Novel Approaches to Screening for Inflicted Childhood Neurotrauma

描述（由申请人提供）：造成的儿童神经损伤(ICN) -由于儿童虐待造成的创伤性脑损伤-是2岁以下儿童创伤性脑损伤（TBI）死亡的主要原因。ICN的识别可能很困难，误诊很常见。准确和及时诊断ICN至关重要；被误诊患有ICN的婴儿很可能回到暴力环境中，再次受伤或死亡。目前还没有基于证据的策略或工具来筛查ICN。本研究的长期目标是建立一种基于证据的方法来评估ICN高危婴儿。在过去的四年里，我们已经证明了两种脑特异性生物标志物（神经元特异性烯醇化酶和髓鞘碱性蛋白）的血清浓度的增加对脑损伤是敏感的和特异性的，并且可以用作ICN的筛查工具。我们还推导了一个敏感和特定的临床决策规则（CDR）预测ICN使用易于测量的临床和实验室变量。当前提案的具体目标是：(1)执行一个双站点，前瞻性确定研究，评估血清生物标志物在高危婴儿中筛查ICN的使用(2)，通过使用多重头技术和常规凝胶电泳/质谱的二维差异相结合创建生物标志物谱，提高生物标志物检测ICN的敏感性和特异性(3)，前瞻性地验证先前推导的CDR，并比较单独CDR与生物标志物联合使用CDR的准确性。如果这些工具能够有效地筛查儿童营养不良，它们将有助于降低虐待儿童致死的主要原因造成的发病率和死亡率。与公共卫生的相关性：造成的儿童神经创伤（ICN）——通常被称为摇晃婴儿综合症——是虐待儿童致死的主要原因。为了避免受伤的儿童回到暴力环境中再次受伤或被杀害，正确的诊断至关重要。本研究评估了筛查ICN的两种方法：通过测量血液中某些化学物质的水平，以及将某些实验室和临床信息结合到临床决策规则中。通过改进对ICN的评估和诊断，我们将能够降低这种毁灭性儿童虐待的发病率和死亡率。

DESCRIPTION (provided by applicant): Inflicted childhood neurotrauma (ICN) - traumatic brain injury due to child abuse - is the leading cause of death from traumatic brain injury (TBI) in children less than 2 yrs of age. Recognition of ICN can be difficult and misdiagnosis is common. Accurate and timely diagnosis of ICN is of critical importance; infants with ICN who are misdiagnosed are likely to return to a violent environment and be re-injured or killed. There are currently no evidence- based strategies or tools to screen for ICN. The long-term objective of this research is to create an evidence-based approach to evaluating infants at high-risk of ICN. Over the past four years, we have demonstrated that increases in the serum concentrations of two brain- specific biomarkers - neuron specific enolase and myelin basic protein - are sensitive and specific for brain injury and may be able to be used as a screening tool for ICN. We have also derived a sensitive and specific clinical decision rule (CDR) for predicting ICN using easily measured clinical and laboratory variables. The specific aims of the current proposal are (1) to perform a two-site, prospective definitive study to evaluate the use of serum biomarkers to screen for ICN in high-risk infants (2) to improve the sensitivity and specificity of biomarkers for detection of ICN by creating biomarker profiles using a combination of multiplex bead technology and conventional two-dimensional difference in gel electrophoresis/mass spectroscopy (3) to validate prospectively the previously derived CDR and to compare the accuracy of the CDR alone to the CDR in combination with biomarkers. If these tools are effective for screening for ICN, they would be instrumental in decreasing morbidity and mortality from the leading cause of death from child abuse. Relevance to public health: Inflicted childhood neurotrauma (ICN) - often referred to as shaken baby syndrome - is the leading cause of death from child abuse. Proper diagnosis is essential in order to avoid returning an injured child to a violent environment where he or she may be re-injured or killed. This study evaluates two ways to screen for ICN: by measuring the levels of certain chemicals in the blood and by combining certain laboratory and clinical information into a clinical decision rule. By improving evaluation and diagnosis of ICN, we will be able to decrease morbidity and mortality from this devastating type of child abuse.