{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,14]],"date-time":"2026-08-14T04:30:45Z","timestamp":1786681845022,"version":"build-2736575974"},"reference-count":28,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,8,14]],"date-time":"2026-08-14T00:00:00Z","timestamp":1786665600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Endocrinol."],"abstract":"\n Objective<\/jats:title>\n To investigate relation between climatic exposures and intrahepatic cholestasis of pregnancy (ICP) in Chinese cities Shanghai and Sanya.<\/jats:p>\n <\/jats:sec>\n \n Background<\/jats:title>\n 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.<\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n This is a two-center retrospective cohort study included 48, 081 pregnant women from Shanghai (31\u00b0N, temperate) and Sanya (18\u00b0N, 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.<\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n GAM analysis revealed that temperature, sunlight and PM\n 2.5<\/jats:sub>\n 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&lt;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.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusion<\/jats:title>\n \n High temperature, intense sunlight exposure, and high PM\n 2.5<\/jats:sub>\n concentration across preconception and mid-pregnancy serves as major climatic correlates of ICP incidence.\n <\/jats:p>\n <\/jats:sec>","DOI":"10.3389\/fendo.2026.1924211","type":"journal-article","created":{"date-parts":[[2026,8,14]],"date-time":"2026-08-14T04:22:30Z","timestamp":1786681350000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Relation of climatic exposures with intrahepatic cholestasis of pregnancy in a two-center retrospective cohort"],"prefix":"10.3389","volume":"17","author":[{"given":"Xiao","family":"Chen","sequence":"first","affiliation":[{"name":"Shanghai Key Laboratory of Maternal Fetal Medicine, Shanghai Institute of Maternal-Fetal Medicine and Gynecologic Oncology, Shanghai First Maternity and Infant Hospital, School of Medicine, Tongji University","place":["Shanghai, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chang","family":"Zou","sequence":"additional","affiliation":[{"name":"Shanghai Key Laboratory of Maternal Fetal Medicine, Shanghai Institute of Maternal-Fetal Medicine and Gynecologic Oncology, Shanghai First Maternity and Infant Hospital, School of Medicine, Tongji University","place":["Shanghai, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yang","family":"Liu","sequence":"additional","affiliation":[{"name":"Shanghai Key Laboratory of Maternal Fetal Medicine, Shanghai Institute of Maternal-Fetal Medicine and Gynecologic Oncology, Shanghai First Maternity and Infant Hospital, School of Medicine, Tongji University","place":["Shanghai, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruru","family":"Zhao","sequence":"additional","affiliation":[{"name":"Shanghai Key Laboratory of Maternal Fetal Medicine, Shanghai Institute of Maternal-Fetal Medicine and Gynecologic Oncology, Shanghai First Maternity and Infant Hospital, School of Medicine, Tongji University","place":["Shanghai, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hanxiang","family":"Sun","sequence":"additional","affiliation":[{"name":"Shanghai Key Laboratory of Maternal Fetal Medicine, Shanghai Institute of Maternal-Fetal Medicine and Gynecologic Oncology, Shanghai First Maternity and Infant Hospital, School of Medicine, Tongji University","place":["Shanghai, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaosong","family":"Liu","sequence":"additional","affiliation":[{"name":"Shanghai Key Laboratory of Maternal Fetal Medicine, Shanghai Institute of Maternal-Fetal Medicine and Gynecologic Oncology, Shanghai First Maternity and Infant Hospital, School of Medicine, Tongji University","place":["Shanghai, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qinxin","family":"Shen","sequence":"additional","affiliation":[{"name":"Shanghai Key Laboratory of Maternal Fetal Medicine, Shanghai Institute of Maternal-Fetal Medicine and Gynecologic Oncology, Shanghai First Maternity and Infant Hospital, School of Medicine, Tongji University","place":["Shanghai, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuanyuan","family":"Yang","sequence":"additional","affiliation":[{"name":"Shanghai Key Laboratory of Maternal Fetal Medicine, Shanghai Institute of Maternal-Fetal Medicine and Gynecologic Oncology, Shanghai First Maternity and Infant Hospital, School of Medicine, Tongji