Prenatal air pollution and neurodevelopment: a longitudinal neuroimaging study of mechanisms and early risk for ADHD in Puerto Rican children

本研究旨在研究以下因素对神经发育的影响(特别是对ADHD表型的风险) 产前接触空气污染和检查两种潜在机制，产前产妇 炎症和子代睡眠障碍。流行病学研究支持这种联系；然而， 研究尚未确定(1)重要的暴露时期，(2)污染物暴露的影响独立于 社会经济地位和逆境，(3)后代的性别影响，(4)潜在的机制。由于空气污染 在弱势社区中暴露的风险往往更高；不考虑社会经济和 参与者的逆境史存在报告混淆效果的风险。我们将通过以下方式解决差距 检查产前PM2.5暴露对神经发育的影响(通过MRI)，同时控制 出生后PM2.5、关键环境因素(代际逆境、SES、家庭功能)，以及 多基因多动症风险。我们将对后代的脑白质进行两次检查，分别是在婴儿期(~2周)和 儿童期(2-9岁)。我们将在两代波多黎各人的流行病学队列中工作，这些人已经 自2000年以来一直被跟踪，并仔细描述了逆境、家庭功能和精神疾病的特征。 我们将研究回声过多的儿童(第二代；G2的S)，他们目前正在婴儿期接受扫描 (UH3OD023328)，并提议重新评估学步儿童脑白质发育(n=84；12-24个月)或 儿童期(n=98；6-9岁)。我们将为母亲产前PM2.5暴露的影响编制指数，使用High 解析的时空预测模型(并通过便携式实时空气质量数据进行补充 子样本中的传感器)对G2‘S ADHD相关神经回路和表型进行研究，同时对照 上述变量。这项研究的主要目的是检查神经发育 产前PM2.5暴露的后果和测试两种拟议的潜在机制：(Aim1)产前 母体炎症，或(目标2)子代睡眠不足(通过家庭活动评估测量)。 母体炎症是一种产前机制，因此我们在目标1中假设神经回路改变 将出现在婴儿期和幼儿/儿童期核磁共振检查中。因为后代睡眠是一种出生后的机制， 在这个变化性(目标2)假设中，我们预测了幼儿/儿童ADHD神经回路的改变，但不是 在新生儿身上。我们也有可能找到对这两个目标的支持，在这种情况下，我们将独特地准备好 检查累积效应和交互效应。我们还将测试婴儿性别的调节作用(目标3)，以及 基于临床前研究，假设男性会表现出对产前空气更敏感 污染。这项研究将是第一次利用婴儿纵向神经成像来了解产前空气 污染暴露。我们将独一无二地将产前PM2.5暴露的影响与 出生后因素和PM2.5对大脑发育的影响，并测试两种可能的机制，这两种机制都是 潜在的可修改的干预目标。

This study aims to examine the neurodevelopmental consequences (specifically risk for ADHD phenotypes) of prenatal maternal air pollution exposure and to examine two potential mechanisms, prenatal maternal inflammation and offspring sleep disruptions. Epidemiological studies support this association; however, studies have yet to determine (1) important exposure periods, (2) pollutant exposure effects independent of socio-economic status and adversity, (3) offspring sex effects, and (4) the underlying mechanisms. Air pollution exposure is often higher in disadvantaged communities; studies that do not consider the socioeconomic and adversity history of participants run the risk of reporting confounded effects. We will address gaps by examining the influence of prenatal PM2.5 exposure on neurodevelopment (via MRI) while controlling for postnatal PM2.5, critical environmental aspects (intergenerational adversity, SES, family functioning), and polygenetic ADHD risk. We will examine offspring brain white matter twice, in infancy (~2 weeks) and in childhood (2-9 yrs). We will work within a two-generation, epidemiological cohort of Puerto Ricans that has been followed since 2000 and carefully characterized for adversity, family functioning, and psychiatric illness. We will study BYS-ECHO children (Generation 2; G2's), who are currently being scanned during infancy (UH3OD023328) and propose to re-assess white matter development in toddlerhood (n=84; 12-24 mos) or childhood (n=98; 6-9yrs). We will index the effects of mother’s prenatal PM2.5 exposure estimated using highly resolved spatio-temporal prediction models (and supplemented by real-time air quality data via portable sensors in a sub-sample) on G2’s ADHD-related neurocircuitry and phenotypes, while controlling for the aforementioned variables. The overarching aim of this study is to examine the neurodevelopmental consequences of prenatal PM2.5 exposure and test two proposed underlying mechanisms: (Aim1) prenatal maternal inflammation, OR (Aim 2) sleep deficits in offspring (measured via in-home actigraphy assessments). Maternal inflammation is a prenatal mechanism, thus we hypothesize in Aim 1 that neurocircuitry alterations will be present in both infancy and toddler/childhood MRIs. Because offspring sleep is a postnatal mechanism, in this alterative (Aim 2) hypothesis we predict alterations in ADHD neurocircuitry in toddler/childhood, but not in newborns. It is also possible we find support for both aims, in which case we would be uniquely poised to examine cumulative and interactive effects. We will also test the moderating role of infant sex (Aim 3), and based on pre-clinical studies, hypothesize that males would demonstrate more susceptibility to prenatal air pollution. This study will be the first to utilize infant longitudinal neuroimaging to understand prenatal air pollution exposure. We will be uniquely able to disassociate the effects of prenatal PM2.5 exposure from those of postnatal factors and PM2.5 on brain development, and to test two putative mechanisms, both of which are potential modifiable targets for intervention.