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Objective To examine risk factors for neonatal clinical seizures and to determine the independent association with death or neurodevelopmental impairment (NDI) in extremely low birth weight (ELBW) infants. Study design A total of 6499 ELBW infants (401-1000 g) surviving to 36 weeks postmenstrual age (PMA) were included in this retrospective study. Unadjusted comparisons were performed between infants with (n = 414) and without (n = 6085) clinical seizures during the initial hospitalization. Using multivariate logistic regression modeling, we examined the independent association of seizures with late death (after 36 weeks PMA) or NDI after controlling for multiple demographic, perinatal, and neonatal variables. Results Infants with clinical seizures had a greater proportion of neonatal morbidities associated with poor outcome, including severe intraventricular hemorrhage, sepsis, meningitis, and cystic periventricular leukomalacia (all P < .01). Survivors were more likely to have NDI or moderate-severe cerebral palsy at 18 to 22 months corrected age (both P < .01). After adjusting for multiple confounders, clinical seizures remained significantly associated with late death or NDI (odds ratio, 3.15; 95% CI, 2.37-4.19). Conclusion ELBW infants with clinical seizures are at increased risk for adverse neurodevelopmental outcome, independent of multiple confounding factors. (J Pediatr 2010; 157: 720-5)