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，联合国- 了解可能影响胎儿生长的生物学机制和预防孕期暴露 对未来的儿童和成人健康有重要影响。室外空气污染已经被认为是一个重要的-- 健康风险不能导致每年320万人过早死亡和7600万人健康寿命的损失 全球范围内。我们小组和其他人的研究表明，空气污染增加和空气污染减少之间存在联系 出生体重增加(胎儿生长受限的指标)。在我们之前的R01研究中，我们发现当 环境中的颗粒物和气态污染物的浓度在 2008年北京奥运会(8月8日至9月24日；47天)，居住在北京的孕妇所生婴儿 在此期间怀孕8个月的婴儿比出生的婴儿大23g(95%CI=5g，40g) 怀孕8个月的孕妇在2007年或2009年的相同日历日期内怀孕。然而， 孕晚期暴露可能损害胎儿生长(从而损害出生体重)的生物学机制是 到目前为止，人们对此知之甚少。众所周知，氧化应激和炎症可以改变生长和死亡。 子宫内发育，两者都与先兆子痫和胎儿生长受限有关。代谢缺乏症 也与胎儿生长受限有关。一个因素可能会调节这些因素之间的互动 途径是胎盘的生长和发育，是生长和发育的管道、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有利于 发现了对胎儿生长的影响。胎儿的生长也在一定程度上受基因控制。 印记，一种独特的表观遗传调控形式，导致父母来源依赖的甲基化和前 压迫感。印迹基因在胎盘功能中发挥着重要作用，包括对营养成分的调节。 变化。总体目标是了解空气污染与出生体重之间的病理生理联系， 我们建议在北京招募660名新怀孕妇女，并检测这些途径的生物标志物。 在怀孕和出生时5次检查时的体内血液或尿液，以及出生时脐带血和胎盘组织中的。 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- 怀孕期间特定环境空气污染物浓度，以评估个人污染物博览会- 苏尔斯。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 首次同时研究空气污染是否会导致这些途径的生物标记物在 孕妇、胎盘和/或胎儿，首次研究空气污染对表观遗传学的影响 调控胎盘中的关键生长调节基因，并首次探索这些途径是否 调节任何出生体重(即胎儿生长)对空气污染暴露的反应。