The United States is in the midst of an obesity epidemic, with over a third of U.S. women of childbearing age being obese (BMI?30 kg/m2). Obesity in this country reflects an ethnic disparity, with non-Hispanic African-American women being nearly twice as likely as white women to be obese. Obese women are at particular risk to end their full-term pregnancies with unplanned cesarean delivery, in large part due to their abnormally slow labors. African-American race confers the highest risk for unplanned cesarean in analyses adjusting for maternal BMI, labor complications, labor interventions, and neonatal size. When obese women have cesarean delivery, they are more likely than normal-weight women to experience significant post-cesarean morbidity and mortality. In vitro research investigating myometrial contractility suggests that the cellular metabolic milieu of obesity may account for the decreased contractile efficiency in labor, longer labor duration, and decreased response to commonly-used interventions like oxytocin infusion that are seen in clinical investigations of obese women. Gaps exist in our understanding of the mechanisms or pathways that link slow labor progress, synthetic oxytocin response, and obesity to risk for unplanned cesarean delivery. The proposed study will investigate the metabolomic profiles that differentiate between obese, African-American women with slow labor progress vs. normal labor progress (Aim 1), and oxytocin sensitivity vs. insensitivity (Aim 2). We plan a nested case-control study of 124 term, obese, African-American women to identify metabolomic profiles activated in serum collected during the 1st and 3rd trimesters of pregnancy from subjects participating in a prospective 5-year study of preterm birth and the microbiome. Detailed chart-review will be performed on the hospital records of obese, term, healthy women achieving active phase labor with singleton, vertex fetus to identify cases and controls for metabolomic comparisons. Differential analysis will then be used to compare metabolite features between groups. The proposed research study and mentored research scientist career development plan are congruent with the applicant?s long-term research goals to understand the biobehavioral determinants and effective intrapartum care management strategies for obese women in order to decrease the incidence of cesarean delivery, its short and long-term adverse consequences, and the cost of healthcare for obese childbearing women. Specific career development goals included in this plan are: 1) developing skills and knowledge in metabolomics research to examine obesity in pregnancy, 2) gain methodological skills in bioinformatics and advanced statistics used in metabolomics investigations, and 3) enhance and refine research skills and program of research to position career as an independent investigator. Results obtained from this study will inform future research and promote new understanding of effective care practices for nurses, nurse-midwives, and physicians as they support the vulnerable population of obese, African-American women through labor to a safe birth outcome.
Obese women, who are known to be over-represented in the United States among lower socio-economic and ethnic minority groups, are at particular risk for slow labor progress leading to cesarean delivery, and have increased morbidity and mortality following this surgery. The proposed project will utilize high-resolution metabolomics to identify metabolic profiles that differentiate obese, African-American women with labor dysfunction and reduced response to oxytocin, a medication that is used to help speed labor progress. The purpose of this project is to promote health, prevent disease, and eliminate health disparities through a better understanding of biomarkers associated with labor dysfunction in African-American, obese women.
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