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

早产，在美国越来越频繁地发生，与显著的 家庭负担和估计每年至少260亿美元的社会成本。心理社会压力及相关 一般而言，生理后遗症可能导致早产，早产中的种族差异也是如此。 众所周知，在未怀孕的成年人中，慢性压力会促进免疫失调。 重要的是，免疫功能发生实质性变化以支持健康妊娠， 循环炎性细胞因子、炎性反应的减弱和细胞介导的炎症反应的损害。 免疫力然而，非常有限的研究已经审查了心理社会压力或 种族可预测整个妊娠期免疫适应的纵向差异。 慢性应激可直接刺激促炎细胞因子的产生， 免疫系统在暴露于生物挑战时以夸张的方式作出反应。过度 母体循环炎症标志物的升高和炎症反应的倾向， 与不良围产期健康结果有关，包括早产。此外，压力可以 抑制细胞免疫功能。通常通过细胞介导的免疫保持在潜伏状态， 病毒（EBV）可能在免疫抑制条件下重新激活，包括压力。因此，EBV潜伏期 提供了细胞免疫功能的量度。由于细胞介导的免疫抑制，EBV比正常人更容易感染。 怀孕期间比非怀孕期间更容易被激活。此外，EBV再激活与 妊娠期缩短和出生体重较低，尽管尚不清楚这是否起着因果作用或作为一种 病理过程的标志。尽管对健康有独特的影响，但关于以下方面的数据有限： 种族或压力对怀孕期间免疫参数的影响。 目前的研究将建立在文献中的重要空白，通过检查免疫 80名孕妇（40名非洲裔美国人和40名欧洲裔美国人）纵向参数 在怀孕期间。这项研究将a）提供关于免疫适应的更全面的信息 通过检测循环细胞因子水平、体外刺激的细胞因子产生和细胞因子水平， 免疫功能（即，EBV再活化），B）检查在妊娠期的每个三个月中的纵向效应 的压力和种族对这种适应，c）提供初步数据， 特征预测早产风险增加。因此，这项研究旨在最终导致 查明围产期不良结局风险较大的妇女并阐明其机制 潜在的风险增加，为个性化的医疗保健服务提供基础。

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.