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

压力表型和早产：免疫和能量细胞失调以及社会支持的预防作用

• 批准号: 10410500
• 负责人: CYNTHIA GYAMFI-BANNERMAN
• 金额: $ 67.26万
• 依托单位: COLUMBIA UNIVERSITY HEALTH SCIENCES
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-05-18 至 2026-02-28
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10410500
• 关键词: Acute; Affect; Asthma; Attention deficit hyperactivity disorder; Biological; Biological Markers; Birth; Birth Rate; Black race; Blood; Cardiovascular Diseases; Cells; Chronic Kidney Failure; Data; Discrimination; Disease Outcome; First Pregnancy Trimester; Functional disorder; Future; Gene Expression; Gene Expression Profile; Genome; Gestational Age; Hair; Health; Hispanic; Hospitals; Hour; Hydrocortisone; Hypertension; Immune; Infant; Inflammatory; Inherited; Intervention; Kidney Diseases; Knowledge; Laboratories; Life; Life Stress; Maternal Health; Mediating; Mental Depression; Minority Women; Mitochondria; Mitochondrial DNA; Molecular; Moods; Mothers; Neonatal Mortality; Not Hispanic or Latino; Outcome; Phenotype; Physiological; Placenta; Plasma; Pregnancy; Pregnant Women; Premature Birth; Prevention; Preventive; Psyche structure; Psychological Stress; Psychosocial Factor; Psychosocial Stress; Risk; Sampling; Second Pregnancy Trimester; Social support; Socioeconomic Status; Stress; Testing; Tissues; Umbilical Cord Blood; United States; Wheezing; Woman; black women; cytokine; ethnic difference; experience; fetal; immune function; immunological status; indexing; intergenerational; maternal stress; monocyte; neonatal morbidity; novel; pediatric trauma; perceived discrimination; perceived stress; potential biomarker; psychobiology; psychosocial; racial and ethnic; racial and ethnic disparities; stress reactivity; tool; transmission process

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.

项目摘要 与常见的假设和希望不同的是，怀孕以早产 (PTB) 告终的概率约为 1% 10 名女性。每年 PTB 影响全球 1500 万婴儿，美国 386,580 名婴儿。 PTB 是领先的 导致全球和美国新生儿死亡率和发病率的原因，并与未来身体状况不佳的风险相关 （高血压、慢性肾病、喘息/哮喘）和精神（多动症、智商下降）健康。 孕产妇健康也未能幸免：早产的女性患抑郁症、高血压、 晚年发生心血管和肾脏疾病。在美国，PTB 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，非西班牙裔黑人为 14.12% 非西班牙裔白人女性的比例为 9.09%。心理社会压力和童年创伤都与 PTB 风险。 PTB 具有代际影响：早产母亲更有可能早产， 尤其是在黑人女性中。预测 PTB 的生物标志物已被证明是不成功的，并且不能解释 人们逐渐认识到肺结核风险的代际传播，特别是通过母系遗传。 线粒体含有自己的基因组，即线粒体 DNA，是从母亲遗传而来的 代表心理社会体验与其生物嵌入之间的潜在交叉点， 包括通过免疫失调导致潜在疾病的结果。我们的目标是应用线粒体 心理生物学方法来描述生活压力的机制——包括歧视和童年 创伤——导致少数族裔女性患 PTB 的风险不成比例，并评估线粒体的潜在风险 该出生结果的生物标志物。在 n=175 名孕妇的自然减员样本中，我们将测试以下内容 三个目标： 目标 1：确定数据驱动的方法是否可以解决多个妊娠第一个月的心理社会问题（自我 报告压力歧视、24小时动态情绪、社会支持）、生命历程（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）产生独特的应激分布 这部分解释了出生时胎龄的种族/民族差异。目标 2：确定分子指数 母亲（抽血 3 次）、胎盘和胎儿脐带血中的线粒体和免疫功能 介导妊娠第一期母亲应激表型与早孕年龄风险之间的关联 出生。目标 3：评估在治疗过程中压力水平是否降低和/或社会支持是否得到改善 怀孕与线粒体和免疫功能的分子指数相关，并且（探索性） 相对于国家和医院标准，早产风险降低。这种不利的新概念框架 健康结果 (1) 纳入了导致风险的心理社会因素的证据，(2) 旨在解释 种族/民族差异，以及（3）利用尖端的线粒体知识和工具更好地 描述 PTB 的病理生理学特征并确定其干预和预防的新目标。