Stress, Race, and Immune Adaptation Across Pregnancy: Predictors of Preterm Birth

怀孕期间的压力、种族和免疫适应：早产的预测因素

• 批准号: 8114488
• 负责人: Lisa Michelle Christian
• 金额: $ 19.06万
• 依托单位: OHIO STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-07-04 至 2013-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8114488
• 关键词: Accounting; Address; Adult; African American; American; Antibodies; Attenuated; Australia; Biological; Birth Rate; Canada; Case Study; Cells; Cellular Immunity; Cellular Stress; Cervical Ripening; Chronic stress; Conflict (Psychology); Data; Developed Countries; Employee Strikes; Enzyme-Linked Immunosorbent Assay; Epstein-Barr Virus latency; Europe; European; Exhibits; Exposure to; Family; Fetal Development; Health; Health Services; Health behavior; Human Herpesvirus 4; Immune; Immune system; Immunosuppression; Impairment; In Vitro; Infection; Inflammatory; Inflammatory Response; Knowledge; Lead; Length; Link; Literature; Low Birth Weight Infant; Measurement; Measures; Mediating; Membrane; Meta-Analysis; Methodology; Minority; Outcome; Pathologic Processes; Perinatal; Physiological; Play; Pregnancy; Pregnancy Outcome; Pregnancy Trimesters; Pregnant Women; Premature Birth; Premature Labor; Process; Production; Psychological Stress; Psychosocial Stress; Race; Research; Risk; Role; Rupture; Socioeconomic Status; Stress; Testing; United States; Virus; Woman; attenuation; base; cost; cytokine; design; immune function; inflammatory marker; novel; perinatal health; therapy design

Preterm delivery, an increasingly frequent occurrence in the United States, is associated with significant family burden and an estimated societal cost of at least $26 billion per year. Psychosocial stress and related physiological sequelae may contribute to preterm birth in general, as well as racial disparities in preterm birth. It is well-established that among nonpregnant adults, chronic stress promotes immune dysregulation. Importantly, immune function changes substantially to support healthy pregnancy, with mild elevations in circulating inflammatory cytokines, attenuation of inflammatory responses, and impairment of cell-mediated immunity. However very limited research has examined the extent to which measures of psychosocial stress or race predict differential immune adaptation longitudinally across pregnancy. Chronic stress can directly stimulate the production of proinflammatory cytokines and prime the immune system to respond in an exaggerated manner upon exposure to biological challenges. Excessive elevations in maternal circulating inflammatory markers and a tendency toward inflammatory responding have been associated with adverse perinatal health outcomes, including preterm birth. In addition, stress can suppress cellular immune function. Typically kept in a latent state by cell-mediated immunity, Epstein-Barr Virus (EBV) may reactivate under conditions of immunosuppression, including stress. Thus, EBV latency provides a measure of cellular immune function. Due to suppression of cell-mediated immunity, EBV is more likely to be reactivated during pregnancy than nonpregnancy. Further, EBV reactivation has been associated with shorter gestation and lower birth weight, although it is not known if this plays a causal role or serves as a marker of a pathological process. Despite unique implications for health, limited data are available regarding effect of race or stress on immune parameters during pregnancy. The current study will build upon and address important gaps in the literature by examining immune parameters among 80 pregnant women (40 African-American and 40 European-American) longitudinally across pregnancy. This research will a) provide more comprehensive information about immune adaptation during pregnancy by examining circulating cytokine levels, in vitro stimulated cytokine production, and cellular immune function (i.e., EBV reactivation) longitudinally during each trimester of pregnancy, b) examine effects of stress and race on such adaptation and, c) provide preliminary data regarding whether differential immune profiles predict increased risk of preterm birth. Thus, this research is designed to ultimately lead to the identification of women at greater risk for negative perinatal outcomes and elucidation of mechanisms underlying increased risk, providing a basis for individualized health care services.

早产交付是美国越来越频繁发生的，与大量相关 家庭负担和估计每年至少260亿美元的社会成本。社会心理压力和相关 生理后遗症总体上可能有助于早产，以及早产的种族差异。 良好的公认是，在非怀孕的成年人中，慢性应激会促进免疫失调。 重要的是，免疫功能发生了实质性变化以支持健康的怀孕，轻度升高 循环炎性细胞因子，炎症反应的衰减以及细胞介导的损害 免疫。但是，非常有限的研究研究了心理压力或 种族在整个怀孕期间纵向预测免疫适应性。 慢性应激可以直接刺激促炎性细胞因子的产生，并将 免疫系统在暴露于生物学挑战时以夸张的方式做出反应。过多的 母体循环炎症标记和炎症反应的趋势的升高有 与不良的围产期健康结果有关，包括早产。另外，压力可以 抑制细胞免疫功能。通常通过细胞介导的免疫力保持潜在状态Epstein-Barr 病毒（EBV）可能在免疫抑制条件下重新激活，包括压力。因此，EBV延迟 提供了细胞免疫功能的度量。由于抑制细胞介导的免疫力，EBV更多 怀孕期间可能比未怀孕重新激活。此外，EBV重新激活已关联 妊娠较短和较低的出生体重，尽管尚不清楚这是否起因果角色或作为一个 病理过程的标记。尽管对健康有着独特的影响，但有关有限的数据可用 种族或压力对怀孕期间免疫参数的影响。 当前的研究将通过检查免疫来建立并解决文献中的重要差距 80位孕妇（40名非裔美国人和40名欧美）的参数纵向 整个怀孕。这项研究将a）提供有关免疫适应的更全面的信息 在怀孕期间，通过检查循环细胞因子水平，体外刺激细胞因子的产生和细胞 免疫功能（即EBV重新激活）在每个三个月的妊娠中期，b）检查影响 这种适应性的压力和种族以及c）提供有关差异免疫的初步数据 概况预测早产的风险增加。因此，这项研究旨在最终导致 鉴定妇女面临着更大的阴性围产期结局风险和机制的阐明 潜在的风险增加，为个性化的医疗服务提供了基础。