INTERLEUKIN-6 CONCENTRATIONS IN UMBILICAL-CORD PLASMA ARE ELEVATED INNEONATES WITH WHITE-MATTER LESIONS ASSOCIATED WITH PERIVENTRICULAR LEUKOMALACIA

OBJECTIVE: Periventricular leukomalacia, a common brain white matter l esion in preterm neonates, is a major risk factor for cerebral palsy. Recently, cytokines (i.e., tumor necrosis factor and interleukin-1 bet a) have been implicated as mediators for the development of periventri cular leukomalacia. The purpose of this study was to examine the relat ionship between umbilical cord plasma levels of tumor necrosis factor- alpha, interleukin-1 beta, interleukin-6, and interleukin-1 receptor a ntagonist and the occurrence of periventricular leukomalacia in preter m neonates. STUDY DESIGN: Umbilical cord blood was collected from 172 consecutive preterm births (25 to 36 weeks). Periventricular leukomala cia-associated lesions were diagnosed by brain ultrasonography within the first 3 days of life. Tumor necrosis factor-alpha, interleukin-1 b eta, interleukin-6, and interleukin-1 receptor antagonist were measure d by sensitive and specific enzyme-linked immunoassay methods. Umbilic al cord arterial pH was measured at birth. Statistical analysis was pe rformed with multiple logistic regression and receiver operating chara cteristic curve analysis. RESULTS: Periventricular leukomalacia-associ ated lesions were present in 14.5% (25/172) of infants. Plasma concent rations of interleukin-6 but not of tumor necrosis factor-alpha, inter leukin-1 beta, and interleukin-1 receptor antagonist were significantl y higher in neonates with periventricular leukomalacia-associated lesi ons than in those without these lesions (median 718, range <226 to 32, 000 pg/ml vs median <226, range <226 to 43,670 pg/ml; p < 0.0001). An interleukin-6 value greater than or equal to 400 pg/ml had a sensitivi ty of 72% (18/25) and a specificity of 74% (108/147) in the identifica tion of periventricular leukomalacia-associated lesions. Multivariate analysis showed that umbilical cord interleukin-6 was an independent r isk factor for periventricular leukomalacia (odds ratio 6.2, p < 0.002 ) after correction for known confounding variables (i.e., gestational age at birth, umbilical artery pH, chorioamnionitis). CONCLUSIONS: Int erleukin-6 concentrations in umbilical cord plasma are elevated in neo nates with periventricular leukomalacia-associated lesions. Our data s upport the hypothesis that periventricular leukomalacia may be the res ult of cytokine-mediated brain injury.