This supplemental application extends the evaluation of oral inflammation and infection, effects on pregnancy to the potential impact on premature newborns and the leading complications of prematurity, lung and brain damage. The general hypothesis is that subclinical infection, possibly originating in periodontal disease, affects the inflammatory and immune responses in women, placing them at higher risk for preterm labor and delivery. Pro-inflammatory cytokines, associated with periodontal disease and intrauterine infection, have been implicated in the initiation of preterm labor. Our proposed studies will assess how these maternal processes affect the inflammatory cascade in the premature low birth eight infant and the risk for inflammatory complication of prematurity. Prenatal infection and inflammation are associated with brain injury in premature newborns, in particular intraventricular hemorrhage and periventricular leukomalacia. Inflammatory cytokines are found in the tracheal secretions of premature newborns who later develop bronchopulmonary dysplasia. Necrotizing enterocolitis is another serious life-threatening complication of prematurity associated with elevations in pro-inflammatory cytokines. Genetic polymorphisms encoding IL-1beta and TNFalpha are associated with increased cytokine expression and may predispose to an exaggerated inflammatory response. We will measure pro-inflammatory cytokines in pregnant women and compare them to those in their premature newborns. Cytokines will be correlated with the inflammatory complications of prematurity: bronchopulmonary dysplasia, intraventricular hemorrhage/periventricular leukomalacia, and necrotizing enterocolitis, using logistic regression analysis. Polymorphisms will be identified and correlated with these inflammatory complications with the abundance of cytokine protein and mRNA in tracheal aspirates cells and in blood. We will test whether a panel of mediators identified at risk with high sensitivity and specificity. Our long-term aim is to develop markers that identify newborns at highest risk and provide the basis for future therapy to prevent these complications of prematurity.
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