Preterm birth is more prevalent in African Americans than European Americans and contributes to 3.4 times more African American infant deaths. Models of social inequity do not appreciably account for this marked disparity and molecular genetic studies have yet to characterize whether allelic differences that exist between races contribute to this gap. It has been hypothesized that the effect of social and environmental determinants of health (SEDH) are mediated through DNA-based epigenetic changes, such as methylation. However, due to the paucity of research in this area many questions remain: To what extent do SEDHs result in biological changes that influence liability to preterm birth? Can a pregnant woman be identified as "at risk" for a poor pregnancy outcome based on her epigenetic, gene expression profiles and history of SEDHs? To answer these questions we will study 200 pregnant African American and European American women recruited through VCU Medical Center clinics. These women will be prospectively tracked at defined intervals throughout pregnancy to measure a broad array of social, economic, behavioral and stress-related measures and obtain blood, decidual and placental tissue samples for methylation, gene expression and genotype studies. The analytic strategy will take advantage of a longitudinal, repeated measures design to identify robust, causal environmental-biological mechanisms that both influence preterm birth and account for racial differences in preterm birth rates. The goals of the three specific aims are to: 1) identify robust environmental and biological predictors of preterm birth;2) integrate these predictors to identify causal environmental-biological mechanisms of preterm birth and;3) quantify the extent to which these predictors and mechanisms account for the overrepresentation of preterm birth in African Americans.
Three specific aims are proposed:
Aim 1 : Employ data reduction and prioritization methods to develop a set of optimal environmental and biological measures and identify those constructs that correlate with preterm birth.
Aim 2 : Identify causal mechanisms of preterm birth that integrates environmental and biological risk factors through epigenetic processes.
Aim 3 : Determine if the influence of race on preterm birth persists over and above the mechanisms identified in Aim 2.
The potential that adverse environmental and social exposures can be biologically remembered to result in an individual having an increased risk for developing health conditions, such as poor pregnancy outcomes, has only recently been recognized. Understanding the interplay between environmental and biological factors underlying this memory will refine our understanding of the normal as well as pathologic processes underlying parturition. and could lead to innovative approaches to reduce the incidence of preterm labor.
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