advancements lie in the elucidation of synergistic risk interactions between pollutants and the protective antagonistic effects of greenness, as well as highlighting the risk impact of preconceptional environmental exposures. Our study, conducted in the context of the "three-child policy" in China, provides epidemiological evidence for policy-making to safeguard maternal and neonatal health.