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: 9108099
• 负责人: Anne Starling
• 金额: $ 7.94万
• 依托单位: UNIVERSITY OF COLORADO DENVER
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-05-01 至 2018-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9108099
• 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; Epidemiologic Studies; Epidemiologist; Epidemiology; Epigenetic Process; Evaluation; Exposure to; Faculty; Fatty acid glycerol esters; Genomics; Geographic Information Systems; Geography; Growth; Health; Height; Infant; Inflammation; Informatics; Interleukin-6; K-Series Research Career Programs; Lead; Life; Link; 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; Perinatal Exposure; Phase; Play; Plethysmography; Pregnancy; Pregnant Women; Prevention; Reporting; Research; Risk; Role; Sampling; Science of genetics; Serum; Smoking; 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; early childhood; early life exposure; environmental chemical; epigenetic marker; experience; fetal; follow-up; gestational weight gain; in utero; inflammatory marker; lifetime risk; mortality; obesity in children; obesity risk; offspring; postnatal; prenatal; prenatal exposure; prenatal influence; prevent; programs; public health priorities; public health relevance; skills; traffic-related air pollution; trafficking

 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） 预防儿童肥胖是紧急的公共卫生优先事项。疾病控制与预防中心报告说，2012年，美国有17％的儿童和青少年患有肥胖症，肥胖症儿童可能会出现更高的终生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和相关不良心脏代谢结果的发展。具体而言，怀孕期间的母体暴露于颗粒和气态空气污染物可能会导致后代肥胖的编程和产后生长轨迹的改变。先前的流行病学研究已经确定了空气污染的暴露与儿童期超重或肥胖之间的关联，但很少考虑在产前期间的暴露，或者在母亲或婴儿中测量的生物学因素可以介导观察到的关系。拟议的研究是对产前暴露于交通相关的空气污染的作用的深入评估，这可能在后代肥胖和幼儿期的超重和肥胖症中发挥作用，考虑到母体和脐带血液中的炎症标志物，以及在昏迷血液中DNA甲基化的表观遗传标记。该职业发展奖的总体目的是将候选人推向环境流行病学领域的独立研究生涯，重点是在产前期间接触环境有毒物质的长期健康影响。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，实施高级统计方法来评估可能的灾难性调解，以及在流行病学研究中的表观遗传标记物的分析和解释。这些技能将通过指导的独立研究，课程工作以及与流行病学，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领域的经验丰富的教师合作。候选人将使用空间建模方法来估计居民在现有的纵向出生前队列研究中，居民在怀孕期间接触与交通相关的空气污染，重点是肥胖和相关心脏代谢疾病的发育起源。将分析存储的母子和脐带血清样品的全身性炎症标记，这可能与交通相关的空气污染暴露以及超重和肥胖的后代风险有关。在裁决的独立时期，候选人将使用在物质期间开发的暴露评估来估计产前暴露与交通相关的空气污染与后代肥胖和肥胖之间的关联。将作为该关联的介体可能研究脐血血液中的母体和胎儿全身炎症和后代DNA甲基化。该项目将对空气污染流行病学领域和影响儿童肥胖风险的早期生活因素做出重大贡献。