A Precision Medicine Approach to Fetal Growth Restriction Among Black Women

About This Grant

MODIFIED PROJECT SUMMARY/ABSTRACT Fetal growth restriction (FGR) is a leading cause of fetal and neonatal mortality among Black women, affecting 10-15% of pregnancies. Known risk factors like placental insufficiency or economic status do not fully explain disparities in FGR. However, by integrating evidence from maternal physiology with nutrition-obesity research, I have developed the hypothesis that low maternal serum triglycerides (TG) may be a key factor in FGR development among Black women. This is based on strong evidence that 1) FGR is a state of fetal nutrient deprivation, 2) high maternal TGs are required for fetal growth, and 3) on average, Black women have lower TG levels during pregnancy, possibly due to genetic variations in the lipoprotein lipase gene that are common among African ancestry and rare for other ancestries. Genetic variation may lead to higher TG uptake in maternal tissues, fewer TGs for fetal growth, and ultimately to FGR. Hence, in this proposal, I aim to define the role of genetics, maternal and placental lipids, and extrinsic exposures in FGR among Black women. I am seeking a K01 career development award to acquire the training, mentorship, and dedicated time to test my hypothesis and to launch a successful independent research career. I have a strong background in 1) obesity and metabolism, 2) precision nutrition, and 3) maternal-fetal medicine research. However, to perform the proposed research and future studies, I need to meet the following training objectives: (1) perform high-quality translational investigation of lipid metabolism in pregnancy, (2) acquire fundamental skills in the collection and analysis of genetic data, and (3) analyze and interpret fetal growth and placental development, and 4) enhance my professional and project management skills. In synergy with my training objectives, my research aims are: Aim 1. Identify genetic polymorphisms and metabolic pathways that associate with FGR among Black women, Aim 2. Determine the association of maternal TG with FGR, birthweight, and placental TG transfer, and Aim 3. Identify modifiable protective factors that are associated with adequate fetal growth in Black women. To meet these objectives, I have established a strong multi-site scientific and professional development committee across three highly collaborative institutions with strong research infrastructure and state-of-the-art facilities. My primary mentors are Sarah K. England, PhD (maternal physiology) and Clay F. Semenkovich, MD (lipid metabolism); my specialized mentors are Camille E. Powe, MD (pregnancy genomics) and Teri R. Hernandez, RD, PhD (pregnancy metabolism). Together, we have developed a training plan with hands-on experiences, didactic training, meetings, and seminar series to ensure my success. Overall, this award will provide me with the protected time and resources to develop the requisite expertise to rigorously test my hypothesis and prepare an innovative R01 grant application as I launch my independent career as a translational scientist who conducts well-executed, objective, and impactful research. Completion of the proposed aims will lay the foundation for novel precision medicine interventions to reduce FGR among Black women.