Chlorinated polyfluorinated ether sulfonates (Cl-PFESAs) are one kind of replacement chemistry for perfluorooctanesulfonate (PFOS). Recent studies have shown that Cl-PFESAs could interfere with thyroid function in animal models. However, epidemiological evidence on the link between Cl-PFESAs and thyroid function remains scarce. In this study, we focused on two representative legacy perfluoroalkyl substances (PFAS), including PFOS and perfluorooctanoic acid (PFOA), and two PFOS alternatives (6:2 and 8:2 Cl-PFESAs) in the general adult population from a cross-sectional study, the “Isomers of C8 Health Project in China”. Three serum thyroid hormones (THs), thyroid stimulating hormone (TSH), free triiodothyronine (FT3), and free thyroxine (FT4), were measured. We fitted generalized linear regression, restricted cubic spline regression, and Bayesian kernel machine regression models to assess associations of individual Cl-PFESAs, legacy PFAS, and PFAS mixtures with THs, respectively. We found individual PFAS and their mixtures were nonlinearly associated with THs. The estimated changes of the TSH level (μIU/mL) at the 95th percentile of 6:2 Cl-PFESA and PFOS against the 5th percentile were −0.74 (95% CI: −0.94, −0.54) and −1.18 (95% CI: −1.37, −0.98), respectively. The present study provided epidemiological evidence for the association of 6:2 Cl-PFESA with thyroid hormone levels in the general adult population.

The neurotoxic effects of prenatal exposure to per- and polyfluoroalkyl substances (PFAS) on offspring animals are well-documented. However, epidemiological evidence for legacy PFAS is inconclusive, and for alternative PFAS, it is little known. In this investigation, we selected 718 mother–child pairs from the Chinese Maoming Birth Cohort Study and measured 17 legacy and alternative PFAS in the third-trimester serum. Neuropsychological developments (communication, gross motor function, fine motor function, problem solving ability, and personal–social skills) were assessed at 3, 6, 12, 18, 24, and 36 months using the Ages and Stages Questionnaires 3rd edition. Trajectories of each subscale were classified into persistently low and persistently high groups via group-based trajectory modeling. Logistic regression and grouped weighted quantile sum were fitted to assess the potential effects of individual PFAS and their mixtures, respectively. Higher linear PFHxS levels were associated with elevated odds for the persistently low trajectories of communication (OR = 1.73; 95% CI: 1.12, 2.66) and problem solving ability (OR = 2.11; 95% CI: 1.14, 3.90). Similar findings were observed for linear PFOS, 1m-PFOS, PFDA, PFDoDA, PFUnDA, and legacy PFAS mixture. However, no association was observed for alternative PFAS and their mixture. We provided insights into the longitudinal links between prenatal legacy/alternative PFAS exposure and neuropsychological development trajectories over the first 3 years of life.

Glucocorticoid plays a key role in the growth and organ maturation of fetus. However, the effect of glucocorticoid on the association between per-and polyfluoroalkyl substance (PFAS) exposure and fetal growth is still unknown. We detected cord cortisol (active glucocorticoid in human) and 34 PFAS concentrations in the maternal serum samples, which were collected from 202 mother-fetus pairs in the Maoming Birth Cohort from 2015 to 2018. The mediation effect of cord cortisol on the association between maternal PFAS and the neonatal growth index (NGI) was estimated. We found that higher PFAS concentrations were associated with lower NGI in terms of ponderal index, birth weight (BW), head circumference (HC), and its z-scores (BWZ and HCZ) (P < 0.05). Fetal cortisol could mediate 12.6−27.3% of the associations between PFAS and NGI. Specifically, cord cortisol mediated the association between branched perfluorooctane sulfonate (branched PFOS) and HCZ by 20.4% and between perfluorooctanoate (PFOA) and HCZ by 27.3%. Our findings provide the first epidemiological data evincing that fetal cortisol could mediate the association between prenatal PFAS exposure and fetal growth. Further investigations are recommended to elucidate the interactions among cord cortisol, PFAS, and fetal growth.