{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T00:52:00Z","timestamp":1788915120464,"version":"build-2803163510"},"reference-count":41,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2025,7,1]],"date-time":"2025-07-01T00:00:00Z","timestamp":1751328000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2025,7,1]],"date-time":"2025-07-01T00:00:00Z","timestamp":1751328000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2025,7,1]],"date-time":"2025-07-01T00:00:00Z","timestamp":1751328000000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-017"},{"start":{"date-parts":[[2025,7,1]],"date-time":"2025-07-01T00:00:00Z","timestamp":1751328000000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-037"},{"start":{"date-parts":[[2025,7,1]],"date-time":"2025-07-01T00:00:00Z","timestamp":1751328000000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-012"},{"start":{"date-parts":[[2025,7,1]],"date-time":"2025-07-01T00:00:00Z","timestamp":1751328000000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-029"},{"start":{"date-parts":[[2025,7,1]],"date-time":"2025-07-01T00:00:00Z","timestamp":1751328000000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-004"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82173487"],"award-info":[{"award-number":["82173487"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100013115","name":"Zhejiang Provincial Program for the Cultivation of High-Level Innovative Health Talents","doi-asserted-by":"publisher","award":["2020\\u201318"],"award-info":[{"award-number":["2020\\u201318"]}],"id":[{"id":"10.13039\/501100013115","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100013115","name":"Zhejiang Provincial Program for the Cultivation of High-Level Innovative Health Talents","doi-asserted-by":"publisher","award":["2010\\u201318"],"award-info":[{"award-number":["2010\\u201318"]}],"id":[{"id":"10.13039\/501100013115","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004731","name":"Natural Science Foundation of Zhejiang Province","doi-asserted-by":"publisher","award":["LTGY24H260002"],"award-info":[{"award-number":["LTGY24H260002"]}],"id":[{"id":"10.13039\/501100004731","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004731","name":"Natural Science Foundation of Zhejiang Province","doi-asserted-by":"publisher","award":["LQ21H040004"],"award-info":[{"award-number":["LQ21H040004"]}],"id":[{"id":"10.13039\/501100004731","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Environmental Research"],"published-print":{"date-parts":[[2025,7]]},"DOI":"10.1016\/j.envres.2025.121534","type":"journal-article","created":{"date-parts":[[2025,4,4]],"date-time":"2025-04-04T01:37:59Z","timestamp":1743730679000},"page":"121534","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":2,"special_numbering":"C","title":["Association of metal mixtures during the second trimester with gestational hypothyroidism and its mediation by metabolites"],"prefix":"10.1016","volume":"276","author":[{"ORCID":"https:\/\/orcid.org\/0009-0009-7080-7102","authenticated-orcid":false,"given":"Chenjun","family":"Tang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yexinyi","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yinyin","family":"He","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenyi","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yun","family":"Huang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenjun","family":"Du","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2177-6970","authenticated-orcid":false,"given":"Jing","family":"Guo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guangdi","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.envres.2025.121534_bib1","first-page":"636","article-title":"Guideline on diagnosis and management of thyroid diseases during pregnancy and postpartum (2nd edition)","volume":"35","year":"2019","journal-title":"Chinese Journal of Endocrinology and Metabolism"},{"key":"10.1016\/j.envres.2025.121534_bib2","doi-asserted-by":"crossref","first-page":"1282","DOI":"10.1002\/sim.3016","article-title":"Mediation analysis via potential outcomes models","volume":"27","author":"Albert","year":"2008","journal-title":"Stat. Med."