Premature birth is a national health crisis occurring at a rate approximating 12%. Recent research hasdemonstrated that maternal periodontal disease is a risk factor for both premature birth and low birth weight.Importantly, individuals in minority populations, and particularly African Americans, are at increased risk forboth premature birth and periodontal diseases. We have previously demontrated that subset of periodontitispatients exhibit elevated levels of the antiphospholipid antibody anticardiolipin (anti-CL). These antibodieshave been linked with miscarriages and premature birth. In a preliminary retrospective analysis of birthweight and gestation of babies born to women who were later identified to have periodontal disease, wefound strong associations between maternal levels of anti-CL and both birth weight and prematurity.However, this observation requires further study because the average time between the births and theperiodontal examinations and antibody determinations was nearly 10 years. Placental proinflammatorycytokines are found to be dominant in placenta! insufficient-growth restricted fetuses, and we haveadditionally observed that anti-CL was able to form immune complexes with both oral pathogens andminimally-modified LDL. When these complexes interacted with dendritic cells (DCs), production ofproinflammatory cytokines (IL-12p70 and IFN-y) by both DC and stimulated lymphocytes was enhanced.Thus, both the procoagulant and proinflammatory properties of antiphospholipids may contribute toincreased risk for preterm birth observed in mothers with periodontal infections. We therefore hypothesizethat periodontitis contributes to the occurrence of placental insufficiency that leads to restricted growth andpremature birth due to induction of anti-CL by the periodontal microflora. We propose to address thishypothesis by determining the association of periodontitis and anti-CL with the severity of fetal growthrestriction in 400 women with premature labor. We will further characterize the immunohistopathologicalchanges in the placenta and cytokine profiles that might account for the occurrence of fetal growthrestriction. Furthermore, we will assess the pathogenicity of anti-CL from mothers with periodontitis in amouse pregnancy model, and examine the ability of P. gingivalis to induce such antibody. These studiesaddress a previously unstudied mechanism linking chronic oral infection and fetal growth restriction.
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