Longitudinal analysis reveals early-pregnancy associations between perfluoroalkyl sulfonates and thyroid hormone status in a Canadian prospective birth cohort.
Serum perfluoroalkyl acids (PFAAs) have been linked to disruption of maternal thyroid hormone homeostasis, but results have varied between studies which we hypothesized was due to timing of the thyroid hormone measurements, variability in PFAA isomer patterns, or presence of other stressors. In a longitudinal study design, we investigated the time-dependency of associations between PFAA isomers and thyroid hormones during pregnancy and post-partum while considering thyroid peroxidase antibody (TPOAb) status and mercury (Hg) co-exposure. In participants of a prospective Canadian birth cohort (n = 494), free thyroxine (FT4), free triiodothyronine (FT3), thyroid stimulating hormone (TSH) and TPOAb were quantified in maternal plasma collected in each trimester and 3-months postpartum, and 25 PFAAs (15 linear and 10 branched) and Hg were quantified in samples collected during the second trimester. Perfluorohexane sulfonate (PFHxS) and total branched isomers of perfluorooctane sulfonate (PFOS) were positively associated with TSH in mixed-effect models, with strongest associations early in gestation. Throughout pregnancy and post-partum, PFHxS was inversely associated with FT4, consistent with elevated TSH, while Hg was inversely associated with FT3. In TPOAb-positive women, negative associations were found between PFUnA and FT4, and 1m-PFOS and TSH, supporting previous studies that thyroid disorder could increase susceptibility to PFAA-mediated hormone dysregulation. Hg did not confound associations but was a significant interaction term, revealing further positive associations between PFOS isomers (∑3m+4m-PFOS) and TSH. Higher perfluoroalkyl sulfonate exposures were associated with higher TSH and/or lower FT4, strongly suggestive that PFHxS and branched PFOS isomers are risk factors for subclinical maternal hypothyroidism. Isomer-specific analysis is important in future studies, as crude measures of 'total-PFOS' masked the associations of branched isomers. A concerning result was for PFHxS which had consistent negative associations with FT4 at all time points and a positive association with TSH in early pregnancy when fetal development is most sensitive to disruption.
Reardon AJF
，Khodayari Moez E
，Dinu I
，Goruk S
，Field CJ
，Kinniburgh DW
，MacDonald AM
，Martin JW
，APrON Study
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Perfluoroalkyl acids in pregnant women from Nunavik (Quebec, Canada): Trends in exposure and associations with country foods consumption.
Perfluoroalkyl acids (PFAAs) are persistent and ubiquitous environmental contaminants that potentially disrupt endocrine system functions. While some PFAAs (perfluorooctane sulfonate (PFOS), perfluorooctanoic acid (PFOA)) are regulated, currently used fluorotelomer alcohols (FTOHs) can be transported to the Arctic and are degraded in a number of PFAAs which biomagnify in Arctic wildlife (e.g. perfluorononanoic acid (PFNA), perfluorodecanoic acid (PFDA), perfluoroundecanoic acid (PFUdA)).
From 2004 to 2017, 279 pregnant Inuit women were recruited as part of biomonitoring projects in Nunavik. Our goal was to evaluate: (i) time-trends in plasma/serum PFAAs levels in pregnant Nunavimmiut women between 2004 and 2017; (ii) compare plasma/serum PFAAs levels in Nunavimmiut women in 2016-2017 to those measured in women of childbearing age in the Canadian Health Measure Survey (CHMS); and (iii) evaluate the associations of PFAAs levels with the consumption of country foods and pregnancy and maternal characteristics during pregnancy in the 97 participants recruited in 2016-2017.
Individual blood sample were collected for serum or plasma PFAAs (PFOS, PFOA, pentafluorobenzoic acid (PFBA), perfluorohexanoic acid (PFHxA), perfluorobutanesulfonic acid (PFBS), perfluorohexane-1-sulfonic acid (PFHxS), PFNA, PFDA, PFUdA) analyses. Socio-demographic data, pregnancy and maternal characteristics and country foods consumption were documented using a questionnaire. Omega-3 and -6 polyunsaturated fatty acids (PUFA) were measured in red blood cell membranes and their ratio used as a biomarker of marine country foods consumption. Time-trends in PFAAs levels were evaluated using ANCOVA models adjusted for relevant co-variables. Serum/plasma levels of PFAAs in the 97 pregnant women aged 16 to 40 years old and recruited in 2016-2017 were compared to those measured in women aged 18 to 40 years old from the CHMS cycle 5 (2016-2017) using the geometric means (GM) and 95% confidence intervals (95% CI). Multivariate regression analyses were performed to examine associations between concentrations of PFAAs and country foods consumption data.
