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

摘要 非洲裔美国女性的早产率是白人女性的1.5倍(37周) 女人。非裔美国人的高肺结核发病率是长期存在的健康差距，对 非洲裔美国婴儿的健康。导致非裔美国女性结核病差异的一个因素是 由于经历种族歧视和生活在弱势社区而造成的长期压力。的确， 怀孕的非洲裔美国妇女更有可能遭受种族歧视，生活在不利地位 与怀孕的白人妇女相比。虽然研究，包括我们自己的，表明种族 歧视和弱势社区与肺结核的风险有关，肺结核的生物学机制是 这些因素的作用还不是很清楚。我们最重要的假设是，种族因素造成的慢性压力 歧视和弱势社区与脂质体谱的变化有关，这可能 通过增加全身炎症水平来产生更高的肺结核风险。抑郁症状可能 也处于慢性应激、脂类、全身炎症和肺结核之间的途径。我们的目标是：(1) 确定慢性应激对脂质体谱的影响；(2)确定脂体谱对 全身性炎症和抑郁症状；以及(3)检查脂质体谱是否与较低的 出生时胎龄与肺结核发病风险。 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裔美国女性 区域。将通过措施收集种族歧视、邻里条件和抑郁症状 在我们之前的研究中使用过。皮质醇水平将在头发中进行测量，这是一种衡量慢性压力的创新指标。 全身性炎症将通过血浆细胞因子(如白介素6)、趋化因子和C反应来衡量 蛋白。血浆脂质体谱将由“猎枪”Orbitrap高分辨率/精确质量测定 光谱分析。通过利用迄今为止建立的最全面的全球脂质体谱分析方法，我们将 非洲孕妇血浆中数百种脂质分析物的分子组成测定 美国女性。我们将根据医疗记录测量出生时的孕周。我们亦会考虑 在我们的分析中，怀孕的时间，因为产前数据是在三个不同的时间点收集的。学生 将直接参与拟议项目的所有各级，包括征聘和保留参与者， 头发采集、血样管理和结果传播。拟议的研究将提供 为学生提供批判性的翻译研究经验，重点是鼓励少数民族学生 高等教育。这项拟议的研究与美国国立卫生研究院阐明机制的使命高度相关 肺结核潜在的健康差距。我们的长期目标是根据慢性压力和 生物标志物，将在临床实践中具有潜在的用途，并成为干预措施消除的目标 非裔美国女性肺结核方面的差异。

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.