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Objective To determine if selected pro-inflammatory and anti-inflammatory cytokines and/or mediators of inflammation reported to be related to the development of cerebral palsy (CP) predict neurodevelopmental outcome in extremely low birth weight infants. Study design Infants with birth weights <= 1000 g (n = 1067) had blood samples collected at birth and on days 3 +/- 1, 7 +/- 1, 14 +/- 3, and 21 +/- 3 to examine the association between cytokines and neurodevelopmental outcomes. The analyses were focused on 5 cytokines (interleukin [IL] 1 beta; IL-8; tumor necrosis factor-a; regulated upon activation, normal T-cell expressed, and secreted (RANTES); and IL-2) reported to be most predictive of CP in term and late preterm infants. Results IL-8 was higher on days 0-4 and subsequently in infants who developed CP compared with infants who did not develop CP in both unadjusted and adjusted analyses. Other cytokines (IL-12, IL-17, tumor necrosis factor-beta, soluble IL r alpha, macrophage inflammatory protein 1 beta) were found to be altered on days 0-4 in infants who developed CP. Conclusions CP in former preterm infants may, in part, have a late perinatal and/or early neonatal inflammatory origin. (J Pediatr 2011;159:919-25)