Endocrine Abstracts

Background: Perfluoroalkyl substances (PFAS) are endocrine disrupting chemicals, with elimination half-lives ranging from four to eight years. Experimental studies found PFAS able to interfere with thyroid hormone-binding proteins. During the first 20 weeks of gestation (GW), the fetus is reliant on placental transfer of maternal thyroid hormones, mainly free thyroxine (FT4). However, previous studies investigating associations between exposure to PFAS and thyroid hormone status mainly focused on blood samples from late pregnancy or umbilical cord with mixed findings.

Objectives: To investigate associations between concentrations of PFAS and FT4 and thyroid-stimulating hormone (TSH) in early pregnancy.

Methods: In Odense Child Cohort (OCC), a single-center study, we measured maternal pregnancy serum concentrations of five PFAS: perfluorohexane sulfonic acid (PFHxS), perfluorooctane sulfonic acid (PFOS), perfluorooctanoic acid (PFOA), perfluorononanoic acid (PFNA), perfluorodecanoic acid (PFDA); and FT4 and TSH in 1,048 pregnant women at median gestational week 12 (25th, 75th percentile: 10, 15). Multivariate linear regression models were performed to estimate associations between concentrations of PFAS and FT4 and TSH.

Results: Included women had a mean age of 30.2 (± 4.5 SD) years and median pre-pregnancy BMI of 23.5 (5th, 95th percentiles: 19.2, 32.5) kg/², and 58.7% were nulliparous. A doubling in PFOS, PFOA, and PFNA concentrations was associated with an increment in FT4 concentration by 1.85% (95% CI: 0.66%, 3.05%), 1.29% (95% CI: 0.21%, 2.39%), and 1.70% (95% CI: 0.48%, 2.94%), respectively, in adjusted analyses. A statistically significant dose-response relationship was observed across exposure quartiles for PFOS, PFOA, and PFNA in the association with FT4. No association was found between concentrations of PFAS and TSH in adjusted analyses.

Conclusion and persepectives: Exposure to PFOS, PFOA, and PFNA was associated with higher FT4 concentrations in women during early pregnancy. Our observed associations between exposure to PFAS and FT4 concentrations were small in magnitude, nonetheless, the effects may be greater in populations with higher concentrations of PFAS exposure. The clinical significance of these findings remains to be elucidated. At population level, the demonstrated potential disruption of maternal thyroid hormone status in response to PFAS exposure during early pregnancy may affect offspring neurodevelopment. Hence, the findings are of general public interest, which supports the necessity of a follow-up of offspring in the OCC to assess putative long-term implications on neurodevelopment.