title: A product of immunoreactive trypsinogen and pancreatitis-associated protein as second-tier strategy in cystic fibrosis newborn screening.
abstract: 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.
  
  
  
  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.
  
  
  
  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.
  
  
  
  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.
authors.affiliation: Department of Pediatrics, Medizinische Fakultät Carl Gustav Carus, Technische Universität Dresden, Fetscherstraße 74, 01307 Dresden, Germany.
authors.forename: Sophia
authors.initials: S
authors.lastname: Weidler
authors.affiliation: Department of Internal Medicine, Mayo Clinic, 200 First Street SW, Rochester, MN 55905, USA.
authors.forename: Konrad H
authors.initials: KH
authors.lastname: Stopsack
authors.affiliation: Department of Pediatrics, Medizinische Fakultät Carl Gustav Carus, Technische Universität Dresden, Fetscherstraße 74, 01307 Dresden, Germany.
authors.forename: Jutta
authors.initials: J
authors.lastname: Hammermann
authors.affiliation: Division of Pediatric Pulmonology and Allergy and Cystic Fibrosis Center, Department of Pediatrics III, Children's Hospital, University of Heidelberg, Im Neuenheimer Feld 430, 69120 Heidelberg, Germany.
authors.forename: Olaf
authors.initials: O
authors.lastname: Sommerburg
authors.affiliation: Division of Pediatric Pulmonology and Allergy and Cystic Fibrosis Center, Department of Pediatrics III, Children's Hospital, University of Heidelberg, Im Neuenheimer Feld 430, 69120 Heidelberg, Germany; Department of Translational Pulmonology, Translational Lung Research Center Heidelberg (TLRC), Member of the German Center for Lung Research (DZL), University of Heidelberg, Im Neuenheimer Feld 156, D-69120 Heidelberg, Germany.
authors.forename: Marcus A
authors.initials: MA
authors.lastname: Mall
authors.affiliation: Department of General Pediatrics, Division of Metabolic Diseases and Newborn Screening Center, Department of Pediatrics I, Children's Hospital, University of Heidelberg, Im Neuenheimer Feld 430, D-69120 Heidelberg, Germany.
authors.forename: Georg F
authors.initials: GF
authors.lastname: Hoffmann
authors.affiliation: Department of General Pediatrics, Division of Metabolic Diseases and Newborn Screening Center, Department of Pediatrics I, Children's Hospital, University of Heidelberg, Im Neuenheimer Feld 430, D-69120 Heidelberg, Germany.
authors.forename: Dirk
authors.initials: D
authors.lastname: Kohlmüller
authors.affiliation: Department of General Pediatrics, Division of Metabolic Diseases and Newborn Screening Center, Department of Pediatrics I, Children's Hospital, University of Heidelberg, Im Neuenheimer Feld 430, D-69120 Heidelberg, Germany.
authors.forename: Jürgen G
authors.initials: JG
authors.lastname: Okun
authors.affiliation: Department of Biology and Medical Genetics, 2nd Faculty of Medicine, Charles University Prague and Motol University Hospital, V Uvalu 84, Prague CZ 150 06, Czech Republic.
authors.forename: Milan
authors.initials: M
authors.lastname: Macek
authors.affiliation: Department of Pediatrics, University Hospital Kralovske Vinohrady, 3rd Faculty of Medicine, Charles University, Srobarova 50, Prague, CZ 100 34, Czech Republic.
authors.forename: Felix
authors.initials: F
authors.lastname: Votava
authors.affiliation: Department of Biology and Medical Genetics, 2nd Faculty of Medicine, Charles University Prague and Motol University Hospital, V Uvalu 84, Prague CZ 150 06, Czech Republic.
authors.forename: Veronika
authors.initials: V
authors.lastname: Krulišová
authors.affiliation: Department of Biology and Medical Genetics, 2nd Faculty of Medicine, Charles University Prague and Motol University Hospital, V Uvalu 84, Prague CZ 150 06, Czech Republic.
authors.forename: Miroslava
authors.initials: M
authors.lastname: Balaščaková
authors.affiliation: Department of Pediatrics, 2nd Faculty of Medicine, Charles University Prague and Motol University Hospital, V Uvalu 84, PragueCZ 150 06, Czech Republic.
authors.forename: Veronika
authors.initials: V
authors.lastname: Skalická
authors.affiliation: Department of Pediatrics, Medizinische Fakultät Carl Gustav Carus, Technische Universität Dresden, Fetscherstraße 74, 01307 Dresden, Germany.
authors.forename: Min Ae
authors.initials: MA
authors.lastname: Lee-Kirsch
authors.affiliation: Institute of Clinical Chemistry and Laboratory Medicine, Medizinische Fakultät Carl Gustav Carus, Technische Universität Dresden, Fetscherstraße 74, 01307 Dresden, Germany. Electronic address: marina.stopsack@uniklinikum-dresden.de.
authors.forename: Marina
authors.initials: M
authors.lastname: Stopsack
mesh_terms: D002623:Chemistry Techniques, Analytical; D003550:Cystic Fibrosis / Q000097:blood / Q000175:diagnosis; D005260:Female; D006801:Humans; D007231:Infant, Newborn; D008297:Male; D015997:Neonatal Screening / Q000379:methods*; D000073718:Pancreatitis-Associated Proteins / Q000032:analysis*; D012189:Retrospective Studies; D012680:Sensitivity and Specificity; D014362:Trypsinogen / Q000032:analysis / Q000276:immunology
chemical_list: D000073718:Pancreatitis-Associated Proteins; D014362:Trypsinogen
keywords: Cutoff; Cystic fibrosis; Immunoreactive trypsinogen; Newborn screening; Pancreatitis-associated protein