ORIGINAL RESEARCH article
Front. Public Health
Sec. Environmental Health and Exposome
Environmental Exposure to Per-and Polyfluoroalkyl Substances and Childhood Congenital Heart Disease: A Mixed Analysis
Provisionally accepted
Xian Ting Jiao1
Liqing Zhao1
Yuejuan Xu1Jiawei Gao1Weifeng Tang1Yurong Wu1Ling Yang1Jihong Huang1
Yi Guo2*
Kun Sun1*
Sun Chen1*- 1Xinhua Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
- 2Shanghai First Maternity and Infant Hospital, Shanghai, China
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Background: Per-and polyfluoroalkyl substances (PFAS) exposure is associated with various health risks. However, limited research has explored their potential connection with congenital heart disease (CHD). Objective: This study aimed to investigate the relationship between different types of PFAS and childhood CHD using a mixed analysis approach. Methods: A hospital-based case-control study was conducted involving 282 children with CHD and 282 control participants. Plasma samples were analyzed for 19 PFAS congeners. Logistic regression, Bayesian kernel-machine regression (BKMR), and weighted quantile sum (WQS) models were employed to assess the association between individual PFAS and PFAS mixtures with CHD risk. Results: Analysis of 564 subjects revealed higher plasma concentrations of various PFAS compounds in the CHD-group. Logistic regression identified significant associations between CHD risk and specific PFAS, notably 6:2 Chlorinated polyfluoroalkyl ether sulfonic acid (6:2 Cl-PFESA)(OR=1.65; 95%CI:1.40-1.94), 8:2 8:2 Cl-PFESA(OR=1.69; 95%CI: 1.69-2.19), Perfluorobutanoic acid (PFBA)(OR=2.68; 95%CI: 2.28-3.15), Perfluorobutane sulfonic acid (PFBS)(OR=2.38; 95%CI: 1.77-3.22), Perfluorohexanoic acid (PFHxA)(OR=2.62; 95%CI: 1.99-3.45), and Perfluorotetradecanoic acid (PFTeDA)(OR=2.18; 95%CI: 1.81-2.63). BKMR analysis confirmed these findings. WQS analysis emphasized PFBA, 8:2 Cl-PFESA, PFHxA, and PFTeDA as key contributors to the association between PFAS mixture exposure and CHD risk. Conclusions: Exposure to PFAS mixtures was associated with an increased risk of CHD in children, with 6:2 Cl-PFESA, 8:2 ClPFESA, PFBA, PFHxA, and PFTeDA playing significant roles.
Keywords: Per- and polyfluoroalkyl substances, congenital heart disease, Mixed analysis, bayesian kernel-machine regression, weighted quantile sum
Received: 03 Jul 2025; Accepted: 10 Nov 2025.
Copyright: © 2025 Jiao, Zhao, Xu, Gao, Tang, Wu, Yang, Huang, Guo, Sun and Chen. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence:
Yi Guo, gy_guoyi@tongji.edu.cn
Kun Sun, sunkun@xinhuamed.com.cn
Sun Chen, chensun@xinhuamed.com.cn
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