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。心理社会压力及其相关因素 生理后遗症通常可能导致早产，以及早产的种族差异。 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，免疫功能发生了很大的变化，以支持健康的怀孕，在 循环炎性细胞因子、炎症反应减弱和细胞介导性损伤 豁免权。然而，非常有限的研究考察了心理社会压力的测量或 种族预测妊娠期间纵向上的差异免疫适应。 慢性应激可直接刺激促炎细胞因子的产生，并使 免疫系统在暴露于生物挑战时以夸大的方式做出反应。过份 母血循环炎症标志物的升高和炎症反应的趋势 与不良的围产期健康结局有关，包括早产。此外，压力可能会 抑制细胞免疫功能。通常由细胞介导的免疫保持在潜伏状态，爱泼斯坦-巴尔 病毒(EBV)在免疫抑制的情况下可能会重新激活，包括应激。因此，EBV潜伏期 提供了一种衡量细胞免疫功能的指标。由于抑制了细胞介导的免疫，EBV 在怀孕期间比非怀孕期间更有可能重新激活。此外，EBV的重新激活已经与 妊娠时间较短，出生体重较低，尽管尚不清楚这是否起到了因果作用或起到了 病理过程的标志。尽管对健康有独特的影响，但有关以下方面的数据有限 孕期种族或应激对免疫指标的影响 目前的研究将通过检查免疫来建立和解决文献中的重要空白 80名孕妇(40名非裔美国人和40名欧洲裔美国人)的纵向参数 在怀孕期间。这项研究将a)提供更全面的免疫适应信息。 在妊娠期间，通过检测循环细胞因子水平，体外刺激细胞因子的产生，以及细胞 妊娠每三个月的纵向免疫功能(即EBV重新激活)，b)检查效果 关于压力和种族对这种适应的影响，以及，c)提供了关于差异免疫 个人资料预测早产风险增加。因此，这项研究旨在最终导致 确认围产期不良结局风险较高的妇女并阐明其机制 潜在的风险增加，为个性化医疗服务提供了基础。

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.