Prenatal Exposure to Per- and Polyfluoroalkyl Substances and Maternal Thyroid Function during Pregnancy in a Cohort with High Familial Likelihood of Autism Spectrum Disorder

Thyroid hormones supplied by the mother are essential for fetal brain development but could be disrupted by per- and polyfluoroalkyl substances (PFAS). We explored how prenatal PFAS exposures relate to maternal thyroid function in pregnant participants from the MARBLES cohort. We analyzed 212 serum samples from 151 pregnant women who later had a child with diagnosis of autism spectrum disorder (ASD), nontypical development (non-TD), or typical development (TD) by age 3. We quantified nine PFAS, total triiodothyronine (TT3), total thyroxine (TT4), free thyroxine (FT4), and thyroid-stimulating hormone. We used a linear mixed effect model for individual and coexposure effects and Bayesian kernel machine regression (BKMR) for mixture effects. We conducted a mixed graphical model with a child neurodevelopmental classification as an exploratory analysis. Perfluorooctanesulfonate (PFOS) and perfluorohexanesulfonate (PFHxS) were associated with TT4 (per 1-unit increase in ln-transformed concentrations β [95% confidence interval, CI]: 1.005 [0.108, 1.903] for PFOS; -0.581 [-1.160, -0.002] for PFHxS) and FT4-to-TT4 ratio (-0.153 [-0.270, -0.036] for PFOS; 0.090 [0.013, 0.166] for PFHxS). In the network map, PFAS were directly and indirectly associated with non-TD diagnosis, while TT3 was conditionally associated with non-TD. These findings indicate that prenatal PFAS exposure could interfere with maternal thyroid function, potentially impacting fetal neurodevelopment.