Comparison of different IRT-PAP protocols to screen newborns for cystic fibrosis in three central European populations

Abstract Background In recent years different IRT/PAP protocols have been evaluated, but the individual performance remains unclear. To optimize the IRT/PAP strategy we compared protocols from three regional CF newborn screening centers (Heidelberg, Dresden, and Prague). Methods We evaluated the effect of elevating the IRT-cut-off from 50 to 65μg/l (~97.5th to ~99.0th percentile), the need of a failsafe protocol (FS, IRT≥99.9th percentile) and the relative performance using either two IRT-dependent PAP-cut-offs or one PAP-cut-off. Findings Elevation of the IRT cut-off to 65μg/l (~99.0th percentile) increased the PPV significantly (Dresden: 0.065 vs. 0.080, p Conclusions For best performance we suggest an IRT/PAP protocol with an IRT-cut-off close to the 99.0th percentile, FS, and a single PAP-cut-off.