Fine Particulate Matter, Fetal Growth & Neurodevelopment: Examining Critical Windows of Susceptibility

项目总结/摘要 空气污染与一系列健康结果相关;而从历史上看，重点一直是心肺功能 最近的毒理学和流行病学证据表明，神经毒性效应，特别是颗粒物（PM）。 产前和产后暴露于PM与儿童神经发育不良结果有关，尽管重要的是， 关于接触的关键窗口的问题仍然没有答案。考虑到儿童的发展潜力（ 除胎儿外），暴露时间对于确定预后-结果关系的具体性质至关重要。缺乏 详细的曝光数据（例如，在大型儿科队列中，生命过程中的多个个体水平暴露估计值 研究阻碍了确定决定儿童健康的因素之间复杂的相互作用， 与环境暴露敏感性的临界窗口有关的假设。在子宫内暴露于PM可能 对儿童神经发育结果有直接影响，这种影响可能受到（或在 通过子宫内胎儿生长介导和调节的产前暴露。到目前为止，胎儿生长在儿童中的作用 神经发育的研究主要基于早产儿或小于胎龄儿（SGA）的研究。而 方便和低成本，出生时的测量不能捕捉胎儿生长的动态性质。此外，人体测量 出生时的测量提供了一个特别差的代表胎儿生长在怀孕早期，这可能是一个重要的 暴露于许多环境污染物，如空气污染。拟议研究的主要目标是 评估空气动力学直径< 2.5微米（PM2.5）的PM暴露对儿童认知功能的关键窗口 和行为结果，这项研究的第二个目标是更好地了解 胎儿生长的作用，特别是头部的生长，在因果通路连接PM2.5儿童神经发育。这 研究将在来自INMA（西班牙INFancia y Medio Ambiente）项目的儿童中进行，该项目是一个出生网络， 西班牙的军队INMA是独一无二的，包括广泛的标准化和客观的措施，儿童神经认知和 多个时间点的行为结果，胎儿生长的系列指标（每名妇女至少三次超声检查）， 广泛的居住和健康史。其中许多数据在其他大型儿童队列中无法获得。鉴于迅速 在胎儿发育过程中，婴儿期和幼儿期的发育，更完整的了解机制 产前和产后空气污染暴露影响儿童神经发育的途径，以及 易感性，可以为旨在减少早期暴露并最终减少疾病负担的干预措施提供信息。我 建议利用在既定妊娠队列中收集的大量数据， 评估和评价个人住宅PM2.5暴露的估计，并应用新的统计方法， 确定对PM2.5敏感的关键窗口。这项研究将解决差距，目前的关键障碍，我们的能力， 将儿童健康模式转化为儿科健康促进和疾病预防战略。

Project Summary/Abstract Air pollution is associated with a range of health outcomes; while historically, the focus has been on cardiopulmonary effects, recent toxicological and epidemiologic evidence indicates neurotoxic effects, especially of particulate matter (PM). Pre- and post-natal exposure to PM has been associated with adverse child neurodevelopmental outcomes, though important questions regarding critical windows of exposure remain unanswered. Given the developmental potential of children (in addition to the fetus), exposure timing is critical in determining the specific nature of exposure-outcome relationships. Lack of detailed exposure data (e.g., multiple individual-level exposure estimates over the life course) in large pediatric cohort studies hinders efforts to define the complex interplay of factors that determine child health and carefully examine hypotheses related to critical windows of susceptibility to environmental exposures. While in utero exposure to PM may have a direct effect on child neurodevelopmental outcomes, it is possible that this effect is moderated by (or in the case of prenatal exposures mediated through and moderated by) in utero fetal growth. Thus far, the role of fetal growth in child neurodevelopment has been largely based on studies in children born preterm or small-for-gestational age (SGA). While convenient and low cost, measures at birth do not capture the dynamic nature of fetal growth. Additionally, anthropometric measures at birth provide a particularly poor proxy of fetal growth during early pregnancy, which may be an important period of exposure for many environmental contaminants, such as air pollution. The primary goal of the proposed study is to evaluate critical windows of exposure to PM with aerodynamic diameter < 2.5 microns (PM2.5) on child cognitive function and behavioral outcomes at ages four and seven and the secondary goal of this study is to gain a better understanding of the role of fetal growth, and head growth in particular, in the causal pathway linking PM2.5 to child neurodevelopment. This study will be conducted among children from the INMA (Spanish INfancia y Medio Ambiente) project, a network of birth cohorts in Spain. INMA is unique in includes extensive standardized and objective measures of child neurocognitive and behavioral outcomes at multiple time points, serial indicators of fetal growth (at least three ultrasounds per woman) and extensive residential and health histories. Many of these data are unavailable in other large childhood cohorts. Given rapid development during fetal development, infancy and early childhood, a more complete understanding of the mechanism through which pre- and postnatal air pollution exposures affect child neurodevelopment, as well as potential windows of susceptibility, may inform interventions aimed at reducing early exposures and ultimately decreasing disease burden. I propose capitalizing on a wealth of data collected in an established pregnancy cohort, utilizing new approaches for assessment and evaluation of estimates of individual residential PM2.5 exposures, and applying novel statistical methods to identify critical windows of susceptibility to PM2.5. This study will address gaps that present critical barriers to our ability to translate models of child health into strategies for pediatric health promotion and disease prevention.