Associations between perfluoroalkyl acids (PFASs) and maternal thyroid hormones in early pregnancy: a population-based cohort study.
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.
To examine associations between maternal serum PFAS levels and maternal thyroid hormone levels in the early 2nd trimester of pregnancy.
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).
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.
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.
Webster GM
，Venners SA
，Mattman A
，Martin JW
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Prenatal exposure to perfluoroalkyl substances and cord plasma lipid concentrations.
The effect of prenatal exposure to perfluoroalkyl substances (PFAS) on lipid concentrations in newborns is unknown. Using data from the Shanghai-Minhang Birth Cohort Study, we prospectively assessed the health effects of prenatal exposure to individual and multiple PFAS on cord lipid concentrations. Maternal plasma samples collected at 12-16 weeks of gestation were analyzed for eleven PFAS, and cord blood samples were analyzed for lipids: total cholesterol (TC), triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C). We used multiple linear regression models to evaluate the associations of each individual PFAS with each lipid parameter, and used Bayesian Kernel Machine Regression (BKMR) models to assess the overall and single-exposure effects of eight PFAS with the detection rate above 80% on cord lipid concentrations. In multiple linear regression models, for each unit increase in ln-transformed maternal concentrations of perfluorononanoic acid (PFNA), perfluorodecanoic acid (PFDA), perfluoroundecanoic acid (PFUdA), and perfluorotridecanoic acid (PFTrDA), ln-transformed TC concentration decreased by 0.15 mg/dL (95% confidence interval (CI): -0.25, -0.05), 0.12 mg/dL (95% CI: -0.19, -0.05), 0.12 mg/dL (95% CI: -0.19, -0.05), and 0.05 mg/dL (95% CI: -0.09, -0.01), respectively, and ln-transformed HDL-C concentration decreased by 0.17 mg/dL (95% CI: -0.29, -0.05), 0.12 mg/dL (95% CI: -0.20, -0.03), 0.12 mg/dL (95% CI: -0.20, -0.03), and 0.06 mg/dL (95% CI: -0.11, -0.00), respectively. Statistically significant inverse associations were also observed between ln-transformed concentrations of PFDA, PFUdA, or PFTrDA and ln-transformed cord concentrations of TG and LDL-C. In BKMR models, the mixture of eight PFAS showed suggestively inverse association with all ln-transformed lipid concentrations, such that ln-transformed TC concentration of exposure to the 75th percentile of the mixture was 0.11 units (95% credible interval, -0.21, -0.01) lower than the 25th percentile exposure. Our findings indicated that prenatal exposure to PFAS may disrupt lipid metabolism in newborns.
Tian Y
，Miao M
，Ji H
，Zhang X
，Chen A
，Wang Z
，Yuan W
，Liang H
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Association between perfluoroalkyl substance exposure and thyroid hormone/thyroid antibody levels in maternal and cord blood: The Hokkaido Study.
Thyroid antibodies (TAs) are the most common cause of hypothyroidism during gestation. Although previous studies found that prenatal exposure to perfluoroalkyl substances (PFASs) disrupts thyroid hormones (THs) in humans, their effects on TAs during the perinatal period have not been investigated.
To explore the associations between prenatal exposure to eleven different PFASs from two different groups (carboxylates and sulfonates) and the expression of THs and TAs in maternal and cord blood while considering maternal TA status.
In a prospective birth cohort (the Hokkaido Study), we included 701 mother‑neonate pairs recruited in 2002-2005 for whom both prenatal maternal and cord blood samples were available. Eleven PFASs were measured in maternal plasma obtained at 28-32 weeks of gestation using ultra-performance liquid chromatography coupled with triple quadrupole tandem mass spectrometry. THs and TAs including thyroid stimulating hormone (TSH), free triiodothyronine (FT3), free thyroxine (FT4), thyroid peroxidase antibody (TPOAb), and thyroglobulin antibody (TgAb) were measured in maternal blood during early pregnancy (median 11 gestational weeks), and in cord blood at birth.
The median levels of TgAb and TPOAb in maternal serum were 15.0 and 6.0 IU/mL, respectively. The median TgAb level in neonates was 38.0 IU/mL, and TPOAb were detected in only 12.3% of samples. Maternal FT3 level was positively associated with PFAS levels in both TA-positive and TA-negative mothers. Maternal perfluorooctanoate was inversely associated with maternal TPOAb. Among boys, some maternal PFASs were associated with higher TSH and lower FT3 levels in maternal TA-negative group, while perfluorodecanoic acid was associated with lower TSH in maternal TA-positive group. Among girls, some PFAS of mothers showed associations with lower TSH and higher FT3 in maternal TA-negative group, while perfluorododecanoic acid was associated with lower FT4 in maternal TA-positive. Maternal PFASs showed associations with boy's TgAb inversely in maternal TA-negative group and with girl's TgAb positively in maternal TA-positive group.
Our results suggest thyroid disrupting effects of PFAS exposure and susceptibility vary depending on maternal TA levels.
Itoh S
，Araki A
，Miyashita C
，Yamazaki K
，Goudarzi H
，Minatoya M
，Ait Bamai Y
，Kobayashi S
，Okada E
，Kashino I
，Yuasa M
，Baba T
，Kishi R
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