Maternal Exposure to Air Pollution and Early Pregnancy Outcomes

项目总结/摘要 普通人群暴露于空气污染是普遍的。同样，流产也是一种非常常见的 结果影响高达75%的受精卵和30%的已确认妊娠。新兴人类数据 空气污染对早期妊娠结果，特别是早期流产产生负面影响; 然而，证据是有限的，具体的机制和易感性的时间窗口仍然是， 被确定。到目前为止，也有一些战略，以抵消或尽量减少不利的健康 空气污染的后果。确定可能改善负面影响的潜在饮食因素 空气污染对生殖的影响将具有重大的公共卫生意义，因为这些暴露往往是 比个人暴露在空气污染中更容易直接改变。使用经过验证的时空回归 空气污染暴露模型，经验证的饮食问卷，个人空气污染监测器，以及新的 代谢组学生物标志物，这个K99/R 00奖申请将决定空气污染的程度， 其特定成分影响生殖力，饮食改变这些关联的潜力，以及可能的 在马萨诸塞州的波士顿，使用一组接受体外受精的妇女进行研究。博士 奥黛丽·加斯金斯将由环境流行病学专家弗朗辛·拉登博士和环境卫生和环境卫生专家迈克尔·卡耐基博士指导。 Jorge Chavarro是营养和生殖流行病学的领导者。申请人还将密切合作 与Joel Schwartz、布伦特库尔、Russ豪瑟和Chirag Patel博士合作，进一步发展她在环境领域的专业知识。 流行病学在K99阶段的奖励，加斯金斯博士将建立在她的专业知识，营养和 生殖流行病学，并将接受使用经验证的模型进行空气污染暴露评估的培训， 预测环境暴露和空气污染监测器，以测量连续的个人暴露。加斯金斯医生会 还接受“-omic”数据分析方面的培训，以预测R 00阶段， 收集的血液样本将用于利用代谢组学确定新的空气污染早期效应标志。 本申请中提出的研究结果可能会为公共卫生策略提供信息，以早期预防 流产是最常见的不良妊娠结局，同时增加了我们对 空气污染影响早孕终点的机制。所有这一切都将有可能通过 使用一种新的研究人群，接受体外受精的妇女，其中许多早期发育 通过代谢组学，可以观察到新的生物标志物。的突出 在空气污染和代谢组学等研究领域与该领域主要领导人的培训机会将 大大提高候选人的技能和能力，并使她成为一个成功和独立的人。 作为一名环境和生殖流行病学家。

PROJECT SUMMARY/ABSTRACT Exposure to air pollution in the general population is universal. Similarly, pregnancy loss is an all too common outcome affecting up to 75% of fertilized ova and 30% of recognized pregnancies. Emerging human data suggest that air pollution negatively affects early pregnancy outcomes, particularly early pregnancy loss; however the evidence is limited and the specific mechanisms and time window of susceptibility still remain to be determined. To date there are also few strategies to counteract or minimize the adverse health consequences of air pollution. Identifying potential dietary factors that could ameliorate the negative reproductive effects of air pollution would be of great public health significance as these exposures tend to be easier to directly modify than personal exposure to air pollution. Using validated spatial-temporal regression models of air pollution exposure, validated dietary questionnaires, personal air pollution monitors, and novel metabolomics biomarkers, this K99/R00 award application will determine the extent to which air pollution and its specific constituents affect fecundity, the potential for diet to modify these associations, and the possible mechanisms of action using a cohort of women undergoing in vitro fertilization in Boston, Massachusetts. Dr. Audrey Gaskins will be mentored by Dr. Francine Laden, an expert in environmental epidemiology, and Dr. Jorge Chavarro, a leader in nutrition and reproductive epidemiology. The applicant will also collaborate closely with Drs. Joel Schwartz, Brent Coull, Russ Hauser, and Chirag Patel to further her expertise in environmental epidemiology. During the K99 phase of the award, Dr. Gaskins will build on her expertise in nutritional and reproductive epidemiology and will be trained in air pollution exposure assessment using validated models to predict ambient exposure and air pollution monitors to measure continuous personal exposure. Dr. Gaskins will also receive training in the analysis of “-omic” data in anticipation of the R00 phase where prospectively collected blood samples will be used to identify novel early effect markers of air pollution using metabolomics. Findings from the research proposed in this application may inform public health strategies to prevent early pregnancy loss, the most common adverse pregnancy outcome, while increasing our understanding of the mechanisms by which air pollution affects early pregnancy endpoints. All of this will be possible through the use of a novel study population, women undergoing in vitro fertilization where many early developmental measures can be observed and novel biomarkers can be assessed through metabolomics. The outstanding training opportunities in research areas such as air pollution and metabolomics with key leaders in the field will greatly enhance the skills and capabilities of the candidate and position her for a successful and independent career as an environmental and reproductive epidemiologist.