Abruptio placentae (AP), the premature separation of the normally implanted placenta, is a life threatening obstetric complication of pregnancy (Cunningham, 1989). The etiology of AP is unknown though results from previous studies suggest some risk factors, several of which may be amenable to modification. Briefly, results from several small studies suggest that low maternal intake of folate and other B vitamins may be associated with an increased risk of AP. An emerging literature concerning homocyst(e)ine concentrations in the blood of women with a history of AP, corroborates and expands upon those earlier findings. There is also some evidence suggestive of an association between maternal infection/inflammatory status and increased risk of AP. We seek to build on this body of work by conducting a case-control study of AP in Lima, Peru. We will use a case-control design that includes, collecting maternal and placental samples (used for testing biological markers) and multivariate logistic regression analysis to assess the relation between risk of AP and biological markers of low folate, vitamin B6, and vitamin B)2. Maternal serum homocyst(e)ine will be assessed in approximately 400 AP cases and 400 controls as part of our aim of evaluating the metabolic consequence of low folate and other B vitamins in relation to risk of AP. Additionally, we will assess hypotheses concerning maternal infection/inflammatory status [as measured by C-reactive protein (CRP) and the pro- inflammatory cytokines such as tumor necrosis factor-a (TNF-a) and the soluble receptor for TNF-oc (sTNFpSS), and clinical and/or histological chorioamnionitis] as risk factors of AP. In addition to addressing the primary hypotheses, data collected for the proposed study will allow for a reevaluation of the association between AP risk and other putative risk factors. Risk factors to be considered includeyoung and advanced maternal age, grand multiparity(parity > 5), maternal smoking, prior history of stillbirth, c-section delivery and other adverse pregnancy outcomes. The ultimate goals of our proposed research are to increase the ability to identify pregnant women at high risk of experiencing AP, and to further understand the mechanisms by which AP occurs. Results from our proposed research have a very high potential for yielding etiologic and clinical information that may prove to be effective in the identification of subgroups of women at greatest need for specific preventive interventions and specialized clinical care. Results from the proposed study could have practical significance in developing alternative, practical preventative interventions for AP and other adverse pregnancy outcomes (e.g., preeclampsia and preterm delivery). Folate and other B vitamins could be easily manipulated in the diet either by supplement use or by specific choice of foods if evidence from this and other studies indicates a benefit.