Epidemiology of Perfluorinated Compounds in Pregnancy and Risk of Preeclampsia

描述(由申请人提供)：本提案描述了一项关于生殖健康和不良妊娠结局流行病学的培训计划，特别是先兆子痫。这项拟议的研究项目检查了孕妇血浆中全氟化合物的浓度，以及这些污染物和心血管疾病生物标记物变化之间的可能联系，以及随后患先兆子痫的风险。这里描述的项目和指导计划旨在培养申请者将流行病学工具应用于复杂的产科和环境问题的能力，并将这一研究培训纳入未来作为独立医生-科学家的职业生涯。指导小组由北卡罗来纳大学的生殖和环境流行病学家、北卡罗来纳大学的内科流行病学家、北卡罗来纳大学的妇产科医生和国家环境健康科学研究所的生物标记物环境流行病学家组成，他们将定期会面，以确保这位研究员在实现目标方面取得足够的进展。含氟化合物(PFC)是一种在环境和人体内持续存在的人造化学物质。虽然接触这些化学物质在普通人群中很普遍[1]，但这种接触对人类健康的影响在很大程度上是未知的。动物研究表明，大剂量PFC暴露会对健康产生多种影响，包括血脂异常、发育异常和死产[11]。有限的人类流行病学证据表明，高剂量暴露可能会产生一些代谢影响[4，5]，但在孕妇中暴露于低水平的PFC可能造成的后果尚不清楚。孕妇体内PFC浓度升高的一个看似合理的结果可能是增加了先兆子痫的风险。子痫前期是一种严重的妊娠障碍，以新发的高血压和蛋白尿为特征，通常在怀孕20周后发生。先兆子痫对母亲和胎儿的健康构成严重威胁，严重情况下唯一可用的治疗方法是分娩婴儿。这可能会导致早产和早产的长期后果。先兆子痫被认为有遗传和环境两方面的原因，但这些原因仍然不清楚[23]。本研究的具体目的是：1)研究妊娠中期血浆PFC浓度与子痫前期的关系；2)研究妊娠中期PFC浓度与某些临床生化指标的关系，以阐明PFC影响妊娠生理的机制。为了实现这些目标，本研究建议使用现有的以人口为基础的挪威母子队列研究。这项建议直接涉及国家环境健康科学研究所的目标，因为它旨在确定一种广泛存在的环境污染物是否可能导致人类疾病。了解这些持久性污染物对人类健康的影响，对于负责监管全氟碳化物生产和使用的决策者来说至关重要。

DESCRIPTION (provided by applicant): This proposal describes a training program in reproductive health and the epidemiology of adverse pregnancy outcomes, specifically preeclampsia. The proposed research project examines the plasma concentration of per fluorinated compounds in pregnant women, and the possible association between these contaminants and altered cardiovascular disease biomarkers, and the subsequent risk of preeclampsia. The project and mentoring plan described here aim to develop the applicant's ability to apply epidemiologic tools to complex obstetric and environmental problems and to integrate this research training into a future career as an independent physician-scientist. The mentorship team, composed of a reproductive and environmental epidemiologist at UNC, a physician-epidemiologist at UNC, an obstetrician-gynecologist at UNC, and a biomarker-based environmental epidemiologist at the National Institute of Environmental Health Sciences, will meet regularly to ensure the fellow's adequate progress toward her goal. Per fluorinated compounds (PFCs) are man-made chemicals that persist in the environment and in the human body. While exposure to these chemicals is widespread in the general population [1], the effect of this exposure on human health is largely unknown. Animal studies have shown a variety of health effects resulting from high-dose PFC exposure, including dyslipidemia, developmental abnormalities, and stillbirth [11]. Limited epidemiologic evidence in humans suggests that some metabolic effects may result from high-dose exposure [4, 5], but the possible consequences of PFC exposure at low levels in pregnant women are unknown. One plausible effect of elevated PFC concentration in pregnant women could be an increased risk of preeclampsia. Preeclampsia is a serious disorder of pregnancy characterized by new-onset hypertension and proteinuria, typically after 20 weeks of pregnancy. Preeclampsia poses a serious health risk to mother and fetus, and the only available treatment in severe cases is the delivery of the infant. This may lead to preterm delivery and the long-term sequel of prematurity. Preeclampsia is believed to have both genetic and environmental causes, but these causes remain obscure [23]. This specific aims of this study are: 1) to examine the possible association between mid-pregnancy plasma PFC concentrations and preeclampsia, and 2) to examine the relationship between mid-pregnancy PFC concentrations and certain clinical chemistries, which may elucidate the mechanism by which PFCs affect pregnancy physiology. To accomplish these aims, this study proposes to use the existing population-based Norwegian Mother and Child Cohort Study. This proposal directly addresses the goals of the National Institute of Environmental Health Sciences, in that it aims to identify whether a widespread environmental contaminant may contribute to human disease. Knowledge about the human health effects of these persistent pollutants is essential to decision-makers who are responsible for regulating the production and use of PFCs.