Prenatal air pollution, fetal development and early childhood obesity risk

产前空气污染、胎儿发育和儿童早期肥胖风险

• 批准号: 10170357
• 负责人: Carrie Van Doren Breton
• 金额: $ 64.05万
• 依托单位: UNIVERSITY OF SOUTHERN CALIFORNIA
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-06-01 至 2023-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10170357
• 关键词: 4 year old; Abdomen; Address; Adipose tissue; Adult; Affect; Age-Months; Air Pollutants; Air Pollution; Basal metabolic rate; Birth; Birth Weight; Blood; Blood flow; Body Weight; Body fat; Body mass index; Brain; Caliber; Carbon; Child; Childhood; Clinical; Communication; County; Data; Deposition; Development; Doppler Ultrasound; Elderly; Environmental Exposure; Environmental Risk Factor; Etiology; Exposure to; Fatty acid glycerol esters; Femur; Fetal Development; Fetal Growth; Fetal Liver; Fetal Weight; Fossil Fuels; Gestational Diabetes; Glucose; Growth; Head; Head circumference; Health; Hispanics; Hormonal; Human; Infant; Insulin Resistance; Length; Leptin; Life; Liver; Los Angeles; Low Birth Weight Infant; Low income; Measurement; Measures; Mediating; Metabolic; Metabolic dysfunction; Metabolism; Monitor; Neonatal; Nitrogen Dioxide; Nutrient; Obesity; Outcome; Overweight; Ozone; Participant; Particulate; Particulate Matter; Perfusion; Phenotype; Placenta; Play; Pregnancy; Pregnant Women; Prevention strategy; Proteins; Public Health; Risk; Role; Shunt Device; Source; Structure of ductus venosus; Testing; Time; Ultrasonography; Umbilical Cord Blood; Umbilical vein; Venous; absorption; adipokines; adiponectin; adult obesity; cohort; design; early childhood; early life exposure; environmental stressor; fetal; fetal blood; fetal programming; fine particles; food consumption; in utero; infancy; innovation; intrauterine environment; maternal serum; newborn adiposity; obesity in children; obesity risk; offspring; prenatal; prenatal environmental exposure; prenatal exposure; psychosocial stressors; rapid weight gain; response; sex; social stressor

ABSTRACT A growing body of evidence suggests that prenatal and early-life exposures to environmental stressors play a role in the etiology of multiple childhood health outcomes including childhood obesity and metabolic dysfunction. One pervasive exposure of concern is particulate air pollution. Prenatal exposure to air pollution has been associated with adverse fetal growth outcomes, including decreased biparietal diameter, head and abdominal circumference, femur length, and low birth weight. At the same time, prenatal air pollution has also been associated with increased risk for childhood obesity. One explanation for this apparent paradox is a fetal programming hypothesis, which holds that a maladaptive intrauterine environment leads to an adaptive response that alters the fetal metabolic and hormonal milieu designed for intrauterine survival. Thus, growth restriction in utero is associated with greater catch-up growth in infancy and obesity risk later in life. A more sophisticated metric of fetal development—the Doppler ultrasound assessment of umbilical venous perfusion of the fetal liver—also influences fetal growth by prioritizing nutrient allocation for prenatal fat deposition when essential nutrients are plentiful. Moreover, the adipokines leptin and adiponectin play key roles in fetal- maternal metabolism. We hypothesize that air pollution decreases fetal growth and negatively alters fetal liver blood flow which in turn increases the risk of catch-up growth and obesity in later childhood. We further hypothesize that adiponectin and leptin may mediate these observed effects. We will investigate these hypotheses in a subset of 500 participants in the longitudinal pregnancy cohort of low income, predominantly Hispanic, pregnant women known as the Maternal And Developmental Risks from Environmental and Social Stressors (MADRES) Cohort. The specific aims include investigating the effects of personal prenatal air pollution (NO2, BC, BrC, PM2.5 mass, its components and sources) exposure on 1) ultrasound-derived fetal growth measures and 2) childhood adiposity and early childhood growth trajectories from 0 - 2 years, 3) whether associations are modified by maternal BMI, GDM, and infant sex, and 4) whether protein levels of leptin and adiponectin in maternal serum, placenta, and cord blood mediate associations between air pollutant exposures and infant growth and adiposity. This proposal addresses a critical gap in our current understanding of the etiology of childhood obesity risk by investigating the specific role of prenatal environmental exposures to air pollution, and specific constituents of air pollution, using state-of-the-art personal monitoring to reduce exposure measurement error and innovative phenotyping of fetal growth (fetal liver blood flow).

抽象的 越来越多的证据表明，产前和生命早期暴露于环境压力源中起着重要作用。 在多种儿童健康结果（包括儿童肥胖和代谢）的病因学中的作用 功能障碍。一种普遍令人担忧的暴露是颗粒物空气污染。产前暴露于空气污染 与不良的胎儿生长结果相关，包括双顶径、头部和 腹围、股骨长度和低出生体重。与此同时，产前空气污染也 与儿童肥胖风险增加有关。对这一明显悖论的一种解释是胎儿 编程假说，该假说认为，适应不良的宫内环境会导致适应不良的宫内环境。 改变为宫内生存而设计的胎儿代谢和激素环境的反应。因此，增长 子宫内的限制与婴儿期的追赶性生长和以后的肥胖风险有关。一个更多 胎儿发育的复杂指标——脐静脉灌注的多普勒超声评估 胎儿肝脏的影响——也会通过优先考虑产前脂肪沉积的营养分配来影响胎儿的生长 必需的营养素很丰富。此外，脂肪因子瘦素和脂联素在胎儿 母体代谢。我们假设空气污染会降低胎儿的生长并对胎儿产生负面影响 胎儿肝脏血流量增加了儿童后期追赶性生长和肥胖的风险。 我们进一步假设脂联素和瘦素可能介导这些观察到的效应。我们将 在低生育率纵向妊娠队列中的 500 名参与者的子集中研究这些假设 收入，主要是西班牙裔，孕妇被称为孕产妇和发育风险 环境和社会压力源 (MADRES) 队列。具体目标包括调查以下因素的影响： 个人产前空气污染（NO2、BC、BrC、PM2.5 质量、其成分和来源）暴露于 1) 超声衍生的胎儿生长测量和 2) 儿童肥胖和儿童早期生长轨迹 从 0 到 2 岁，3) 关联是否会因母亲 BMI、GDM 和婴儿性别而改变，以及 4) 是否 母体血清、胎盘和脐带血中瘦素和脂联素的蛋白质水平介导关联 空气污染物暴露与婴儿生长和肥胖之间的关系。该提案解决了我们的一个关键差距 通过调查产前检查的具体作用，目前对儿童肥胖风险病因学的了解 使用最先进的技术，了解空气污染的环境暴露情况以及空气污染的具体成分 个人监测，以减少暴露测量误差和胎儿生长的创新表型（胎儿 肝血流量）。