Document Type

Dissertation

Date of Degree

Summer 2014

Degree Name

PhD (Doctor of Philosophy)

Degree In

Epidemiology

First Advisor

Audrey F. Saftlas

Abstract

Preeclampsia is a leading cause of maternal and infant morbidity and mortality worldwide. For the first aim, a systematic literature review and meta-analysis was performed to examine the associations between maternal lipid concentrations during pregnancy (HDL-C, LDL-C, non-HDL-C, total cholesterol, and triglycerides) with subsequent risk of preeclampsia. Data from the Study of Pregnancy-induced Hypertension in Iowa, a population-based, case control study of preeclampsia and gestational hypertension, was used to address the other two aims: 1) elucidate the independent contribution of physical activity, an important modifier of dyslipidemia, on the risk of preeclampsia, and 2) to evaluate the association between the genetic susceptibility for dyslipidemia and the risk of preeclampsia.

Published reports examining lipid levels during pregnancy and preeclampsia have been inconsistent. Meta-analyses demonstrated that preeclampsia was associated with elevated total cholesterol, non-HDL-C, and triglyceride levels, regardless of gestational age at time of blood draw, and lower levels of HDL-C in the third trimester. A marginal association was also found with LDL-C levels. Statistical heterogeneity was detected in all analyses.

Physical activity has been hypothesized to reduce the risk of preeclampsia, but previous studies have had a range of limitations resulting in mostly suggestive, though nonsignificant findings. After adjustments, increasing levels of LTPA (trend, p=0.02) and increasing amounts of time spent active each day (trend, p=0.03) were significantly associated with a reduced risks of preeclampsia (trend, p=0.02). Increasing amounts of time spent sitting per day was marginally associated with the risk of preeclampsia (trend; p=0.10), and those women who were active an average of more than 8.25 hours per day had the most significantly reduced risk of preeclampsia (adjusted OR 0.58, 95% CI 0.36, 0.95).

In examining the effects of a woman's genetic susceptibility to dyslipidemia as a risk factor for preeclampsia, we found that the more risk alleles a woman has for dyslipidemic levels of HDL-C, the greater her risk for developing preeclampsia. While this relationship was of marginal statistical significance, these results are suggestive of a relationship that may help elucidate the pathogenesis of preeclampsia.

Our findings demonstrate the contribution of maternal lipid concentrations during pregnancy on preeclampsia risk, and suggest a behavioral modification that could help counter that increased risk. Additionally, implications of HDL-C genetics in preeclampsia risk identify potential genetic and biologic pathways to be explored in the pathogenesis of preeclampsia.

Keywords

Cholesterol, Genetics, Lipids, Physical Activity, Preeclampsia

Pages

xiv, 169 pages

Bibliography

Includes bibliographical references (pages 151-169).

Copyright

Copyright 2014 Cassandra Nichole Spracklen

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