Novel Approaches to Screening for Inflicted Childhood Neurotrauma

描述（由申请人提供）：儿童期神经创伤（ICN）-虐待儿童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。ICN的准确和及时诊断至关重要;误诊的ICN婴儿很可能返回暴力环境并再次受伤或死亡。目前还没有循证策略或工具来筛查ICN。这项研究的长期目标是建立一种基于证据的方法来评估ICN高风险婴儿。在过去的四年中，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和特异的，并且可以用作ICN的筛选工具。我们还得出了一个敏感和具体的临床决策规则（CDR）预测ICN使用容易测量的临床和实验室变量。本提案的具体目标是：（1）执行两个站点，一项前瞻性确定性研究，旨在评价血清生物标志物在高危婴儿中筛查ICN的用途（2），通过使用多重微珠技术和凝胶电泳/质谱中的常规二维差异组合创建生物标志物图谱，提高生物标志物检测ICN的灵敏度和特异性（3）前瞻性验证先前推导的CDR，并比较单独CDR与CDR与生物标志物组合的准确性。如果这些工具能有效地筛查ICN，它们将有助于减少虐待儿童导致死亡的主要原因的发病率和死亡率。与公共卫生的相关性：儿童神经创伤（ICN）-通常被称为摇晃婴儿综合征-是虐待儿童死亡的主要原因。正确的诊断是必不可少的，以避免将受伤的儿童送回暴力环境，使其可能再次受伤或死亡。这项研究评估了两种筛查ICN的方法：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。通过改善对ICN的评估和诊断，我们将能够降低这种毁灭性虐待儿童的发病率和死亡率。公共卫生相关性：摇晃婴儿综合征是虐待儿童死亡的主要原因。许多死于摇晃婴儿综合征的儿童以前曾被看护人摇晃过，但他们的症状（例如呕吐或易怒）被医疗专业人员误诊。误诊使他们回到一个暴力的家庭，在那里他们再次受伤。我们研究的目的是找到方法来帮助医生在儿童再次受伤和/或死亡之前最初出现摇晃婴儿综合征时识别它。

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. PUBLIC HEALTH RELEVANCE: Shaken baby syndrome is the leading cause of death from child abuse. Many children who die of shaken baby syndrome have been shaken previously by a caretaker but their symptoms (e.g. vomiting or irritability) are misdiagnosed by a medical professional. The misdiagnosis allows them to return to a violent home where they are re-injured. The goal of our study is to find ways to help doctors identify shaken baby syndrome when it initially presents before children are re-injured and/or killed.