Cytokines and neurodevelopmental outcomes in extremely low birth weight infants

Abstract

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] 1β; IL-8; tumor necrosis factor-α; 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-β, soluble IL rα, macrophage inflammatory protein 1β) 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.

Figure

Cytokine levels (median values) in infants with CP and in those without CP. Overall, IL-8 but not IL-1β, TNF-α, RANTES, or IL-2 differed on days 0–21 between the infants who went on to develop CP and those without CP. Statistical results of the comparison of cytokine levels at each time point are identified. (*p < 0.05 for comparison of infants with versus those without CP)