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

细颗粒物，胎儿生长

• 批准号: 10227264
• 负责人: Kristina Walker Whitworth
• 金额: $ 33.75万
• 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/10227264
• 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.

项目摘要/摘要 空气污染与一系列健康结果有关；虽然历史上，重点一直放在心肺 效果，最近的毒理学和流行病学证据表明神经毒性作用，尤其是颗粒物（PM）。 产前和后PM的暴露与不良儿童神经发育结果有关，尽管很重要 有关曝光关键窗口的问题仍未得到解答。鉴于儿童的发展潜力（在 除胎儿外，暴露时机对于确定暴露结果关系的特定性质至关重要。缺少 大儿科同胞 研究阻碍了定义确定儿童健康的因素的复杂相互作用的努力，并仔细检查 与对环境暴露易感性的关键窗口有关的假设。在子宫里暴露于PM时 对儿童神经发育结果有直接影响，这种效果可能由 通过子宫胎儿生长介导并调节的产前暴露。到目前为止，胎儿生长在儿童中的作用 神经发育主要基于对出生的早产儿童或小胎龄（SGA）的研究。尽管 便利和低成本，出生时的措施不会捕获胎儿生长的动态性质。另外，人体测量学 出生时的措施提供了怀孕初期胎儿生长特别差的措施，这可能很重要 许多环境污染物（例如空气污染）的暴露期。拟议的研究的主要目标是 评估儿童认知功能的空气动力学直径<2.5微米（PM2.5）的关键窗口 和四岁和七岁的行为结果，这项研究的次要目标是更好地了解 在将PM2.5与儿童神经发育联系起来的因果途径中，胎儿生长的作用尤其是头部生长。这 研究将在INMA（西班牙昆虫y Medio Ambiente）项目的儿童中进行，这是一个出生网络 西班牙队列。 INMA独特，包括对儿童神经认知的广泛标准化和客观度量 在多个时间点的行为结果，胎儿生长的串行指标（每位女性至少三个超声波）和 广泛的住宅和健康历史。这些数据中的许多数据在其他大型童年队列中都无法使用。迅速 胎儿发育期，婴儿期和幼儿期的发展，对机制有更完整的理解 产后和产后空气污染暴露会影响儿童神经发育以及潜在的窗户 敏感性可能会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 提出利用新方法来利用在既定的怀孕队列中收集的大量数据 评估和评估个人住宅PM2.5暴露的估计值，并将新颖的统计方法应用于 确定对PM2.5敏感性的关键窗口。这项研究将解决对我们能力的关键障碍的差距 将儿童健康模型转化为儿科健康促进和疾病预防的策略。