Nicole Carlson - US grants

DESCRIPTION (provided by applicant): The United States is in the midst of an obesity epidemic, with nearly half of U.S. women of childbearing age being either overweight (BMI 25-29.9) or obese (BMI¿30). Obesity in this country reflects an ethnic disparity, with non- Hispanic black and Hispanic women disproportionately affected. 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. Obese women pregnant with their first babies (nulliparous women) are at the highest risk for unplanned cesarean delivery. 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 to hasten labor that are clinically observed in obese populations. Gaps exist in our understanding of the correct timing and use of technological interventions in the labors of obese women. The proposed study will investigate the labor management of obese, nulliparous women to discover the practices associated with decreased risk of cesarean delivery. A Comparative Effectiveness approach will be used to describe and compare two different labor management models (obstetrician model vs. nurse-midwife model) against the outcome of cesarean delivery in a sample of obese, nulliparous women. Retrospective database analysis and detailed chart-review will be performed on the hospital records of obese, nulliparous women delivering at the University of Colorado Hospital, where approximately 40% of births are managed by nurse-midwives. Logistic regression and hazard analysis will be used to examine the differences in intervention use, intervention timing, and delivery outcomes between samples of obese, nulliparous women in the nurse-midwife vs. obstetrician models of labor care. Matched samples of obese women will be created via propensity score analysis. Biologic effect of obesity on women's response to exogenous oxytocin in labor will also be examined. The proposed research study and training plan are congruent with the applicant's long-term research goals to understand the biobehavioral determinants and effective intrapartum care management strategies for obese nulliparous women in order to decrease the incidence of cesarean delivery, its short and long-term adverse consequences, and the cost of healthcare for nulliparous childbearing women. 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, nulliparous women through labor to a safe birth outcome.

Project Summary/Abstract 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.

Project Abstract Maternal mortality in the US continues to rise, outpacing rates in nearly every other developed country. Over half of women who experience pregnancy-related death do not have risk factors that are identifiable prior to labor. For these women, the cascade of events ending in death or morbidity often begins with labor dysfunction. Current literature on the physiologic determinants of labor dysfunction suggests that lipotoxicity may account for decreased uterine contractile strength and coordination. Lipotoxicity is a system-wide condition occurring when excess free fatty acids are deposited in cellular membranes and non-adipose tissues, causing chronic inflammation and cellular dysfunction in both obese and non-obese women. Black women are 3-4 times more likely to die of pregnancy complications than non-Hispanic white women, and social determinants of health appear to increase their risk of experiencing changes in metabolism during pregnancy. We theorize that alterations in lipid profiles may provide a missing link connecting Black women's pregnancy experiences, health, and labor outcomes. The proposed study will use a systems biology approach to determine how the lipid changes that precede labor dysfunction develop over the course of pregnancy in a cohort of Black women receiving prenatal care in a freestanding birth center (Aim1), and measure the extent to which these lipid changes are influenced by pregnancy health, including maternal behaviors, body composition, social determinants of health, and serum adipose tissue hormones (Aim 2). Finally, we will evaluate the influence of prenatal model of care on pregnancy health and lipid perturbations during pregnancy, comparing the birth center cohort to a cohort of Black women receiving prenatal care in a hospital setting (Aim 3). Recruitment of the birth center cohort will target retention of 150 women who begin prenatal care in first trimester for planned questionnaire and blood collections. Following the completion of labor, detailed chart- review will be performed to identify cases and comparisons for labor dysfunction comparisons. For our final analyses examining the influence of prenatal model of care on lipids and labor outcomes, we will leverage questionnaire and lipidomics data from an existing cohort of 167 Black women with similar levels of perinatal risk to the birth center cohort who received prenatal care in nearby hospital clinics. Differential analysis will then be used to compare lipid features and pregnancy exposures between groups. The proposed research study brings together cutting-edge technology and a multi-disciplinary team with scientific expertise in labor dysfunction, body composition measurement, comprehensive nutritional and physical activity analysis, lipidomics, racial disparities investigations, and systems biology approaches to confront labor dysfunction--one of the most impactful conditions affecting maternal morbidity and mortality. Results obtained from this study will provide functional information to make the identification of biomarkers that predict labor dysfunction a real possibility, changing the future for early detection, targeted intervention, and prevention of labor dysfunction.