Yoon B H, Romero R, Yang S H, Jun J K, Kim I O, Choi J H, Syn H C
Department of Obstetrics and Gynecology, College of Medicine, Seoul National University, Korea.
Am J Obstet Gynecol. 1996 May;174(5):1433-40. doi: 10.1016/s0002-9378(96)70585-9.
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.
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.
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).
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.
脑室周围白质软化是早产儿常见的脑白质病变，是脑瘫的主要危险因素。最近，细胞因子（即肿瘤坏死因子和白细胞介素-1β）被认为是脑室周围白质软化发展的介质。本研究的目的是探讨脐血血浆中肿瘤坏死因子-α、白细胞介素-1β、白细胞介素-6和白细胞介素-1受体拮抗剂水平与早产儿脑室周围白质软化发生之间的关系。
收集172例连续早产（25至36周）的脐血。在出生后的头3天内通过脑超声诊断脑室周围白质软化相关病变。采用灵敏且特异的酶联免疫吸附测定法测量肿瘤坏死因子-α、白细胞介素-1β、白细胞介素-6和白细胞介素-1受体拮抗剂。出生时测量脐动脉pH值。采用多元逻辑回归和受试者工作特征曲线分析进行统计分析。
14.5%（25/172）的婴儿存在脑室周围白质软化相关病变。与无这些病变的新生儿相比，有脑室周围白质软化相关病变的新生儿血浆白细胞介素-6浓度显著升高，而肿瘤坏死因子-α、白细胞介素-1β和白细胞介素-1受体拮抗剂浓度无显著差异（中位数718，范围<226至32,000 pg/ml，对比中位数<226，范围<226至43,670 pg/ml；p<0.0001）。白细胞介素-6值≥400 pg/ml在识别脑室周围白质软化相关病变时的敏感性为72%（18/25），特异性为74%（108/147）。多变量分析显示，在校正已知的混杂变量（即出生时的胎龄、脐动脉pH值、绒毛膜羊膜炎）后，脐血白细胞介素-6是脑室周围白质软化的独立危险因素（比值比6.2，p<0.002）。
有脑室周围白质软化相关病变的新生儿脐血血浆中白细胞介素-6浓度升高。我们的数据支持脑室周围白质软化可能是细胞因子介导的脑损伤结果这一假说。
