Viral pathogenesis of chronic inflammatory lesions of the placenta

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.