Maternal serum perfluoroalkyl substance mixtures and thyroid hormone concentrations in maternal and cord sera: The HOME Study

https://doi.org/10.1016/j.envres.2020.109395Get rights and content

Highlights

  • Mixture models assessed maternal PFAS with maternal and cord thyroid hormones.

  • PFAS mixtures were not strongly associated with maternal or cord thyroid hormones.

  • PFOS had a positive trending association with thyroid stimulating hormone.

  • Associations between PFAS and thyroid hormones may be modified by TPOAb status.

Abstract

Background

Per- and polyfluoroalkyl substances (PFAS) are ubiquitous. Previous studies have found associations between PFAS and thyroid hormones in maternal and cord sera, but the results are inconsistent. To further address this research question, we used mixture modeling to assess the associations with individual PFAS, interactions among PFAS chemicals, and the overall mixture.

Methods

We collected data through the Health Outcomes and Measures of the Environment (HOME) Study, a prospective cohort study that between 2003 and 2006 enrolled 468 pregnant women and their children in the greater Cincinnati, Ohio region. We assessed the associations of maternal serum PFAS concentrations measured during pregnancy with maternal (n = 185) and cord (n = 256) sera thyroid stimulating hormone (TSH), total thyroxine (TT4), total triiodothyronine (TT3), free thyroxine (FT4), and free triiodothyronine (FT3) using two mixture modeling approaches (Bayesian kernel machine regression (BKMR) and quantile g-computation) and multivariable linear regression. Additional models considered thyroid autoantibodies, other non-PFAS chemicals, and iodine deficiency as potential confounders or effect measure modifiers.

Results

PFAS, considered individually or as mixtures, were generally not associated with any thyroid hormones. A doubling of perfluorooctanesulfonic acid (PFOS) had a positive association with cord serum TSH in BKMR models but the 95% Credible Interval included the null (β = 0.09; 95% CrI: −0.08, 0.27). Using BKMR and multivariable models, we found that among children born to mothers with higher thyroid peroxidase antibody (TPOAb), perfluorooctanoic acid (PFOA), PFOS, and perfluorohexanesulfonic acid (PFHxS) were associated with decreased cord FT4 suggesting modification by maternal TPOAb status.

Conclusions

These findings suggest that maternal serum PFAS concentrations measured in the second trimester of pregnancy are not strongly associated with thyroid hormones in maternal and cord sera. Further analyses using robust mixture models in other cohorts are required to corroborate these findings.

Introduction

Per- and polyfluoroalkyl substances (PFAS) are environmentally persistent synthetic chemicals detected in air, dust, soil, drinking water, and consumer products (Blum et al., 2015). Widely produced in industrialized countries beginning in the 1940s and 1950s (Lindstrom et al., 2011), more than 4,700 fluorine-containing compounds are now estimated to exist, although not all are currently used in consumer products (Birnbaum, 2018). PFAS, including perfluorooctanoic acid (PFOA), perfluorooctanesulfonic acid (PFOS), perfluorononanoic acid (PFNA), and perfluorohexanesulfonic acid (PFHxS), readily cross the placenta and are detected in the blood of virtually all pregnant women, children, and neonates (Ballesteros et al., 2017; Braun, 2016). Due to some of these chemicals’ long half-lives (ranging from 2.5 to 7.3 years) (Caron-Beaudoin et al., 2019) and bioaccumulative properties and toxicity in animal studies (Lindstrom et al., 2011), research quantifying associations between PFAS and health outcomes during sensitive windows of development is imperative.

PFAS are potential thyroid disruptors. In animal studies, individual PFAS have been shown to alter circulating levels of thyroid hormone (Ramhøj et al., 2018; Stahl et al., 2011; Yu et al., 2009). Epidemiological studies have assessed the relationship between various PFAS and thyroid hormones of mothers, neonates, and children (Berg et al., 2015; Chan et al., 2011; Kim et al., 2011; Lopez-Espinosa et al., 2012; Preston et al., 2018; Reardon et al., 2019; Wang et al., 2013, 2014; Webster et al., 2014), but the findings are conflicting (Ballesteros et al., 2017). Effect measure modification by autoantibody and iodine status contribute to the “multiple hit hypothesis” (Webster et al., 2014); a theory that thyroid function may be more susceptible to disruption by chemicals such as PFAS if the system is already impacted by multiple stressors. Consequently, some authors have suggested that TPOAb, TgAb, and iodine status are effect measure modifiers of PFAS’ association with thyroid hormones, but observations vary by study (Itoh et al., 2019; Preston et al., 2018; Reardon et al., 2019; Webster et al., 2014, 2016). However, another reason for inconsistent findings could be the mixture of PFAS in the population. To our knowledge, no study has assessed associations of PFAS mixtures with maternal or cord serum thyroid hormones. Further, our study will be one of very few studies that has assessed effect measure modification by autoantibody and iodine status as an additional exploratory analyses. Disentangling the contributions of individual elements of PFAS mixtures and quantifying the effect of the overall mixture is necessary to understand the impact of PFAS on thyroid hormones.

