[Newborn Screening on Cystic Fibrosis in Germany: Comparison of the new Screening Protocol with an Alternative...

Background For the new cystic fibrosis (CF) newborn screening program in Germany the Federal Joint Committee (G-BA) implemented a new screening protocol using immunoreactive trypsinogen (IRT) as first and pancreatitis associated protein (PAP) as second tier. Gene analysis with a panel of 31 CFTR-mutations is used as third tier to increase the positive predictive value (PPV) which is known to be low in pure biochemical IRT/PAP protocols. Methods For post hoc analysis the data pool (n=372 906) of a study evaluating a pure biochemical IRT/PAP protocol was used for assessment of the 3-step G-BA protocol in comparison with an alternative screening protocol recommended by the authors. The difference between the 2 protocols is the procedure when IRT>99.9^th percentile. In the G BA protocol PAP and DNA analysis will be by-passed while in the alternative protocol only the PAP step will be circumvented. Results Both 3-tier IRT/PAP+SN/DNA protocols did not lose sensitivity due to addition of genetic analysis when the results were compared to those of the 2-tier biochemical IRT/PAP protocol. However, the protocols provide different results regarding PPV. The G-BA protocol showed with 351 a much higher number of false-positively detected newborns (PPV 20.2%) when compared to 31 false-positively detected newborns in the alternative protocol (PPV 69.6%). Conclusions The G-BA protocol had a worse performance when compared with the alternative protocol recommended by the authors. The higher number of false-positively detected newborns using the G-BA protocol will lead to more consultations including sweat tests, will create more anxiety in parents, and will result in higher costs after screening.