Possible correlation between high levels of IL-18 in the cord blood of pre-term infants and neonatal development of periventricular leukomalacia and cerebral palsy

Abstract

Periventricular leukomalacia (PVL) is a neonatal white matter damage of the brain of pre-term infants that often leads to cerebral palsy (CP). At present, diagnosis of PVL can be done by magnetic resonance imaging (MRI) and ultrasonography only when the infant is at least one week of age. No biochemical methods are available to identify high-risk infants at birth. Cytokines are usually not present in the cord blood but recently an elevation of IL-6 and TNF-alpha levels has been reported in amniotic fluid, cord blood and brain sections of infants with white matter damages. Levels of interleukin-18 (IL-18), a pleiotropic cytokines expressed in the brain and many other tissues, are highly sensitive to pathophysiological changes to raise the possibility that IL-18 may provide a useful indicator of PVL. The cord blood from 17 pre-term infants with PVL, 38 pre-term infants without PVL, and 30 normal full-term infants were retrospectively analysed for IL-18, IL-6, IL-1beta, and TNF-alpha. The possible factors involved in alteration of IL-18 concentration in relation to PVL and CP were examined. IL-18 is undetectable in the cord blood of normal full-term infants. However, high levels of IL-18 exist in the cord blood samples obtained from pre-term infants who neonatally developed PVL followed by CP. For pre-term infants under 35 weeks of gestation, seven out of eight showing more than 200 pg/ml of IL-18 (87.5%) developed PVL neonatally, with five of them subsequently developing CP. In contrast, only five out of 38 pre-term infants with less than 100 pg/ml of IL-18 (13.2%) developed PVL. For pre-term infants with less than 30 weeks of gestation, eight out of nine showing more than 100 pg/ml of IL-18 (88.9%) developed PVL, with six of these eight (75%) developing CP later. In conclusion, the presence of high levels of IL-18 in the cord blood of the pre-term infants is correlated with the incidence of PVL and CP and may provide a prognostic marker applicable at birth.