Associations between Perfluoroalkyl acids (PFASs) and maternal thyroid hormones in early pregnancy: A population-based cohort study

• PFASs were associated with a hypothyroid effect in pregnant women with high TPOAb.
• PFASs exacerbated already low fT4 and high TSH in these women.
• No associations were found in women with normal TPOAb.
• Associations were found in early pregnancy, in a population with low PFAS exposure.

BackgroundAssociations 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.ObjectivesTo examine associations between maternal serum PFAS levels and maternal thyroid hormone levels in the early 2nd trimester of pregnancy.MethodsParticipants 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).ResultsMedian 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.ConclusionsPFASs 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.