Maternal Exposure to Air Pollution and Early Pregnancy Outcomes

项目摘要/摘要 在普通人群中暴露在空气污染中是普遍的。同样，流产也是一种非常普遍的现象。 结果影响高达75%的受精卵和30%的公认妊娠。新兴的人类数据 表明空气污染对早孕结局有负面影响，尤其是早孕丢失； 然而，证据有限，易感性的具体机制和时间窗口仍然存在。 要下定决心。到目前为止，也几乎没有什么策略来抵消或减少对健康的不利影响 空气污染的后果。找出可以缓解负面影响的潜在饮食因素 空气污染的生殖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修改。使用经过验证的时空回归 空气污染暴露的模型、有效的饮食调查问卷、个人空气污染监测器，以及 代谢组学生物标志物，这项K99/R00奖申请将确定空气污染和 它的特定成分影响繁殖力，饮食改变这些联系的可能性，以及可能的 使用在马萨诸塞州波士顿进行体外受精的妇女队列的作用机制。Dr。 奥黛丽·加斯金斯将由环境流行病学专家弗朗辛·拉登博士和弗朗辛·拉登博士指导。 豪尔赫·查瓦罗，营养和生殖流行病学的领导者。申请者还将密切合作 与Joel Schwartz博士、Brent Coull博士、Russ Hauser博士和Chirag Patel博士共同促进她在环境方面的专业知识 流行病学。在K99奖项阶段，加斯金斯博士将利用她在营养和营养方面的专业知识 并将接受空气污染暴露评估方面的培训，使用经过验证的模型来 预测环境暴露和空气污染监测，以测量持续的个人暴露。加斯金斯医生会 还接受了预期R00阶段的“经济”数据分析方面的培训 收集的血液样本将被用来利用代谢组学识别空气污染的新的早期影响标志。 在本申请中提出的研究结果可能会为公共卫生战略提供参考，以预防早期 妊娠丢失，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。所有这些都将通过 利用一种新的研究人群，接受体外受精的妇女许多早期发育 可以通过代谢组学观察措施和评估新的生物标记物。杰出的 在空气污染和代谢组学等研究领域与该领域的主要领导者进行培训的机会将 大大提高应聘者的技能和能力，使她成为一个成功和独立的人 环境和生殖流行病学家的职业生涯。

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.