Nutrition and the Genetics of Prematurity

点击翻译按钮获取中文摘要

DESCRIPTION (provided by applicant): This project addresses gene-environment interactions that contribute to the racial disparity in preterm birth. We have found that there are specific changes in the lower genital tract inflammatory milieu early in pregnancy that predispose women to preterm birth. We have also found that these alterations in the lower genital tract inflammatory milieu are more common among black women, and that black women are more likely than white women to possess cytokine promoter gene polymorphisms that are related to infection- related preterm birth. Understanding the influence of environment and gene-environment interactions on inflammation is critical to understanding the racial disparity in preterm birth. Nutritional status' influence on immunity has both epidemiological and biological plausibility. We posit that biologic responses to nutritional status may affect preterm birth via changes in lower genital tract immunity that predispose to upper genital tract infection/inflammation. We also hypothesize that inflammatory genotype influences the nature of the lower genital tract inflammation that occurs among women with an unfavorable nutritional status before and during pregnancy, and that these effects are further modified by race. We aim to determine if nutritional status periconceptionally and during pregnancy is associated with preterm birth. To this end, we will enroll 1200 women over 4 years in a prospective cohort study. Nutritional status is represented by dietary intake, nutritional biomarkers in maternal blood and nails, pre-pregnancy body mass index, and weight gain. We aim to determine if unfavorable nutritional status in pregnancy promotes a lower genital tract inflammatory milieu that increases the risk of preterm birth. Inflammatory milieu is represented by important cervical cytokines, vaginal pH, and vaginal neutrophils prior to 10 weeks and at 24-28 weeks. We aim to evaluate whether inflammatory gene polymorphisms alter the impact of nutrition on lower genital tract inflammation and on the risk of preterm birth, thus establishing a gene-environment interaction. DNA will be extracted from maternal blood to genotype all subjects for polymorphisms in order to determine if there are genotypes or genotype patterns that modify the impact of nutritional status on lower genital tract immunity and on the risk of preterm birth. Finally, we aim to identify how race modifies the interaction between inflammatory gene polymorphisms and nutrition on lower genital tract immunity and the risk of preterm birth.