Nonpersistent chemical exposure, placental development, and maternal pre- and post-pregnancy cardiovascular health

项目总结/摘要 在美国，越来越多的妇女正在经历怀孕并发症，如 先兆子痫、子痫和妊娠期高血压，可以把自己和孩子的直接 长期健康处于危险之中。特别是，这些妊娠期高血压疾病与以下因素有关： 妇女产后心血管疾病发病率增加。这种联系似乎是胎盘， 这一器官既调节营养流向发育中的胎儿，又影响母体心血管功能。 非持久性内分泌干扰化学品（EDCs），包括塑料和邻苯二甲酸酯中的双酚 在个人护理产品中发现，与心血管疾病有关，也可能是 与胎盘功能障碍有关在我的硕士，博士和博士后培训过程中，我 已经开始在环境和生殖流行病学方面开发一系列已发表的研究成果， 特别强调识别潜在的生物学机制。我以前的教育和经验 使我能够很好地进行我提出的K99/R 00研究项目：研究孕产妇之间的关系， 暴露于非持久性内分泌干扰物，胎盘功能障碍的生物标志物，以及母体 妊娠前后的心血管疾病。独立之路奖将提供 我需要额外的指导和专业知识，以过渡到教师，并成功地竞争资金作为一个 首席调查员我的培训计划包括正式课程、工作坊和研讨会、指导性阅读， 和学徒发展技能1）内分泌干扰物，环境流行病学和暴露评估，2） 先进的统计方法，和3）胎盘和心血管健康之间的交叉。在K99 在我的研究阶段，我将利用纽约大学（NYU）目前收集的数据 儿童健康和环境研究（CHES），包括产前母体生物标志物和 问卷调查数据以及产后母体心血管指标。在R 00阶段，我将 来自纽约大学影响生殖成功和怀孕时间的因素的额外孕前数据 （一）学习。具体目的包括：1）检查母体产前尿邻苯二甲酸酯与 双酚水平对母体胎盘发育生物标志物的影响，以及内分泌干扰物对妊娠的特异性影响。 出生时胎盘大小，2）检查产前尿邻苯二甲酸酯和双酚水平的关系， 妊娠三个月对产后1年和2年母体临床心血管危险因素的影响 CHES，以及3）评估母亲孕前邻苯二甲酸酯和双酚暴露之间的关系， 孕前心血管危险因素、妊娠时间和胎盘生长发育 结合CHES和FIRST数据。这些培训和研究活动将增加我的专业知识， 环境流行病学家，并准备我成功地竞争R 01资金作为一个独立的 重点是生殖健康和妇女健康调查员。

PROJECT SUMMARY/ABSTRACT In the United States, increasing numbers of women are experiencing pregnancy complications such as preeclampsia, eclampsia, and gestational hypertension that can put their own and their children’s immediate and long-term health at risk. In particular, these hypertensive disorders of pregnancy are associated with increased incidence of postnatal cardiovascular disease in women. The link appears to be the placenta, an organ that both regulates nutrient flow to the developing fetus and influences maternal cardiovascular function. Nonpersistent endocrine disrupting chemicals (EDCs), including bisphenols found in plastics and phthalates found in personal care products, have been associated with cardiovascular disease and may also be associated with placental dysfunction. Over the course of my masters, doctoral, and postdoctoral training, I have begun to develop a portfolio of published research in both environmental and reproductive epidemiology, with a particular emphasis on identifying underlying biological mechanisms. My prior education and experience positions me well to undertake my proposed K99/R00 research project: examining relations among maternal exposure to nonpersistent EDCs, biomarkers of placental dysfunction, and indicators of maternal cardiovascular disease both before and after pregnancy. This Pathway to Independence Award will provide the additional mentorship and expertise I need to transition to faculty and successfully compete for funding as a principal investigator. My training plan includes formal courses, workshops and seminars, directed readings, and apprenticeships to develop skills in 1) EDCs, environmental epidemiology, and exposure assessment, 2) advanced statistical methods, and 3) the intersection between placental and cardiovascular health. In the K99 phase of my research, I will leverage data currently being collected in the New York University (NYU) Children’s Health and Environment Study (CHES) that includes both prenatal maternal biomarker and questionnaire data as well as postnatal maternal cardiovascular measures. In the R00 phase, I will incorporate additional preconception data from the NYU Factors Influencing Reproductive Success and Time to Pregnancy (FIRST) Study. Specific Aims include 1) examining relations of maternal prenatal urinary phthalate and bisphenol levels to maternal biomarkers of placental development, and trimester-specific effects of EDCs on placental size at birth, 2) examining relations of prenatal urinary phthalate and bisphenol levels measured in three trimesters of pregnancy to maternal clinical cardiovascular risk factors at 1 and 2 years postpartum in CHES, and 3) assessing relations among maternal preconception phthalate and bisphenol exposure, preconception cardiovascular risk factors, time to pregnancy, and placental growth and development using combined CHES and FIRST data. These training and research activities will increase my expertise as an environmental epidemiologist and prepare me to successfully compete for R01 funding as an independent investigator with a focus on reproductive and women’s health.