Interleukin-6 concentrations in umbilical cord plasma are elevated in neonates with white matter lesions associated with periventricular leukomalacia,☆☆,,★★

Presented at the Fifteenth Annual Meeting of the Society of Perinatal Obstetricians, Atlanta, Georgia, January 23-28, 1995.
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Abstract

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-1β) 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-α, interleukin-1β, interleukin-6, and interleukin-1 receptor antagonist and the occurrence of periventricular leukomalacia in preterm neonates. STUDY DESIGN: 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-α, interleukin-1β, 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-α, interleukin-1β, 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 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. (AM J OBSTET GYNECOL 1996;174:1433-40.)

Section snippets

Study design

We examined the relationship between umbilical cord plasma TNF-α, IL-6, IL-1β, and IL-1ra concentrations and the occurrence of periventricular leukomalacia–associated white matter lesions occurring within 3 days of birth in 172 consecutive preterm neonates (gestational age <36 weeks) delivered at Seoul National University Hospital. Neonates were excluded if umbilical cord blood could not be obtained, if they had major congenital malformations, or if they died before the examination.

Umbilical cord plasma

Umbilical

RESULTS

Over the study period 281 preterm neonates (gestational age <36 weeks) were delivered. Among these, 96 were excluded (75 because blood could not be retrieved from the umbilical cord at birth and 21 because of congenital anomalies). Thirteen infants could not be evaluated for periventricular leukomalacia–associated lesions (two neonates who had abnormal periventricular white matter echogenicity in the first scan but died before 5 days after birth and 11 neonates who died in the delivery room

COMMENT

This is the first report to document a relationship between umbilical cord plasma IL-6 concentrations and the development of periventricular leukomalacia–associated lesions. Our data clearly demonstrate that periventricular leukomalacia–associated lesions occurred more frequently in newborns with detectable umbilical cord plasma IL-6 than in those without detectable IL-6 (21.2% [20/94] vs 6.4% [5/78]; p < 0.01]. Moreover, the logistic regression analysis demonstrated that the umbilical cord

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    From the Departments of Obstetrics and Gynecology,a Radiology,b and Pediatrics,c College of Medicine, Seoul National University, and the Perinatology Branch, National Institute of Child Health and Human Development.d

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    Supported by grant No. 94-0403-11-01-3 from the Korea Science and Engineering Foundation and grant No. 03-94-030 from the Seoul National University Hospital Research Fund.

    Reprint requests: Bo Hyun Yoon, MD, PhD, Department of Obstetrics and Gynecology, Seoul National University, Seoul, 110-744, Korea.

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