Statistically-significant downward time trends were noted for concentrations of PFOS, PFOA and PFHxS in pregnant Nunavik women between 2004 and 2017. Conversely, between 2011 and 2016-2017, PFNA, PFDA and PFUdA maternal serum levels increased by 19, 13 and 21% respectively. Among participants in 2016-2017, mean concentrations for PFNA (GM: 2.4 μg/L), PFDA (0.53 μg/L) and PFUdA (0.61 μg/L) were higher than those measured in women aged 18-40 years old in the Cycle 5 (2016-2017) of the CHMS. PFOA (0.53 μg/L) and PFHxS (0.26 μg/L) were lower than in CHMS, whereas PFBA, PFHxA and PFBS were not detected in 2016-2017. Ratios of serum/plasma levels of PFNA/PFOA, PFNA/PFOS, PFNA/PFHxS and PFUdA/PFDA were significantly higher in the 97 pregnant women from Nunavik recruited in 2016-2017 compared to CHMS, highlighting their distinct exposure profile. In multivariate models, PFHxS, PFOS, PFNA, PFDA and PFUdA levels in 2016-2017 were strongly associated with the omega-3/omega-6 PUFA ratio, indicating a positive association between marine country foods consumption and higher exposure to PFAAs.
The exposure of pregnant women to long-chain PFAAs (PFNA, PFDA and PFUdA) increased from 2004 to 2017 in Nunavik. Associations noted between PFAAs levels and the omega-3/omega-6 ratio highlights the importance of implementing additional strict regulations on PFAAs and their precursors to protect the high nutritional quality and cultural importance of country foods in Nunavik.
Caron-Beaudoin É
，Ayotte P
，Blanchette C
，Muckle G
，Avard E
，Ricard S
，Lemire M
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Perfluorinated alkyl acids in the serum and follicular fluid of UK women with and without polycystic ovarian syndrome undergoing fertility treatment and associations with hormonal and metabolic parameters.
Women with polycystic ovarian syndrome (PCOS) undergoing treatment for infertility could be a sensitive subpopulation for endocrine effects of exposure to perfluorinated alkyl acids (PFAAs), persistent organic pollutants with potential endocrine activity. Women with, PCOS (n = 30) and age- and BMI-matched controls (n = 29) were recruited from a UK fertility clinic in 2015. Paired serum and follicular fluid samples were collected and analysed for 13 PFAAs. Sex steroid and thyroid hormones, and metabolic markers were measured and assessed for associations with serum PFAAs. Four PFAAs were detected in all serum and follicular fluid samples and concentrations in the two matrices were highly correlated (R2 > 0.95): perfluorooctane sulfonate (PFOS), perfluorooctanoic acid (PFOA), perfluorohexane sulfonate (PFHxS), and perfluorononanoic acid (PFNA). Serum PFOS was positively associated with age (1 ng/mL per yr, p < 0.05) and was higher in PCOS cases than controls (geometric mean [GM] 3.9 vs. 3.1 ng/mL, p < 0.05) and in women with irregular vs. regular menstrual cycles (GM 3.9 vs. 3.0 ng/mL, p = 0.01). After adjustment for confounders, serum testosterone was significantly associated with PFOA, PFHxS, PFNA, and the molar sum of the four frequently detected serum PFAAs (approximately 50 percent increase per ln-unit) among controls but not PCOS cases. HbA1c in PCOS cases was inversely associated with serum PFOA, PFHxs, and sum of PFAAs (2-3 mmol/mol per ln-unit). In controls, fasting glucose was positively associated with serum PFOA and sum of PFAAs (0.25 nmol/L per ln-unit increase in PFAAs). Few other associations were observed. The analyses and findings here should be considered exploratory in light of the relatively small sample sizes and large number of statistical comparisons conducted. However, the data do not suggest increased sensitivity to potential endocrine effects of PFAAs in PCOS patients.
Heffernan AL
，Cunningham TK
，Drage DS
，Aylward LL
，Thompson K
，Vijayasarathy S
，Mueller JF
，Atkin SL
，Sathyapalan T
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