During the past decade, use of organophosphate compounds as flame retardants and plasticizers has increased. Numerous studies investigating biomarkers (i.e., urinary metabolites) demonstrate ubiquitous human exposure and suggest that human exposure may be increasing. To formally assess temporal trends, we combined data from 14 U.S. epidemiologic studies for which our laboratory group previously assessed exposure to two commonly used organophosphate compounds, tris(1,3-dichloro-2-propyl) phosphate (TDCIPP) and triphenyl phosphate (TPHP). Using individual-level data and samples collected between 2002 and 2015, we assessed temporal and seasonal trends in urinary bis(1,3-dichloro-2-propyl) phosphate (BDCIPP) and diphenyl phosphate (DPHP), the metabolites of TDCIPP and TPHP, respectively. Data suggest that BDCIPP concentrations have increased dramatically since 2002. Samples collected in 2014 and 2015 had BDCIPP concentrations that were more than 15 times higher than those collected in 2002 and 2003 (10^β = 16.5; 95% confidence interval from 9.64 to 28.3). Our results also demonstrate significant increases in DPHP levels; however, increases were much smaller than for BDCIPP. Additionally, results suggest that exposure varies seasonally, with significantly higher levels of exposure in summer for both TDCIPP and TPHP. Given these increases, more research is needed to determine whether the levels of exposure experienced by the general population are related to adverse health outcomes.

Maternal and neonatal thyroid function is critical for growth and neurodevelopment. Exposure to individual per- and polyfluoroalkyl substances (PFAS) can alter circulating thyroid hormone levels, but few studies have investigated effects of combined exposure to multiple PFAS. Estimate associations of exposure to multiple PFAS during early pregnancy with maternal and neonatal thyroid function. The study population consisted of 726 mothers and 465 neonates from Project Viva, a Boston, Massachusetts area longitudinal pre-birth cohort. We measured six PFAS [perfluorooctanoate (PFOA), perfluorooctane sulfonate (PFOS), perfluorononanoate (PFNA), perfluorohexane sulfonate (PFHxS), 2-(N-ethyl-perfluorooctane sulfonamido)acetate (EtFOSAA), and 2-(N-methyl-perfluorooctane sulfonamido)acetate (MeFOSAA)] and thyroxine (T₄), Free T₄ Index (FT₄I), and thyroid stimulating hormone (TSH) in maternal plasma samples collected during early pregnancy, and neonatal T₄ in postpartum heel sticks. We estimated individual and joint effects of PFAS exposure with thyroid hormone levels using weighted quantile sum (WQS) regression and Bayesian kernel machine regression (BKMR), and evaluated potential non-linearity and interactions among PFAS using BKMR. Higher concentrations of the PFAS mixture were associated with significantly lower maternal FT₄I, with MeFOSAA, EtFOSAA, PFOA, and PFHxS contributing most to the overall mixture effect in BKMR and WQS regression. In infants, higher concentrations of the PFAS mixture were associated with lower T₄ levels, primarily in males, with PFHxS and MeFOSAA contributing most in WQS, and PFHxS contributing most in BKMR. The PFAS mixture was not associated with maternal T₄ or TSH levels. However, in maternal BKMR analyses, ln-PFOS was positively associated with T₄ levels (Δ25^th to 75th percentile: 0.21 µg/dL; 95% credible interval: -0.03, 0.47) and ln-PFHxS was associated with a non-linear effect on TSH levels. These findings support the hypothesis that there may be combined effects of prenatal exposure to multiple PFAS on maternal and neonatal thyroid function, but the direction and magnitude of these effects may vary across individual PFAS.

