Viral pathogenesis of chronic inflammatory lesions of the placenta

项目摘要 早产和宫内生长受限是美国重要的公共卫生问题， 分别影响10%和3-9%的新生儿。这些不良的妊娠结局会增加 死亡率和终身发病率，以及每年超过260亿美元的巨额货币成本。 宫内/胎盘炎症导致超过一半的早产。许多研究都与 对胎盘炎症的研究主要集中在急性炎症过程，这通常是由细菌引起的。 感染的羊膜腔，并鲜为人知的触发器或机制，启动和维持 慢性胎盘炎（CPI）。众所周知，一些CPI与病毒感染有关，例如 巨细胞病毒，但在大多数情况下，CPI的病因仍然不明。我们假设大多数CPI是 胎盘病毒感染引起的慢性炎症反应。我们将全面分析胎盘组织 以确定病毒和抗病毒炎症特征是否与CPI相关。 此外，我们将测试在怀孕期间收集的母亲血液，以确定我们是否可以识别病毒 和/或将预测CPI发展的宿主信号。最后，我们将测试新生儿脐带血， 病毒感染或宿主信号的存在与胎盘或母体血液中观察到的一致。本研究 有可能导致CPI预测或诊断测试的开发，它将帮助我们 了解CPI是如何触发和发展的，以便我们最终能够设计预防性或 治疗性治疗最终，我们预测和/或预防CPI的能力将改善妊娠结局， 儿童健康。

PROJECT SUMMARY Preterm birth and intrauterine growth restriction are significant public health problems in the United States, affecting 10% and 3-9% of births, respectively. These adverse pregnancy outcomes result in increased risk of mortality and lifelong morbidities, in addition to substantial monetary costs of >$26 billion annually. Intrauterine/placental inflammation contributes to more than half of preterm birth. Much of the research related to placental inflammation has focused on acute inflammatory processes, which are typically driven by bacterial infections in the amniotic cavity, and little is known about the triggers or mechanisms that initiate and sustain chronic placental inflammation (CPI). It is well known that some CPI is associated with viral infection, such as cytomegalovirus, but in most cases, the etiology of CPI remains unknown. We hypothesize that most CPI is a chronic inflammatory reaction to viral infection in the placenta. We will comprehensively analyze placental tissue from pregnant women to determine whether viruses and antiviral inflammatory profiles are associated with CPI. Furthermore, we will test maternal blood collected during pregnancy to determine whether we can identify a viral and/or host signal that will predict development of CPI. Lastly, we will test neonatal umbilical cord blood for the presence of viral infection or host signal consistent with that seen in the placenta or maternal blood. This study has the potential to lead to the development of a predictive or diagnostic test for CPI, and it will help us to understand how CPI is triggered and progresses so that we may ultimately be able to design a preventative or therapeutic treatment. Ultimately, our ability to predict and/or prevent CPI will improve pregnancy outcomes and child health.