Schrott Rose, Ladd-Acosta Christine, Padmanabhan Vasantha, Barr Dana Boyd, Breton Carrie V, Cardenas Andres, Carignan Courtney C, Dabelea Dana, Dunlop Anne L, Fallin Danielle M, Hivert Marie-France, Howerton Ellen M, Knight Anna K, Oken Emily, Peterson Alicia K, Petriello Michael C, Ruden Douglas, Schmidt Rebecca J, Smith Alicia K, Starling Anne P, Yang Ivana V, Zhu Yeyi, Goodrich Jaclyn M
Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD 21205, United States.
Department of Pediatrics, University of Michigan, Ann Arbor, MI 48109, United States.
Environ Epigenet. 2025 Apr 24;11(1):dvaf010. doi: 10.1093/eep/dvaf010. eCollection 2025.
Gestation is a vulnerable window when exposure to per- and polyfluoroalkyl substances (PFAS) may impact child development and health. Epigenetic modification, including DNA methylation (DNAm), may be one mechanism linking prenatal PFAS exposure to offspring outcomes. We tested associations between prenatal PFAS and newborn DNAm in 1017 participants from 6 cohorts in the US Environmental influences on Child Health Outcomes consortium. Concentrations of PFAS [perfluorooctanesulfonic acid (PFOS), perfluorooctanoic acid (PFOA), perfluorohexanesulfonic acid (PFHxS), perfluorononanoic acid (PFNA), and perfluorodecanoic acid] were measured in maternal serum or plasma. DNAm was quantified in newborn dried blood spot or umbilical cord blood leukocytes using the Infinium HumanMethylation450 (450K) or MethylationEPIC (EPIC) arrays. We tested associations between prenatal PFAS and neonatal blood DNAm on the 450K ( = 772) and EPIC ( = 245) arrays; results were meta-analysed across the platforms. Regional changes in DNAm were investigated, and findings were checked for replication in the Michigan Mother-Infant Pairs (MMIP) cohort ( = 140). Following correction for false discovery rate ( = 0.1 for meta-analyses), we identified an association between PFHxS and one cytosine-guanine (CpG) mapped to ( = 0.065) that replicated in MMIP ( = .006). PFOS was associated with six CpG sites, of which five were mapped to the genes , and . One differentially methylated region (DMR) was associated with prenatal PFOA exposure, and one DMR was associated with PFOS exposure. In this multicohort analysis including a diverse group from the USA, PFOA, PFOS, PFHxS, and PFNA exposures in pregnancy were associated with offspring DNAm, and the implications for children's health merit further exploration.
孕期是一个脆弱的时期，在此期间接触全氟和多氟烷基物质（PFAS）可能会影响儿童发育和健康。表观遗传修饰，包括DNA甲基化（DNAm），可能是将产前PFAS暴露与后代结局联系起来的一种机制。我们在美国儿童健康结果环境影响联盟的6个队列中的1017名参与者中测试了产前PFAS与新生儿DNAm之间的关联。在孕妇血清或血浆中测量了PFAS[全氟辛烷磺酸（PFOS）、全氟辛酸（PFOA）、全氟己烷磺酸（PFHxS）、全氟壬酸（PFNA）和全氟癸酸]的浓度。使用Infinium HumanMethylation450（450K）或MethylationEPIC（EPIC）阵列对新生儿干血斑或脐带血白细胞中的DNAm进行定量。我们在450K（n = 772）和EPIC（n = 245）阵列上测试了产前PFAS与新生儿血液DNAm之间的关联；对各平台的结果进行了荟萃分析。研究了DNAm的区域变化，并在密歇根母婴对（MMIP）队列（n = 140）中检查了研究结果的重复性。在校正错误发现率（荟萃分析为0.1）后，我们发现PFHxS与一个映射到的胞嘧啶-鸟嘌呤（CpG）之间存在关联（P = 0.065），该关联在MMIP队列中得到了重复（P = 0.006）。PFOS与6个CpG位点相关，其中5个映射到基因、和。一个差异甲基化区域（DMR）与产前PFOA暴露相关，一个DMR与PFOS暴露相关。在这项包括来自美国不同群体的多队列分析中，孕期暴露于PFOA、PFOS、PFHxS和PFNA与后代DNAm相关，对儿童健康的影响值得进一步探索。
