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JAMA Netw Open. 2019 Oct 2;2(10):e1912902. doi: 10.1001/jamanetworkopen.2019.12902.

Association of Exposure to Ambient Air Pollution With Thyroid Function During Pregnancy.

Author information

Departments of Pediatrics, Environmental Medicine, and Population Health, School of Medicine, New York University, New York.
ISGlobal, Barcelona, Spain.
Spanish Consortium for Research on Epidemiology and Public Health, Madrid, Spain.
Universitat Pompeu Fabra, Barcelona, Spain.
Biodonostia Health Research Institute, San Sebastian, Spain.
Public Health Division of Gipuzkoa, Basque Government, San Sebastian, Spain.
Department of Social Medicine, University of Crete, Heraklion, Greece.
Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles.
Epidemiology and Environmental Health Joint Research Unit, The Foundation for the Promotion of Health and Biomedical Research of Valencia Region, Universitat Jaume I-Universitat de València, Valencia, Spain.
Instituto Universaitario de Oncología del Principado de Asturias, Departament of Medicine, University of Oviedo, Oviedo, Spain.
Department of Pediatric Endocrinology and Diabetes, Maine Medical Center, Portland.
Center for Outcomes Research and Evaluation, Maine Medical Center Research Institute, Portland.
Channing Division of Network Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts.
Department of Environmental Health, Harvard T.H. Chan School of Public Health, Boston, Massachusetts.
Hospital del Mar Research Institute, Barcelona, Spain.
Clinical Microbiology Laboratory, Attikon University Hospital, Medical School, National and Kapodistrian University of Athens, Athens, Greece.
Department of Public Health and Preventive Medicine, University of Basque Country, Bilbao, Spain.
Academic Center for Thyroid Diseases, Department of Internal Medicine, Erasmus Medical Center, Rotterdam, the Netherlands.
Department of Child and Adolescent Psychiatry, Erasmus Medical Center-Sophia Children's Hospital, Rotterdam, the Netherlands.
Division of Chronic Disease Research Across the Lifecourse, Department of Population Medicine, Harvard Medical School and Harvard Pilgrim Health Care Institution, Boston, Massachusetts.
Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, Massachusetts.
Department of Chemistry, University of Crete, Heraklion, Greece.
Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, Massachusetts.
Department of Public Health, Amsterdam Public Health Research Institute, Amsterdam University Medical Center, University of Amsterdam, Amsterdam, the Netherlands.



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.


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.


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.

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