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

产前空气污染暴露与后代肥胖风险的机制研究

• 批准号: 9490474
• 负责人: Anne Starling
• 金额: $ 24.48万
• 依托单位: UNIVERSITY OF COLORADO DENVER
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-07-01 至 2020-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9490474
• 关键词: Address; Adolescent; Affect; Age; Air; Air Pollutants; Air Pollution; Aromatic Polycyclic Hydrocarbons; Award; Biological; Biological Factors; Biometry; Birth; Blood Cells; Body Composition; Body mass index; Carbon Monoxide; Centers for Disease Control and Prevention (U.S.); Child; Childhood; Chronic Disease; Cohort Studies; Collaborations; DNA Methylation; Data; Development; Diet; Ecology; Environmental Epidemiology; Environmental Exposure; Environmental Pollutants; Environmental Risk Factor; Epidemiologic Methods; Epidemiologist; Epidemiology; Epigenetic Process; Evaluation; Exposure to; Faculty; Fatty acid glycerol esters; Follow-Up Studies; Genomics; Geographic Information Systems; Geography; Growth; Health; Height; Infant; Inflammation; Inflammation Mediators; Informatics; Interleukin-6; K-Series Research Career Programs; Lead; Life; Link; Longitudinal cohort; Maternal Exposure; Measurement; Measures; Mediating; Mediation; Mediator of activation protein; Mentors; Metabolic; Metabolic Diseases; Methods; Modeling; Modification; Morbidity - disease rate; Mothers; Obesity; Outcome; Overweight; Parents; Particulate; Particulate Matter; Pathway interactions; Phase; Play; Plethysmography; Pregnancy; Pregnant Women; Prevention; Reporting; Research; Risk; Role; Sampling; Science of genetics; Serum; Specimen; Statistical Methods; TNF gene; Techniques; Toxic Environmental Substances; Training; Umbilical Cord Blood; Umbilical cord structure; Visit; Weights and Measures; Work; atmospheric sciences; base; cardiovascular disorder risk; career; cohort; density; disorder prevention; disorder risk; early childhood; early life exposure; environmental chemical; epidemiology study; epigenetic marker; experience; fetal; gestational weight gain; in utero; inflammatory marker; lifetime risk; maternal cigarette smoking; maternal obesity; methylation biomarker; mortality; obesity in children; obesity risk; offspring; postnatal; prenatal; prenatal exposure; prenatal influence; prevent; public health priorities; public health relevance; skills; spatial epidemiology; traffic-related air pollution

 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.

 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说，2012年美国17%的儿童和青少年患有肥胖症，肥胖儿童可能会经历更高的年龄特异性发病率和死亡率的终身风险。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良心脏代谢结果。具体而言，母亲在怀孕期间暴露于颗粒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改变的编程。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，但很少关注产前暴露，或测量母亲或婴儿中可能介导所观察到的关系的生物因素。拟议的研究是对产前暴露于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发挥的作用进行深入评估，将母体和脐带血中的炎症标志物以及脐带血中DNA甲基化的表观遗传标志物视为介质。该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的长期健康影响。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来评估可能的因果调解，以及分析和解释流行病学研究中的表观遗传标记。这些技能将通过指导独立研究，课程工作，并与经验丰富的教师在流行病学，地理和环境科学，大气科学，遗传学和基因组学，生物统计学和信息学领域的合作。候选人将使用空间建模方法来估计住宅暴露于交通相关的空气污染在怀孕期间在现有的纵向出生前队列研究，重点是肥胖和相关的心脏代谢紊乱的发展起源。将分析储存的母体和脐带血清样本的全身炎症标志物，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。在该奖项的独立期间，候选人将使用在指导期间开发的暴露评估来估计产前暴露于交通相关的空气污染与后代肥胖和肥胖之间的关联。母体和胎儿全身炎症和后代脐带血中DNA甲基化将作为可能的相关介质进行研究。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。