GROUPS OF HISTOPATHOLOGIC ABNORMALITIES IN BRAINS OF VERY-LOW-BIRTH-WEIGHT INFANTS

The neuropathologic changes in brains of very premature infants are we ll recognized but relatively few studies have attempted to identify if specific neuropathologic features cluster together. These data could assist in determining pathogenetic mechanisms of immature brain injury . The goal of this study is to identify which, if any, combinations of histologic features occur together. We identified the presence or abs ence of 19 histologic features in the brains of 67 infants from a mult icenter study of 1,665 prematurely born infants whose birthweight was 500-1,500 grams. We used clustering algorithms and factor analysis to group pathologic features that occurred together. Our results indicate that certain histopathologic features do cluster. For example, telenc ephalic white matter astrocytosis occurs in 2 groups: 1) associated wi th amphophilic globules, and, 2) in an uncorrelated group, associated with focal macrophage deposits and coagulative necroses. Parenchymal h emorrhage was not found to be associated with any telencephalic leukoe ncephalopathy, regardless of whether characterized by rarefaction, ast rocytosis, focal coagulative necroses, or foci of macrophages in the w hite matter. Intraventricular hemorrhage and germinal matrix hemorrhag e were not seen together more often than by chance expectation. Intrav entricular hemorrhage was only marginally associated with parenchymal hemorrhage. Our data indicate that specific histopathologic features t end to preferentially cluster with each other in groups. This clusteri ng may represent the manifestation of a common mechanism for each. The se data should be valuable indicators for future research attempting t o establish pathogenesis.