Jeannette E Dankert-Roelse1, Marelle J Bouva2, Bernadette S Jakobs3, Hettie M Janssens4, Karin M de Winter-de Groot5, Yvonne Schönbeck6, Johan J P Gille7, Vincent A M Gulmans8, Rendelien K Verschoof-Puite9, Peter C J I Schielen10, Paul H Verkerk11. 1. School for Public Health and Primary Care, Dept Pediatrics, Maastricht University Medical Centre, Debyelaan 25, 6229 HX Maastricht, the Netherlands. Electronic address: jeannettedankert@gmail.com. 2. Reference Laboratory for Neonatal Screening, Centre for Health Protection, National Institute for Public Health and the Environment (RIVM), Postbus 1, 3720 BA Bilthoven, the Netherlands. Electronic address: marelle.bouva@rivm.nl. 3. Department of Clinical Chemistry and Haematology, Elisabeth-Twee Steden (ETZ) Hospital, Hilvarenbeekseweg 60, 5022 GC Tilburg, the Netherlands. Electronic address: b.jakobs@etz.nl. 4. Department of Pediatric Pulmonology, Erasmus Medical Center, Sophia's Children's Hospital, Doctor Molewaterplein 40, 3015 GD Rotterdam, the Netherlands. Electronic address: h.janssens@erasmusmc.nl. 5. Department of Pediatric Pulmonology, Wilhelmina Children's Hospital, University Medical Centre Utrecht, Utrecht University, Lundlaan 6, 3584 EA Utrecht, the Netherlands. Electronic address: k.m.dewinter@umcutrecht.nl. 6. TNO, Dept Child Health, Schipholweg 77, 2316 ZL Leiden, the Netherlands. Electronic address: yvonne.schonbeck@tno.nl. 7. Department of Clinical Genetics, VU University Medical Centre, de Boelelaan 1118, 1081 HV Amsterdam, the Netherlands. Electronic address: jjp.gille@vumc.nl. 8. Dutch Cystic Fibrosis Foundation (NCFS), Doctor Albert Schweitzerweg 3, 3744 MG Baarn, the Netherlands. Electronic address: v.gulmans@ncfs.nl. 9. Department of Vaccine Supply and Prevention Programmes, National Institute for Public Health and the Environment (RIVM), Postbus 1, 3720 BA Bilthoven, the Netherlands. Electronic address: rendelien.verschoof@rivm.nl. 10. Reference Laboratory for Neonatal Screening, Centre for Health Protection, National Institute for Public Health and the Environment (RIVM), Postbus 1, 3720 BA Bilthoven, the Netherlands. Electronic address: peter.schielen@rivm.nl. 11. TNO, Dept Child Health, Schipholweg 77, 2316 ZL Leiden, the Netherlands. Electronic address: paul.verkerk@tno.nl.
Abstract
BACKGROUND: Newborn screening for cystic fibrosis (NBSCF) was introduced in the Dutch NBS program in 2011 with a novel strategy. METHODS: Dutch NBSCF consisted of four steps: immuno-reactive trypsin (IRT), Pancreatitis-associated Protein (PAP), DNA analysis by Inno-LiPa (35 mutations), extended gene analysis (EGA) as fourth step and as safety net. Only samples with two CFTR-variants were considered screen-positive, but samples with one disease-causing variant were considered also screen-positive from April 2013. The first 5 years of NBSCF were evaluated during a follow-up ranging from 2 to 6.8 years for sensitivity, specificity, positive predictive value (PPV), ratio of CF/Cystic Fibrosis Screen Positive infants with an Inconclusive Diagnosis (CFSPID) and median age at diagnosis, and were compared to other novel strategies for NBSCF and European Cystic Fibrosis Society (ECFS) Best Practice Standards of Care. RESULTS: NBSCF achieved a sensitivity of 90% (95% CI 82%-94%), specificity of 99.991% (95% CI 99.989%-99.993%), PPV of 63% (95% CI 55%-69%), CF/CFSPID ratio of 4/1, and median age at diagnosis of 22 days, if samples with two variants as well as samples with one disease-causing variant were considered screen-positive. CONCLUSION: The program achieved the goal to minimize the number of false positives and showed a favourable performance but sensitivity and CF/CFSPID ratio did not meet criteria of EFCS Best Standards of Care. Changed cut-off values for PAP and IRT and classification of R117H-7T/9T to non-pathogenic may improve sensitivity to ≥95% and CF/CFSPID ratio to 10/1. PPV is estimated to be around 60%.
BACKGROUND: Newborn screening for cystic fibrosis (NBSCF) was introduced in the Dutch NBS program in 2011 with a novel strategy. METHODS: Dutch NBSCF consisted of four steps: immuno-reactive trypsin (IRT), Pancreatitis-associated Protein (PAP), DNA analysis by Inno-LiPa (35 mutations), extended gene analysis (EGA) as fourth step and as safety net. Only samples with two CFTR-variants were considered screen-positive, but samples with one disease-causing variant were considered also screen-positive from April 2013. The first 5 years of NBSCF were evaluated during a follow-up ranging from 2 to 6.8 years for sensitivity, specificity, positive predictive value (PPV), ratio of CF/Cystic Fibrosis Screen Positive infants with an Inconclusive Diagnosis (CFSPID) and median age at diagnosis, and were compared to other novel strategies for NBSCF and European Cystic Fibrosis Society (ECFS) Best Practice Standards of Care. RESULTS:NBSCF achieved a sensitivity of 90% (95% CI 82%-94%), specificity of 99.991% (95% CI 99.989%-99.993%), PPV of 63% (95% CI 55%-69%), CF/CFSPID ratio of 4/1, and median age at diagnosis of 22 days, if samples with two variants as well as samples with one disease-causing variant were considered screen-positive. CONCLUSION: The program achieved the goal to minimize the number of false positives and showed a favourable performance but sensitivity and CF/CFSPID ratio did not meet criteria of EFCS Best Standards of Care. Changed cut-off values for PAP and IRT and classification of R117H-7T/9T to non-pathogenic may improve sensitivity to ≥95% and CF/CFSPID ratio to 10/1. PPV is estimated to be around 60%.
Authors: Hamed Horati; Hettie M Janssens; Camilla Margaroli; Mieke Veltman; Marta Stolarczyk; Matthew B Kilgore; Jeffrey Chou; Limin Peng; Harm A M W Tiddens; Joshua D Chandler; Rabindra Tirouvanziam; Bob J Scholte Journal: J Cyst Fibros Date: 2020-02-10 Impact factor: 5.482
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