Newborn Screening, Malnutrition and Lung Disease in Children with Cystic Fibrosis

描述(申请人提供)：囊性纤维化(CF)是最常见的缩短生命的遗传疾病之一，在美国的发病率为1：4000活产儿。Cf以胃肠道和肺部表现为特征。营养不良和发育迟缓很普遍，甚至在通过新生儿筛查(NBS)确诊的婴儿中也会发生。阻塞性肺病合并反复呼吸道感染是不可避免的。尽管生存年龄的中位数稳步提高，在2008年达到37岁，但20%的CF死亡仍然发生在20岁之前。这项研究的总体目标是通过流行病学和临床研究，量化儿童CF中的NBS、营养不良和肺部疾病之间的关系，最终目标是制定循证指南，以提高CF的诊断、医疗保健和健康结果的质量。具体目标是：1)通过使用自1985年以来收集的三个持续的免费数据库，即CF基金会患者登记处、CF NBS项目的威斯康星随机临床试验(RCT)和威斯康星常规CF NBS计划，来检验CF中的营养不良和肺部疾病是由“基线风险”(例如，人口学、诊断、基因、表型)和“纵向风险”(例如，前几年的变化)确定的假设；2)测试在常规和研究环境中实施的CF NBS同样有效的假设；通过比较威斯康星州常规CFNBS队列(生于1994-2003年)和威斯康星州RCT CFNBS队列(生于1985-1994年)的营养和肺结果，以及3)通过实施前瞻性观察研究，从三个州(威斯康星州、IN和UT)的四个CF中心登记2011-2015年出生后不久通过NBS确诊的CF婴儿，以系统地获得关于母乳喂养(唯一/部分、持续时间)和配方奶(类型、卡路里密度、每隔一段时间检查一次母乳喂养对营养和肺结果的潜在益处和风险。没有其他调查拥有类似的研究人员和工具来开展拟议的工作。首席调查员是一位国家公认的慢性肺病流行病学家，她在利用大型复杂的纵向数据库进行结果研究方面的专业知识而闻名。自2002年以来，在NIDDK的支持下，首席研究员与特定目标1相关的工作产生了新的、基于证据的知识，改善了CF的临床实践。鉴于从2010年开始在全国范围内实施社区卫生服务，完成具体目标2和3对临床和公共卫生的影响在不久的将来也是可以预见的。完成这笔赠款将促进对CF营养不良和肺部疾病进展的关键决定因素的了解，改善CF的临床实践，改善CF儿童的健康结局，并解决关于与CF相关的母乳喂养潜在好处和风险的争议，以便制定最佳喂养指南。

DESCRIPTION (provided by applicant): Cystic fibrosis (CF) is one of the most common life-shortening genetic disorders with an incidence of 1:4000 live births in the US. CF is characterized by gastrointestinal and pulmonary manifestations. Malnutrition and growth faltering are prevalent, and occur even in infants diagnosed through newborn screening (NBS). Obstructive lung disease with recurrent respiratory infections is inevitable. Although median age of survival has improved steadily and reached 37 years in 2008, 20% of CF deaths still occur before 20 years of age. The overall objective of this research is to quantify the associations among NBS, malnutrition and lung disease in children with CF through epidemiological and clinical studies, with the ultimate goal of developing evidence-based guidelines for improving the quality of diagnosis, medical care and health outcomes of CF. Specific Aims are: 1) to test the hypothesis that malnutrition and lung disease in CF are determined by "baseline risk" (e.g., demographics, diagnosis, genotype, phenotype), and "longitudinal risk" (e.g., changes in the preceding years) by using three ongoing, complimentary databases collected since 1985, namely, the CF Foundation Patient Registry, the Wisconsin Randomized Clinical Trial (RCT) of CF NBS Project and the Wisconsin Routine CF NBS Program, 2) to test the hypothesis that CF NBS implemented in the routine and research settings are similarly effective, by comparing nutritional and pulmonary outcomes of the Wisconsin Routine CF NBS cohort (born 1994-2003) to the Wisconsin RCT CF NBS cohort (born 1985-1994), and 3) to test the hypothesis that exclusive breastfeeding is associated with higher risk of growth faltering but lower risk of respiratory infections in the first two years of life, by conducting a prospective observational study that enrolls CF infants diagnosed through NBS in 2011-2015 soon after birth from four CF Centers in three states (WI, IN and UT) to systematically obtain detailed data on breastfeeding (exclusive/partial, duration) and formula (type, caloric density, amount) at frequent intervals in order to examine the potential benefits and risks of breastfeeding on nutritional and pulmonary outcomes. No other investigation has comparable researchers and tools to conduct the proposed work. The Principal Investigator is a nationally recognized CF epidemiologist known for her expertise in utilizing large complex longitudinal databases for outcome studies. With NIDDK's support since 2002, the Principal Investigator's work related to Specific Aim 1 has generated new, evidence-based knowledge that improved the clinical practices of CF. In view of the nationwide implementation of CF NBS beginning 2010, the clinical and public health impacts as a result of completing Specific Aims 2 and 3 are also foreseeable in the near future. Accomplishing this grant will advance the understanding of critical determinants of malnutrition and lung disease progression in CF, improve clinical practices of CF, enhance health outcomes of children with CF, and resolve the controversy on the potential benefits and risks of breastfeeding associated with CF in order to establish optimal feeding guidelines.