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

本子项目是利用由NIH/NCRR资助的中心赠款提供的资源的众多研究子项目之一。子项目和研究者（PI）可能已经从另一个NIH来源获得了主要资金，因此可以在其他CRISP条目中表示。列出的机构是中心的，不一定是研究者的机构。尽管囊性纤维化（CF）是白人人群中最常见的、危及生命的常染色体隐性遗传疾病，但通常在诊断和开始治疗方面存在延误。过去二十年的进步使得CF筛查成为可能，常规采集新生儿血液标本，通过DNA分析确定胰蛋白酶原水平和CF突变。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在医学上是有益的，没有重大风险。“医学上有益”是指营养和/或肺部状况改善，而“风险”包括实验室错误、潜在医源性医学后遗症、沟通不畅或误解以及不利的社会心理后果。具体目的包括评估与CF新生儿筛查相关的获益、风险、成本、生活质量和认知功能，并描述CF的特征流行病学特征。自1985年以来，一项全面的随机临床试验强调早期诊断是关键变量。通过人体测量学和生物化学方法评估了营养状况，结果表明筛选组有显著的益处。回答关于肺预后的重要问题将需要5年以上的随访评估，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。如果这项研究的基础问题得到了良好的回答，那么结合胰蛋白酶原和DNA检测的新生儿筛查很可能会成为识别CF新病例的常规方法，并且在婴儿早期进行诊断将可以预防许多临床重要问题，如营养不良。然而，如果在全国范围内实施CF新生儿筛查，必须填补几个流行病学空白，这将需要更精确的疾病病程数据，并确定铜绿假单胞菌肺部感染的危险因素。该项目将产生这些重要信息，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，并首次描述整个儿童期CF的诊断和治疗成本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.