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

摘要 非裔美国妇女的早产率（<37周）是白色妇女的1.5倍 妇女非洲裔美国人的高PTB率是一个长期存在的健康差距，对非洲裔美国人的健康产生了负面影响。 非裔美国婴儿的健康。造成非裔美国妇女PTB差异的一个因素是 由于经历种族歧视和生活在弱势社区而产生的慢性压力。的确， 怀孕的非洲裔美国妇女更有可能遭受种族歧视，生活在弱势群体中。 与怀孕的白色妇女相比。包括我们自己在内的研究表明， 歧视和弱势社区与PTB的风险有关，PTB的生物机制， 这些因素的作用还不清楚。我们的总体假设是，由于种族歧视造成的慢性压力 歧视和弱势社区与脂质组分布的变化有关， 通过增加全身炎症水平发挥作用，产生更高的PTB风险。抑郁症状可能 在慢性应激、脂质体、全身性炎症和PTB之间的通路中也是如此。我们的目标是：（1） 确定慢性应激对脂质组谱的影响;（2）确定脂质组谱对慢性应激的影响。 全身性炎症和抑郁症状;和（3）检查脂质组谱是否与较低的 出生时的胎龄和PTB的风险。 在这个纵向设计中，我们将招募150名居住在底特律大都市的非洲裔美国妇女， 区种族歧视，邻里条件和抑郁症状将收集的措施 在我们之前的研究中使用。皮质醇水平将在头发中测量，这是一种衡量慢性压力的创新方法。 全身炎症将通过血浆细胞因子（例如，白细胞介素-6）、趋化因子和C反应 蛋白将通过“鸟枪式”Orbitrap高分辨率/准确质量测定血浆脂质组谱 光谱法通过利用迄今为止建立的最全面的全球脂质组分析方法，我们将 测定来自非洲孕妇的血浆中数百种脂质分析物的分子组成 美国女人我们将根据医疗记录测量出生时的胎龄。我们亦会考虑 在我们的分析中，妊娠时间，因为产前数据在三个不同的时间点收集。学生 将直接参与拟议项目的各个层面，包括招募和留住参与者， 毛发采集、血样管理和结果传播。这项研究将提供 为学生提供关键的翻译研究经验，重点是鼓励少数民族学生 高等教育拟议的研究与NIH阐明机制的使命高度相关 PTB中潜在的健康差异。我们的长期目标是确定基于慢性压力的肺结核风险， 生物标志物，这将在临床实践中有潜在的用途，并成为干预的目标，以消除 非洲裔美国妇女的PTB差异。

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.