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: 9380415
• 负责人: DAVID Quincy RICH
• 金额: $ 51.46万
• 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/9380415
• 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; 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.

胎儿生长受限是未来儿童和成人发病率和死亡率的重要危险因素。因此， 了解生物学机制，预防怀孕期间可能影响胎儿生长的暴露 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一个严重的... 每年造成320万人过早死亡和7600万年的健康寿命损失 在全球我们小组和其他人的工作表明，空气污染的增加和空气质量的下降之间存在联系。 出生体重增加（胎儿生长受限的代表）。在我们之前的R 01研究中，我们发现， 年内，空气中的颗粒物和气体污染物浓度大幅下降， 2008年北京奥运会（8月8日至9月24日; 47天），婴儿出生的孕妇生活在北京 在此期间妊娠8个月的孕妇，其出生的婴儿比在此期间出生的婴儿大23 g（95%CI = 5 g，40 g）。 2007年或2009年同一日历日期怀孕8个月的孕妇。然而，在这方面， 妊娠晚期暴露可能损害胎儿生长（因此影响出生体重）的生物学机制如下 迄今为止基本上不为人知。众所周知，氧化应激和炎症可以改变生长和脱蛋白。 子宫内流产，两者均与先兆子痫和胎儿生长受限有关。代谢缺陷 也与胎儿生长受限有关。一个可能介导这些因素之间相互作用的因素 胎盘是胎盘的生长和发育，是胎盘生长和发育的管道、控制器和锚， 胎儿的发育。胎盘生长和循环模式发育的改变可能会促进 对胎儿的生长有影响。胎儿的生长也部分受到基因组上的基因控制， 印迹，一种独特的表观遗传调控形式，导致起源依赖于父母的甲基化和前 压力。印记基因在胎盘功能中发挥重要作用，包括调节营养素表达， 变化总体目标是了解空气污染和出生体重之间的病理生理途径， 我们建议在北京招募660名新怀孕的妇女，并在MA中测量这些途径的生物标志物， 妊娠期间和出生时5次访视时的胸骨血液或尿液，以及出生时的脐带血和胎盘组织。 我们将在同一次访问中测量燃烧产生的污染物的内部剂量，并估计地址- 整个怀孕期间空气污染物的特定环境浓度，以评估个人污染物暴露， 当然。代表不同暴露持续时间的多个暴露度量允许我们检查关键的 污染物可能对生物标志物和出生体重产生强烈影响的时间窗口。这将是 第一项研究同时检查空气污染是否会引起这些途径的生物标志物的变化， 孕妇，胎盘和/或胎儿，第一个研究空气污染对表观遗传的影响 调节胎盘中的关键生长调节基因，并首次探索这些途径是否 介导任何出生体重（即胎儿生长）对空气污染暴露的反应。