Importance: Air pollutants interact with estrogen nuclear receptors, but their effect on thyroid signaling is less clear. Thyroid function is of particular importance for pregnant women because of the thyroid’s role in fetal brain development. Objective: To determine the short-term association of exposure to air pollution in the first trimester with thyroid function throughout pregnancy. Design, Setting, and Participants: In this cohort study, 9931 pregnant women from 4 European cohorts (the Amsterdam Born Children and Their Development Study, the Generation R Study, Infancia y Medio Ambiente, and Rhea) and 1 US cohort (Project Viva) with data on air pollution exposure and thyroid function during pregnancy were included. The recruitment period for the Amsterdam Born Children and Their Development Study was January 2003 to March 2004; for Generation R, April 2002 to January 2006; for Infancia y Medio Ambiente, November 2003 to January 2008; for Rhea, February 2007 to February 2008; and for Project Viva, April 1999 to November 2002. Statistical analyses were conducted from January 2018 to April 2019. Main Outcomes and Measures: Residential air pollution concentrations (ie, nitrogen oxide and particulate matter [PM]) during the first trimester of pregnancy were estimated using land-use regression and satellite-derived aerosol optical depth models. Free thyroxine, thyrotropin, and thyroid peroxidase antibody levels were measured across gestation. Hypothyroxinemia was defined as free thyroxine below the fifth percentile of the cohort distribution with normal thyrotropin levels, following the American Thyroid Association guidelines. Results: Among 9931 participants, the mean (SD) age was 31.2 (4.8) years, 4853 (48.9%) had more than secondary educational levels, 5616 (56.6%) were nulliparous, 404 (4.2%) had hypothyroxinemia, and 506 (6.7%) tested positive for thyroid peroxidase antibodies. Concentrations of nitrogen dioxide and PM with an aerodynamic diameter of 2.5 μm or less (PM2.5) were lower and had less variation in women in the US cohort than those in European cohorts. No associations of nitrogen oxide with thyroid function were found. Higher exposures to PM2.5 were associated with higher odds of hypothyroxinemia in pregnant women (odds ratio per 5-μg/m3 change, 1.21; 95% CI, 1.00-1.47). Although exposure to PM with an aerodynamic diameter of 10 μm or less was not significantly associated with hypothyroxinemia, the coefficient was similar to that for the association of PM2.5 with hypothyroxinemia (odds ratio per 10-μg/m3 change, 1.18; 95% CI, 0.93-1.48). Absorbances of PM2.5 and PM with aerodynamic diameter from 2.5 to 10 μg and were not associated with hypothyroxinemia. There was substantial heterogeneity among cohorts with respect to thyroid peroxidase antibodies (P for heterogeneity, <.001), showing associations of nitrogen oxide and PM with thyroid autoimmunity only in the women in the Generation R Study. Conclusions and Relevance: The findings of this study suggest that first-trimester exposures to PM2.5 were associated with mild thyroid dysfunction throughout pregnancy. The association of PM2.5 exposure with thyroid function during pregnancy is of global health importance because air pollution exposure is widespread and hypothyroxinemia may adversely influence the brain development of offspring.

The Generation R Study was conducted by the Erasmus Medical Center in close collaboration with the Faculty of Social Sciences of the Erasmus University Rotterdam, the Municipal Health Service Rotterdam area, Rotterdam, and the Stichting Trombosedienst & Artsenlaboratorium Rijnmond, Rotterdam. Infancia y Medio Ambiente was funded by grants Red INMA G03/176 and CB06/02/0041 FIS-FEDER PI03/1615, PI04/1509, PI04/1112, PI04/1931, PI042018, PI05/1079, PI05/1052, PI06/0867, PI06/1213, PI07/0314, PI09/02311, PI09/02647, PI11/02591, PI11/02038, PI13/1944, PI13/2032, PI13/02429, PI14/00891, PI14/01687, PI16/1288, and PI17/00663, and Miguel Servet-FEDER CP11/00178, CP15/00025, MSII16/00051, MS13/00054, and CPII18/00018 from the Instituto de Salud Carlos III; grant CIRIT 1999SGR 00241 from the Generalitat de Catalunya; grants FISABIO UGP 15-230, UGP-15-244, and UGP-15-249 from the Generalitat Valenciana; grant 2005111093 from the Department of Health of the Basque Government; grant DFG06/002 from the Provincial Government of Gipuzkoa, annual agreements with the municipalities in the study area (Zumarraga, Urretxu, Legazpi, Azkoitia, Azpeitia, and Beasain); grants FP7/2007-2011-GA#211250, FP7-ENV-2011 cod 282957, HEALTH.2010.2.4.5-1 from the EU Commission; the Obra Social Cajastur and Fundación Liberbank; the Universidad de Oviedo; the Centro de Investigación Biomedica en Red Epidemiología y Salud Pública. ISGlobal is a member of the CERCA Programme, Generalitat de Catalunya. The Rhea project was supported by European projects (EU FP6-2003-Food-3-A NewGeneris, EU FP6. STREP Hiwate, EU FP7 ENV.2007.1.2.2.2. Project No 211250 Escape, EU FP7-2008-ENV-1.2.1.4 Envirogenomarkers, EU FP7-HEALTH-2009-single-stage CHICOS, EU FP7 ENV.2008.1.2.1.6. Proposal No 226285 ENRIECO) and the Greek Ministry of Health (Program of Prevention of Obesity and Neurodevelopmental Disorders in Preschool Children, in Heraklion district, Crete, Greece, 2011-2014). Project Viva was funded by grants R01 HD 034568, UH3 OD023286, K23 ES024803 from the National Institutes of Health.