ASSESSMENT OF THE BENEFITS, RISKS AND COSTS OF NEONATAL SCREENING FOR CF

这个子项目是利用由NIH/NCRR资助的中心拨款提供的资源的许多研究子项目之一。子项目和调查员(PI)可能从另一个NIH来源获得了主要资金，因此可能会出现在其他CRISE条目中。列出的机构是针对中心的，而不一定是针对调查员的机构。(来自CRISP网站)尽管囊性纤维化(CF)是白人人群中最常见的、威胁生命的常染色体隐性遗传疾病，但诊断和治疗的启动往往会延误。过去二十年的进步使得通过常规采集新生儿血液样本和通过DNA分析测定胰蛋白酶原水平和CF突变来进行CF筛查成为可能。我们的总体目标是解决以下假设：通过新生儿筛查早期诊断CF将是医学上有益的，没有重大风险。“医学上有益的”指的是更好的营养和/或肺状况，而“风险”包括实验室差错、潜在的医源性医学后遗症、误解或误解以及不良的心理社会后果。具体目标包括评估与CF新生儿筛查相关的益处、风险、成本、生活质量和认知功能，以及描述CF的特征流行病学特征。自1985年以来，一项强调早期诊断为关键变量的全面随机临床试验一直在进行中。营养状况已经通过人体测量和生化方法进行了评估，结果表明在筛查组中有显著的好处。回答有关肺结果的重要问题将需要五年多的后续评估，重点是肺功能测量和定量胸部放射学，包括高分辨率计算机断层扫描。如果这项研究背后的问题得到了积极的回答，那么使用胰酶原和DNA检测相结合的新生儿筛查很可能成为识别新的CF病例的常规方法，而且在婴儿早期诊断将有助于预防许多临床上重要的问题，如营养不良。然而，如果在全国范围内实施CF新生儿筛查，必须弥合几个流行病学差距，这将需要关于这种疾病病程的更准确的数据，并确定肺部感染铜绿假单胞菌的危险因素。该项目将产生这一重要信息，以及关于早期或延迟诊断的CF儿童的生活质量和认知功能的基本数据。我们还将阐明筛查的风险，并首次说明整个儿童期CF的诊断和治疗费用以及筛查的成本效益。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. (from CRISP website) Although cystic fibrosis (CF) is the most common, life-threatening autosomal recessive genetic disorder of the white population, there are often delays in diagnosis and hence initiation of treatment. Advances of the past two decades have made CF screening feasible using routinely collected neonatal blood specimens and determining trypsinogen levels and CF mutations by DNA analyses. Our overall goal is to address the following hypothesis: Early diagnosis of CF through neonatal screening will be medically beneficial without major risks. "Medically beneficial" refers to better nutritional and/or pulmonary status, whereas "risks" include laboratory errors, potential iatrogenic medical sequelae, miscommunication or misunderstanding and adverse psychosocial consequences. Specific aims include assessment of the benefits, risks, costs, quality of life, and cognitive function associated with CF neonatal screening and delineation of the characteristic epidemiologic features of CF. A comprehensive, randomized clinical trial emphasizing early diagnosis as the key variable has been underway since 1985. Nutritional status has been assessed by anthropometric and biochemical methods, and the results have demonstrated significant benefits in the screened group. Answering the important questions about pulmonary outcome will require five more years of follow-up evaluation focused on lung function measures and quantitative chest radiology, including high resolution computerized tomography. If the questions underlying this study are answered favorably, it is likely that neonatal screening using a combination of trypsinogen and DNA tests will become the routine method for identifying new cases of CF and that diagnosis in early infancy will allow prevention of many clinically-significant problems such as malnutrition. If CF neonatal screening is implemented nationally, however, several epidemiologic gaps must be closed, and this will require more precise data on the course of this disease and determination of risk factors for pulmonary infections with Pseudomonas aeruginosa. This project will generate that important information, as well as essential data on the quality of life and cognitive function of children with CF who experience early or delayed diagnosis. We will also clarify the risks of screening and delineate for the first time the costs of diagnosis and treatment of CF throughout childhood as well as the cost-effectiveness of screening.