},{"key":"10.1016\/j.envres.2025.121534_bib3","doi-asserted-by":"crossref","first-page":"1245","DOI":"10.1089\/thy.2022.0699","article-title":"Maternal thyroid function during pregnancy and offspring white matter microstructure in early adulthood: a prospective birth cohort study","volume":"33","author":"Bj\u00f6rnholm","year":"2023","journal-title":"Thyroid"},{"key":"10.1016\/j.envres.2025.121534_bib4","doi-asserted-by":"crossref","first-page":"493","DOI":"10.1093\/biostatistics\/kxu058","article-title":"Bayesian kernel machine regression for estimating the health effects of multi-pollutant mixtures","volume":"16","author":"Bobb","year":"2015","journal-title":"Biostatistics"},{"key":"10.1016\/j.envres.2025.121534_bib5","doi-asserted-by":"crossref","DOI":"10.3390\/ijms19051501","article-title":"Overview of cadmium thyroid disrupting effects and mechanisms","volume":"19","author":"Buha","year":"2018","journal-title":"Int. J. Mol. Sci."},{"key":"10.1016\/j.envres.2025.121534_bib6","article-title":"Plasma lipid profile and intestinal microflora in pregnancy women with hypothyroidism and their correlation with pregnancy outcomes","volume":"12","author":"Cai","year":"2021","journal-title":"Front. Endocrinol."},{"key":"10.1016\/j.envres.2025.121534_bib7","doi-asserted-by":"crossref","first-page":"4057","DOI":"10.1210\/jc.2004-2344","article-title":"Muscle metabolism and exercise tolerance in subclinical hypothyroidism: a controlled trial of levothyroxine","volume":"90","author":"Caraccio","year":"2005","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"10.1016\/j.envres.2025.121534_bib8","doi-asserted-by":"crossref","first-page":"2003","DOI":"10.1039\/b907243h","article-title":"RRLC-MS\/MS-based metabonomics combined with in-depth analysis of metabolic correlation network: finding potential biomarkers for breast cancer","volume":"134","author":"Chen","year":"2009","journal-title":"Analyst"},{"key":"10.1016\/j.envres.2025.121534_bib9","doi-asserted-by":"crossref","first-page":"579","DOI":"10.1111\/j.1365-2265.1992.tb02268.x","article-title":"Effect of selenium supplementation on thyroid hormone metabolism in an iodine and selenium deficient population","volume":"36","author":"Contempr\u00e9","year":"1992","journal-title":"Clin. Endocrinol."},{"key":"10.1016\/j.envres.2025.121534_bib10","doi-asserted-by":"crossref","DOI":"10.1016\/j.scitotenv.2021.151288","article-title":"Exposure to common-use pesticides, manganese, lead, and thyroid function among pregnant women from the Infants' Environmental Health (ISA) study, Costa Rica","volume":"810","author":"Corrales Vargas","year":"2022","journal-title":"Sci. Total Environ."},{"key":"10.1016\/j.envres.2025.121534_bib11","doi-asserted-by":"crossref","first-page":"501","DOI":"10.1016\/S2213-8587(20)30061-9","article-title":"Association of maternal thyroid function with birthweight: a systematic review and individual-participant data meta-analysis","volume":"8","author":"Derakhshan","year":"2020","journal-title":"Lancet Diabetes Endocrinol."},{"key":"10.1016\/j.envres.2025.121534_bib12","doi-asserted-by":"crossref","first-page":"547","DOI":"10.1016\/j.metabol.2009.08.018","article-title":"Thyroid-stimulating hormone stimulates lipolysis in adipocytes in culture and raises serum free fatty acid levels in vivo","volume":"59","author":"Gagnon","year":"2010","journal-title":"Metabolism"},{"key":"10.1016\/j.envres.2025.121534_bib13","doi-asserted-by":"crossref","first-page":"31","DOI":"10.21101\/cejph.a7796","article-title":"Are the elements zinc, copper, magnesium, and rubidium related to nutrition and iodine deficiency in pregnant Bulgarian women from iodine deficient region?","volume":"32","author":"Georgieva Bacelova","year":"2024","journal-title":"Cent Eur J Public Health"},{"key":"10.1016\/j.envres.2025.121534_bib14","doi-asserted-by":"crossref","DOI":"10.3390\/ijms25179288","article-title":"Crucial interactions between altered plasma trace elements and fatty acids unbalance ratio to management of systemic arterial hypertension in diabetic patients: focus on endothelial dysfunction","volume":"25","author":"Gouaref","year":"2024","journal-title":"Int. J. Mol. Sci."},{"key":"10.1016\/j.envres.2025.121534_bib15","doi-asserted-by":"crossref","first-page":"1185","DOI":"10.1016\/j.envint.2018.10.038","article-title":"Associations of blood metal exposure with thyroid hormones in Chinese pregnant women: a cross-sectional study","volume":"121","author":"Guo","year":"2018","journal-title":"Environ. Int."},{"key":"10.1016\/j.envres.2025.121534_bib16","doi-asserted-by":"crossref","first-page":"206","DOI":"10.1080\/10937400902902062","article-title":"The effects of metals as endocrine disruptors","volume":"12","author":"Iavicoli","year":"2009","journal-title":"J. Toxicol. Environ. Health B Crit. Rev."},{"key":"10.1016\/j.envres.2025.121534_bib17","doi-asserted-by":"crossref","DOI":"10.1289\/EHP5838","article-title":"A quantile-based g-computation approach to addressing the effects of exposure mixtures","volume":"128","author":"Keil","year":"2020","journal-title":"Environ. Health Perspect."