Newborn screening strategy for cystic fibrosis: A field study in an area with high allelic heterogeneity

To verify to what extent mutation analysis on blood spot could improve cystic fibrosis neonatal screening in an area with high allelic heterogeneity, we designed a special protocol. Spot trypsin estimation at birth, trypsin re-testing after 1 month, meconium lactase testing and mutation analysis of \u394F508, R1162X and N1303K, were retrospectively clustered according to different patterns (trypsin/lactase/mutation; trypsin/lactase/re-testing; trypsin/mutation) and compared. The programme, which lasted 2 years (1993-94) and covered most of North-eastern Italy, included 95 553 screened newborns. Thirty-four affected babies were detected by screening and one by meconium ileus (incidence 1/2730). The combined use of trypsin, lactase and mutation analysis in cystic fibrosis neonatal screening permits a better sensitivity compared to the two other combinations (34 diagnoses vs 32 in both cases). Moreover, the higher specificity of the former method (false positives 42 vs 148) allows a reduction of recalls, which cause considerable anxiety. We confirm in trypsin-positive newborns an increased frequency of cystic fibrosis heterozygotes (1/17)