Interleukin-6 concentrations in umbilical cord plasma are elevated in neonates with white matter lesions associated with periventricular leukomalacia.
OBJECTIVE
Periventricular leukomalacia, a common brain white matter lesion in preterm neonates, is a major risk factor for cerebral palsy. Recently, cytokines (i.e., tumor necrosis factor and interleukin-1(beta)) have been implicated as mediators for the development of periventricular leukomalacia. The purpose of this study was to examine the relationship between umbilical cord plasma levels of tumor necrosis factor-alpha, interleukin-1(beta), interleukin-6, and interleukin-1 receptor antagonist and the occurrence of periventricular leukomalacia in preterm neonates.


METHODS
Umbilical cord blood was collected from 172 consecutive preterm births (25 to 36 weeks). Periventricular leukomalacia-associated lesions were diagnosed by brain ultrasonography within the first 3 days of life. Tumor necrosis factor-alpha, interleukin-1(beta) interleukin-6, and interleukin-1 receptor antagonist were measured by sensitive and specific enzyme-linked immunoassay methods. Umbilical cord arterial pH was measured at birth. Statistical analysis was performed with multiple logistic regression and receiver operating characteristic curve analysis.


RESULTS
Periventricular leukomalacia-associated lesions were present in 14.5% (25/172) of infants. Plasma concentrations of interleukin-6 but not of tumor necrosis factor-alpha, interleukin-1(beta), and interleukin-1 receptor antagonist were significantly higher in neonates with periventricular leukomalacia-associated lesions 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 > or = 400 pg/ml had a sensitivity of 72% (18/25) and a specificity of 74% (108/147) in the identification of periventricular leukomalacia-associated lesions. Multivariate analysis showed that umbilical cord interleukin-6 was an independent risk 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
Interleukin-6 concentrations in umbilical cord plasma are elevated in neonates with periventricular leukomalacia-associated lesions. Our data support the hypothesis that periventricular leukomalacia may be the result of cytokine-mediated brain injury.
Yoon
B H
BH
Department of Obstetrics and Gynecology, College of Medicine, Seoul National University, Korea.
Romero
R
R
Yang
S H
SH
Jun
J K
JK
Kim
I O
IO
Choi
J H
JH
Syn
H C
HC
D000328:Adult; D002097:C-Reactive Protein / Q000032:analysis; D005260:Female; D005312:Fetal Blood / Q000737:chemistry*; D006801:Humans; D007124:Immunoenzyme Techniques; D007231:Infant, Newborn; D007234:Infant, Premature; D007375:Interleukin-1 / Q000097:blood; D015850:Interleukin-6 / Q000097:blood*; D007969:Leukomalacia, Periventricular / Q000097:blood*; D009994:Osmolar Concentration; D011247:Pregnancy; D012372:ROC Curve; D017472:Receptors, Interleukin-1 / Q000037:antagonists & inhibitors; D012680:Sensitivity and Specificity; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis
D007375:Interleukin-1; D015850:Interleukin-6; D017472:Receptors, Interleukin-1; D014409:Tumor Necrosis Factor-alpha; D002097:C-Reactive Protein