Elsevier

Environment International

Volume 104, July 2017, Pages 33-40
Environment International

Thyroid hormone parameters during pregnancy in relation to urinary bisphenol A concentrations: A repeated measures study

https://doi.org/10.1016/j.envint.2017.04.001Get rights and content

Highlights

  • Widespread exposure to BPA still exists in the U.S.

  • We measured BPA and thyroid hormone parameters during pregnancy.

  • Maternal BPA was inversely associated with TSH across pregnancy.

  • Thyroid hormone disruption during pregnancy could influence fetal development.

Abstract

Background

Maternal supply of thyroid hormones during pregnancy serves a critical role in fetal development. Although animal and in vitro studies provide evidence for thyroid hormone disruption as a result of bisphenol A (BPA) exposure, there is still a lack of evidence in human studies, particularly in the context of pregnancy.

Objectives

We aimed to explore the associations between urinary BPA concentrations and plasma thyroid hormone parameters during gestation in pregnant women, and also investigated potential windows of vulnerability during gestation.

Methods

Our study population included 116 cases of preterm birth and 323 controls from a nested case-control study. We measured BPA in urine and thyroid hormone parameters in plasma samples collected at up to four study visits during pregnancy (median for each visit: 9.64, 17.9, 26.0, and 35.1 weeks gestation). We used linear mixed models for repeated measures analyses, and multivariate linear regression models stratified by study visit to explore potential windows of susceptibility.

Results

In our repeated measures analysis, BPA and thyrotropin (TSH) were inversely associated. An interquartile range (IQR) increase in BPA was associated with an 8.21% decrease in TSH (95% confidence interval [CI]: − 14.2, − 1.83), and a 4.79% increase in free T4 (95% CI: 0.82, 8.92). BPA and TSH were also inversely associated in our cross-sectional analyses at visits 3 and 4.

Conclusions

Our results suggest that TSH is inversely associated with urinary BPA in a consistent manner across pregnancy. Disruption of TSH levels during pregnancy can potentially impact child development and interfere with normal birth outcomes.

Introduction

Although regulations have increasingly restricted the production and use of bisphenol A (BPA) in several consumer products made of polycarbonate plastics (National Conference of State Legislature, 2015), there is continuing evidence that widespread exposure to BPA still exists in the U.S. population (Andra et al., 2015). Furthermore, previous human exposure studies have shown detectable levels of urinary BPA in a majority of pregnant women in the U.S. (Braun et al., 2011, Woodruff et al., 2011). Human exposure to BPA has been hypothesized to disrupt critical hormones in the endocrine system (Vandenberg et al., 2012). There are several animal and in-vitro studies providing evidence that BPA exposure can affect biochemical processes that disrupt the production, secretion, or circulation of thyroid hormones (Boas et al., 2012, Richter et al., 2007, Tilley and Fry, 2015).

Within the hypothalamic-pituitary-thyroid (HPT) axis, thyrotropin (TSH) – a glycoprotein hormone originating from the pituitary gland – stimulates the thyroid gland to produce the thyroid hormones triiodothyronin (T3), and thyroxine (T4) (Tingi et al., 2016). T3 and T4 circulate throughout the body to affect target sites, in addition to negatively regulating TSH production at the pituitary gland (Tingi et al., 2016). Homeostatic regulation of the HPT axis during gestation is critical for the developing fetus, and maternal thyroid hormone levels have varying impacts on the fetus throughout periods of gestation (Tingi et al., 2016). During the first 10–12 weeks of gestation, the fetus's entire supply of thyroid hormones comes from the mother, and coincides with fetal neurodevelopmental events such as brain stem and cerebral neurogenesis (Moog et al., 2017, Préau et al., 2015). After this period, the fetal thyroid gland begins to mature and produce thyroid hormones, but is not fully functional until 18–20 weeks gestation (Moog et al., 2017, Tingi et al., 2016). Maternal thyroid hormones also affect the maturation of various other tissues and organs in the fetus, in addition to stimulating the placental secretion of hormones that influence the supply of fetal glucose (Moog et al., 2017, Vissenberg et al., 2015).

Thyroid disease states such as hyperthyroidism and hypothyroidism are associated with adverse health outcomes during pregnancy (Institute of Medicine, 2007, Krassas et al., 2010, Neale and Burrow, 2004), and associated with stillbirth, miscarriage, preeclampsia, preterm delivery, cardiovascular disorders, and neurodevelopmental disorders in fetuses (Haddow et al., 1999, Luewan et al., 2011, Männistö et al., 2013). In addition to overt thyroid disease, subclinical perturbations of thyroid hormone levels are also suspected of adversely affecting child and maternal health during pregnancy (Negro and Mestman, 2011). Recent review articles and meta-analyses suggest that subclinical hypothyroidism is associated with a higher risk for pre-eclampsia, pregnancy loss, placental abruption, premature rupture of membranes, preterm delivery, and neonatal mortality (Maraka et al., 2016, Tingi et al., 2016, van den Boogaard et al., 2011). These findings emphasize the need to continue investigating potential causes and consequences of changes in subclinical thyroid hormone levels during pregnancy.

