Higher free thyroxine associated with PFAS exposure in first trimester. The Odense Child Cohort

Environ Res. 2022 Sep;212(Pt D):113492. doi: 10.1016/j.envres.2022.113492. Epub 2022 May 18.


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 serum-PFAS concentrations and thyroid hormone status in early pregnancy as reflected by FT4 and thyroid-stimulating hormone (TSH).

Methods: In the Odense Child Cohort, 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 1048 pregnant women at median GW 12 (25th, 75th percentile: 10, 15). Multivariate linear regression models were performed to estimate associations between PFAS exposure and thyroid hormone status.

Results: 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: Exposure to PFOS, PFOA, and PFNA was associated with higher FT4 concentrations in women during early pregnancy. The potential clinical implications of these findings remain to be clarified.

Keywords: Developmental toxicity; Early pregnancy; Perfluoroalkyl substances; Thyroid hormones; Thyrotropin; Thyroxine.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alkanesulfonic Acids*
  • Child
  • Environmental Pollutants*
  • Female
  • Fluorocarbons*
  • Humans
  • Placenta
  • Pregnancy
  • Pregnancy Trimester, First
  • Thyroid Hormones
  • Thyrotropin
  • Thyroxine


  • Alkanesulfonic Acids
  • Environmental Pollutants
  • Fluorocarbons
  • Thyroid Hormones
  • Thyrotropin
  • Thyroxine