},{"key":"10.1016\/j.envres.2025.121534_bib18","doi-asserted-by":"crossref","DOI":"10.1016\/j.envres.2022.113413","article-title":"Associations of exposure to metal and metal mixtures with thyroid hormones: results from the NHANES 2007\u20132012","volume":"212","author":"Kim","year":"2022","journal-title":"Environ. Res."},{"key":"10.1016\/j.envres.2025.121534_bib19","doi-asserted-by":"crossref","first-page":"441","DOI":"10.1097\/01.med.0000433066.24541.88","article-title":"Selenium and the thyroid","volume":"20","author":"K\u00f6hrle","year":"2013","journal-title":"Curr. Opin. Endocrinol. Diabetes Obes."},{"key":"10.1016\/j.envres.2025.121534_bib20","doi-asserted-by":"crossref","first-page":"392","DOI":"10.1097\/MED.0000000000000190","article-title":"Selenium and the thyroid","volume":"22","author":"K\u00f6hrle","year":"2015","journal-title":"Curr. Opin. Endocrinol. Diabetes Obes."},{"key":"10.1016\/j.envres.2025.121534_bib21","doi-asserted-by":"crossref","first-page":"158","DOI":"10.1038\/s41574-021-00604-z","article-title":"Assessment and treatment of thyroid disorders in pregnancy and the postpartum period","volume":"18","author":"Lee","year":"2022","journal-title":"Nat. Rev. Endocrinol."},{"key":"10.1016\/j.envres.2025.121534_bib22","article-title":"Association of differential metabolites with small intestinal microflora and maternal outcomes in subclinical hypothyroidism during pregnancy","volume":"11","author":"Li","year":"2021","journal-title":"Front. Cell. Infect. Microbiol."},{"key":"10.1016\/j.envres.2025.121534_bib23","doi-asserted-by":"crossref","first-page":"1065","DOI":"10.1016\/j.ajcnut.2024.02.016","article-title":"Maternal plasma phospholipid polyunsaturated fatty acids in early pregnancy and thyroid function throughout pregnancy: a longitudinal study","volume":"119","author":"Li","year":"2024","journal-title":"Am. J. Clin. Nutr."},{"key":"10.1016\/j.envres.2025.121534_bib24","doi-asserted-by":"crossref","DOI":"10.1016\/j.envint.2020.106114","article-title":"Low levels of arsenic exposure during pregnancy and maternal and neonatal thyroid hormone parameters: the determinants for these associations","volume":"145","author":"Liang","year":"2020","journal-title":"Environ. Int."},{"key":"10.1016\/j.envres.2025.121534_bib25","doi-asserted-by":"crossref","first-page":"1163","DOI":"10.1002\/jat.3283","article-title":"Combined toxicity of heavy metal mixtures in liver cells","volume":"36","author":"Lin","year":"2016","journal-title":"J. Appl. Toxicol."},{"key":"10.1016\/j.envres.2025.121534_bib26","doi-asserted-by":"crossref","first-page":"1153","DOI":"10.1186\/1471-2458-13-1153","article-title":"Thyroid volume, goiter prevalence, and selenium levels in an iodine-sufficient area: a cross-sectional study","volume":"13","author":"Liu","year":"2013","journal-title":"BMC Public Health"},{"key":"10.1016\/j.envres.2025.121534_bib27","doi-asserted-by":"crossref","DOI":"10.1016\/j.envint.2019.105451","article-title":"Association of blood metal exposure with testosterone and hemoglobin: a cross-sectional study in Hangzhou Birth Cohort Study","volume":"136","author":"Luo","year":"2020","journal-title":"Environ. Int."},{"key":"10.1016\/j.envres.2025.121534_bib28","doi-asserted-by":"crossref","DOI":"10.3389\/fendo.2023.1145153","article-title":"Nickel as a potential disruptor of thyroid function: benchmark modelling of human data","volume":"14","author":"Maric","year":"2023","journal-title":"Front. Endocrinol."},{"key":"10.1016\/j.envres.2025.121534_bib29","doi-asserted-by":"crossref","DOI":"10.1136\/bmj.g4929","article-title":"Diagnosis and management of subclinical hypothyroidism in pregnancy","volume":"349","author":"Negro","year":"2014","journal-title":"Bmj"},{"key":"10.1016\/j.envres.2025.121534_bib30","doi-asserted-by":"crossref","DOI":"10.1016\/j.chemosphere.2020.128350","article-title":"Heavy metal associated health hazards: an interplay of oxidative stress and signal transduction","volume":"262","author":"Paithankar","year":"2021","journal-title":"Chemosphere"},{"key":"10.1016\/j.envres.2025.121534_bib31","doi-asserted-by":"crossref","first-page":"652","DOI":"10.1111\/cen.14072","article-title":"Changes in subtypes of overt thyrotoxicosis and hypothyroidism following iodine fortification","volume":"91","author":"Petersen","year":"2019","journal-title":"Clin. Endocrinol."