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Prenatal exposure to long-chain, short-chain and emerging PFASs and cognitive development in young children: Evidence
Limei Chen1, Hongmei Hou2, Yao Li3
1The Affiliated Wuxi Center for Disease Control and Prevention of Nanjing Medical University, Wuxi Center for Disease Control and Prevention, Wuxi Medical Center, Nanjing Medical University, Wuxi, 214023, Jiangsu, China; Ecosystem Change and Population Health Research Group, School of Public Health and Social Work, Queensland University of Technology, Brisbane, 4059, QLD, Australia.
Background And Objective:
Perfluoroalkyl and polyfluoroalkyl substances (PFASs) are persistent pollutants with potential neurotoxic effects, but evidence on short-chain and emerging PFASs remains scarce. To examine associations between prenatal PFAS exposure, particularly short-chain and emerging compounds, and cognitive outcomes in 2.5-year-old children, considering sex-specific effects and the potential mediating role of maternal thyroid hormones (THs).
Methods:
In 202 mother-child pairs from the Wuxi Birth Cohort (2019-2021), 23 PFASs and maternal THs were measured in serum. Child cognition was assessed using the Wechsler Preschool and Primary Scale of Intelligence-Fourth Edition. Statistical models including linear regression, restricted cubic splines (RCS) and Bayesian kernel machine regression (BKMR) were used to examine both linear and non-linear associations between prenatal exposure to individual and combined PFASs and offspring neurodevelopment. Mediation analysis was conducted to investigate whether maternal thyroid function mediated these associations.
Results:
Higher maternal PFBA (short-chain) levels were significantly associated with lower verbal comprehension index scores in boys [β = -2.13, 95 % confidence interval (CI): -4.05, -0.20]. Elevated maternal levels of the short-chain PFAS PFHxS were significantly associated with lower working memory index scores (β = -3.90, 95 % CI: -7.48, -0.32), with similar adverse associations also observed for long-chain PFASs such as PFOA (β = -5.20, 95 % CI: -10.20, -0.20) and PFOS (β = -2.03, 95 % CI: -3.50, -0.55). Notably, RCS models revealed several short-chain PFASs, including PFHxA and PFPeA, showed significant nonlinear associations with cognitive outcomes such as working memory index (WMI)and visual spatial index. In contrast, PFAS mixtures showed no significant effects. Although several PFASs was associated with maternal thyroid hormone levels, mediation was not supported.
Conclusion:
Prenatal exposure to specific short and long chain PFASs may impair early cognitive development, with sex-specific and nonlinear patterns. These findings highlight the need for further research and regulation of emerging PFASs.
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