PULMONARY BENEFITS OF CYSTIC FIBROSIS NEONATAL SCREENING

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Despite the fact that cystic fibrosis (CF) is the most common lethal hereditary disorder of Caucasians, there are often delays in diagnosis and referral to centers that provide comprehensive care. Thus, over the past three decades, there has been a great deal of interest in establishing a reliable method for early detection of this disease. A relatively recent advance that appears promising involves measurement of immunoreactive trypsinogen (IRT) on dried neonatal blood spots collected at the time of mass screening for other inborn errors of metabolism; it has been shown that this test can be linked to DNA analysis for detecting CF mutations. Although generally considered beneficial, newborn screening programs have been burdened with three kinds of adverse effects: errors (false-positives and false-negatives), miscommunication/ misunderstanding, and stigmatization. Furthermore, it has not been established in a controlled study that early diagnosis will be generally cost-effective and medically beneficial for CF patients, particularly in regard to the chronic lung disease which usually determines an individual patient's prognosis. Because the efficacy of implementing aggressive treatment for presymptomatic CF patients is controversial, it is important to perform a controlled study of both benefits and risks before mass screening is instituted in the United States. Accordingly, we are investigating CF neonatal screening to evaluate both the potential pulmonary and nutritional benefits, as well as the medical and psychosocial risks. Our design involves randomly screening half the newborn population of Wisconsin using the radioimmunoassay for trypsinogen on dried neonatal blood spots coupled to DNA analysis. We are comparing patients identified as having CF during early infancy with children diagnosed through the conventional health care delivery system. Special attention is being given to comparative evaluation of nutritional status and pulmonary disease in the two groups and to assessment of potential psychosocial problems in the screened population. Hypotheses being tested include the following: (1) the majority of CF patients can be diagnosed as neonates by the IRT/DNA two-tiered screening test; (2) the process of early diagnosis (screening and sweat testing) will not have long-term harmful psychosocial impacts; (3) diagnosis in early infancy will prevent malnutrition and growth retardation; and (4) those diagnosed with CF as neonates will have less pulmonary disease than age-matched patients in the unscreened population.