BACKGROUND: In cystic fibrosis newborn screening (CFNBS), immunoreactive trypsinogen (IRT) and pancreatitis-associated protein (PAP) can be used as screening parameters. We evaluated the IRT×PAP product as second-tier parameter in CFNBS in newborns with elevated IRT. METHODS: Data on 410,111 screened newborns including 78 patients with classical cystic fibrosis (CF) from two European centers were retrospectively analyzed by discrimination analysis to identify a screening protocol with optimal cutoffs. We also studied differences in PAP measurement methods and the association of IRT and PAP with age. RESULTS: PAP values differed systematically between fluorometric and photometric assays. The IRT×PAP product showed better discrimination for classical CF than PAP only as second-tier screening parameter (p<0.001). In CF patients, IRT decreased while PAP values remained high over years. In newborns without CF, IRT decreased after birth over weeks while PAP increased within days. CONCLUSIONS: The IRT×PAP product performs well as second-tier cutoff parameter for CFNBS. Screening quality parameters depend on the analytic method and on age at blood collection.

Department of Biology and Medical Genetics 2nd Faculty of Medicine Charles University Prague and Motol University Hospital 5 Uvalu 84 Prague CZ 150 06 Czech Republic

Department of General Pediatrics Division of Metabolic Diseases and Newborn Screening Center Department of Pediatrics 1 Children's Hospital University of Heidelberg Im Neuenheimer Feld 430 D 69120 Heidelberg Germany

Department of Internal Medicine Mayo Clinic 200 1st Street SW Rochester MN 55905 USA

Department of Pediatrics 2nd Faculty of Medicine Charles University Prague and Motol University Hospital 5 Uvalu 84 PragueCZ 150 06 Czech Republic

Department of Pediatrics Medizinische Fakultät Carl Gustav Carus Technische Universität Dresden Fetscherstraße 74 01307 Dresden Germany

Department of Pediatrics University Hospital Kralovske Vinohrady 3rd Faculty of Medicine Charles University Srobarova 50 Prague CZ 100 34 Czech Republic

Division of Pediatric Pulmonology and Allergy and Cystic Fibrosis Center Department of Pediatrics 3 Children's Hospital University of Heidelberg Im Neuenheimer Feld 430 69120 Heidelberg Germany

Division of Pediatric Pulmonology and Allergy and Cystic Fibrosis Center Department of Pediatrics 3 Children's Hospital University of Heidelberg Im Neuenheimer Feld 430 69120 Heidelberg Germany; Department of Translational Pulmonology Translational Lung Research Center Heidelberg University of Heidelberg Im Neuenheimer Feld 156 D 69120 Heidelberg Germany

Institute of Clinical Chemistry and Laboratory Medicine Medizinische Fakultät Carl Gustav Carus Technische Universität Dresden Fetscherstraße 74 01307 Dresden Germany

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