A mechanistic study of prenatal air pollution exposure and offspring obesity risk

 描述(由申请人提供) 预防儿童肥胖是一项紧迫的公共卫生优先事项。疾病控制和预防中心报告称，2012年美国有17%的儿童和青少年患有肥胖症，肥胖症儿童可能会经历更高的年龄相关发病率和死亡率的终生风险。早期生活中的环境暴露可能会促进儿童肥胖的发展和相关的不利心脏代谢结果。具体地说，母亲在怀孕期间暴露于颗粒物和气态空气污染物可能会导致后代肥胖和出生后生长轨迹的改变。以前的流行病学研究已经确定了空气污染暴露与儿童超重或肥胖之间的联系，但很少研究产前暴露于空气污染的情况，或者测量母亲或婴儿中可能调节观察到的关系的生物因素。这项拟议的研究深入评估了产前暴露于与交通相关的空气污染可能在后代肥胖和儿童早期超重和肥胖中所起的作用，考虑到母血和脐带血中的炎性标志物以及脐带血中DNA甲基化的表观遗传学标志物。这一职业发展奖的总体目标是推动候选人进入环境流行病学的独立研究生涯，重点是产前暴露于环境毒物对健康的长期影响。在该奖项的指导培训期间获得的分析技能将包括使用基于地理信息系统的空间暴露评估和建模方法、实施先进的统计方法以评估可能的因果调解，以及在流行病学研究中分析和解释表观遗传标记。这些技能将通过在流行病学、地理学和环境科学、大气科学、遗传学和基因组学以及生物统计学和信息学等领域的有指导的独立学习、课程工作和与经验丰富的教师的合作来发展。在一项现有的纵向产前队列研究中，候选人将使用空间建模方法来估计居民在怀孕期间暴露于与交通相关的空气污染中，这项研究的重点是肥胖和相关心脏代谢障碍的发育根源。储存的孕妇和脐带血清样本将被分析以寻找全身炎症的标志，这可能与交通相关的空气污染暴露以及后代超重和肥胖的风险有关。在奖励的独立期内，候选人将使用在指导期制定的暴露评估来评估产前暴露于与交通相关的空气污染与后代肥胖和肥胖之间的联系。母体和胎儿的全身炎症和子代脐带血中的DNA甲基化将被调查为可能的关联中介。该项目将对空气污染流行病学和影响儿童肥胖风险的早期环境因素领域做出重大贡献。

 DESCRIPTION (provided by applicant) The prevention of childhood obesity is an urgent public health priority. The Centers for Disease Control and Prevention reported that 17% of children and adolescents in the US had obesity in 2012, and children with obesity may experience higher lifetime risks of age-specific morbidity and mortality. Environmental exposures in early life may promote the development of obesity and related adverse cardio-metabolic outcomes in children. Specifically, maternal exposure to particulate and gaseous air pollutants during pregnancy may lead to programming of offspring adiposity and altered postnatal growth trajectories. Previous epidemiologic studies have identified associations between air pollution exposure and childhood overweight or obesity, but have rarely looked at exposures in the prenatal period, or measured biological factors in the mother or infant that could mediate the observed relationship. The proposed research is an in-depth evaluation of the role that prenatal exposure to traffic-related air pollution may play in offspring adiposity and early childhood overweight and obesity, considering as mediators both inflammatory markers in maternal and umbilical cord blood, and epigenetic markers of DNA methylation in umbilical cord blood. The overall aim of this Career Development Award is to advance the candidate into an independent research career in environmental epidemiology, with an emphasis on the long-term health effects of exposure to environmental toxicants during the prenatal period. The analytical skills acquired during the mentored training period of this award will include the use of geographic information systems-based methods of spatial exposure assessment and modeling, the implementation of advanced statistical methods to evaluate possible causal mediation, and the analysis and interpretation of epigenetic markers in epidemiologic studies. These skills will be developed through mentored independent study, course work, and collaboration with experienced faculty in the fields of Epidemiology, Geography and Environmental Sciences, Atmospheric Science, Genetics and Genomics, and Biostatistics and Informatics. The candidate will use spatial modeling methods to estimate residential exposure to traffic-related air pollution during pregnancy in an existing longitudinal pre-birth cohort study focused on the developmental origins of obesity and related cardio-metabolic disorders. Stored maternal and umbilical cord serum samples will be analyzed for markers of systemic inflammation, which may be linked to traffic-related air pollution exposure and also to offspring risk for overweight and obesity. During the independent period of the award, the candidate will use the exposure assessment developed in the mentored period to estimate associations between prenatal exposure to traffic-related air pollution and offspring adiposity and obesity. Maternal and fetal systemic inflammation and offspring DNA methylation in umbilical cord blood will be investigated as possible mediators of the association. The project will make a substantial contribution to the field of air pollution epidemiology and the early-life environmental factors that influence childhood obesity risk.