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 i nclude 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.
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