Newborn screening for identification & prospective followup of infants with SMA

新生儿筛查识别

• 批准号: 8257921
• 负责人: KATHRYN J. SWOBODA
• 金额: $ 88.05万
• 依托单位: UNIVERSITY OF UTAH
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-04-20 至 2016-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8257921
• 关键词: Accounting; Acute; Advisory Committees; Affect; Attitude; Biological Assay; Birth; Caring; Child; Clinical; Clinical Research; Communities; Consent; Country; DNA; Data; Databases; Detection; Development; Diagnosis; Disease; Disease Progression; Documentation; Early Diagnosis; Early identification; Early treatment; Enrollment; Ethics; Family; Guidelines; Health; Hereditary Disease; Home environment; Incidence; Infant; Intervention; Laboratories; Medical; Modeling; Morbidity - disease rate; Motor; Motor Neurons; Natural History; Neonatal Screening; Newborn Infant; Nutritional; Outcome; Outcome Measure; Parents; Perception; Performance; Phase; Pilot Projects; Play; Policies; Population; Predictive Value; Process; Protocols documentation; Public Health; Recommendation; Reporting; Research; Research Personnel; Risk; Role; SMN1 gene; SMN2 gene; Screening procedure; Siblings; Spinal Muscular Atrophy; Symptoms; Testing; Validation; Variant; Werdnig-Hoffmann Disease; base; clinical care; cohort; design; dosage; evidence based guidelines; follow-up; improved; infancy; interdisciplinary approach; mortality; multidisciplinary; neuron loss; preference; programs; prospective; psychosocial; respiratory; standard of care; tool

DESCRIPTION (Provided by Applicant): With an incidence of 1 in 10,000 births, spinal muscular atrophy (SMA) is one of the most common lethal genetic diseases. In the past decade, the development and increasingly widespread implementation of standard of care protocols and proactive nutritional as well as respiratory support has dramatically improved survival in babies with the severe infantile variant, SMA type I, which accounts for more than 50% of affected children. However, improved survival has not resulted in improved motor outcomes in those identified following the onset of symptoms, largely due to rapid progression during the acute phase, followed by a plateau phase characterized by up to several years of functional stability. Preliminary observations from the STOP SMA study, in which younger siblings were identified early in infancy and enrolled in a subspecialty-based medical home with access to proactive care protocols, have demonstrated improved motor outcomes and survival as compared to their older siblings as well as to a cohort of natural history subjects. This suggests that early intervention may play a significant role in limiting motor neuron loss in the most acute phase of disease progression, resulting in a significant improvement in morbidity, mortality, and motor function. The investigators propose to implement a multi-state, multi-region newborn screening (NBS) pilot study to assess the feasibility of a DNA-based assay for homozygous SMN1 deletion to detect infants at risk for the development of SMA, in the NBS laboratory setting. In doing so, they hypothesize: 1) that the incidence of affected newborns will parallel predictions from early pilot data, and 2) that identification of infants at risk for SMA via NBS will improve outcomes, including morbidity, mortality, and motor function, as compared to a natural history cohort provided the same proactive nutritional, respiratory, and clinical care protocols via a subspecialty-based medical home. In the current application, the investigators will also explore ethical, regulatory, and policy issues regarding the use of NBS to pilot screen for SMA to identify the most optimal consent model. To attempt to improve outcomes in the pre-symptomatic population identified with NBS, they will implement and assess the impact of a multidisciplinary approach to management on health outcomes of SMA infants identified via the proposed pilot. Screening 400,000 newborns, the investigators expect to identify at least 40 infants at risk for SMA. Specifically, these infants will be enrolled in a subspecialty-based medical home to coordinate and provide access to proactive care interventions and protocols. Finally, the investigators will evaluate the psychosocial impact of early diagnosis on SMA infants and their families. Successful completion of this project will be of value on many fronts, providing the NBS community with an assessment of the accuracy with which the proposed assay identifies those at risk for symptom development, determining the current feasibility and acceptance for a primary DNA-based screening platform, providing the opportunity to prospectively assess outcomes in a group of pre-symptomatically diagnosed infants with early access to coordinated proactive care, and an improved understanding of the impact of early diagnosis for SMA infants and their families. NARRATIVE: It is imperative to provide information on the impact of screening and treatment of conditions, such as spinal muscular atrophy (SMA), prior to recommendations that such conditions be included in newborn screening (NBS) panels. This project will evaluate NBS for SMA. The study has four aims; 1) explore the ethical, regulatory, and policy issues; 2) implement evaluate NBS to detect infants at risk for development of SMA; 3) implement and assess a medical home model to provide early diagnosis and management of care; and 4) evaluate psychosocial impact of early diagnosis. This project is directly relevant to improving the public's health with evidence-based recommendations for public health programs that affect virtually every newborn in the country.

