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).

摘要 越来越多的证据表明，产前和生命早期暴露于环境压力源， 在多种儿童健康结局病因学中的作用，包括儿童肥胖和代谢 功能障碍一个令人担忧的普遍暴露是颗粒空气污染。产前暴露于空气污染 与不利的胎儿生长结果有关，包括双顶径减小，头和 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。对这一明显的矛盾现象的一种解释是， 编程假设，认为适应不良的宫内环境导致适应性 改变胎儿代谢和激素环境的反应，为宫内生存而设计。因此，增长 宫内限制与婴儿期更大的追赶性生长和以后生活中肥胖的风险有关。一个更 胎儿发育的复杂指标--多普勒超声评估脐静脉血流灌注 胎儿肝脏-也影响胎儿生长的优先营养分配产前脂肪沉积时， 必需的营养物质丰富。此外，脂肪因子瘦素和脂联素在胎儿发育中起关键作用。 母体代谢我们假设空气污染会降低胎儿的生长， 胎儿肝脏血流量，这反过来又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 在一个500名低血糖纵向妊娠队列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（MADRES）队列。具体目标包括调查 个人产前空气污染（NO2，BC，BrC，PM2.5质量，其组分和来源）暴露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 0 - 2岁，3）母亲BMI、GDM和婴儿性别是否改变了相关性，以及4） 母体血清、胎盘和脐带血中的瘦素和脂联素蛋白水平介导了相关性 空气污染物暴露与婴儿生长和肥胖之间的关系。这一建议解决了我们在这方面的一个关键差距。 通过调查产前肥胖的特殊作用， 环境暴露于空气污染，以及空气污染的具体成分，使用最先进的 个人监测，以减少暴露测量误差和创新的胎儿生长表型（胎儿 肝血流）。