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

本研究旨在检查神经发育的后果（特别是ADHD表型的风险）， 产前产妇空气污染暴露，并检查两个潜在的机制，产前产妇 炎症和后代睡眠中断。流行病学研究支持这种关联;然而， 研究尚未确定（1）重要的暴露期，（2）污染物暴露效应独立于 社会经济地位和逆境，（3）后代性别效应，（4）潜在机制。空气污染 在弱势群体中，暴露往往更高;不考虑社会经济和 参与者的逆境史有报告混杂效应的风险。我们将通过以下方式弥补差距： 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ADHD风险我们将在婴儿期（~2周）和新生儿期（~ 12周）检查后代脑白色物质两次。 童年（2-9岁）。我们将在两代波多黎各人的流行病学队列中开展工作， 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。 我们将研究BYS-ECHO儿童（第2代; G2），他们目前正在婴儿期接受扫描 （UH 3 OD 023328），并建议重新评估幼儿期（n=84; 12-24个月）的白色物质发育，或 儿童期（n=98; 6- 9岁）。我们将使用高浓度的PM2.5指数来评估母亲产前PM2.5暴露的影响。 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的ADHD相关神经回路和表型的影响，同时控制 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，并测试两个提出的潜在机制：（Aim 1）产前 母体炎症，或（目标2）后代睡眠不足（通过家庭活动记录评估测量）。 母体炎症是一种产前机制，因此我们在Aim 1中假设， 将出现在婴儿和幼儿/儿童MRI中。因为后代的睡眠是出生后的机制， 在这个替代（目标2）假设中，我们预测了幼儿/儿童期ADHD神经回路的改变，但没有 在新生儿中。我们也有可能找到对这两个目标的支持，在这种情况下，我们将独一无二地准备好， 研究累积效应和交互效应。我们还将检验婴儿性别的调节作用（目标3）， 根据临床前研究，假设男性对产前空气更敏感 污染这项研究将是第一个利用婴儿纵向神经成像来了解产前空气 污染暴露。我们将能够独特地将产前PM2.5暴露的影响与那些 出生后因素和PM2.5对大脑发育的影响，并测试两种假定的机制，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.