Center for Innovative Design and Analysis, Colorado School of Public Health, University of Colorado Anschutz Medical Campus, Aurora, CO, USA.
Center for Innovative Design and Analysis, Colorado School of Public Health, University of Colorado Anschutz Medical Campus, Aurora, CO, USA; Department of Biostatistics and Informatics, Colorado School of Public Health, University of Colorado Anschutz Medical Campus, Aurora, CO, USA.
Environ Res. 2023 Aug 15;231(Pt 2):116215. doi: 10.1016/j.envres.2023.116215. Epub 2023 May 22.
Per- and polyfluoroalkyl substances (PFAS) are ubiquitous, environmentally persistent chemicals, and prenatal exposures have been associated with adverse child health outcomes. Prenatal PFAS exposure may lead to epigenetic age acceleration (EAA), defined as the discrepancy between an individual's chronologic and epigenetic or biological age.
We estimated associations of maternal serum PFAS concentrations with EAA in umbilical cord blood DNA methylation using linear regression, and a multivariable exposure-response function of the PFAS mixture using Bayesian kernel machine regression.
Five PFAS were quantified in maternal serum (median: 27 weeks of gestation) among 577 mother-infant dyads from a prospective cohort. Cord blood DNA methylation data were assessed with the Illumina HumanMethylation450 array. EAA was calculated as the residuals from regressing gestational age on epigenetic age, calculated using a cord-blood specific epigenetic clock. Linear regression tested for associations between each maternal PFAS concentration with EAA. Bayesian kernel machine regression with hierarchical selection estimated an exposure-response function for the PFAS mixture.
In single pollutant models we observed an inverse relationship between perfluorodecanoate (PFDA) and EAA (-0.148 weeks per log-unit increase, 95% CI: -0.283, -0.013). Mixture analysis with hierarchical selection between perfluoroalkyl carboxylates and sulfonates indicated the carboxylates had the highest group posterior inclusion probability (PIP), or relative importance. Within this group, PFDA had the highest conditional PIP. Univariate predictor-response functions indicated PFDA and perfluorononanoate were inversely associated with EAA, while perfluorohexane sulfonate had a positive association with EAA.
Maternal mid-pregnancy serum concentrations of PFDA were negatively associated with EAA in cord blood, suggesting a pathway by which prenatal PFAS exposures may affect infant development. No significant associations were observed with other PFAS. Mixture models suggested opposite directions of association between perfluoroalkyl sulfonates and carboxylates. Future studies are needed to determine the importance of neonatal EAA for later child health outcomes.
全氟和多氟烷基物质（PFAS）是无处不在的、环境持久的化学物质，产前暴露与儿童健康不良后果有关。产前 PFAS 暴露可能导致表观遗传年龄加速（EAA），定义为个体的实际年龄与表观遗传或生物年龄之间的差异。
我们使用线性回归估计母体血清 PFAS 浓度与脐带血 DNA 甲基化中的 EAA 之间的关联，并使用贝叶斯核机器回归对 PFAS 混合物的多变量暴露-反应函数进行估计。
在一个前瞻性队列中，从 577 对母婴中检测了母体血清中的 5 种 PFAS（中位数：妊娠 27 周）。使用 Illumina HumanMethylation450 阵列评估脐带血 DNA 甲基化数据。EAA 是通过回归胎龄与基于脐带血的特定表观遗传时钟计算得到的表观遗传年龄的残差来计算的。线性回归测试了每个母体 PFAS 浓度与 EAA 之间的关联。具有层次选择的贝叶斯核机器回归估计了 PFAS 混合物的暴露-反应函数。
在单污染物模型中，我们观察到全氟癸酸（PFDA）与 EAA 呈负相关（每增加一个对数单位，-0.148 周，95%CI：-0.283，-0.013）。具有层次选择的全氟烷基羧酸盐和磺酸盐混合物分析表明，羧酸盐的组后验纳入概率（PIP）或相对重要性最高。在这个组中，PFDA 的条件 PIP 最高。单变量预测因子-反应函数表明，PFDA 和全氟壬酸与 EAA 呈负相关，而全氟己烷磺酸盐与 EAA 呈正相关。
母体妊娠中期血清 PFDA 浓度与脐带血中的 EAA 呈负相关，表明 PFAS 产前暴露可能影响婴儿发育的途径。其他 PFAS 未观察到显著关联。混合模型表明，全氟烷基磺酸盐和羧酸盐之间的关联方向相反。需要进一步的研究来确定新生儿 EAA 对以后儿童健康结果的重要性。