University","place":["Shanghai, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiaoling","family":"Du","sequence":"additional","affiliation":[{"name":"Shanghai Key Laboratory of Maternal Fetal Medicine, Shanghai Institute of Maternal-Fetal Medicine and Gynecologic Oncology, Shanghai First Maternity and Infant Hospital, School of Medicine, Tongji University","place":["Shanghai, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,8,14]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.5603\/GP.a2018.0067","article-title":"The role of ABC transporters' gene polymorphism in the etiology of intrahepatic cholestasis of pregnancy","volume":"89","author":"Pi\u0105tek","year":"2018","journal-title":"Ginekologia Polska"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1440-1746.1997.tb00410.x","article-title":"Review: intrahepatic cholestasis. A puzzling disorder of pregnancy","volume":"12","author":"Reyes","year":"1997","journal-title":"J Gastroenterol Hepatol"},{"key":"B3","doi-asserted-by":"publisher","first-page":"16307","DOI":"10.1038\/s41598-020-73378-5","article-title":"Prevalence and risk factors of intrahepatic cholestasis of pregnancy in a Chinese population","volume":"10","author":"Gao","year":"2020","journal-title":"Sci Rep"},{"key":"B4","doi-asserted-by":"publisher","first-page":"60","DOI":"10.1186\/s12884-016-0852-9","article-title":"Associations between maternal lipid profile and pregnancy complications and perinatal outcomes: a population-based study from China","volume":"16","author":"Jin","year":"2016","journal-title":"BMC Pregnancy Childbirth"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1002\/hsr2.1901","article-title":"Global incidence of intrahepatic cholestasis of pregnancy: a protocol for systematic review and meta-analysis","volume":"7","author":"Sadeghi","year":"2024","journal-title":"Health Sci Rep"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.2147\/imcrj.s299354","article-title":"The recurrent liver disorder of a pregnant mother: intrahepatic cholestasis of pregnancy - a case report and literature review","volume":"14","author":"Tamiru","year":"2021","journal-title":"Int Med Case Rep J"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1515\/jpm-2014-0089","article-title":"Fetal complications due to intrahepatic cholestasis of pregnancy","volume":"43","author":"\u0160imj\u00e1k","year":"2015","journal-title":"J Perinatal Med"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.3748\/wjg.v21.i23.7134","article-title":"Review of a challenging clinical issue: intrahepatic cholestasis of pregnancy","volume":"21","author":"Ozkan","year":"2015","journal-title":"World J Gastroenterol"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.5114\/ceh.2018.80122","article-title":"The role of metabolic disorders in the pathogenesis of intrahepatic cholestasis of pregnancy","volume":"4","author":"Men\u017cyk","year":"2018","journal-title":"Clin Exp Hepatol"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.51821\/84.3.013","article-title":"Triggers of benign recurrent intrahepatic cholestasis and its pathophysiology: a review of literature","volume":"84","author":"Halawi","year":"2021","journal-title":"Acta Gastro-Enterologica Belgica"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1111\/1471-0528.17174","article-title":"Intrahepatic cholestasis of pregnancy - time to redefine the reference range of total serum bile acids: a cross-sectional study","volume":"129","author":"Huri","year":"2022","journal-title":"BJOG: Int J Obstetrics Gynaecology"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1007\/s12539-019-00335-w","article-title":"Population scale retrospective analysis reveals potential risk of cholestasis in pregnant women taking omeprazole, lansoprazole, and amoxicillin","volume":"11","author":"Zhang","year":"2019","journal-title":"Interdiscip Sci-Comput Life Sci"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1016\/j.ecoenv.2025.118010","article-title":"Associations between fine particulate matter and its constituents and intrahepatic cholestasis of pregnancy","volume":"293","author":"Li","year":"2025","journal-title":"Ecotoxicology Environ Saf"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1016\/j.cgh.2021.01.029","article-title":"The epidemiology of UK autoimmune liver disease varies with geographic latitude","volume":"19","author":"Webb","year":"2021","journal-title":"Clin Gastroenterol Hepatology: Off Clin Pract J Am Gastroenterological Assoc"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.14309\/ctg.0000000000000357","article-title":"Identification of a latitude gradient in the prevalence of primary biliary