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细胞因子水平与脓毒症早产儿脑白质损伤的关系。

Association between high cytokine levels with white matter injury in preterm infants with sepsis.

机构信息

Department of Pediatrics, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil.

出版信息

Pediatr Crit Care Med. 2012 Mar;13(2):183-7. doi: 10.1097/PCC.0b013e3182231074.

DOI:10.1097/PCC.0b013e3182231074
PMID:21666535
Abstract

OBJECTIVE

To examine the association among interleukin-6, interleukin-8, tumor necrosis factor-α, interleukin-10, and interleukin-1β and white matter injury in very-low-birth-weight infants with clinical sepsis and to help predict infants at risk for development of white matter injury.

DESIGN

A prospective cohort study was carried out.

SETTING

Neonatal intensive care unit.

PATIENTS

Very low birth weight infants with clinical early-onset sepsis. Exclusion criteria were death before 14 days, major malformations, and congenital infections.

INTERVENTION

Ultrasound brain scans were carried out on the third day and weekly until the sixth week of life or discharge and confirmed by a magnetic resonance image performed in the first year. Plasma was assayed for interleukin-6, interleukin-8, tumor necrosis factor-α, interleukin-10, and interleukin-1β in the same sample collected for sepsis work-up. Mann-Whitney, chi-square, t tests, multiple regression, and receiver operating characteristic analysis were applied.

MEASUREMENTS AND MAIN RESULTS

From July 2005 to October 2007 we studied 84 very-low-birth-weight infants, 27 (32%) with white matter injury, and 57 (68%) control subjects (with no white matter injury). Proven early-onset sepsis and necrotizing enterocolitis were high risk for white matter injury after adjustment for gestational age and birth weight (relative risk, 3.04; 1.93-4.80 and relative risk, 2.2; 1.31-3.74, respectively). Interleukin-6, interleukin-8, and tumor necrosis factor-α levels were higher in infants with white matter injury than in control subjects (p < .0001). Interleukin-1β and interleukin-10 were similar. The areas under the curve for interleukin-6, interleukin-8, and tumor necrosis factor-α were 0.96 (0.92-0.99), 0.97 (0.94-1.0), and 0.93 (0.86-0.99), respectively. Interleukin-8 ≥100 pg/mL was the best predictor of white matter injury; the sensitivity and specificity were 96% and 83%, respectively, and negative predictive value was 98%.

CONCLUSIONS

Very-low-birth-weight infants with proven early-onset sepsis, necrotizing enterocolitis, and high plasma levels of interleukin-6, interleukin-8, and tumor necrosis factor-α are at high risk for white matter injury.

摘要

目的

探讨白细胞介素 6、白细胞介素 8、肿瘤坏死因子-α、白细胞介素 10 和白细胞介素 1β与极低出生体重儿临床败血症性脑白质损伤的关系,以期预测易发生脑白质损伤的患儿。

设计

前瞻性队列研究。

地点

新生儿重症监护病房。

对象

伴有临床早发性败血症的极低出生体重儿。排除标准为:14 天前死亡、严重畸形和先天性感染。

干预措施

于生后第 3 天、每周直至生后第 6 周进行超声脑扫描,且于生后第 1 年进行磁共振成像以确认。在用于败血症检查的同一标本中检测白细胞介素 6、白细胞介素 8、肿瘤坏死因子-α、白细胞介素 10 和白细胞介素 1β。应用 Mann-Whitney、卡方、t 检验、多元回归和受试者工作特征分析。

测量和主要结果

2005 年 7 月至 2007 年 10 月,我们研究了 84 例极低出生体重儿,其中 27 例(32%)存在脑白质损伤,57 例(68%)为对照组(无脑白质损伤)。经校正胎龄和出生体重后,证实的早发性败血症和坏死性小肠结肠炎是脑白质损伤的高危因素(相对危险度分别为 3.04[95%CI 1.93-4.80]和 2.2[95%CI 1.31-3.74])。白细胞介素 6、白细胞介素 8 和肿瘤坏死因子-α水平在伴有脑白质损伤的患儿中高于对照组(均 P<0.0001)。白细胞介素 1β和白细胞介素 10 相似。白细胞介素 6、白细胞介素 8 和肿瘤坏死因子-α 的曲线下面积分别为 0.96(0.92-0.99)、0.97(0.94-1.0)和 0.93(0.86-0.99)。白细胞介素 8≥100pg/ml 是脑白质损伤的最佳预测因子;其灵敏度和特异性分别为 96%和 83%,阴性预测值为 98%。

结论

证实有早发性败血症、坏死性小肠结肠炎和高血浆白细胞介素 6、白细胞介素 8 和肿瘤坏死因子-α水平的极低出生体重儿易发生脑白质损伤。

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