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: 10618991
• 负责人: CYNTHIA GYAMFI-BANNERMAN
• 金额: $ 66.88万
• 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 2026-11-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10618991
• 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 Cycle Stages; 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; ethnic disparity; experience; fetal; immune function; immunological status; improved; indexing; intergenerational; maternal stress; monocyte; neonatal morbidity; novel; pediatric trauma; perceived discrimination; perceived stress; potential biomarker; psychobiology; psychosocial; racial difference; racial disparity; stress reactivity; stress reduction; 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一致的是，妊娠以早产（PTB）结束， 十个女人。每年PTB影响全世界1500万婴儿，美国386，580名。PTB是领先的 因为全球和美国，新生儿死亡率和发病率，并与未来的风险， （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、 心血管疾病和肾脏疾病。在美国，PTB发病率的种族和民族差异是 戏剧性和独立的社会经济地位（SES）：总体而言，14.12%的非西班牙裔黑人相比， 非西班牙裔白色妇女的比例为9.09%。心理压力和童年创伤都与 PTB的风险。PTB具有代际影响：早产的母亲更有可能早产， 尤其是黑人女性。预测PTB的生物标志物已被证明是不成功的，并且不能解释 这一新的认识，特别是通过母亲的遗传代际传播的肺结核风险。 线粒体，包含自己的基因组，线粒体DNA，是从母亲遗传的， 代表了心理社会经验和它们的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。我们的目标是将线粒体 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-导致少数民族妇女PTB的不成比例的风险，并评估线粒体作为潜在的 这一生育结果的生物标志物。在一个样本中，n=175名孕妇，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适用于多个，第一个三个月的心理社会（自我）， 报告压力辨别、24小时动态情绪、社会支持）、生命历程（头发皮质醇、儿童期 创伤）和生物学变量（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差异。目的2：筛选分子指标 线粒体和免疫功能的母亲（3倍抽血），胎盘，和胎儿脐带血， 介导妊娠早期母体压力表型与早期孕龄风险之间的关联， 出生目的3：评估在治疗过程中，压力水平的降低和/或社会支持的改善是否 妊娠与线粒体和免疫功能的分子指标相关，（探索性） 与国家和医院标准相比，早产风险降低。这种新的概念框架， 健康结果（1）包括有助于风险的心理社会因素的证据，（2）旨在解释 种族/民族差异，（3）利用尖端的线粒体知识和工具，以更好地 描述PTB的病理生理学特征，并确定新的干预和预防目标。