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.

Public Health Relevance

Exposure to per fluorinated compounds (PFCs) is widespread in the general population. The health effects of this exposure are unknown, but it is plausible that higher levels of exposure may be related to complications of pregnancy, including preeclampsia. If PFCs are determined to be environmental causes of preeclampsia, this would have broad public health consequences, as preeclampsia is a common disease and contributes to a high burden of maternal and infant mortality, particularly in the absence of appropriate medical management.

National Institute of Health (NIH)
National Institute of Environmental Health Sciences (NIEHS)
Individual Predoctoral NRSA for M.D./Ph.D. Fellowships (ADAMHA) (F30)
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Special Emphasis Panel (ZRG1-F16-L (20))
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Humble, Michael C
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University of North Carolina Chapel Hill
Public Health & Prev Medicine
Schools of Public Health
Chapel Hill
United States
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Starling, Anne P; Umbach, David M; Kamel, Freya et al. (2014) Pesticide use and incident diabetes among wives of farmers in the Agricultural Health Study. Occup Environ Med 71:629-35
Starling, Anne P; Engel, Stephanie M; Richardson, David B et al. (2014) Perfluoroalkyl substances during pregnancy and validated preeclampsia among nulliparous women in the Norwegian Mother and Child Cohort Study. Am J Epidemiol 179:824-33
Starling, Anne P; Engel, Stephanie M; Whitworth, Kristina W et al. (2014) Perfluoroalkyl substances and lipid concentrations in plasma during pregnancy among women in the Norwegian Mother and Child Cohort Study. Environ Int 62:104-12
Wang, Yan; Starling, Anne P; Haug, Line S et al. (2013) Association between perfluoroalkyl substances and thyroid stimulating hormone among pregnant women: a cross-sectional study. Environ Health 12:76