Sommerburg Olaf, Stahl Mirjam, Hammermann Jutta, Okun Jürgen G, Kulozik Andreas, Hoffmann Georg, Mall Marcus
Sektion für Pädiatrische Pneumologie & Allergologie und Mukoviszidose-Zentrum, Zentrum für Kinder- und Jugendmedizin, Universitätsklinikum Heidelberg.
Klinik und Poliklinik für Kinder- und Jugendmedizin, Universitätsklinikum Dresden.
Klin Padiatr. 2017 Mar;229(2):59-66. doi: 10.1055/s-0042-124187. Epub 2017 Apr 25.
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. 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 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. 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%). 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.
在德国新的囊性纤维化（CF）新生儿筛查项目中，联邦联合委员会（G-BA）实施了一项新的筛查方案，该方案以免疫反应性胰蛋白酶原（IRT）作为一级指标，胰腺炎相关蛋白（PAP）作为二级指标。使用包含31种CFTR突变的基因分析作为三级指标，以提高阳性预测值（PPV），因为在单纯的生化IRT/PAP方案中，阳性预测值较低。为了进行事后分析，一项评估单纯生化IRT/PAP方案的研究的数据池（n = 372906）被用于评估三步G-BA方案，并与作者推荐的另一种筛查方案进行比较。这两种方案的区别在于IRT>99.9百分位数时的操作流程。在G-BA方案中，将绕过PAP和DNA分析步骤，而在另一种方案中，仅会规避PAP步骤。当将两种三层IRT/PAP+SN/DNA方案的结果与两层生化IRT/PAP方案的结果进行比较时，由于添加了基因分析，两种方案均未丧失敏感性。然而，在PPV方面，两种方案提供了不同的结果。与另一种方案中31例假阳性检测的新生儿（PPV 69.6%）相比，G-BA方案显示出351例假阳性检测的新生儿数量要多得多（PPV 20.2%）。与作者推荐的另一种方案相比，G-BA方案的表现更差。使用G-BA方案检测出的假阳性新生儿数量较多，这将导致更多包括汗液测试在内的会诊，会给家长带来更多焦虑，并会导致筛查后的成本更高。
