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

• Published in: Journal of cystic fibrosis 2014-01, Vol.13 (1), p.15-23
• Main Authors: Sommerburg, Olaf, Krulisova, Veronika, Hammermann, Jutta, Lindner, Martin, Stahl, Mirjam, Muckenthaler, Martina, Kohlmueller, Dirk, Happich, Margit, Kulozik, Andreas E, Votava, Felix, Balascakova, Miroslava, Skalicka, Veronika, Stopsack, Marina, Gahr, Manfred, Macek, Milan, Mall, Marcus A, Hoffmann, Georg F
• Format: Article
• Language: English
• Subjects: Antigens, Neoplasm - analysis; Antigens, Neoplasm - blood; Antigens, Neoplasm - genetics; Biochemical screening; Biomarkers, Tumor - analysis; Biomarkers, Tumor - blood; Biomarkers, Tumor - genetics; Chemistry, Clinical - methods; Chemistry, Clinical - standards; Cystic fibrosis; Cystic Fibrosis - blood; Cystic Fibrosis - diagnosis; Cystic Fibrosis - genetics; Cystic Fibrosis Transmembrane Conductance Regulator - genetics; Dried Blood Spot Testing - methods; Dried Blood Spot Testing - standards; Europe; Genetic Testing - methods; Genetic Testing - standards; Humans; Immunoreactive trypsinogen; Infant, Newborn; Lectins, C-Type - analysis; Lectins, C-Type - blood; Lectins, C-Type - genetics; Neonatal Screening - methods; Neonatal Screening - standards; Newborn screening; Pancreatitis associated protein; Pancreatitis-Associated Proteins; Prospective Studies; Pulmonary/Respiratory; Retrospective Studies; Sensitivity and Specificity; Trypsinogen - analysis; Trypsinogen - blood; Trypsinogen - genetics
• ISSN: 1569-1993; 1873-5010
• DOI: 10.1016/j.jcf.2013.06.003

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.