Derivation and Validation of a Serum Biomarker Panel to Identify Infants With Acute Intracranial Hemorrhage
Derivation and Validation of a Serum Biomarker Panel to Identify Infants With Acute Intracranial Hemorrhage
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DOI：
10.1001/jamapediatrics.2017.0429
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发表时间：
2017-06-01
期刊：
影响因子：
26.1
通讯作者：
Kochanek, Patrick M.
中科院分区：
文献类型：
--
作者：
Berger, Rachel Pardes;Pak, Brian J.;Kochanek, Patrick M.
重要性虐待头部创伤是身体虐待导致死亡的主要原因。漏诊虐待性头部创伤，特别是轻度创伤，是常见的，并导致发病率和死亡率增加。血清生物标志物可能有潜力作为定量的床旁筛查工具，以提醒医生颅内hemorrhages.Objective的可能性，以确定和验证一组生物标志物，可能是一个多变量模型的基础，以确定颅内出血在良好的外观婴儿使用Ziplex系统。和参与者使用二元logistic回归建立一个包含3种血清生物标志物的多变量模型（基质金属肽酶-9、神经元特异性烯醇化酶和血管细胞粘附分子-1）和1个临床变量（总血红蛋白）。然后对该模型进行了前瞻性验证。使用Flow-Thru微阵列技术在Ziplex系统上进行多重生物标志物测量，Ziplex系统具有作为床旁系统的潜力。该模型在I级儿科创伤中心的3个儿科急诊科（匹兹堡大学医学中心匹兹堡儿童医院，宾夕法尼亚州匹兹堡;初级儿童医院，盐湖，犹他州;和Lurie儿童医院，芝加哥，伊利诺伊州）中进行了测试，这些婴儿因出现使其遭受虐待性头部创伤风险增加的症状而就诊。该研究于2006年11月至2014年4月在匹兹堡儿童医院进行，2010年6月至2013年8月在小学儿童医院进行，2011年1月至2013年8月在Lurie儿童医院进行。主要结局和指标一个数学模型，可以预测婴儿在虐待性头部创伤风险增加时的急性颅内出血。婴儿脑损伤评分的生物标志物前瞻性地应用于599例患者。平均（SD）年龄为4.7（3.1）个月。52%是男孩，78%是白色，8%是西班牙裔。在临界值为0.182时，该模型对急性颅内出血的敏感性为89.3%（95% CI，87.7-90.4），特异性为48.0%（95% CI，47.3-48.9）。阳性和阴性预测值分别为21.3%和95.6%。该模型是既不敏感，也不具体的非创伤性脑异常，孤立的颅骨骨折，或慢性颅内hemorrhagies.CONCLUSION和RELEVANCE婴儿脑损伤评分的生物标志物，一个多变量模型，使用3血清生物标志物浓度和血清血红蛋白，可以识别婴儿急性颅内出血。准确和及时地识别颅内出血的婴儿没有外伤史，其中创伤可能不是鉴别诊断的一部分，有可能降低发病率和死亡率的虐待性头部创伤。
IMPORTANCE Abusive head trauma is the leading cause of death from physical abuse. Missing the diagnosis of abusive head trauma, particularly in its mild form, is common and contributes to increased morbidity and mortality. Serum biomarkers may have potential as quantitative point-of-care screening tools to alert physicians to the possibility of intracranial hemorrhage.OBJECTIVE To identify and validate a set of biomarkers that could be the basis of a multivariable model to identify intracranial hemorrhage in well-appearing infants using the Ziplex System.DESIGN, SETTING, AND PARTICIPANTS Binary logistic regressionwas used to develop a multivariable model incorporating 3 serum biomarkers (matrix metallopeptidase-9, neuron-specific enolase, and vascular cellular adhesion molecule-1) and 1 clinical variable (total hemoglobin). The model was then prospectively validated. Multiplex biomarker measurements were performed using Flow-Thru microarray technology on the Ziplex System, which has potential as a point-of-care system. The model was tested at 3 pediatric emergency departments in level I pediatric trauma centers (Children's Hospital of Pittsburgh of University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania; Primary Children's Hospital, Salt Lake City, Utah; and Lurie Children's Hospital, Chicago, Illinois) among well-appearing infants who presented for care owing to symptoms that placed them at increased risk of abusive head trauma. The study took place from November 2006 to April 2014 at Children's Hospital of Pittsburgh, June 2010 to August 2013 at Primary Children's Hospital, and January 2011 to August 2013 at Lurie Children's Hospital.MAIN OUTCOMES AND MEASURES A mathematical model that can predict acute intracranial hemorrhage in infants at increased risk of abusive head trauma.RESULTS The multivariable model, Biomarkers for Infant Brain Injury Score, was applied prospectively to 599 patients. The mean (SD) age was 4.7 (3.1) months. Fifty-two percent were boys, 78% were white, and 8% were Hispanic. At a cutoff of 0.182, the model was 89.3% sensitive (95% CI, 87.7-90.4) and 48.0% specific (95% CI, 47.3-48.9) for acute intracranial hemorrhage. Positive and negative predictive values were 21.3% and 95.6%, respectively. The model was neither sensitive nor specific for atraumatic brain abnormalities, isolated skull fractures, or chronic intracranial hemorrhage.CONCLUSION AND RELEVANCE The Biomarkers for Infant Brain Injury Score, a multivariable model using 3 serum biomarker concentrations and serum hemoglobin, can identify infants with acute intracranial hemorrhage. Accurate and timely identification of intracranial hemorrhage in infants without a history of trauma in whom trauma may not be part of the differential diagnosis has the potential to decrease morbidity and mortality from abusive head trauma.