Life-course stressors, Mitochondrial Dysfunction, and the Risk of Preterm Birth among Black Women

Modified Project Summary/Abstract Section ABSTRACT The goal of this study is to clarify the role of mitochondrial function/dysfunction (e.g., mitochondrial DNA copy number [mtDNAcn] and mitochondrial function/dysfunction related proteins) as a mediator between life-course stressors (such as social factors and chronic stress) and the risk of preterm birth (PTB) among pregnant Black females. Additionally, this study will examine the inheritance of mitochondrial function/dysfunction from Black mothers to their infants and explore how mitochondrial function may serve as a protective factor against PTB. This proposed K99/R00 research will deepen our understanding of risk factors for PTB, providing valuable insights into both environmental and biological risks, as well as protective factors relevant to pregnant Black females, who experience disproportionately high rates of PTB compared to other populations in the U.S. This research aligns with the NIMHD Minority Health and Health Disparities Research Framework by advancing the understanding and reduction of health disparities and promoting health. In the K99 phase, a secondary data analysis will be conducted using clinical and demographic data, questionnaire responses, pregnancy outcomes, and buccal swab samples collected previously from generally healthy, pregnant Black females. A total of 100 participants will be randomly selected from the parent R01 study, including 50 Black females who experienced term deliveries and 50 Black females who delivered preterm, all of whom were enrolled between 24-30 weeks of gestation. Aim 1: Determine how mitochondrial dysfunction (i.e., mtDNAcn and mitochondrial function/dysfunction related proteins) mediates the associations of life-course stressors with the risk of PTB among pregnant Black females. In the R00 phase, we will recruit pregnant Black females and after giving birth, their term and preterm infants (122 pairs: 122 Black mothers and 122 infants). Aim 2: Determine the potential inheritance of mitochondrial dysfunction from pregnant Black females previously exposed to life-course stressors to their own preterm infants. Aim 3 (Exploratory): Explore mitochondrial function-related proteins that protect against stressors-induced PTB within this at-risk population. This NIH Pathway to Independence Award (K99/R00) will allow me to gain skills and knowledge in 1) assessment of life-course stressors during pregnancy, 2) health disparity research, 3) mitochondrial function/dysfunction in pregnant Black females and PTB, and 4) mediation model analysis, all facilitating my transition to independence and my preparation for future R01s and other grants focused on improving birth outcomes among this health disparity population.