Chronic Stress, Lipidome Profiles and Preterm Birth in African American Women

摘要

ABSTRACT African American women have 1.5 times the rates of preterm birth (PTB)(<37 weeks) compared with white women. The high PTB rate for African Americans is a longstanding health disparity that negatively affects the health of African American infants. A contributing factor to the PTB disparity for African American women is chronic stress due to experiencing racial discrimination and living in disadvantaged neighborhoods. Indeed, pregnant African American women are more likely to experience racial discrimination and live in disadvantaged neighborhoods compared with pregnant white women. While studies, including our own, suggest that racial discrimination and disadvantaged neighborhoods are related to risk of PTB, the biological mechanism by which these factors operate is not understood. Our overarching hypothesis is that chronic stress due to racial discrimination and disadvantaged neighborhoods is associated with changes in the lipidome profile that may act via increased levels of systemic inflammation to produce a higher risk of PTB. Depressive symptoms may also be in the pathway between chronic stress, the lipidomes, systemic inflammation and PTB. We aim to: (1) Determine the impact of chronic stress on lipidome profiles; (2) Determine the impact of lipidome profiles on systemic inflammation and depressive symptoms; and (3) Examine if a lipidome profile is related to lower gestational age at birth and risk of PTB. In this longitudinal design, we will enroll 150 African American women who live in the Detroit metropolitan area. Racial discrimination, neighborhood conditions and depressive symptoms will be collected by measures used in our prior studies. Cortisol levels will be measured in hair, an innovative measure of chronic stress. Systemic inflammation will be measured by plasma cytokines (e.g., Interleukin-6), chemokines and C-reactive protein. Plasma lipidome profiles will be determined by “shotgun” Orbitrap high resolution/accurate mass spectrometry. By utilizing the most comprehensive global lipidome profiling method established to date, we will determine molecular compositions of several hundred lipid analytes in plasma obtained from pregnant African American women. We will measure gestational age at birth from medical records. We will also consider the timing of pregnancy in our analyses, as the prenatal data are collected at three distinct time points. Students will be directly involved at all levels of the proposed project including recruitment and retention of participants, hair collection, blood sample management and dissemination of results. The proposed study will provide critical translational research experience for students, with emphasis on encouraging minority students in higher education. The proposed research is highly relevant to NIH’s mission to elucidate mechanisms underlying health disparities in PTB. Our long term goal is to identify risk of PTB based on chronic stress and biomarkers, which will have potential use in clinical practice and be a target for interventions to eliminate disparities in PTB for African American women.