Prenatal exposure to some per- and polyfluoroalkyl substances (PFASs) may disrupt maternal and neonatal thyroid function, which is critical for normal growth and neurodevelopment. We examined associations of PFAS exposure during early pregnancy with maternal and neonatal thyroid hormone levels. We studied 732 mothers and 480 neonates in Project Viva, a longitudinal prebirth cohort in Boston, Massachusetts. We quantified six PFASs, including perfluorooctanoic acid (PFOA) and perfluorooctane sulfonate (PFOS), and maternal thyroid hormones [thyroxine (T₄), Free T₄ Index (FT₄I), thyroid stimulating hormone (TSH)] in plasma samples collected at a median 9.6 wk gestation and neonatal T₄ levels from postpartum heel sticks. We estimated associations of PFAS concentrations with thyroid hormone levels using covariate-adjusted linear regression models and explored effect measure modification by maternal thyroid peroxidase antibody (TPOAb) status and infant sex. PFAS concentrations were not associated with maternal T₄, but PFOA, perfluorohexane sulfonate (PFHxS), and 2-(N-methyl-perfluorooctane sulfonamido) acetate (MeFOSAA) were inversely associated with maternal FT₄I [e.g., -1.87% (95% confidence interval (CI): -3.40, -0.31) per interquartile (IQR) increase in PFOA]. PFAS concentrations [PFOA, PFOS, and perfluorononanoate (PFNA)] were inversely associated with TSH levels in TPOAb-positive women only. Prenatal PFOS, PFOA, and PFHxS concentrations were inversely associated with T₄ levels in male [e.g., PFHxS, quartile 4 vs.1: -2.51μg/dL (95% CI: -3.99, -1.04 )], but not female neonates [0.40μg/dL (95% CI: -0.98, 1.79)]. In this study, prenatal exposure to some PFASs during early pregnancy was inversely associated with maternal FT₄I and neonatal T₄ in male infants. These results support the hypothesis that prenatal exposure to PFASs influences thyroid function in both mothers and infants. https://doi.org/10.1289/EHP2534.

Hypertensive disorders of pregnancy (HDP), defined here as hypertensive disorders with onset in pregnancy (i.e., gestational hypertension, preeclampsia, and preeclampsia superimposed on chronic hypertension), affect up to 10% of pregnancies in the United States and are associated with substantial maternal and neonatal morbidity and mortality. Per- and polyfluoroalkyl substances (PFAS) are associated with adverse cardiometabolic outcomes during pregnancy, but associations between PFAS and HDP are inconsistent and joint effects of PFAS mixtures have not been evaluated. We studied 1,558 pregnant individuals from the Project Viva cohort, recruited during 1999–2002. We quantified concentrations of eight PFAS in plasma samples (median 9.7 weeks of gestation). Using clinical records, we calculated trimester-specific mean systolic (SBP) and diastolic (DBP) blood pressure and categorized HDP status [no HDP (normotensive & chronic hypertension), gestational hypertension, preeclampsia]. We estimated associations of individual PFAS with HDP using multinomial logistic regression and estimated associations with blood pressure using linear regression. We used Bayesian kernel machine regression (BKMR) and quantile g-computation to assess joint effects of the PFAS mixture on HDP and blood pressure measures. Four percent of participants developed preeclampsia and 7% developed gestational hypertension. We observed higher odds of gestational hypertension, but not preeclampsia, per doubling of perfluorooctanoate (PFOA) [OR = 1.51 (95% confidence interval: 1.12, 2.03)], perfluorooctane sulfonate (PFOS) [OR = 1.38 (1.04, 1.82)], and perfluorohexane sulfonate [OR = 1.28 (1.06, 1.54)] concentrations. We observed higher mean DBP per doubling of PFOA [2nd trimester (T2): 0.39 mmHg (−0.01, 0.78); 3rd trimester (T3): 0.56 mmHg (0.14, 0.98)] and PFOS [T2: 0.46 mmHg (0.11, 0.82); T3: 0.43 mmHg (0.05, 0.80)]. The PFAS mixture was positively associated with odds of gestational hypertension [75th vs. 50th percentile: OR = 1.14 (95% credible interval:1.03, 1.25), BKMR] and mean DBP [T2 = 0.17 mmHg (−0.06, 0.40); T3 = 0.22 mmHg (−0.03, 0.48), BKMR]. These findings suggest that exposure to certain PFAS may increase the odds of gestational hypertension during pregnancy, with potential implications for subsequent maternal and child health outcomes.