{"title":"Gestational exposure to poly/perfluoroalkyl substances and risk of congenital structural malformations: A nested case-control study.","authors":"Yanhong Wu, Yilin Lv, Shuang Ran, Wanqin Xie, Haiyan Zhou, Ziwei Zhang, Huamin Yuan, Xingli Li","doi":"10.1016/j.reprotox.2025.109074","DOIUrl":null,"url":null,"abstract":"<p><p>Congenital structural malformations (CSM) have become a significant public health and social issue, affecting the health status of children and the level of population quality. Emerging research increasingly suggests that environmental pollutants may contribute to the development of CSM. However, current epidemiologic evidence on the effects of per- and polyfluoroalkyl substances (PFAS) on CSM is limited and restrictive. A nested case-control study examined how maternal exposure to PFAS during pregnancy affects the risk of CSM. Logistic regression and Bayesian kernel machine regression (BKMR) were used to assess the effects of single PFAS and PFAS mixture exposure on CSM. Perfluorodecanoic acid (PDA) showed a strong positive association with CSM in the logistic regression model (Adjusted OR: 4.79, 95% CI: 1.55 ~ 18.52). The BKMR analysis indicated an increased risk of CSM as PFAS mixture levels rose above the 55th percentile. Individual PFAS were ranked by posterior inclusion probabilities (PIPs), with PDA (PIP = 1.00), perfluorooctanoic acid (PFOA) (PIP = 1.00), potassium 9-chlorohexadecafluoro-3-oxanonane-1-sulfonate (9Cl_PF3ONS) (PIP = 0.88), and perfluorononanoic acid (PFNA) (PIP = 0.82) contributing most to the mixture's effect on CSM. No significant interactions were observed between PFAS mixtures when other exposures were held constant at the 50th percentile. In conclusion, we found that prenatal exposure to PDA and PFAS mixtures was significantly linked to a heightened risk of CSM, with PDA, PFOA, 9Cl_PF3ONS, and PFNA being significant contributors to the mixture effect. In addition, our study did not identify any previous interactions of PFAS.</p>","PeriodicalId":21137,"journal":{"name":"Reproductive toxicology","volume":" ","pages":"109074"},"PeriodicalIF":2.8000,"publicationDate":"2025-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Reproductive toxicology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1016/j.reprotox.2025.109074","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"REPRODUCTIVE BIOLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
Congenital structural malformations (CSM) have become a significant public health and social issue, affecting the health status of children and the level of population quality. Emerging research increasingly suggests that environmental pollutants may contribute to the development of CSM. However, current epidemiologic evidence on the effects of per- and polyfluoroalkyl substances (PFAS) on CSM is limited and restrictive. A nested case-control study examined how maternal exposure to PFAS during pregnancy affects the risk of CSM. Logistic regression and Bayesian kernel machine regression (BKMR) were used to assess the effects of single PFAS and PFAS mixture exposure on CSM. Perfluorodecanoic acid (PDA) showed a strong positive association with CSM in the logistic regression model (Adjusted OR: 4.79, 95% CI: 1.55 ~ 18.52). The BKMR analysis indicated an increased risk of CSM as PFAS mixture levels rose above the 55th percentile. Individual PFAS were ranked by posterior inclusion probabilities (PIPs), with PDA (PIP = 1.00), perfluorooctanoic acid (PFOA) (PIP = 1.00), potassium 9-chlorohexadecafluoro-3-oxanonane-1-sulfonate (9Cl_PF3ONS) (PIP = 0.88), and perfluorononanoic acid (PFNA) (PIP = 0.82) contributing most to the mixture's effect on CSM. No significant interactions were observed between PFAS mixtures when other exposures were held constant at the 50th percentile. In conclusion, we found that prenatal exposure to PDA and PFAS mixtures was significantly linked to a heightened risk of CSM, with PDA, PFOA, 9Cl_PF3ONS, and PFNA being significant contributors to the mixture effect. In addition, our study did not identify any previous interactions of PFAS.
期刊介绍:
Drawing from a large number of disciplines, Reproductive Toxicology publishes timely, original research on the influence of chemical and physical agents on reproduction. Written by and for obstetricians, pediatricians, embryologists, teratologists, geneticists, toxicologists, andrologists, and others interested in detecting potential reproductive hazards, the journal is a forum for communication among researchers and practitioners. Articles focus on the application of in vitro, animal and clinical research to the practice of clinical medicine.
All aspects of reproduction are within the scope of Reproductive Toxicology, including the formation and maturation of male and female gametes, sexual function, the events surrounding the fusion of gametes and the development of the fertilized ovum, nourishment and transport of the conceptus within the genital tract, implantation, embryogenesis, intrauterine growth, placentation and placental function, parturition, lactation and neonatal survival. Adverse reproductive effects in males will be considered as significant as adverse effects occurring in females. To provide a balanced presentation of approaches, equal emphasis will be given to clinical and animal or in vitro work. Typical end points that will be studied by contributors include infertility, sexual dysfunction, spontaneous abortion, malformations, abnormal histogenesis, stillbirth, intrauterine growth retardation, prematurity, behavioral abnormalities, and perinatal mortality.