The aim of this study is to better understand the relationship between placental pathology and risk of intraventricular hemorrhage (IVH). We address two specific hypotheses. 1) Morphologic correlates of pregnancy-induced hypertension (PIH) are associated with a decreased risk of IVH. 2) Morphologic correlates of amniotic sac inflammation (ASI) are associated with an increased risk of IVH. Maternal, neonatal, and placental data were analyzed by univariate and multivariate methods in this prospective cohort study of 1095 very low birth weight infants. A cluster analysis model was used to categorize the placental pathologic features into clusters, the two main ones being PIH and ASI. Deliveries were subdivided by the interval between membrane rupture and delivery as an index of preexisting infection (<1 h) and ascending infection (> or =1 h). Univariate analysis supports both hypotheses. However, in multivariate models that adjusted for such potential confounders as gestational age, labor, and route of delivery, the only associations that persisted were the increased risk of IVH associated with the presence of chorionic or umbilical vasculitis in infants born within 1 h of membrane rupture. Placental correlates of PIH do not provide additional information about IVH risk independent of the presence of other components of the PIH and ASI clusters, and confounders such as gestational age, labor, and route of delivery. Placental correlates of ASI, specifically the fetal responses of chorionic and umbilical vasculitis to preexisting infection, are associated with an increased risk of IVH independent of confounders. Cytokines may provide the link between placental inflammation and fetal/neonatal brain hemorrhage.