Abstract
Background: In a cohort study of preterm infants increased plasma concentrations of proinflammatory cytokines were associated with premature rupture of membranes, arterial hypotension and cerebral damage.Objective: To evaluate in a follow-up if early postnatal levels of cytokines in preterm infants predict neuro-cognitive outcome at 2 years of age.Methods: A prospective cohort study of 71 surviving infants <32 gestational weeks. Plasma concentrations of proinflammatory (TNF-alfa, IL-1beta, IFN-gamma, IL-2, IL-6, IL-8, IL-12) and modulatory (IL-4, IL-10) cytokines were analyzed in umbilical cord and at 6, 24 and 72 h age. Intraventricular hemorrhage (IVH) and white matter brain damage (WMD) was assessed with ultrasound. Neuro-cognitive outcome at 24 months corrected age was evaluated using Bayley Scales of Infant Development (Mental Developmental Index (MDI) and Psychomotor Developmental Index (PDI)) and a standardized neurological examination (Neurological Optimality Score (NOS)).Results: 64 infants (mean gestational age (GA) 27.1 wks) were assessed at 24 (0.5) months (mean, SD). NOS correlated with both MDI and PDI (r=0.60 p<0.001 and r=0.70 p<0.001 respectively). GA correlated with MDI, PDI and NOS (r=0.34 p=0.006, r=0.42 p=0.001 and r=0.40, p=0.001 respectively). Male gender had lower NOS (p=0.03). Cord levels of the proinflammatory cytokineTNF-alfa were inversely correlated with PDI (r=-0.33 p=0.014) and levels of the modulatory cytokine IL-10 at 24 h correlated positively with PDI and NOS (r=0.42 p=0.001 and r=0.32, p=0.015 respectively) after adjustment for GA and gender. Infants with IVH grade III/IV or WMD (n=8) had lower median (range) MDI and NOS, 74 (50–106) and 63 (36–76), respectively, as compared to infants without brain injury (n=56): 88 (50–116) and 71 (58–78), respectively. Differences remained after adjustment for GA, gender and parental education.Conclusion: An early inflammatory response in preterm infants is associated with perinatal brain injury and might be prognostic for adverse neuro-cognitive outcome at 2 years of age.
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