Stress Phenotypes and Preterm Birth: Immune and Energetic Cellular Dysregulation and the Preventive Effect of Social Support

项目摘要 与通常的假设和希望不同的是，怀孕在早产(PTB)中终止的时间约为1/4。 10个女人。每年全球有1500万婴儿感染肺结核，美国有386,580名婴儿感染。PTB是领先的 全球和美国新生儿死亡和发病率的原因，并与未来身体状况不佳的风险有关 (高血压、慢性肾脏疾病、喘息/哮喘)和精神(多动症、智商下降)健康。 产妇健康也不能幸免：早产的妇女患抑郁症、高血压、 晚年的心血管和肾脏疾病。在美国，肺结核发病率的种族和民族差异是 戏剧性且独立于社会经济地位(SES)：总体而言，非西班牙裔黑人的比例为14.12% 非西班牙裔白人女性的失业率为9.09%。心理社会压力和童年创伤都与 肺结核的风险。肺结核具有代际影响：早产的母亲更有可能早产， 尤其是在黑人女性中。预测肺结核的生物标志物被证明是不成功的，并且没有解释 这种对结核病风险代际传播的新认识，特别是通过母系遗传。 线粒体，其中包含自己的基因组，线粒体DNA，是从母亲和 代表了心理社会体验及其生物嵌入之间的潜在交叉点， 包括通过免疫失调，在潜在的疾病结果中。我们的目标是应用线粒体 心理生物学方法描绘生活压力的机制--包括歧视和童年 创伤--在少数民族妇女中导致不成比例的肺结核风险，并评估线粒体的潜力 这一出生结局的生物标志物。在175名自然减员后孕妇的样本中，我们将测试以下内容 三个目标：目标1：确定以数据为导向的方法是否适用于多个月、前三个月的心理社会(自我 报告压力歧视、24小时不间断情绪、社会支持)、生活过程(头发皮质醇、童年 创伤)和生物变量(急性实验室生理应激反应)产生独特的应激状态 这在一定程度上解释了出生时孕龄的种族/民族差异。目标2：确定分子指数 母亲(3倍采血)、胎盘和胎儿脐带血的线粒体和免疫功能 在妊娠早期应激表型与早孕风险之间的中介作用 出生。目标3：评估压力水平的降低和/或社会支持的改善 怀孕与线粒体和免疫功能的分子指数和(探索性)有关 与国家和医院标准相比，降低了早产的风险。对这一不利因素的新概念框架 健康结果(1)纳入了导致风险的心理社会因素的证据，(2)旨在说明 种族/民族差异，以及(3)利用尖端线粒体知识和工具更好地 确定肺结核的病理生理学特征，并确定干预和预防的新靶点。

PROJECT ABSTRACT At odds with common assumptions — and hope, pregnancy ends in preterm birth (PTB) for approximately 1 in 10 women. Yearly PTB affects 15 million infants worldwide and 386,580 in the United States. PTB is the leading cause of global, and U.S., neonatal mortality and morbidity and is associated with future risk for poor physical (higher blood pressure, chronic kidney disease, wheeze/asthma) and mental (ADHD, IQ decrements) health. Maternal health is not spared: women who deliver preterm are at an increased risk for depression, hypertension, cardiovascular and renal disease later in life. In the U.S., the racial and ethnic disparities in PTB rates are dramatic and independent of socio-economic status (SES): overall, 14.12% for Non-Hispanic Black compared to 9.09% for Non-Hispanic White women. Psychosocial stress and childhood trauma each are associated with risk for PTB. PTB has an intergenerational impact: mothers born preterm are more likely to give birth pretern, especially amongst Black women. Biomarkers to predict PTB have proven unsuccessful, and do not account for this emerging recognition of intergenerational transmission of PTB risk specifically via maternal heritage. Mitochondria, which contain their own genome, the mitochondria DNA, are inherited from the mother and represent a potential intersection point between psychosocial experiences and their biological embedding, including via immune dysregulation, in underlying disease outcomes. We aim to apply a mitochondria psychobiology approach to delineate by which mechanisms life stress — including discrimination and childhood trauma — results in disproportionate risk of PTB in minority women, and evaluate mitochondria as potential biomarkers of this birth outcome. In a sample of post-attrition n=175 pregnant women we will test the following three aims: Aim 1: To determine whether a data driven approach to multiple, 1st trimester psychosocial (self- report stress discrimination, 24-hour ambulatory mood, social support), lifecourse (hair cortisol, childhood trauma), and biological variables (acute laboratory physiological stress reactivity) generate unique stress profiles that partially explain the racial/ethnic differences in gestational age at birth. Aim 2: To identify molecular indices of mitochondrial and immune functioning in the mother (3x blood draw), placenta, and fetal cord blood that mediate the association between 1st trimester maternal stress phenotypes and risk for earlier gestational age at birth. Aim 3: To evaluate if reduction in stress levels and/or improvement in social support over the course of pregnancy is associated with molecular indices of mitochondrial and immune functioning and (exploratory) reduced risk of earlier birth relative to national and hospital norms. This new conceptual framing of this adverse health outcome (1) incorporates evidence of the psychosocial factors contributing to risk, (2) aims to account for the racial/ethnic disparities, and (3) harnesses cutting-edge mitochondria knowledge and tools to better characterize PTB’s pathophysiology and identify novel targets for its intervention and prevention.