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

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 (from CRISP网站） 虽然囊性纤维化（CF）是白色人群中最常见的、危及生命的常染色体隐性遗传病，但诊断往往会延迟，但这些都可以通过使用DNA分析进行新生儿筛查来克服。该项目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。“医学上有益的”是指更好的长期营养和/或肺部状态，有望导致更好的生活质量（QoL）。具体目标包括评估整个儿童期的营养状况，包括相关的结果，如社会心理和认知功能;肺部疾病的演变、进展和流行病学;新生儿筛查的成本效益。自1985年以来，一项以早期诊断为关键变量的综合性随机临床试验一直在进行中，并涉及筛选和对照CF患者，这些患者参加了有史以来最长的儿童慢性疾病队列随访研究。通过人体测量和生化方法评估了营养状况，结果表明，筛查组的幼儿具有显着益处。然而，有趣的观察需要更多的数据来得出结论，包括早期营养不良导致的永久性生长迟缓的证据，以及与延迟诊断相关的认知功能明显改变的证据。在筛选组和对照组的肺部结局方面也获得了有争议的数据，但结果仍不确定。关于慢性肺病决定因素的流行病学研究结果需要澄清，包括基因型-表型关系、营养不良的影响以及呼吸道感染在引起结构性肺损伤中的作用。因此，回答有关肺部结局的关键问题将需要5年以上的随访评估。此外，生活质量和成本效益的研究需要扩大，以完成这些独特的组成部分。在CF基金会资助的一项综合研究中获得的心理社会数据将用于我们对新生儿筛查相关长期成本的分析和成本效益的计算。如果其余问题得到积极回答，新生儿筛查很可能将成为全国范围内识别新CF病例的常规方法，并且婴儿早期的诊断将有助于预防许多具有临床意义的问题。该项目的结果导致19个州目前正在筛查新生儿CF，而其他州正在考虑胰蛋白酶原/DNA检测，但迫切需要更多关于营养，肺部，心理社会和经济结果的数据来支持新的卫生政策计划。该项目有可能通过促进对所有新生儿的分子遗传学筛查来显著影响医疗保健。

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, but these can be overcome with newborn screening using DNA analysis. The project's 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 long term nutritional and/or pulmonary status, hopefully leading to better quality of life (QoL). Specific aims include assessment of nutritional status throughout childhood, including associated outcomes such as psychosocial and cognitive functioning; the evolution, progression and epidemiology of lung disease; and newborn screening cost effectiveness. A comprehensive, randomized clinical trial with early diagnosis as the key variable has been underway since 1985 and has involved screened and control CF patients enrolled in the longest cohort follow-up study ever for a chronic disease of childhood. Nutritional status has been assessed by anthropometric and biochemical methods and the results have demonstrated significant benefits in young children of the screened group. Intriguing observations requiring more data for conclusions, however, include evidence of permanent growth retardation from early malnutrition and apparently altered cognitive function associated with delayed diagnosis. Provocative data have also been obtained on pulmonary outcomes in the screened and control groups, but the results remain inconclusive. Epidemiologic findings on the determinants of chronic lung disease need to be clarified, including genotype-phenotype relationships, the impact of malnutrition, and the role of respiratory infections in causing structural lung damage. Thus, answering key questions about pulmonary outcomes will require five more years of follow-up evaluation. In addition, studies on QoL and cost effectiveness need to be extended to complete these unique components. Psychosocial data obtained in an integrated study funded by the CF Foundation will be used in our analyses of the long-term costs associated with newborn screening and calculation of cost-effectiveness. If the remaining questions are answered favorably, it is likely that newborn screening will become the routine method nationwide for identifying new cases of CF and that diagnosis in early infancy will allow prevention of many clinically significant problems. Results from this project have led to 19 states currently screening newborns for CF, while others are considering trypsinogen/DNA testing, but more data on nutritional, pulmonary, psychosocial and economic outcomes are sorely needed to support new health policy plans. This project has the potential to impact healthcare quite significantly by promoting molecular genetics screening of all newborn infants.