Olaf Sommerburg1, Veronika Krulisova2, Jutta Hammermann3, Martin Lindner4, Mirjam Stahl5, Martina Muckenthaler5, Dirk Kohlmueller4, Margit Happich6, Andreas E Kulozik6, Felix Votava7, Miroslava Balascakova2, Veronika Skalicka8, Marina Stopsack9, Manfred Gahr3, Milan Macek2, Marcus A Mall10, Georg F Hoffmann11. 1. Division of Paediatric Pulmonology & Allergy and Cystic Fibrosis Center, Department of Paediatrics III, Children's Hospital, University of Heidelberg, Im Neuenheimer Feld 430, D-69120 Heidelberg, Germany; Translational Lung Research Centre Heidelberg (TLRC), Member of the German Center for Lung Research (DZL), Im Neuenheimer Feld 350, D-69120 Heidelberg, Germany. Electronic address: olaf.sommerburg@med.uni-heidelberg.de. 2. Department of Biology and Medical Genetics, University Hospital Motol and 2nd Faculty of Medicine, Charles University, V Uvalu 84, Prague 5, CZ 150 06, Czech Republic. 3. Pediatric Department, University Hospital of Dresden, Fetscherstr. 74, D-01307 Dresden, Germany. 4. Division of Metabolic Diseases and Newborn Screening Center, Department of Paediatrics I, Children's Hospital, University of Heidelberg, Im Neuenheimer Feld 430, D-69120 Heidelberg, Germany. 5. Division of Paediatric Pulmonology & Allergy and Cystic Fibrosis Center, Department of Paediatrics III, Children's Hospital, University of Heidelberg, Im Neuenheimer Feld 430, D-69120 Heidelberg, Germany; Translational Lung Research Centre Heidelberg (TLRC), Member of the German Center for Lung Research (DZL), Im Neuenheimer Feld 350, D-69120 Heidelberg, Germany. 6. Division of Paediatric Pulmonology & Allergy and Cystic Fibrosis Center, Department of Paediatrics III, Children's Hospital, University of Heidelberg, Im Neuenheimer Feld 430, D-69120 Heidelberg, Germany. 7. Department of Pediatrics, University Hospital Kralovske Vinohrady and 3rd Faculty of Medicine, Charles University, Srobarova 50, Prague 10, CZ 100 34, Czech Republic. 8. Department of Pediatrics, University Hospital Motol and 2nd Faculty of Medicine, Charles University, V Uvalu 84, Prague 5, CZ 100 06, Czech Republic. 9. Institute of Clinical Chemistry and Laboratory Medicine, University Hospital of Dresden, Fetscherstr. 74, D-01307 Dresden, Germany. 10. Division of Paediatric Pulmonology & Allergy and Cystic Fibrosis Center, Department of Paediatrics III, Children's Hospital, University of Heidelberg, Im Neuenheimer Feld 430, D-69120 Heidelberg, Germany; Translational Lung Research Centre Heidelberg (TLRC), Member of the German Center for Lung Research (DZL), Im Neuenheimer Feld 350, D-69120 Heidelberg, Germany; Department of Translational Pulmonology, University of Heidelberg, Im Neuenheimer Feld 350, D-69120 Heidelberg, Germany. 11. Translational Lung Research Centre Heidelberg (TLRC), Member of the German Center for Lung Research (DZL), Im Neuenheimer Feld 350, D-69120 Heidelberg, Germany; Division of Metabolic Diseases and Newborn Screening Center, Department of Paediatrics I, Children's Hospital, University of Heidelberg, Im Neuenheimer Feld 430, D-69120 Heidelberg, Germany.
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 65 μg/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 65 μg/l (~99.0th percentile) increased the PPV significantly (Dresden: 0.065 vs. 0.080, p < 0.0001, Prague: 0.052 vs. 0.074, p < 0.0001) without reducing sensitivity. All three IRT/PAP protocols showed a trend towards a higher sensitivity with FS than without and when using one PAP-cut-off instead of two IRT-dependent PAP-cut-offs. 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.
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 65 μg/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 65 μg/l (~99.0th percentile) increased the PPV significantly (Dresden: 0.065 vs. 0.080, p < 0.0001, Prague: 0.052 vs. 0.074, p < 0.0001) without reducing sensitivity. All three IRT/PAP protocols showed a trend towards a higher sensitivity with FS than without and when using one PAP-cut-off instead of two IRT-dependent PAP-cut-offs. 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.
Authors: Jan David; Petr Chrastina; Hana Vinohradska; Eva Al Taji; Andrea Holubova; Eva Hlidkova; Viktor Kozich; Felix Votava Journal: Eur J Pediatr Date: 2018-08-22 Impact factor: 3.183
Authors: Maximilian Zeyda; Andrea Schanzer; Pavel Basek; Vera Bauer; Ernst Eber; Helmut Ellemunter; Margit Kallinger; Josef Riedler; Christina Thir; Franz Wadlegger; Angela Zacharasiewicz; Sabine Renner Journal: Diagnostics (Basel) Date: 2021-02-13