Premature birth is the leading cause of perinatal mortality and morbidity worldwide. The Perinatology Research Branch has defined preterm labor as a syndrome and determined that at least 25% of all preterm births are born to women with sub-clinical intrauterine infection. Moreover, we have provided evidence that many premature neonates are critically ill before birth and proposed that the onset of premature labor has survival value in the context of intrauterine infection. The goal of this project is to understand the pathophysiology of premature labor and delivery and the focus of our research this year is to determine the role of maternal inflammation in premature labor, as well as the potential diagnostic and prognostic value of matrix metalloproteinase 8 (MMP-8) in patients with preterm labor and intact membranes and preterm premature rupture of membranes (PROM). Our work resulted in the following findings: 1. Normal pregnancy is associated with phenotypic and metabolic changes of granulocytes and monocytes consistent with activation of the cellular components of the innate immune response. This physiologic activation is proposed to be a compensatory mechanism to maintain host defense against infection when the adaptive component of the immune response is suppressed. These findings explain the susceptibility of pregnant women to microbial products. 2. Systemic maternal infection and preeclampsia (a leading cause of maternal death and indicated preterm delivery) are associated with evidence of activation of granulocytes and monocytes over that observed in normal pregnant women. These observations support a role for systemic inflammation in the mechanisms of disease of preeclampsia. 3. Preterm labor with intact membranes was associated with a significant increase in basal intracellular oxygen radical species as well as oxidative burst in monocytes and granulocytes. This suggests that the maternal immune system is involved in the mechanisms responsible for preterm labor even in the absence of demonstrable infection. 4. The amniotic fluid concentrations of MMP-8 were found to identify patients at risk for intraamniotic infection, inpending preterm delivery, and adverse neonatal outcome in patients with preterm labor and intact membranes, as well as in patients with preterm premature rupture of membranes. Thus, MMP-8 determinations may have diagnostic and prognostic value in clinical obstetrics.
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