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Objective. Previous multicenter studies have shown significant center differences in neonatal characteristics and morbidities. This study evaluated center differences in outcome at 18 to 22 months among extremely low birth weight (ELBW; 401- 1000 g) infants after adjusting for demographics and antenatal interventions, and it identified neonatal interventions associated with outcome differences. Methods. We assessed the outcome of 2478 liveborn infants who were admitted in 1993 and 1994 to the 12 centers of the Neonatal Research Network of the National Institute of Child Health and Human Development; 1483 (60%) infants survived to 18 to 22 months, and 1151 (78%) had comprehensive evaluations. Logistic regression analyses were performed to identify center differences and the association of 4 neonatal interventions - active resuscitation, postnatal steroids, ventilator treatment for less than or equal to 27 days, and full enteral feedings less than or equal to 24 days - with adverse outcomes ( cerebral palsy, low Bayley scores, and neurodevelopmental impairment [NDI]), after adjusting for demographics and antenatal interventions. Results. Using bivariate analyses, significant center differences were identified for mortality, antenatal and postnatal interventions, social and environmental variables, neonatal morbidities, and neurodevelopmental outcomes for the 12 centers. After adjustment for maternal and infant demographics and antenatal interventions, the percentage of ELBW infants who had died or had NDI at 18 to 22 months ranged from 52% to 85%. Active resuscitation and postnatal steroids were associated with increases of NDI of 11.8% and 19.3%, whereas shorter ventilation support and shorter time to achieve full enteral feeds were associated with decreases in NDI of 20.7% and 17.3%, respectively. Conclusion. There are large and disturbing differences among centers in outcomes at 18 to 22 months after adjusting for demographic and antenatal interventions. Center differences in postnatal interventions associated with differences in outcome can provide hypotheses for testing in clinical trials to improve outcome