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