描述（由申请人提供）：脊柱肌肉萎缩（SMA）的发生率为10,000分之1，是最常见的致命遗传疾病之一。 在过去的十年中，护理标准方案和主动营养和呼吸支持的发展和越来越广泛的实施已大大改善了严重的婴儿变种I型I型婴儿的生存率，占受影响儿童的50％以上。 然而，提高的生存率并未导致症状发作后发现的运动结果改善，这在很大程度上是由于急性阶段的快速进展，其次是高原阶段，其特征是多达几年的功能稳定性。 Stop SMA研究的初步观察结果是，在该研究中，早期就确定了年轻的兄弟姐妹，并参与了具有主动护理方案的基于专科的医学院，与较旧的兄弟姐妹以及自然历史科目的较旧的兄弟姐妹相比，已经有了提高的运动结果和生存率。 这表明，早期干预可能在限制运动神经元损失的最急性阶段的疾病进展中起重要作用，从而显着改善发病率，死亡率和运动功能。 研究人员建议在NBS实验室环境中实施多州多区域新生儿筛查（NBS）试点研究，以评估基于DNA的纯合SMN1缺失的基于DNA的测定法，以检测NBS实验室中SMA的风险。 在这样做的过程中，他们假设：1）受影响的新生儿的发生率将与早期的试点数据相似，而2）鉴定通过NBS的SMA风险的鉴定将改善结果，包括发病率，死亡率和运动功能，与自然历史群体相比，与自然历史的同龄人相比，提供了相同的主动营养，呼吸，呼吸道治疗方案，可以通过临床医疗方案进行临床医疗方案。 在当前的应用程序中，研究人员还将探讨有关使用NBS在SMA中使用NB的道德，监管和政策问题，以确定最佳同意模型。 为了改善NBS确定的症状前人群的结果，他们将实施和评估多学科管理方法对通过拟议的飞行员确定的SMA婴儿健康结果的影响。 筛查40万名新生儿，调查人员预计至少有40名有SMA风险的婴儿。 具体而言，这些婴儿将被注册为基于专科的医疗家庭，以协调并提供积极的护理干预措施和方案。 最后，研究人员将评估早期诊断对SMA婴儿及其家人的社会心理影响。 该项目的成功完成将在许多方面具有价值，从而评估了拟议的测定法可以评估拟议的测定的准确性，确定了有症状发展风险的人，确定了当前的可行性和对基于DNA的筛查平台的可行性和接受度，从而提供了有机会在预期诊断出诊断出的临时访问量的前瞻性上的机会，并确定了对临时诊断的临时影响，并确定了一系列临时诊断的临时疗法，并提供了一系列临床的影响，并在一组诊断的访问量上，并提供了一种有效的诊断，并提供了一个良好的诊断，并提供了一个临时诊断的影响，并提供了良好的诊断，并提供了良好的访问量。 SMA婴儿及其家人。 叙述：必须提供有关筛查和治疗状况的影响的信息，例如脊柱肌肉萎缩（SMA），然后建议将这种情况包括在新生儿筛查（NBS）面板中。 该项目将评估SMA的NBS。 该研究有四个目标。 1）探讨道德，监管和政策问题； 2）实施评估NB，以检测有SMA发育风险的婴儿； 3）实施和评估医疗家庭模型，以提供早期诊断和管理护理； 4）评估早期诊断的社会心理影响。 该项目通过对几乎影响该国每个新生儿的公共卫生计划的循证建议，与改善公众的健康直接相关。