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Circulating Interferon-gamma and White Matter Brain Damage in Preterm Infants

The fetal inflammatory response has been suggested as causal in neonatal morbidity. Serial levels of circulating cytokines were evaluated in 74 infants with a mean gestational age (GA) of 27.1 wk. Pro-inflammatory and modulatory (IL-4, IL-10) cytokines were analyzed from cord blood, and at 6, 24, and 72 h postnatal age. Measure of cytokine burden over time was assessed by calculating the area under curve (AUC) for analyzed levels (0–72 h). Premature rupture of membranes (PROM) was associated with higher levels of IL-2 at birth and at 6 h, of IFN-γ at 6 and 24 h postnatal age and of TNF-α at 6 and 24 h. Levels of IFN-γ at 6, 24, and 72 h were increased in infants developing white matter brain damage (WMD) compared with those without WMD. Infants with arterial hypotension requiring dopamine treatment had an increase in IL-6 with a peak at 6 h of age. Severe intraventricular hemorrhage (IVH) was associated with increase in AUC, whereas WMD was associated with increase in AUC. A fetal immune response with increased postnatal levels of IFN-γ was associated with development of WMD. PROM was associated with a T-helper 1 cytokine response with increased levels of IFN-γ. Type of inflammatory response appears of importance for subsequent morbidity.