Of particular relevance to child and maternal health are the interactions between BPA and thyroid hormones during pregnancy. Human health studies that examined BPA and thyroid hormones in adults (Geens et al., 2015, Meeker et al., 2009a, Meeker and Ferguson, 2011, Sriphrapradang et al., 2013, Wang et al., 2012, Wang et al., 2013), and in pregnant women (Chevrier et al., 2013, Romano et al., 2015), have provided evidence suggesting that BPA may affect circulating levels of several thyroid hormone parameters. One of the studies of pregnant women indicated that maternal BPA levels were inversely associated with total T4 (Chevrier et al., 2013), whereas the other study did not show significant relationships between maternal BPA and any of the thyroid hormone parameters measured (Romano et al., 2015). Some of these studies were limited by collection of only a single spot urine and/or blood sample for measurement of BPA and thyroid hormones, having a relatively small sample size, or assessing associations with only a cross-sectional design. Our study is the first to examine this relationship in repeated measurements during pregnancy, which not only provides greater statistical power to assess a more robust exposure assessment, but also characterizes associations between BPA and thyroid hormones across time during gestation by controlling for individual variability. Specifically in our current study, we evaluated the associations between four repeated measures of urinary BPA and plasma thyroid hormone parameters – TSH, total T3, and free and total T4 – collected at up to four study visits in pregnancy. We also sought to identify potential windows of vulnerability during pregnancy by assessing the extent to which these associations varied by gestational age.

Section snippets

Study population

Participants of this current study comprised a subset of pregnant women drawn from a nested case-control study who were initially recruited for a prospective, longitudinal birth cohort at the Brigham and Women's Hospital in Boston, MA (Ferguson et al., 2014a, Ferguson et al., 2015). In previous studies of this cohort, exposures to environmental phthalates and health outcomes such as preterm birth were investigated (Ferguson et al., 2014b), in addition to markers of thyroid function (Johns et

Results

Previous studies of this case-control study population have characterized distributions of BPA and thyroid hormone levels by study visit of sample collection (Cantonwine et al., 2015, Johns et al., 2016). The overall detection rate of BPA in our study sample was 81.1%. Geometric means and standard deviations for all thyroid hormones by study visit were calculated and presented in a previous study (Johns et al., 2016). In Table 1, we present selected percentiles of BPA concentrations by

Discussion

To our knowledge, this is the first epidemiological study to assess the associations between repeated measures of BPA and maternal thyroid hormone parameters in pregnancy. Using repeated measures, our analysis demonstrated that urinary BPA concentrations were inversely associated with levels of TSH in pregnant women and positively associated with free T4. In our stratified analyses, BPA was significantly inversely associated with TSH at visits 3 and 4. BPA was also marginally associated with

Conclusions

In summary, the present study provides further evidence that BPA exposure has the potential to disrupt thyroid hormones in humans. In order to elucidate the mechanisms that may explain these associations, further animal and human studies must be conducted. Given that pregnancy is an especially vulnerable period of time for fetal development and maternal health, it is important to continue advancing our knowledge of the toxicological effects of environmental exposures during pregnancy. Future

Funding

Subject recruitment and sample collection was originally funded by Abbott Diagnostics.

This work was also supported by the National Institute of Environmental Health Sciences, National Institutes of Health (grants R01ES018872, P42ES017198, P01ES022844, P30ES017885, P50ES026049, and T32ES007062).

Support for Max Aung was provided in part by a grant from the Robert Wood Johnson Foundation Health Policy Research Scholars program.

Support for Kelly Ferguson was provided in part by the Intramural

Acknowledgements

We thank K. Kneen, S. Clipper, G. Pace, D. Weller, and J. Bell of NSF International in Ann Arbor, Michigan, for urine BPA analysis; D. McConnell of the CLASS Lab at University of Michigan for assistance in hormone analysis.

References (47)

  • C.A. Richter et al.

    In vivo effects of bisphenol A in laboratory rodent studies

    Reprod. Toxicol.

    (2007)
  • M.E. Romano et al.

    Gestational urinary bisphenol A and maternal and newborn thyroid hormone concentrations: the HOME Study

    Environ. Res.

    (2015)
  • S.K. Tilley et al.

    Hormone Response Pathways as Responders to Environmental Contaminants and Their Roles in Disease

    (2015)
  • E. Tingi et al.

    Benign thyroid disease in pregnancy: a state of the art review

    J. Clin. Trans. Endocrin.

    (2016)
  • D.B. Barr et al.

    Biologic monitoring of exposure to environmental chemicals throughout the life stages: requirements and issues for consideration for the National Children's Study

    Environ. Health Perspect.

    (2005)
  • M. Boas et al.

    Environmental chemicals and thyroid function: an update

    Curr. Opin. Endocrinol. Diabetes Obes.

    (2009)
  • E. van den Boogaard et al.

    Significance of (sub) clinical thyroid dysfunction and thyroid autoimmunity before conception and in early pregnancy: a systematic review

    Hum. Reprod. Update

    (2011)
  • J.M. Braun et al.

    Variability and predictors of urinary bisphenol A concentrations during pregnancy

    Environ. Health Perspect.

    (2011)
  • D.E. Cantonwine et al.

    Urinary bisphenol A levels during pregnancy and risk of preterm birth

    Environ. Health Perspect.

    (2015)
  • J. Chevrier et al.

    Maternal urinary bisphenol a during pregnancy and maternal and neonatal thyroid function in the CHAMACOS study

    Environ. Health Perspect.

    (2013)
  • V.H. Dang et al.

    Estrogen receptors are involved in xenoestrogen induction of growth hormone in the rat pituitary gland

    J. Reprod. Dev.

    (2009)
  • G.M. de Escobar et al.

    Maternal thyroid hormones early in pregnancy and fetal brain development

    Best Pract. Res. Clin. Endocrinol. Metab.

    (2004)
  • K.K. Ferguson et al.

    Environmental phthalate exposure and preterm birth

    JAMA Pediatr.

    (2014)
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    The authors declare they have no actual or potential competing financial interests.

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