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Interleukin-6 concentrations in umbilical cord plasma are elevated in neonates with white matter lesions associated with periventricular leukomalacia
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-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.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-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.
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“The fetal inflammatory response has been linked to the onset of preterm labour, and fetal injury and long-term handicap—including periventricular leucomalacia, cerebral palsy, and chronic lung disease.92, 93, 94”
From Epidemiology and causes of preterm birth (2008) · cites this paper as [92]
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Perinatal infections and cerebral palsy
Ovalı, F. (2015) · Journal of Pediatric Infectious Diseases · doi:10.3233/jpi-2010-0221 · Cited by 2
Christian, L. M., & Porter, K. M. (2014) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2014.06.053 · Cited by 2
Short Cervix: A cause of preterm delivery in young adolescents?
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Pleickhardt, E. P., Celandine, A., Davis, J. M., Chen, M., Schürmann, P., Dörk, T., Dammann, C. E. L., & Dammann, O. (2010) · Early Human Development · doi:10.1016/j.earlhumdev.2010.03.010 · Cited by 2
Relationship between cytokine IL 6 levels and early-onset neonatal morbidity.
Hanzl, M. (2009) · PubMed · Cited by 2
Cord blood myeloperoxidase in preterm infants with periventricular hyperechogenicity.
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Necrotizing Enterocolitis and Short Bowel Syndrome
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Metadata
- Authors
- Yoon, B. H., Romero, R., Yang, S. H., Jun, J. K., Kim, I.-O., Choi, J.-H., & Syn, H. C.
- Affiliations
- Seoul National University (KR)
- Venue
- American Journal of Obstetrics and Gynecology
- Publisher
- Elsevier BV
- Published
- 1996-05
- Volume
- 174
- Issue
- 5
- Pages
- 1433-1440
- ISSN
- 0002-9378 (ISSN-L)
- OpenAlex
- W1964039180
- Cited by
- 584
- References
- 31
- Citations by year
- 2026: 6 · 2025: 3 · 2024: 4 · 2023: 2 · 2022: 13 · 2021: 8 · 2020: 8 · 2019: 9 · 2018: 9 · 2017: 22 · 2016: 14 · 2015: 19 · 2014: 22 · 2013: 22 · 2012: 25
- FWCI
- 21.13
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- American Journal of Obstetrics and Gynecology (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Pediatrics, Perinatology and Child Health › Neonatal and fetal brain pathology
- Health Sciences › Medicine › Obstetrics and Gynecology › Preterm Birth and Chorioamnionitis
- Health Sciences › Medicine › Pediatrics, Perinatology and Child Health › Neonatal and Maternal Infections
- Keywords
- periventricular leukomalacia, interleukin-6, umbilical cord plasma, preterm infants, white matter lesions, TNF-α, IL-1β, interleukin-1 receptor antagonist, cytokines, cerebral palsy risk, umbilical artery pH, biomarkers, risk factors, brain ultrasonography, gestational age
- MeSH terms
- Adult, C-Reactive Protein, Female, Fetal Blood, Humans, Immunoenzyme Techniques, Infant, Newborn, Infant, Premature, Interleukin-1, Leukomalacia, Periventricular, Osmolar Concentration, Pregnancy, ROC Curve, Sensitivity and Specificity, Tumor Necrosis Factor-alpha, Interleukin-6, Receptors, Interleukin-1
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