cholangitis","volume":"12","author":"French","year":"2021","journal-title":"Clin Trans Gastroenterol"},{"key":"B16","first-page":"97","article-title":"Guidelines for clinical diagnosis, treatment and management of intrahepatic cholestasis of pregnancy (2024) [Article in Chinese]. Zhonghua Fu Chan Ke Za Zhi","volume":"59","year":"2024"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1002\/ijgo.70247","article-title":"Distinct response to treatment and characteristics of bile acid composition of early- and late-onset intrahepatic cholestasis of pregnancy: a prospective pilot study","volume":"171","author":"Huang","year":"2025","journal-title":"Int J Gynaecology Obstetrics: Off Organ Int Fed Gynaecology Obstetrics"},{"key":"B18","doi-asserted-by":"publisher","first-page":"49","DOI":"10.1186\/s12940-019-0485-3","article-title":"Maternal exposure to ambient fine particulate matter and fetal growth in Shanghai, China","volume":"18","author":"Cao","year":"2019","journal-title":"Environ Health: A Global Access Sci Source"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1016\/j.pharmr.2026.100120","article-title":"Gut microbiome and bile acid metabolism in liver disease: mechanisms, clinical implications, and therapeutic opportunities","volume":"78","author":"Zhou","year":"2026","journal-title":"Pharmacol Rev"},{"key":"B20","doi-asserted-by":"publisher","first-page":"465","DOI":"10.1038\/s42003-024-06158-w","article-title":"High temperature and humidity in the environment disrupt bile acid metabolism, the gut microbiome, and GLP-1 secretion in mice","volume":"7","author":"Chen","year":"2024","journal-title":"Commun Biol"},{"key":"B21","doi-asserted-by":"publisher","first-page":"89","DOI":"10.1016\/j.apergo.2017.08.008","article-title":"Field study of thermal comfort in non-air-conditioned buildings in a tropical island climate","volume":"66","author":"Lu","year":"2018","journal-title":"Appl Ergon"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.3389\/fgene.2022.874624","article-title":"Prevalence and genetic analysis of thalassemia and hemoglobinopathy in different ethnic groups and regions in Hainan Island, Southeast China","volume":"13","author":"Wang","year":"2022","journal-title":"Front Genet"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.3324\/haematol.10842","article-title":"Liver iron concentrations and urinary hepcidin in beta-thalassemia","volume":"92","author":"Origa","year":"2007","journal-title":"Haematologica"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.12669\/pjms.40.9.8961","article-title":"Iron overload and liver function in patients with beta thalassemia major: a cross sectional study","volume":"40","author":"Faruqi","year":"2024","journal-title":"Pakistan J Med Sci"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajpath.2025.11.008","article-title":"Iron and bile acids synergize to exacerbate congenital cholestatic liver injury via ferroptosis","volume":"196","author":"Ohta","year":"2026","journal-title":"Am J Pathol"},{"key":"B26","doi-asserted-by":"publisher","first-page":"1510","DOI":"10.3390\/ijerph14121510","article-title":"The relationships between PM(2.5) and meteorological factors in China: seasonal and regional variations","volume":"14","author":"Yang","year":"2017","journal-title":"Int J Environ Res Public Health"},{"key":"B27","doi-asserted-by":"publisher","first-page":"1608","DOI":"10.1038\/s41598-022-22974-8","article-title":"Metabolic changes in bile acids with pregnancy progression and their correlation with perinatal complications in intrahepatic cholestasis of pregnant patients","volume":"13","author":"Ma","year":"2023","journal-title":"Sci Rep"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.1016\/j.envres.2022.114345","article-title":"Interactive effects of ambient air pollution and sunshine duration on the risk of intrahepatic cholestasis of pregnancy","volume":"215","author":"Li","year":"2022","journal-title":"Environ Res"}],"container-title":["Frontiers in Endocrinology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fendo.2026.1924211\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,14]],"date-time":"2026-08-14T04:22:31Z","timestamp":1786681351000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fendo.2026.1924211\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,8,14]]},"references-count":28,"alternative-id":["10.3389\/fendo.2026.1924211"],"URL":"https:\/\/doi.org\/10.3389\/fendo.2026.1924211","relation":{},"ISSN":["1664-2392"],"issn-type":[{"value":"1664-2392","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,8,14]]},"article-number":"1924211"}}