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心脏手术后患儿术中循环性脑损伤生物标志物与 1 年神经发育结局的相关性研究。

Association of intraoperative circulating-brain injury biomarker and neurodevelopmental outcomes at 1 year among neonates who have undergone cardiac surgery.

机构信息

Division of Pediatric Cardiology, Department of Pediatrics, Medical University of South Carolina, Charleston, SC.

Department of Public Health Sciences, Medical University of South Carolina, Charleston, SC.

出版信息

J Thorac Cardiovasc Surg. 2019 May;157(5):1996-2002. doi: 10.1016/j.jtcvs.2019.01.040. Epub 2019 Jan 23.

Abstract

BACKGROUND

Neurodevelopmental disability is the most significant complication for survivors of infant surgery for congenital heart disease. In this study we sought to determine if perioperative circulating brain injury biomarker levels are associated with neurodevelopmental outcomes at 12 months.

METHODS

A secondary analysis of a randomized controlled trial of neonates who underwent cardiac surgery was performed. Glial fibrillary acidic protein (GFAP) was measured: (1) before skin incision; (2) immediately after bypass; (3) 4 and (4) 24 hours postoperatively. Linear regression models were used to determine an association with the highest levels of GFAP and Bayley Scales of Infant and Toddler Development third edition (BSID) composite scores.

RESULTS

There were 97 subjects who had cardiac surgery at a mean age of 9 ± 6 days and completed a BSID at 12.5 ± 0.6 months of age. Median (25th-75th percentile) levels of GFAP were 0.01 (0.01-0.02), 0.85 (0.40-1.55), 0.07 (0.05-0.11), and 0.03 (0.02-0.04) ng/mL at the 4 time points, respectively. In univariate analysis GFAP was negatively associated with cognitive, language, and motor composite scores. GFAP levels immediately after bypass differed between institutions; 1.57 (0.92-2.48) versus 0.77 (0.36-1.21) ng/mL (P = .01). After adjusting for center and potential confounders, GFAP was independently associated with BSID motor score (P = .04).

CONCLUSIONS

Higher GFAP levels at the time of neonatal cardiac operations were independently associated with decreased BSID motor scores at 12 months. GFAP might serve as a diagnostic means to acutely identify perioperative brain-specific injury and serve as a benchmark of therapeutic efficacy for investigational treatments, discriminate center-specific effects, and provide early prognostic information for intervention.

摘要

背景

神经发育障碍是婴儿先天性心脏病手术后幸存者最严重的并发症。在这项研究中,我们试图确定围手术期循环性脑损伤生物标志物水平是否与 12 个月时的神经发育结局相关。

方法

对接受心脏手术的新生儿进行随机对照试验的二次分析。测量神经胶质纤维酸性蛋白 (GFAP):(1) 在皮肤切口前;(2) 体外循环后立即;(3) 术后 4 小时;(4) 术后 24 小时。使用线性回归模型来确定与 GFAP 最高水平和贝利婴幼儿发育量表第三版 (BSID) 综合评分的关联。

结果

共有 97 名婴儿在平均年龄为 9±6 天接受心脏手术,并在 12.5±0.6 个月时完成 BSID。GFAP 的中位数(25-75 百分位数)水平分别为 0.01(0.01-0.02)、0.85(0.40-1.55)、0.07(0.05-0.11)和 0.03(0.02-0.04)ng/mL。在单变量分析中,GFAP 与认知、语言和运动综合评分呈负相关。体外循环后即刻的 GFAP 水平在各中心之间存在差异;1.57(0.92-2.48)与 0.77(0.36-1.21)ng/mL(P=0.01)。在调整中心和潜在混杂因素后,GFAP 与 BSID 运动评分独立相关(P=0.04)。

结论

新生儿心脏手术时较高的 GFAP 水平与 12 个月时 BSID 运动评分降低独立相关。GFAP 可能作为一种诊断手段,用于急性识别围手术期脑特异性损伤,并作为治疗效果的基准,用于评估治疗效果、区分中心特异性影响,并提供干预的早期预后信息。

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