This issue is important because of the role of thyroid hormone in brain development, growth, depression, and obesity (Boelaert and Franklyn, 2005; Tanm, 2011). In the brain and nervous system, thyroid hormones regulate cell migration and differentiation, synaptogenesis, and myelination (Bernal, 2007). Among younger individuals, thyroid hormone deficiencies can cause growth delays, intellectual disabilities, and precocious puberty (Papi et al., 2007). Low thyroid hormone during pregnancy may cause neurological impairment (Bernal, 2007) and lowered IQ (Chang and Pearce, 2013) in children.

The objective of this study was to quantify the association of individual and mixtures of PFOA, PFOS, PFNA, and PFHxS measured in maternal serum with thyroid stimulating hormone (TSH), total thyroxine (TT4), total triiodothyronine (TT3), free thyroxine (FT4), and free triiodothyronine (FT3) measured during pregnancy and in cord serum. Additionally, we explored potential effect measure modification of the association of PFAS with thyroid hormones by maternal TPOAb, TgAb, and iodine deficiency status.

Section snippets

Study design and participants

We enrolled 468 pregnant women in the Health Outcomes and Measures of the Environment (HOME) Study from the greater Cincinnati area between March 2003 and January 2006 and 389 delivered singleton infants. Detailed information on the HOME Study have been described elsewhere (Braun et al., 2017). Of the 389 eligible mother-child dyads, 355 had PFAS measurements. At least one cord or maternal thyroid hormone was measured in 305 of the 355 dyads. Both thyroid hormone measurements and PFAS serum

Results

Mother-infant dyads included in at least one of our cord or maternal serum models had similar demographic characteristics (Table 1 and Table S1). The majority of women in our study were between 25 and 35 years old (mean age of 30), non-Hispanic White, married or cohabitating, and had a bachelor's degree or higher. Serum PFAS concentrations were generally lower among women who identified as non-Hispanic Black, had less educational attainment, and were unmarried. Median (IQR) concentrations were

Discussion

We found little evidence to suggest that individual or mixtures of PFAS measured during pregnancy were associated with thyroid hormones measured in maternal or cord sera in this cohort. This was consistent across BKMR, quantile g-computation, and multivariable linear regression models. Across all models we expected effect estimates would be in the same direction (e.g. the association between PFOS and cord serum TSH would be positive in the BKMR, quantile g-computation, and multivariable

Conclusion

This study assessed the individual, overall, and joint exposure effects of maternal PFAS on a variety of maternal and cord sera thyroid hormones using multiple robust statistical techniques in a prospective cohort. Our results showed limited associations between PFAS and the thyroid hormones studied in this cohort. Our results may be generalizable to cohorts of pregnant women and children with comparable PFAS exposures who have similar demographics to the participants of the HOME Study. This

Funding

This work was supported by NIEHS grants P01 ES11261, R01 ES014575, R01 ES020349, R01 ES025214, R01 ES024381, P01 ES022832-02; EPA grant RD-83544201; and NIGMS grant P20 GM104416. Ms. Lebeaux was supported by NIAID grant 2T32AI007519-21. Dr. Doherty was supported by NCI grant R25 CA134286.

CRediT authorship contribution statement

Rebecca M. Lebeaux: Conceptualization, Methodology, Formal analysis, Writing - original draft. Brett T. Doherty: Methodology, Formal analysis, Writing - original draft. Lisa G. Gallagher: Data curation, Formal analysis, Writing - review & editing. R. Thomas Zoeller: Conceptualization, Writing - review & editing. Andrew N. Hoofnagle: Investigation, Writing - review & editing. Antonia M. Calafat: Investigation, Writing - review & editing. Margaret R. Karagas: Resources, Project administration,

Acknowledgements:

The authors would like to thank the HOME Study participants and HOME Study staff.

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