Glenys M Webster1, Scott A Venners2, Andre Mattman3, Jonathan W Martin4. 1. Faculty of Health Sciences, Simon Fraser University, 8888 University Drive, Burnaby, BC, Canada V5A 1S6; Child and Family Research Institute, BC Children's and Women's Hospital, 950 West 28th Avenue, Vancouver, BC, Canada V5Z 4H4. Electronic address: gmwebster@sfu.ca. 2. Child and Family Research Institute, BC Children's and Women's Hospital, 950 West 28th Avenue, Vancouver, BC, Canada V5Z 4H4. Electronic address: scott_venners@sfu.ca. 3. Department of Pathology and Laboratory Medicine, St Paul׳s Hospital, 1081 Burrard Street, Vancouver, BC, Canada V6Z 1Y6. Electronic address: amattman@providencehealth.bc.ca. 4. Division of Analytical & Environmental Toxicology, Department of Laboratory Medicine & Pathology, University of Alberta, 10-102 Clinical Sciences Bluiding, Edmonton, AB, Canada T6G 2G3. Electronic address: jon.martin@ualberta.ca.
Abstract
BACKGROUND: Associations between perfluoroalkyl acids (PFASs) and human thyroid hormone levels remain unclear, especially during early pregnancy when small changes in maternal thyroid hormones can affect fetal brain development. OBJECTIVES: To examine associations between maternal serum PFAS levels and maternal thyroid hormone levels in the early 2nd trimester of pregnancy. METHODS: Participants were euthyroid pregnant women (n=152) enrolled in the Chemicals, Health and Pregnancy (CHirP) study based in Vancouver, Canada. Associations between maternal serum PFASs, including perfluorohexanesulfonate (PFHxS), perfluorononanoate (PFNA), perfluorooctanoate (PFOA) and perfluorooctanesulfonate (PFOS) and repeated measures of maternal thyroid hormones, including free thyroxine (fT4), total thyroxine (TT4) and thyroid stimulating home (TSH) were examined using mixed effects linear models. Associations were considered in all women, then separately in women with high (≥ 9 IU/mL) vs normal (<9 IU/mL) levels of thyroid peroxidase antibody (TPOAb), a marker of autoimmune hypothyroidism (Hashimoto's disease). RESULTS: Median PFAS concentrations (ng/mL) in maternal sera were 1.0 (PFHxS), 0.6 (PFNA), 1.7 (PFOA) and 4.8 (PFOS). PFASs were not associated with fT4, TT4 or TSH among women with normal TPOAb. However, among the 9% of women with high TPOAb (n=14), interquartile range (IQR) increases of PFASs were associated with a 46-69% increase in maternal TSH (95% CIs ranging from 8% to 123%) (PFNA, PFOA and PFOS only), and with a 3% to 7% decrease in maternal fT4 (95% CIs ranging from -18% to 5%) (all 4 PFASs). PFNA was also associated with higher maternal TSH in the whole sample. CONCLUSIONS: PFASs were positively associated with TSH, and weakly negatively associated with fT4 in the subset of pregnant women with high TPOAb, which occurs in 6-10% of pregnancies. PFASs may exacerbate the already high TSH and low fT4 levels in these women during early pregnancy, which is a critical time of thyroid hormone-mediated fetal brain development. The clinical significance of these findings is not clear. We propose a "multiple hit hypothesis" to explain these findings; this hypothesis deserves evaluation in larger, more representative study samples.
BACKGROUND: Associations between perfluoroalkyl acids (PFASs) and human thyroid hormone levels remain unclear, especially during early pregnancy when small changes in maternal thyroid hormones can affect fetal brain development. OBJECTIVES: To examine associations between maternal serum PFAS levels and maternal thyroid hormone levels in the early 2nd trimester of pregnancy. METHODS:Participants were euthyroid pregnant women (n=152) enrolled in the Chemicals, Health and Pregnancy (CHirP) study based in Vancouver, Canada. Associations between maternal serum PFASs, including perfluorohexanesulfonate (PFHxS), perfluorononanoate (PFNA), perfluorooctanoate (PFOA) and perfluorooctanesulfonate (PFOS) and repeated measures of maternal thyroid hormones, including free thyroxine (fT4), total thyroxine (TT4) and thyroid stimulating home (TSH) were examined using mixed effects linear models. Associations were considered in all women, then separately in women with high (≥ 9 IU/mL) vs normal (<9 IU/mL) levels of thyroid peroxidase antibody (TPOAb), a marker of autoimmune hypothyroidism (Hashimoto's disease). RESULTS: Median PFAS concentrations (ng/mL) in maternal sera were 1.0 (PFHxS), 0.6 (PFNA), 1.7 (PFOA) and 4.8 (PFOS). PFASs were not associated with fT4, TT4 or TSH among women with normal TPOAb. However, among the 9% of women with high TPOAb (n=14), interquartile range (IQR) increases of PFASs were associated with a 46-69% increase in maternal TSH (95% CIs ranging from 8% to 123%) (PFNA, PFOA and PFOS only), and with a 3% to 7% decrease in maternal fT4 (95% CIs ranging from -18% to 5%) (all 4 PFASs). PFNA was also associated with higher maternal TSH in the whole sample. CONCLUSIONS: PFASs were positively associated with TSH, and weakly negatively associated with fT4 in the subset of pregnant women with high TPOAb, which occurs in 6-10% of pregnancies. PFASs may exacerbate the already high TSH and low fT4 levels in these women during early pregnancy, which is a critical time of thyroid hormone-mediated fetal brain development. The clinical significance of these findings is not clear. We propose a "multiple hit hypothesis" to explain these findings; this hypothesis deserves evaluation in larger, more representative study samples.
Authors: Anthony J F Reardon; Elham Khodayari Moez; Irina Dinu; Susan Goruk; Catherine J Field; David W Kinniburgh; Amy M MacDonald; Jonathan W Martin Journal: Environ Int Date: 2019-05-28 Impact factor: 9.621
Authors: Emma V Preston; Thomas F Webster; Birgit Claus Henn; Michael D McClean; Chris Gennings; Emily Oken; Sheryl L Rifas-Shiman; Elizabeth N Pearce; Antonia M Calafat; Abby F Fleisch; Sharon K Sagiv Journal: Environ Int Date: 2020-04-17 Impact factor: 9.621
Authors: Marcella Warner; Stephen Rauch; Jennifer Ames; Paolo Mocarelli; Paolo Brambilla; Stefano Signorini; Brenda Eskenazi Journal: Environ Res Date: 2020-02-21 Impact factor: 6.498
Authors: Megan E Romano; Glenys M Webster; Ann M Vuong; R Thomas Zoeller; Aimin Chen; Andrew N Hoofnagle; Antonia M Calafat; Margaret R Karagas; Kimberly Yolton; Bruce P Lanphear; Joseph M Braun Journal: Environ Res Date: 2015-03-17 Impact factor: 6.498
Authors: Sophie A H Boesen; Manhai Long; Maria Wielsøe; Vicente Mustieles; Mariana F Fernandez; Eva C Bonefeld-Jørgensen Journal: Environ Health Date: 2020-10-13 Impact factor: 5.984
Authors: Rebecca M Lebeaux; Brett T Doherty; Lisa G Gallagher; R Thomas Zoeller; Andrew N Hoofnagle; Antonia M Calafat; Margaret R Karagas; Kimberly Yolton; Aimin Chen; Bruce P Lanphear; Joseph M Braun; Megan E Romano Journal: Environ Res Date: 2020-03-16 Impact factor: 6.498