ABSTRACT

A barrier in the children’s environmental health field has been the lack of early-warning systems to identify risks of childhood illness and developmental disorders. We aimed to develop a methodology to identify an accessible biomarker measured in a small amount of blood to distinguish newborns at elevated risk from a toxic prenatal exposure, using air pollutants as a case study. Because air pollutants are associated with altered DNA methylation, we developed a pipeline using DNA methylation signatures measured in umbilical cord blood, which could be used as predictors of prenatal exposure. We used air pollution indicators, including modelled trimester-specific and pregnancy average NO₂ and PM_2.5, and DNA methylation signatures from Illumina arrays measured in two New York City-based longitudinal birth cohorts from the Columbia Centre for Children’s Environmental Health. We developed a screening plus three-part pipeline that incorporates selection, testing, and validation to identify whether DNA methylation can be used to predict exposure to prenatal air pollution indicators, NO₂ and PM_2.5. Applying this pipeline, we found that cord blood DNA methylation could be used to predict high vs. low average pregnancy NO₂ (AUC = 0.60, 95% CI: 0.52–0.68, with validation AUC = 0.60). Similar results were found for high vs. low third trimester NO₂. In this proof of concept study using air pollutants as an example, we provide an approach (with a generalizable analytic pipeline) that can be used for prediction of prenatal exposure to contaminants. This approach has potential to identify children at risk of developmental disorders and illness resulting from prenatal exposure.

摘要

儿童环境卫生领域的一个障碍是缺乏早期预警系统来识别儿童疾病和发育障碍的风险。我们旨在开发一种方法，以空气污染作为案例研究，以鉴定一种在少量血液中测得的可利用的生物标志物，以区分风险较高的新生儿与有毒的产前暴露。由于空气污染物与DNA甲基化的改变有关，因此我们开发了使用在脐带血中测得的DNA甲基化特征的管道，可以将其用作产前暴露的预测指标。我们使用了空气污染指标，包括模拟的孕晚期和妊娠平均NO ₂和PM _2.5，以及来自Illumina阵列的DNA甲基化标记在哥伦比亚儿童环境卫生中心的两个纽约市纵向出生队列中进行了测量。我们开发了包含选择，测试和验证的筛选加三部分管道，以识别DNA甲基化是否可用于预测产前空气污染指标NO ₂和PM _2.5的暴露。应用这一管道，我们发现脐血DNA甲基化可以用来预测平均妊娠NO _2的高低（AUC = 0.60，95％CI：0.52-0.68，验证的AUC = 0.60）。孕晚期NO _2的含量与低期NO _2的含量相似。在此以空气污染物为例的概念验证研究中，我们提供了一种方法（具有通用的分析管道），可用于预测产前污染物的暴露。这种方法有潜力识别因产前暴露而有发育障碍和疾病风险的儿童。