Potential pathophysiologic mechanisms linking air pollution exposure in pregnant women to reduced birth weight

孕妇空气污染暴露与出生体重减轻之间的潜在病理生理机制

• 批准号: 9567836
• 负责人: DAVID Quincy RICH
• 金额: $ 50.07万
• 依托单位: UNIVERSITY OF ROCHESTER
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-09-30 至 2022-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9567836
• 关键词: Address; Adult; Affect; Air; Air Pollutants; Air Pollution; Amino Acids; Antibodies; Benzo(a)pyrene; Biological; Biological Markers; Biometry; Birth; Birth Weight; Blood; Calendar; Caliber; Cessation of life; Child; Country; DNA Methylation; Data; Development; Discipline of obstetrics; Disease; Dose; Enrollment; Epidemiology; Epigenetic Process; Exposure to; Fetal Growth; Fetal Growth Retardation; Fetal Weight; Fetus; Functional disorder; Future; Genes; Goals; Growth; Growth and Development function; Gynecology; Health; High birth weight infant; Hospitals; Impairment; Inflammation; International; Late pregnancy; Lead; Life; Link; Low Birth Weight Infant; Lung; Measurement; Measures; Mediating; Meta-Analysis; Metabolic; Methylation; Monitor; Morbidity - disease rate; Mothers; Neonatology; Nutrient; Outcome; Oxidative Stress; Parents; Particulate Matter; Pathway interactions; Pattern; Placenta; Placentation; Play; Pollution; Pre-Eclampsia; Pregnancy; Pregnant Women; Proxy; Rattus; Regulation; Regulator Genes; Respiratory physiology; Risk; Risk Factors; Role; Sampling; Science; Smoke; Statistical Methods; Term Birth; Tern; Time; Tissue Sample; Tissues; Umbilical Cord Blood; Urine; Vascularization; Visit; Vitamins; Weight Gain; Woman; Work; ambient air pollution; base; clinical care; coarse particles; cohort; epigenetic regulation; experience; fetal; imprint; improved; in utero; mortality; novel; pollutant; pregnant; premature; prevent; receptor mediated endocytosis; reproductive; research study; response

Fetal growth restriction is an important risk factor for future child and adult morbidity and mortality. Thus, un- derstanding biological mechanisms and preventing exposures during pregnancy that can impact fetal growth have important implications for future child and adult health. Outdoor air pollution has been deemed a signifi- cant health risk contributing annually to 3.2 million premature deaths and 76 million years of healthy life lost globally. Work by our group and others have shown associations between increased air pollution and de- creased birth weight (a proxy of fetal growth restriction). In our previous R01 study, we found that when the ambient concentrations of particulate matter and gaseous pollutants were substantially reduced during the 2008 Beijing Olympics (August 8-September 24; 47 days), babies born to pregnant women living in Beijing whose 8th month of pregnancy was during this period, were 23g (95% CI = 5g, 40g) larger than babies born to pregnant women with their 8th month of pregnancy during the same calendar dates in 2007 or 2009. However, the biological mechanisms by which late pregnancy exposure may impair fetal growth (hence birth weight) are largely unknown to date. It is well appreciated that oxidative stress and inflammation can alter growth and de- velopment in utero, with both associated with preeclampsia and fetal growth restriction. Metabolic deficiencies have also been associated with fetal growth restriction. A factor that may mediate interactions between these pathways is the growth and development of the placenta, the conduit, controller, and anchor for the growth and development of the fetus. Alterations in placental growth and circulatory pattern development may have pro- found impacts on the growth of the fetus. Fetal growth is also controlled in part by genes that are genomically imprinted, a unique form of epigenetic regulation resulting in parent-of-origin-dependent methylation and ex- pression. Imprinted genes play a substantial role in placental function, including regulation of nutrient ex- change. With an overall goal to understand the pathophysiologic pathways linking air pollution and birth weight, we propose to enroll 660 newly pregnant women in Beijing, and measure biomarkers of these pathways in ma- ternal blood or urine at 5 visits during pregnancy and at birth, and in cord blood and placental tissue at birth. We will measure internal doses of combustion-generated pollutants at the same visits, and estimate address- specific ambient concentrations of air pollutants throughout pregnancy, to assess personal pollutant expo- sures. The multiple exposure metrics representing different exposure durations allow us to examine critical time windows during which pollutants may have strong effects on biomarkers and birth weight. This will be the first study to simultaneously examine whether air pollution induces changes in biomarkers of these pathways in pregnant women, the placenta, and/or the fetus, the first study to examine effects of air pollution on epigenetic regulation of critical growth regulatory genes in the placenta, and the first to explore whether these pathways mediate any birth weight (i.e. fetal growth) response to air pollution exposure.

胎儿生长限制是未来儿童以及成人发病率和死亡率的重要危险因素。因此， 阐述生物学机制并防止怀孕期间的暴露，可能会影响胎儿生长 对未来的儿童和成人健康具有重要意义。室外空气污染被认为是显着的 无法每年造成320万例过早死亡和7600万年健康生命的健康风险丧生 全球。我们小组和其他人的工作表明，空气污染的增加与降低之间的关联 出生体重（胎儿生长限制的代表）。在我们以前的R01研究中，我们发现 颗粒物物质和气态污染物的环境浓度大大降低了 2008年北京奥运会（8月8日至9月24日； 47天），居住在北京的孕妇出生的婴儿 怀孕的第8个月是在此期间，比出生的婴儿大23克（95％CI = 5G，40G） 孕妇在2007年或2009年的同一日历日期中怀孕了第8个月。但是， 晚期妊娠暴露可能损害胎儿生长（因此出生体重）的生物学机制是 迄今为止，基本上未知。非常理解的是，氧化应激和炎症会改变生长和消除 子宫内的速度，既与先兆子痫和胎儿生长限制有关。代谢缺陷 也与胎儿生长限制有关。可能介导这些相互作用的因素 途径是胎盘的生长和发育，导管，控制器和锚定，用于生长和 胎儿的发展。胎盘生长和循环模式发展的改变可能会产生 发现对胎儿的生长有影响。胎儿生长也部分由基因上的基因控制 印记，一种独特的表观遗传调节形式 压力。印迹基因在胎盘功能中起着重要作用，包括调节营养素的调节 改变。总体目标是了解将空气污染和出生体重联系起来的病理生理途径， 我们建议在北京招募660名新孕妇，并在MA-中测量这些途径的生物标志物 怀孕期间和出生时5次访问时以及脐带血和胎盘组织时进行5次尿液或尿液。 我们将在相同的访问中测量燃烧生成的污染物的内部剂量，并估算地址 - 在整个怀孕期间，特定的空气污染物的浓度，以评估个人污染物的展示 调查。代表不同暴露持续时间的多重暴露指标使我们能够检查关键 污染物可能会对生物标志物和出生体重产生强大影响的时间窗口。这将是 首次研究以同时检查空气污染是否诱导这些途径的生物标志物的变化 孕妇，胎盘和/或胎儿，这是第一个研究空气污染对表观遗传学影响的研究 调节胎盘中临界生长调节基因的调节，以及第一个探索这些途径是否 调解对空气污染暴露的任何出生体重（即胎儿生长）的反应。