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

细颗粒物，胎儿生长

• 批准号: 10216537
• 负责人: Kristina Walker Whitworth
• 金额: $ 36.09万
• 依托单位: BAYLOR COLLEGE OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-08-01 至 2024-02-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10216537
• 关键词: Address; Adverse effects; Affect; Age; Air Pollutants; Air Pollution; Attention deficit hyperactivity disorder; Birth; Blood Vessels; Brain; Caliber; Cardiopulmonary; Child; Child Development; Child Health; Childhood; Cognitive; Cohort Studies; Complex; Conceptions; Cost Measures; Data; Development; Disease; Environmental Exposure; Environmental Pollution; Epidemiology; Evaluation; Exposure to; Fetal Development; Fetal Growth; Fetal Growth Retardation; Fetal Weight; Fetus; Goals; Growth; Head; Head circumference; Health; Health Care Costs; Health Promotion; Impaired cognition; Individual; Intervention; Life Cycle Stages; Link; Measures; Mediating; Mediation; Modeling; Nature; Neurocognitive; Outcome; Particulate Matter; Pathway interactions; Pediatric cohort; Placenta; Predisposition; Pregnancy; Prevalence; Problem behavior; Proxy; Recording of previous events; Role; Small for Gestational Age Infant; Spain; Standardization; Statistical Methods; Time; Toxicology; Translating; Ultrasonography; Woman; autism spectrum disorder; base; behavioral outcome; burden of illness; cognitive development; cognitive function; cohort; disorder prevention; early childhood; early pregnancy; family burden; fine particles; global environment; improved; in utero; infancy; neurodevelopment; neurotoxic; novel; novel strategies; postnatal; prenatal; prenatal exposure

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.

项目概要/摘要 空气污染与一系列健康结果相关；虽然从历史上看，重点一直是心肺 影响，最近的毒理学和流行病学证据表明神经毒性作用，特别是颗粒物（PM）。 产前和产后接触 PM 与儿童神经发育不良结果相关，尽管这一点很重要 有关关键暴露窗口的问题仍未得到解答。鉴于儿童的发展潜力（在 除了胎儿之外），暴露时间对于确定暴露与结果关系的具体性质至关重要。缺少 大型儿科队列中的详细暴露数据（例如，生命历程中多个个体水平的暴露估计） 研究阻碍了定义决定儿童健康的因素之间复杂的相互作用并仔细检查的努力 与环境暴露敏感性关键窗口相关的假设。在子宫内接触 PM 可能 对儿童神经发育结果有直接影响，这种影响可能会受到（或在以下情况下）的调节 通过子宫内胎儿生长介导和调节的产前暴露。到目前为止，胎儿生长对孩子的作用 神经发育主要基于对早产儿或小于胎龄儿 (SGA) 的研究。尽管 方便且成本低，出生时的测量无法捕捉胎儿生长的动态本质。此外，人体测量 出生时的测量提供了妊娠早期胎儿生长情况的特别差的指标，这可能是一个重要的指标 暴露于许多环境污染物（例如空气污染）的时期。拟议研究的主要目标是 评估接触空气动力学直径 < 2.5 微米的 PM (PM2.5) 对儿童认知功能的关键窗口 四岁和七岁的行为结果，这项研究的第二个目标是更好地了解 胎儿生长（尤其是头部生长）在 PM2.5 与儿童神经发育的因果关系中的作用。这 研究将在 INMA（西班牙 INfancia y Medio Ambiente）项目（一个出生网络）的儿童中进行 西班牙的队列。 INMA 的独特之处在于包括儿童神经认知和认知方面的广泛标准化和客观测量 多个时间点的行为结果、胎儿生长的系列指标（每位女性至少进行 3 次超声波检查）以及 广泛的居住史和健康史。其中许多数据在其他大型儿童群体中是无法获得的。给予快速 胎儿发育、婴儿期和幼儿期的发育，更全面地了解其机制 产前和产后的空气污染暴露会影响儿童的神经发育，以及潜在的窗口期 易感性，可以为旨在减少早期暴露并最终减轻疾病负担的干预措施提供信息。我 建议利用在已建立的妊娠队列中收集的大量数据，利用新方法 对个人住宅 PM2.5 暴露估计值进行评估和评估，并应用新颖的统计方法 确定对 PM2.5 敏感的关键窗口。这项研究将解决对我们的能力构成关键障碍的差距 将儿童健康模式转化为儿科健康促进和疾病预防的战略。