},{"key":"10.1016\/j.envres.2025.121534_bib32","doi-asserted-by":"crossref","first-page":"951","DOI":"10.1016\/j.neuro.2007.05.003","article-title":"Effects of manganese on thyroid hormone homeostasis: potential links","volume":"28","author":"Soldin","year":"2007","journal-title":"Neurotoxicology"},{"key":"10.1016\/j.envres.2025.121534_bib33","doi-asserted-by":"crossref","first-page":"1","DOI":"10.18637\/jss.v045.i02","article-title":"Multiple imputation with diagnostics (mi) in R: opening windows into the black box","volume":"45","author":"Su","year":"2011","journal-title":"J. Stat. Software"},{"key":"10.1016\/j.envres.2025.121534_bib34","doi-asserted-by":"crossref","first-page":"5043","DOI":"10.1210\/jc.2018-02492","article-title":"Maternal heavy metal exposure, thyroid hormones, and birth outcomes: a prospective cohort study","volume":"104","author":"Sun","year":"2019","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"10.1016\/j.envres.2025.121534_bib35","doi-asserted-by":"crossref","first-page":"228","DOI":"10.1016\/S2213-8587(13)70109-8","article-title":"Hypothyroidism in pregnancy","volume":"1","author":"Teng","year":"2013","journal-title":"Lancet Diabetes Endocrinol."},{"key":"10.1016\/j.envres.2025.121534_bib36","doi-asserted-by":"crossref","DOI":"10.3390\/ijms232012213","article-title":"Aluminum, arsenic, beryllium, cadmium, chromium, cobalt, copper, iron, lead, mercury, molybdenum, nickel, platinum, thallium, titanium, vanadium, and zinc: molecular aspects in experimental liver injury","volume":"23","author":"Teschke","year":"2022","journal-title":"Int. J. Mol. Sci."},{"key":"10.1016\/j.envres.2025.121534_bib37","doi-asserted-by":"crossref","first-page":"3322","DOI":"10.1021\/acs.jproteome.5b00354","article-title":"Analysis of the human adult urinary metabolome variations with age, body mass index, and gender by implementing a comprehensive workflow for univariate and OPLS statistical analyses","volume":"14","author":"Th\u00e9venot","year":"2015","journal-title":"J. Proteome Res."},{"key":"10.1016\/j.envres.2025.121534_bib38","doi-asserted-by":"crossref","first-page":"1129","DOI":"10.1093\/ajcn\/80.5.1129","article-title":"Appropriate body mass index and waist circumference cutoffs for categorization of overweight and central adiposity among Chinese adults","volume":"80","author":"Wildman","year":"2004","journal-title":"Am. J. Clin. Nutr."},{"key":"10.1016\/j.envres.2025.121534_bib39","first-page":"133","article-title":"Clinical value of serumnon-stimulated thyroglobulin(nS-TG)in differentiated thyroid cancer(DTC)patients in after thyroidectomy","volume":"34","year":"2019","journal-title":"J Clin Lab Med"},{"key":"10.1016\/j.envres.2025.121534_bib40","doi-asserted-by":"crossref","DOI":"10.1016\/j.envpol.2021.116480","article-title":"Associations between metabolic syndrome and four heavy metals: a systematic review and meta-analysis","volume":"273","author":"Xu","year":"2021","journal-title":"Environ Pollut"},{"key":"10.1016\/j.envres.2025.121534_bib41","doi-asserted-by":"crossref","DOI":"10.3389\/fendo.2022.904889","article-title":"Trace elements and the thyroid","volume":"13","author":"Zhou","year":"2022","journal-title":"Front. Endocrinol."}],"updated-by":[{"DOI":"10.1016\/j.envres.2025.121625","type":"erratum","label":"Erratum","source":"publisher","updated":{"date-parts":[[2025,6,15]],"date-time":"2025-06-15T00:00:00Z","timestamp":1749945600000}}],"container-title":["Environmental Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0013935125007856?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0013935125007856?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2025,5,21]],"date-time":"2025-05-21T12:42:39Z","timestamp":1747831359000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0013935125007856"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,7]]},"references-count":41,"alternative-id":["S0013935125007856"],"URL":"https:\/\/doi.org\/10.1016\/j.envres.2025.121534","relation":{"erratum":[{"id-type":"doi","id":"10.1016\/j.envres.2025.121625","asserted-by":"object"}]},"ISSN":["0013-9351"],"issn-type":[{"value":"0013-9351","type":"print"}],"subject":[],"published":{"date-parts":[[2025,7]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Association of metal mixtures during the second trimester with gestational hypothyroidism and its mediation by metabolites","name":"articletitle","label":"Article Title"},{"value":"Environmental Research","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.envres.2025.121534","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2025 Elsevier Inc. All rights are reserved, including those for text and data mining, AI training, and similar technologies.","name":"copyright","label":"Copyright"}],"article-number":"121534"}}