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.

项目摘要/摘要 空气污染与一系列健康后果有关；而从历史上看，重点一直是心肺。 效果，最近的毒理学和流行病学证据表明，神经毒性作用，特别是颗粒物(PM)。 出生前和出生后暴露于PM与儿童神经发育不良结局相关，尽管很重要 关于暴露的关键窗口的问题仍然没有得到回答。考虑到儿童的发展潜力(在 除了胎儿)，暴露时机在确定暴露-结局关系的具体性质方面至关重要。缺欠 大型儿科队列中详细的暴露数据(例如，生命过程中的多个个体水平的暴露估计) 研究阻碍了确定决定儿童健康的因素的复杂相互作用的努力，并仔细检查 与环境暴露易感性的关键窗口相关的假设。而在子宫内暴露于PM可能 对儿童神经发育结果有直接影响，这种影响可能受到以下因素的影响(或在 通过宫内胎儿生长调节和调节的产前暴露。到目前为止，胎儿生长发育在儿童中的作用 神经发育在很大程度上是基于对早产或小于胎龄(SGA)儿童的研究。而当 方便和低成本，出生时的措施没有捕捉到胎儿生长的动态本质。此外，人体测量学 出生时的测量提供了一个特别糟糕的早期怀孕期间胎儿生长发育的指标，这可能是一个重要的 许多环境污染物的暴露期，如空气污染。拟议研究的主要目标是 空气动力学直径2.5微米颗粒物(PM2.5)暴露对儿童认知功能的影响 以及四岁和七岁时的行为结果，这项研究的次要目标是更好地了解 胎儿生长，特别是头部生长，在PM2.5与儿童神经发育之间的因果关系中的作用。这 研究将在出生网络INMA(西班牙婴儿和媒体环境)项目的儿童中进行 在西班牙的队列。INMA的独特之处在于包括广泛的标准化和客观的儿童神经认知和 多个时间点的行为结果，胎儿生长的连续指标(每名妇女至少三次超声波检查)和 广泛的住宅史和健康史。其中许多数据在其他大型儿童队列中是无法获得的。假设速度很快 在胎儿发育过程中，对婴儿期和幼儿期的发育机制有了更完整的认识 通过出生前和出生后空气污染暴露影响儿童神经发育，以及潜在的 敏感性，可能有助于采取旨在减少早期暴露和最终减少疾病负担的干预措施。我 建议利用在既定怀孕队列中收集的丰富数据，利用新的方法 评估和评价个人住宅PM2.5暴露的估计值，并应用新的统计方法 确定易受PM2.5影响的关键窗口。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促进儿科健康和预防疾病的战略。