Prenatal air pollution, fetal development and early childhood obesity risk

摘要 越来越多的证据表明，产前和早期接触环境应激源对 在包括儿童肥胖和代谢在内的多种儿童健康结局的病因中的作用 功能障碍。一个普遍存在的令人担忧的问题是颗粒性空气污染。产前空气污染暴露 与不良的胎儿生长结局有关，包括双顶径、头部和 腹围、股骨长度和低出生体重。与此同时，产前空气污染也已经 与儿童肥胖风险增加有关。对这一明显的悖论的一种解释是胎儿 编程假说，认为不适应的宫内环境会导致适应性 改变胎儿新陈代谢和为宫内生存而设计的激素环境的反应。因此，增长 在子宫内的限制与婴儿期更大的追赶生长和晚年肥胖的风险有关。A更多 胎儿发育的精密测量--脐静脉血流灌注的多普勒超声评估 胎儿肝脏--也会通过优先分配产前脂肪沉积的营养物质来影响胎儿生长 人体必需的营养素非常丰富。此外，脂肪因子瘦素和脂联素在胎儿发育中起着关键作用。 母体新陈代谢。我们假设空气污染会降低胎儿的生长发育并对其产生负面影响。 胎儿肝脏的血液流动，反过来又增加了儿童后期追赶生长和肥胖的风险。 我们进一步假设，脂联素和瘦素可能介导了这些观察到的效应。我们会 在Low的纵向妊娠队列中，在500名参与者中调查这些假设 收入，主要是西班牙裔，孕妇被称为母亲和发育风险来自 环境和社会应激源(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、成分和来源)暴露于1月1日) 超声测量胎儿生长和2)儿童肥胖症和儿童早期生长轨迹 从0-2岁，3)是否受母亲BMI、妊娠期糖尿病和婴儿性别的影响，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水平 空气污染物暴露与婴儿发育和肥胖之间的关系。这项建议解决了我们的 通过调查产前肥胖的具体作用来理解儿童肥胖风险的病因 环境对空气污染的暴露，以及空气污染的特定成分，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 肝脏血流量)。

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).