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Objectives To test the hypothesis that acidosis at birth is associated with the combined primary outcome of death or neurodevelopmental impairment (NDI) in extremely low birthweight (ELBW) infants, and to develop a predictive model of death/NDI exploring perinatal acidosis as a predictor variable. Study design The study population consisted of ELBW infants born between 2002 and 2007 at National Institute of Child Health and Development (NICHD) Neonatal Research Network hospitals. Infants with cord blood gas data and documentation of either mortality prior to discharge or 18-22 month neurodevelopmental outcomes were included. Multiple logistic regression analysis was used to determine the contribution of perinatal acidosis, defined as a cord blood gas with a pH < 7 or base excess (BE) < -12, to death/NDI in ELBW infants. In addition, a multivariable model predicting death/NDI was developed. Results 3979 patients were identified of whom 249 had a cord gas pH < 7 or BE < -12 mEq/L. 2124 patients (53%) had the primary outcome of death/NDI. After adjustment for confounding variables, pH < 7 and BE < -12 mEq/L were each significantly associated with death/NDI (OR=2.5 (1.6, 4.2) and OR=1.5 (1.1, 2.0), respectively). However, inclusion of pH or BE did not improve the ability of the multivariable model to predict death/NDI. Conclusions Perinatal acidosis is significantly associated with death/NDI in ELBW infants. Perinatal acidosis is infrequent in ELBW infants, however, and other factors are more important in predicting death/NDI