Premature birth is a national health crisis occurring at a rate approximating 12%. Recent research has demonstrated 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 for both premature birth and periodontal diseases. We have previously demontrated that subset of periodontitis patients exhibit elevated levels of the antiphospholipid antibody anticardiolipin (anti-CL). These antibodies have been linked with miscarriages and premature birth. In a preliminary retrospective analysis of birth weight and gestation of babies born to women who were later identified to have periodontal disease, we found 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 the periodontal examinations and antibody determinations was nearly 10 years. Placental proinflammatory cytokines are found to be dominant in placenta! insufficient-growth restricted fetuses, and we have additionally observed that anti-CL was able to form immune complexes with both oral pathogens and minimally-modified LDL. When these complexes interacted with dendritic cells (DCs), production of proinflammatory 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 to increased risk for preterm birth observed in mothers with periodontal infections. We therefore hypothesize that periodontitis contributes to the occurrence of placental insufficiency that leads to restricted growth and premature birth due to induction of anti-CL by the periodontal microflora. We propose to address this hypothesis by determining the association of periodontitis and anti-CL with the severity of fetal growth restriction in 400 women with premature labor. We will further characterize the immunohistopathological changes in the placenta and cytokine profiles that might account for the occurrence of fetal growth restriction. Furthermore, we will assess the pathogenicity of anti-CL from mothers with periodontitis in a mouse pregnancy model, and examine the ability of P. gingivalis to induce such antibody. These studies address a previously unstudied mechanism linking chronic oral infection and fetal growth restriction.