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 与共同的假设不一致 - 希望，怀孕在早产（PTB）中结束了约1英寸 10名女性。在美国，年度PTB每年影响全球1500万婴儿，386,580名婴儿。 PTB是领导者 全球和美国的原因，新生儿死亡率和发病率，与身体不良的未来风险有关 （较高的血压，慢性肾脏疾病，喘息/哮喘）和心理（ADHD，智商降低）健康。 孕产妇的健康并不幸运：交付早产的妇女患抑郁症，高血压，高血压的风险增加 心血管和肾脏疾病后期。在美国，PTB利率的种族和种族差异是 戏剧性和独立于社会经济地位（SES）：总体而言，非西班牙裔黑色比较14.12％ 非西班牙裔白人妇女为9.09％。社会心理压力和儿童创伤都与 PTB的风险。 PTB有代际影响：出生的母亲更有可能生育预期， 特别是在黑人妇女中。预测PTB的生物标志物已证明没有成功，并且不考虑 对PTB风险的代际传播的新出现的认识，专门通过材料遗产。 线粒体包含自己的基因组，线粒体DNA，是从母亲那里继承的， 代表社会心理经历与其生物嵌入之间的潜在相交点， 包括免疫失调，在潜在的疾病结局中。我们的目标是应用线粒体 精神生物学方法描述了生命压力的机制 - 包括歧视和童年 创伤 - 少数妇女的PTB风险不成比例，并评估线粒体为潜在 这种出生结果的生物标志物。在引起后n = 175名孕妇的样本中，我们将测试以下 三个目的：目标1：确定数据驱动方法是否采用多个，第一个三个月的心理社会心理（自我） 举报压力歧视，24小时的门诊情绪，社会支持），生命力（皮质醇，童年 创伤）和生物学变量（急性实验室生理压力反应性）产生独特的应力曲线 这部分解释了出生时胎龄的种族/种族差异。目标2：确定分子指数 母亲的线粒体和免疫功能（3x抽血），胎盘和胎儿血液 调解第一例三个月材料应力表型与早期妊娠年龄的风险之间的关联 生日。目标3：评估在整个过程中的压力水平降低和/或社会支持的改善 妊娠与线粒体和免疫功能的分子指数以及（探索性）有关 相对于国家和医院规范，较早出生的风险降低。这种逆境的新概念框架 健康结果（1）结合了导致风险的社会心理因素的证据，（2）旨在说明 种族/种族差异，以及（3）利用尖端的线粒体知识和工具以更好 表征PTB的病理生理学并确定其干预和预防的新目标。