RESUMEN
BACKGROUND: Newborn screening for cystic fibrosis (CF) relies on the measurement of immunoreactive trypsinogen (IRT) originating from the pancreas. The Norfolk, Suffolk and Cambridgeshire screening programme initially exploited the persistent increase in IRT seen in CF (IRT-IRT protocol) and later changed to include mutation analysis as a second tier test (IRT-DNA-IRT protocol). RESULTS: During a 30 year period 582 966 babies have been screened by IRT-IRT and 147 764 by IRT-DNA-IRT (total 730730), resulting in 296 screen positive cases of CF and 29 false negatives (including 10 false negatives with meconium ileus). Ten missed CF cases were pancreatic insufficient, however all were diagnosed before their first birthday, suggesting that a false negative result did not forestall appropriate clinical investigation. The IRT-DNA-IRT protocol had a much improved positive predictive value (PPV) of 85.9% compared to 67.3% for IRT-IRT, excluding CF babies with meconium ileus. The PPVs increased to 82.2% and 98.2% respectively if only well, term babies were considered. The main factor to account for this improvement in PPV has probably been the incorporation of DNA analysis in the second tier testing. CONCLUSIONS: The diagnosis of screen-positive babies proved difficult in a minority of cases with the classification of some patients changing with evolving phenotype. Our results illustrate the importance of collecting outcome data over a long time period for accurate assessment of the screening programme. This study provides evidence that newborn screening for CF is a valid undertaking that detects 95% of unsuspected CF cases presenting before 3 years of age.
