Associations of per- and polyfluoroalkyl substances and alternatives with subclinical hypothyroidism in children: A cross-sectional study in China.

Abstract

There is growing experimental and epidemiological evidence linking perfluoroalkyl and polyfluoroalkyl substances (PFAS) exposure to thyroid dysfunction; however, the association between PFAS and their alternatives to subclinical hypothyroidism in children remains to be elucidated. This study investigated the association between 30 PFASs and thyroid function using serum samples from 194 children (aged 3-17 years) who participated in the Zhejiang Human Biomonitoring Program. Various thyroid function indicators, including free triiodothyronine, free thyroxine (FT4), and thyrotropin, were tested, and subclinical hypothyroidism was diagnosed. Linear regression was employed to examine the associations between individual PFASs and thyroid hormone levels, and logistic regression was applied to assess their associations with subclinical hypothyroidism. The quantile g-computation (qgcomp) method was used to examine the combined and individual effects of PFAS mixtures on thyroid function. Both PFASs and their alternatives were associated with altered thyroid hormone levels and subclinical hypothyroidism. A higher level of perfluorohexanoic acid (PFHpA) was associated with decreased FT4 with a reduction of -0.028 pmol/L (95 % confidence interval [95 % CI]: -0.047, -0.008) per unit increase as well as increased odds of subclinical hypothyroidism (odds ratio [OR] = 1.95; 95 % CI: 1.11, 3.53). Moreover, a higher PFAS mixture was associated with elevated odds of subclinical hypothyroidism (OR = 3.72; 95 % CI: 1.08, 12.85), in which PFHpA, in conjunction with 6:2 chlorinated perfluoroalkyl ether sulfonic acid, accounted for the greatest proportion of the variance. These findings augment our understanding of the adverse effects of PFASs and their alternatives on thyroid homeostasis, underscoring the need for further epidemiological research.