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To identify risk factors implicated in the development of periventricular leukomalacia (PVL) and to evaluate the possible association between PVL with neonatal morbidity.Retrospective case control study.Medical records of neonates admitted to a University Hospital between January 2000 and December 2005.Sixty-nine neonates with PVL born at gestational ages from 24 to 34 weeks. Forty-three of these had a cystic form of PVL (cPVL), whereas 26 had transient periventricular echodensities (PVE).Each case was matched for gestational age and year of birth with one control. The maternal and neonatal medical records were searched. All data was compared between cases with PVL and controls, as well as between cases with cPVL and those with PVE. Stepwise logistic regression analysis was conducted to identify the independent predictors of PVL.Neonates with PVL suffered more frequently from intraventricular hemorrhage (IVH), respiratory distress syndrome type I (RDS I), seizures, sepsis, required more days of both mechanical ventilation and oxygen administration, while the duration of their hospitalization was longer compared to controls. Also, they were born more frequently to mothers who suffered from preterm premature rupture of membranes (PPROM) and clinical chorioamnionitis. We found that male gender, PPROM, preeclampsia, hypocarbia and IVH were independently associated with PVL.This study revealed that preterm neonates born to mothers with PPROM or preeclampsia, as well as neonates who presented with hypocarbia or suffered from IVH, appeared to be at high risk for the development of PVL.