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Objective: The purpose of this study was to evaluate which factors affect the occurrence of neonatal ultrasonographic evidence of severe cerebral lesions in the presence of intrauterine infection. Study Design: From a cohort of 567 singleton neonates who were born between 24.0 and 31.6 weeks of gestation, we identified the 180 infants with histologic and/or clinical evidence of intrauterine infection. We excluded stillbirths and congenital anomalies. Obstetric and neonatal variables were related to evidence of severe neonatal ultrasonographic cerebral lesions with the use of logistic regression analysis. Results: Severe cerebral lesions were identified in 10% of infants (18/180). After we controlled for variables that were clinically relevant, logistic regression analysis demonstrated that ultrasound evidence of severe neonatal cerebral lesions was associated independently with antenatal administration of corticosteroids (adjusted odds ratio, 0.3; 95% CI, 0.11-0.88; P = .03) and occurrence of placental abruption (adjusted odds ratio, 5.4; 95% CI, 1.4-20.7; P = .02). Conclusion: Antenatal administration of corticosteroids in the presence of intrauterine infection has a protective effect on the risk of ultrasonographic evidence of severe neonatal cerebral lesions. © 2008 Mosby, Inc. All rights reserved.