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

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

Akhgar Ghassabian  1 , Livia Pierotti  2   3   4 , Mikel Basterrechea  3   5   6 , Leda Chatzi  7   8 , Marisa Estarlich  3   9 , Ana Fernández-Somoano  3   10 , Abby F Fleisch  11   12 , Diane R Gold  13   14 , Jordi Julvez  2   3   4   15 , Polyxeni Karakosta  7   16 , Aitana Lertxundi  3   5   17 , Maria-Jose Lopez-Espinosa  3   9 , Tessa A Mulder  18   19 , Tim I M Korevaar  18 , Emily Oken  20   21 , Robin P Peeters  18 , Sheryl Rifas-Shiman  20 , Euripides Stephanou  22 , Adonina Tardón  3   10 , Henning Tiemeier  19   23 , Martine Vrijheid  2   3   4 , Tanja G M Vrijkotte  24 , Jordi Sunyer  2   3   4   15 , Mònica Guxens  2   3   4   19
Affiliations

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

Akhgar Ghassabian et al. JAMA Netw Open. .

Abstract

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.

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Conflict of interest statement

Conflict of Interest Disclosures: Dr Basterrechea reported receiving grants from the Instituto de Salud Carlos III and the Department of Health of the Basque Government during the conduct of the study. Dr Fleisch reported receiving grants from the National Institutes of Health during the conduct of the study. Dr Gold reported receiving grants from the National Institutes of Health during the conduct of the study. Dr Lopez-Espinosa reported receiving grants and personal fees from the Instituto de Salud Carlos III and grants from the Alicia Koplowitz Foundation 2017 during the conduct of the study. Dr Oken reported receiving grants from the National Institutes of Health during the conduct of the study. Dr Vrijkotte reported receiving grants from the Netherlands Institute for Research and Development during the conduct of the study and outside the submitted work. Dr Sunyer reported receiving grants from the Instituto de Salud Carlos III, the EU Commission, the Centro de Investigación Biomedica en Red Epidemiología y Salud Pública, and the Generalitat de Catalunya during the conduct of the study. Dr Guxens reported receiving grants from the Instituto de Salud Carlos III, the EU Commission, and the Centro de Investigación Biomedica en Red Epidemiología y Salud Pública during the conduct of the study. No other disclosures were reported.

Figures

Figure 1.
Figure 1.. Distribution of Air Pollutants Averaged Across the First Trimester of Pregnancy
Data on particulate matter (PM) were only available in the Sabadell subcohort of Infancia y Medio Ambiente (INMA). Center line indicates 50th percentile; upper and lower boundaries of boxes, 75th and 25th percentile, respectively; upper whisker, 75th percentile plus 1.5 times the interquartile range; lower whisker, 25th percentile minus 1.5 times the interquartile range; and circles, any value above or below the whiskers. ABCD indicates the Amsterdam Born Children and Their Development Study; Gen R, the Generation R Study; NO2, nitrogen dioxide; NOx, nitrogen oxides; PM2.5, particulate matter less than 2.5 μm; PM10, particulate matter less than 10 μm; and Viva, Project Viva.
Figure 2.
Figure 2.. Association of Exposure to Nitrogen Dioxide (NO2) and Nitrogen Oxides (NOx) in the First Trimester With Thyroid Function During Pregnancy
Odds ratios (ORs) were estimated using random-effects meta-analysis by cohort (the Amsterdam Born Children and Their Development Study [ABCD], Generation R, Infancia y Medio Ambiente [INMA], Rhea, and Project Viva [Viva]). Models were adjusted for pregnant maternal age at enrollment, educational level, country of birth, gestational age at thyroid measurement, smoking and alcohol intake during pregnancy, socioeconomic status, marital status, parity, and prepregnancy body mass index (calculated as weight in kilograms divided by height in meters squared). In addition, analysis in INMA was adjusted for region (Sabadell, Gipuzkoa, Valencia, and Asturias). Data are presented as available in each cohort. Hypothyroxinemia was defined as free thyroxine below the fifth percentile of cohort distribution despite normal thyrotropin (TSH) levels. High TSH concentration was defined as levels higher than the 95th percentile. Size of box indicates weight.
Figure 3.
Figure 3.. Association of Exposure to Particulate Matter With an Aerodynamic Diameter of 2.5 μm or Less (PM2.5) and Particulate Matter With an Aerodynamic Diameter of 10 μm or Less (PM10) in the First Trimester With Thyroid Function During Pregnancy
Odds ratios (ORs) were estimated using random-effects meta-analysis by cohort (the Amsterdam Born Children and Their Development Study [ABCD], Generation R, Infancia y Medio Ambiente [INMA], Rhea, and Project Viva [Viva]). Models were adjusted for pregnant maternal age at enrollment, educational level, country of birth, gestational age at thyroid measurement, smoking and alcohol intake during pregnancy, socioeconomic status, marital status, parity, and prepregnancy body mass index (calculated as weight in kilograms divided by height in meters squared). Data on particulate matter (PM) was only available in the Sabadell region of INMA. Data are presented as available in each cohort. Hypothyroxinemia was defined as free thyroxine below the fifth percentile of cohort distribution despite normal thyrotropin (TSH) levels. High TSH concentration was defined as levels higher than the 95th percentile. Size of box indicates weight.
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