Abstract P245: Early Pregnancy Exposure to Per- And Polyfluoroalkyl Substances and Thyroid Function Throughout Gestation: A Longitudinal Study

Introduction: Thyroid function during pregnancy is pivotal for both maternal and fetal health. Data on environmental determinants of thyroid function in pregnancy are yet limited. We prospectively investigated associations of early pregnancy per- and polyfluoroalkyl substances (PFAS), known environmental endocrine disruptors, with thyroid function longitudinally measured throughout pregnancy. Hypothesis: Early pregnancy PFAS exposure adversely affects thyroid function. Methods: Within the NICHD Fetal Growth Studies-Singleton Cohort, we enrolled 2,802 pregnant women at gestational weeks (gw) 10-14 and measured concentrations of 9 PFAS (NMeFOSAA, PFDA, PFDoDA, PFDS, PFHpA, PFHxS, PFNA, PFOA, PFOS, PFOSA, PFUnDA) in plasma samples collected at enrollment. In a subsample of 321 pregnant women, we determined thyroid markers (fT3, fT4, TSH) at gw 10-14, 15-26, 23-31, 33-39. Associations were assessed with multivariable regressions per standard deviation increase in ln-transformed PFAS (ng/ml), adjusting for age, body mass index, diet, lifestyle and socio-economic factors, and plasma lipids. Results: Plasma PFAS in early pregnancy were associated with markers of thyroid function throughout pregnancy. The associations varied by gestational age. Higher levels of several PFAS were associated with lower TSH and higher fT3 and fT4 levels at gw 10-14. Adjusted beta coefficients [95%CI] with TSH (mIU/L) were: -1.13 [-2.30, 0.05] for PFOS, -3.15 [-4.45, -1.86] for PFDA, -1.75 [-2.95, -0.55] for NMeFOSAA, -1.68 [-3.00, -0.37] for PFNA, -1.29 [-2.62, 0.03] for PFDoDA, -2.07 [-3.30, -0.83] for PFOA, but 1.11 [0.12, 2.09] for PFHxS. Most of these associations were attenuated to non-significant or changed the direction of the association in later pregnancy (for instance, PFOS-TSH association at gw 10-14: -1.13 [-2.30, 0.05], gw 15-26: 0.98 [0.18, 1.78], gw 23-31: 1.31 [0.50, 2.13], PFDA-TSH association at gw 10-14: -3.15 [-4.45, -1.86], at gw 23-31: 1.13 [0.16, 2.11]). Consistent and positive associations across pregnancy were observed for PFOA-fT3 (at gw 10-14: 0.48 [0.05, 0.91], gw 15-26: 0.41 [0.04, 0.78], gw 23-31: 0.42 [0.02, 0.80] pmol/L) and PFHxS-fT4 (at gw 10-14: 0.12 [0.02, 0.21], gw 15-26: 0.67 [0.54, 0.81], gw 23-31: 0.22 [0.12, 0.33], gw 33-39: 0.14 [0.02, 0.26] ng/dL). Conclusions: Plasma levels of selected PFAS congeners in early pregnancy are significantly associated with thyroid markers in pregnancy. The associations varied by gestational timing. These findings indicate a potential environmental impact on thyroid function. In perspective, multiple assessments of PFAS and thyroid markers throughout pregnancy might be necessary and relevant for conducting gestational age-specific interventional trials.