Objective. To identify the risk factors for cystic periventricular leukomalacia (cPVL) and their implications for deciding between immediate delivery and conservative management of preterm prelabor rupture of the membranes (pPROM). Methods. The following risk factors were compared between cPVL infants and 6440 controls: chorioamnionitis, sex, gestational age (GA), birth weight, pPROM, and pPROM-delivery interval. Factor impact on cPVL risk and clinical decision-making was determined by multivariate logistic regression. Results. Overall cPVL prevalence ( ) was 0.99/1000 births. All cPVL infants but one were born <34 weeks of gestation and were <2500？g; 56% had histological chorioamnionitis versus 1.1% of controls (OR 35.9; 95%-CI 12.6–102.7). Because chorioamnionitis is a postnatal diagnosis, logistic regression was performed with prenatally available factors: pPROM-delivery interval >48 hours (OR 9.0; 95%-CI 4.1–20.0), male gender (OR 3.2; 95%-CI 1.4–7.3). GA was not a risk factor if birth weight was included. Risk decreased with increasing fetal weight despite a prolonged pPROM-delivery interval. Conclusion. pPROM-delivery interval is the single most important prenatally available risk factor for the development of cPVL. Immediate delivery favors babies with chorioamnionitis but disfavors those with non infectious pPROM. In the absence of clinical chorioamnionitis fetal weight gain may offset the inflammatory risk of cPVL caused by a prolonged pPROM-delivery interval. 1. Introduction Cerebral palsy includes a group of nonprogressive movement disorders due to brain lesions or abnormalities in early development [1]. Its prevalence of 2 per 1000 newborns overall rises to 77 per 1000 preterms born at below 28 0/7 weeks of gestation [2, 3]. A major cause is cystic periventricular leukomalacia (cPVL) comprising necrosis and subsequent cyst formation of the periventricular white matter: 60–100% of children with cPVL develop cerebral palsy [4–6]. Although the etiology and pathogenesis of cPVL remain unelucidated, several perinatal risk factors appear involved [7]. Birth asphyxia is no longer assumed the principal culprit [8]. Chorioamnionitis is thought to provoke a fetal inflammatory response syndrome associated with increased fetal cytokines that may lead to neonatal brain injury. Several studies indicate that the cytokines can themselves damage white matter without bacteremia being required [8–15]. An important predictor of chorioamnionitis is preterm prelabor rupture of membranes (pPROM) [16]. One-third of women with pPROM have positive amniotic fluid
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