Thursday, April 25, 2024
4/25/2024
DESCRIPTION (provided by applicant): African American women are at markedly increased risk for several adverse pregnancy outcomes including preterm delivery. These ethnic differences are not explained by known risk factors or by genetic variation suggesting that other factors contribute. Chronic low-grade vascular inflammation is an underlying mechanism for many health problems including the initiation, progression and thrombotic complication of atherosclerosis. Metabolic disturbances in lipids, glucose and insulin resistance trigger vascular inflammatory processes. Elevated levels of circulating free fatty acids (FFAs) and individual FFAs that are related to the amount and type of fat in the diet alter the inflammatory response. However, maternal FFAs-mediated inflammation and its influence on the ethnic disparity in adverse pregnancy outcomes have not been studied. The purpose of this study is to examine existing data from an ethnically diverse group of pregnant women to determine whether (i) maternal circulating FFAs and their proportional composition correlate to dietary fat intake and alter the inflammatory response; (ii) there are ethnic differences in the biomarkers of inflammation; (iii) ethnic differences in inflammation give rise to ethnic differences in preterm delivery and a serious complication of pregnancy (preeclampsia) that increase risk of later metabolic disease. The primary outcome to be examined is preterm delivery (<37 weeks gestation); the secondary outcome is preeclampsia. Markers of inflammation will include TNF-a, IL-1, IL-6, IL-8, C-reactive protein, fibrinogen, soluble TNF- receptors 1 and 2 and adiponectin. We hypothesized that low-grade vascular inflammation, as indicated by the markers of inflammation (MOI), is an independent contributor to the ethnic differences in preterm delivery and preeclampsia. Vascular inflammation is altered by circulating free fatty acids which are related to dietary fat intake. Because not all FFAs have the same effect on the inflammatory process, we will identify which fatty acids suppress (protective) inflammation and what fatty acids induce inflammation. The study will utilize existing data and biological specimens which were longitudinally collected from a large prospectively designed cohort study in Camden, New Jersey (N=2,816). The cohort includes healthy low income pregnant women from 3 ethnic groups (African American, Hispanic (mostly ~85% Puerto Rican) and White). The project will have a significant impact on understanding ethnic disparities in pregnancy outcome. Because circulating FFAs are well correlated with dietary fat/FAs intake, modification in the type or amount of fat in the diet will alter circulating FFAs levels, likely reducing vascular inflammation and potentially decreasing the ethnic disparity in poor outcomes. Thus, our data will provide an intriguing insight into racial/ethnic differences in amount and type of fat in the diet, in fatty aid metabolism and in inflammation as contributors to preterm delivery and preeclampsia which increases risk of metabolic disorders in later life.
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