Improving the diagnostic accuracy of a neonatal screening protocol for Cystic Fibrosis: choice of the optimal thresholds for the blood level of immunoreactive trypsin (IRT)

Cystic Fibrosis is an inheritable disease, whose symptoms generally appear in the early infancy, and that causes chronic pulmonary infections, severe nutritional problems and male infertility. CF has an important social impact because of its high incidence (1:3500 live births, in the Mediterranean area) and the heavy caregiving burden for families and health services. Nonetheless, the early diagnosis and treatment were demonstrated to improve patients' quality of life and disease's prognosis. Neonatal screening allows CF diagnosis before any symptoms appear, but may lead to negative results in diseased subjects (false negative) or positive results in healthy subjects (false positive). A false negative result implies delayed diagnosis and therapy with possible severe consequences for the patient, whereas a false positive result requires further tests (DNA test, sweat test), and induce unnecessary discomfort and undue anxiety to the families. In Lombardia the ratio of false to true positive results is 60:1! The research here proposed aims at assessing, on the basis of a large set of data provided by the "Laboratorio di Riferimento Regionale per lo Screening Neonatale dell'A.O. Istituti Clinici di Perfezionamento (ICP)" of Milano (which performs neonatal screening of all babies born in Lombardia, almost 100,000 per year), the performance of possible strategies for the neonatal screening of Cystic Fibrosis (CF), in terms of false negative and positive, and cost-effectiveness ratio. The definition of a rational strategy to be applied to screening protocols to detect with a high degree of certainty CF neonates could save parents the trouble, anxiety and discomfort due to a false positive result, while contributing to reduce costs for the National Health Service in terms of IRT, DNA and sweat tests not performed.