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.

摘要 母亲的心理社会压力经历（例如，压力性生活事件，知觉压力，工作紧张，不良社交 支持）与早产风险增加有关， 被认为是一个关键的机械途径。流行病学研究观察到， 心理社会压力和母体炎症水平。类似地，炎症生物标志物，在 在第二和第三个三个月期间的母体样本与早产有关。然而，在这方面， 心理社会压力和母体炎症如何影响早期至中期胎儿炎症 妊娠情况仍然未知。这是有问题的，因为大多数研究依赖于母体样本作为替代。 怀孕中期的胎儿健康。这种知识差距持续存在，很大程度上是由于后勤和道德方面的原因。 在妊娠中期获得胎儿组织样本的挑战。缩小这一知识差距有其意义 改善整个怀孕期间的胎儿健康，因为怀孕早期母体炎症水平升高 可能导致妊娠后期胎儿炎症水平升高，进而影响胎儿发育 和儿童健康成果。有色人种社区和社会经济地位低的个人经历着 这些人承受着多重心理社会压力的最大负担，而且不成比例地受到结构性歧视的影响。 因此，我们将利用一个独特的队列怀孕的人谁经历了选择性终止妊娠 2010年至2016年期间在加利福尼亚州旧金山弗朗西斯科的第二个三个月期间。这项研究的人群是种族， 种族和人口多样化，主要为有色人种的低收入妇女提供公共卫生服务 保险我们将首次在114个受试者中测量一组由24种炎症生物标志物组成的综合小组， 先前储存的母体和脐带血清以及胎盘样本。同时，我们将量化 促肾上腺皮质激素释放激素（CRH）、FMS样酪氨酸激酶受体（FLT1）和胎盘生长因子 （PlGF）在母体血清中。我们的研究利用了从一个非常重要的时期 期间，将是第一个研究心理社会压力和胎儿炎症之间的关系， 怀孕中期我们将确定丰度的差异，并评估生物标志物之间的相关性。 三个矩阵（目标1）。此外，我们将研究心理社会压力和孕产妇之间的关系， 和胎儿炎症，并使用因子分析为每个矩阵创建炎症评分（目的2）。我们还将 使用结构方程模型来评估脐带血清中测量的炎症是否受 与母体和胎盘炎症水平相关（目的3）。重要的是，我们的研究结果将 提供关于历史上边缘化人口在一个时期内的健康影响的重要见解， 很难研究。了解妊娠中期胎儿炎症的起源及其与 母体炎症可以为未来的研究提供信息，这些研究必须依赖于母体措施作为胎儿炎症的替代品。 炎症和阐明在生物学相关时间段的干预机会，以改善胎儿生长。