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A developing central nervous system is vulnerable to various insults such as infection and ischemia. While increased understanding of the dynamic nature of brain development allows a deeper insight into the pathophysiology of perinatal brain injury, the precise nature of specific fetal and neonatal brain injuries and their short- and long-term clinical consequences need special attention and further elucidation. The current review will describe the pathophysiological aspects and clinical significance of white matter injury of prematurity, a main form of perinatal brain injury in premature newborns, with a particular emphasis on its potential antenatal components.