Prenatal stress exposures and fetal inflammation during mid-gestation

妊娠中期的产前应激暴露和胎儿炎症

• 批准号: 10666896
• 负责人: Stephanie Marie Eick
• 金额: $ 25.54万
• 依托单位: EMORY UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-05-01 至 2025-03-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10666896
• 关键词: Affect; Biological; Biological Markers; Blood; California; Child Health; Color; Communities; Corticotropin-Releasing Hormone; Data; Development; Discrimination; Disparity; Enzyme-Linked Immunosorbent Assay; Equation; Ethics; Ethnic Origin; Etiology; Exposure to; Factor Analysis; Fetal Development; Fetal Growth; Fetal Tissues; Fetal health; Fetus; Future; Health; Human; IL6 gene; IL8 gene; Immune system; Individual; Inflammation; Inflammation Mediators; Inflammatory; Interferons; Intervention; Investigation; Knowledge; Link; Low income; Measures; Mediating; Modeling; Mothers; Occupations; Outcome; PGF gene; Participant; Pathology; Pathway interactions; Patient Self-Report; Persons; Placenta; Positioning Attribute; Pregnancy; Pregnancy Complications; Premature Birth; Premature Labor; Proxy; Psychosocial Stress; Questionnaires; Race; Receptor Protein-Tyrosine Kinases; Risk; Role; Sampling; San Francisco; Scientific Advances and Accomplishments; Second Pregnancy Trimester; Serum; Shapes; Signaling Molecule; Social support; Stress; Stressful Event; Termination of pregnancy; Third Pregnancy Trimester; Time; Tissue Sample; Umbilical Cord Blood; Vascular Endothelial Growth Factor Receptor-1; Woman; adverse birth outcomes; adverse outcome; adverse pregnancy outcome; biological adaptation to stress; chemokine; clinical practice; cohort; critical period; cytokine; developmental disease; early pregnancy; epidemiology study; experience; fetal; healthy pregnancy; improved; insight; low socioeconomic status; marginalization; marginalized population; maternal serum; perceived stress; perinatal health; pregnancy health; pregnant; premature; prenatal; prenatal stress; psychosocial stressors; public health insurance; social disparities; social stressor; stressor; study population; women of color

ABSTRACT Maternal experiences of psychosocial stress (e.g., stressful life events, perceived stress, job strain, poor social support) are associated with an increased risk of preterm birth and inflammation during pregnancy has been implicated as a key mechanistic pathway. Epidemiologic studies have observed positive relationships between psychosocial stressors and maternal inflammation levels. Similarly, inflammatory biomarkers, measured in maternal samples during the second and third trimesters, have been associated with preterm birth. However, how psychosocial stress and maternal inflammation both influence fetal inflammation during early to mid- gestation remains unknown. This is problematic because most studies rely on maternal samples as proxies of fetal health during mid-pregnancy. This knowledge gap persists in large part due to logistical and ethical challenges in obtaining fetal tissue samples during mid-gestation. Closing this knowledge gap has implications for improving fetal health across pregnancy, as elevated levels of maternal inflammation during early pregnancy may lead to elevated levels of fetal inflammation later in gestation, which in turn can affect fetal development and child health outcomes. Communities of color and low socioeconomic status individuals experience the highest burden of multiple psychosocial stressors and are disproportionately affected by structural discrimination. Accordingly, we will utilize a unique cohort of pregnant people who underwent elective pregnancy terminations during the second trimester in San Francisco, CA between 2010 and 2016. This study population is racially, ethnically, and demographically diverse, serving primarily low-income women of color with public health insurance. We will, for the first time, measure a comprehensive panel of 24 inflammatory biomarkers in 114 previously banked maternal and cord sera and placenta samples. In parallel, we will quantify levels of corticotropin-releasing hormone (CRH), FMS-like tyrosine kinase receptor (FLT1), and placental growth factor (PlGF) in maternal sera. Our study, which leverages hard to obtain biospecimens from a critically important time period, will be the first to examine the relationship between psychosocial stress and fetal inflammation during mid-gestation. We will determine differences in abundances and assess correlations among biomarkers across the three matrices (Aim 1). Further, we will examine relationships between psychosocial stress and maternal and fetal inflammation and create inflammation scores for each matrix using factor analysis (Aim 2). We will also use structural equation modeling to assess whether inflammation measured in cord serum is influenced by and associated with maternal and placenta inflammation levels (Aim 3). Importantly, results from our study will provide important insights on the health effects of historically marginalized populations during a time period that is difficult to study. Understanding the origins of fetal inflammation during mid-gestation and its relationship with maternal inflammation can inform future studies that must rely on maternal measures as proxies for fetal inflammation and elucidate intervention opportunities at biologically relevant time periods to improve fetal growth.

抽象的 孕产妇的社会心理压力经历（例如，压力大的生活事件，感知到的压力，工作压力，社会不良 支持）与怀孕期间早产和炎症的风险增加有关 被视为关键机械途径。流行病学研究观察到了 社会心理压力源和母体炎症水平。同样，以 在第二和第三个三体中，孕产妇样品与早产有关。然而， 社会心理压力和母体炎症如何影响早期至中期的胎儿炎症 妊娠仍然未知。这是有问题的，因为大多数研究都依靠母体样本作为代理 怀孕期间的胎儿健康。这种知识差距在很大程度上归功于后勤和道德 在妊娠中期获得胎儿组织样品的挑战。结束这个知识差距有含义 为了改善整个怀孕的胎儿健康，随着怀孕初期的孕产妇炎症水平升高 妊娠后期可能导致胎儿炎症水平升高，进而会影响胎儿发育 和儿童健康结果。有色人种和社会经济地位低的社区个人经历了 多个社会心理压力源的最高负担，受结构歧视的影响不成比例。 因此，我们将利用一个独特的孕妇，他们接受了选修怀孕的终止 在2010年至2016年期间，在加利福尼亚州旧金山的第二个学期中。这项研究人数是种族的， 在种族和人口统计学上多样化，主要为公共卫生提供主要的低收入有色妇女 保险。我们将第一次测量114个炎症生物标志物的全面小组 以前存放了母体和绳索血清和胎盘样品。同时，我们将量化 皮质激素释放激素（CRH），FMS样酪氨酸激酶受体（FLT1）和胎盘生长因子 （PLGF）在母系血清中。我们的研究很难从至关重要的时间中获得生物测量 时期将是第一个检查社会心理压力与胎儿炎症之间关系的人 中期。我们将确定丰度的差异并评估跨生物标志物之间的相关性 三个矩阵（AIM 1）。此外，我们将研究心理压力与母性之间的关系 和胎儿炎症，并使用因子分析为每个基质创建炎症评分（AIM 2）。我们也会 使用结构方程建模来评估脐带血清中测得的炎症是否受到和 与母体和胎盘炎症水平相关（AIM 3）。重要的是，我们的研究结果将 在历史上边缘化人群的健康影响的时期内提供重要见解 很难学习。了解妊娠中期胎儿炎症的起源及其与之的关系 孕产妇炎症可以为未来的研究提供信息，必须依靠母体措施作为胎儿的代理 在生物学上相关的时间段内炎症和阐明干预机会，以改善胎儿生长。