title: Prospective and parallel assessments of cystic fibrosis newborn screening protocols in the Czech Republic: IRT/DNA/IRT versus IRT/PAP and IRT/PAP/DNA.
abstract: Cystic fibrosis (CF) is a life-threatening disease for which early diagnosis following newborn screening (NBS) improves the prognosis. We performed a prospective assessment of the immunoreactive trypsinogen (IRT)/DNA/IRT protocol currently in use nationwide, versus the IRT/pancreatitis-associated protein (PAP) and IRT/PAP/DNA CF NBS protocols. Dried blood spots (DBS) from 106,522 Czech newborns were examined for IRT concentrations. In the IRT/DNA/IRT protocol, DNA-testing was performed for IRT ≥ 65 ng/mL. Newborns with IRT ≥ 200 ng/mL and no detected cystic fibrosis transmembrane conductance regulator gene (CFTR) mutations were recalled for a repeat IRT. In the same group of newborns, for both parallel protocols, PAP was measured in DBS with IRT ≥ 50 ng/mL. In PAP-positive newborns (i.e., ≥1.8 if IRT 50-99.9 or ≥1.0 if IRT ≥ 100, all in ng/mL), DNA-testing followed as part of the IRT/PAP/DNA protocol. Newborns with at least one CFTR mutation in the IRT/DNA/IRT and IRT/PAP/DNA protocols; a positive PAP in IRT/PAP; or a high repeat IRT in IRT/DNA/IRT were referred for sweat testing.
  
  
  CONCLUSIONS
  the combined results of the utilized protocols led to the detection of 21 CF patients, 19 of which were identified using the IRT/DNA/IRT protocol, 16 using IRT/PAP, and 15 using IRT/PAP/DNA. Decreased cut-offs for PAP within the IRT/PAP protocol would lead to higher sensitivity but would increase false positives. Within the IRT/PAP/DNA protocol, decreased PAP cut-offs would result in high sensitivity, an acceptable number of false positives, and would reduce the number of DNA analyses. Thus, we concluded that the IRT/PAP/DNA protocol would represent the most suitable protocol in our conditions.
authors.affiliation: Department of Biology and Medical Genetics, University Hospital Motol and the 2nd Faculty of Medicine, Charles University, V Úvalu 84, 15006 Prague 5, Czech Republic.
authors.forename: Veronika
authors.initials: V
authors.lastname: Krulišová
authors.forename: Miroslava
authors.initials: M
authors.lastname: Balaščaková
authors.forename: Veronika
authors.initials: V
authors.lastname: Skalická
authors.forename: Tereza
authors.initials: T
authors.lastname: Piskáčková
authors.forename: Andrea
authors.initials: A
authors.lastname: Holubová
authors.forename: Jana
authors.initials: J
authors.lastname: Paděrová
authors.forename: Petra
authors.initials: P
authors.lastname: Křenková
authors.forename: Lenka
authors.initials: L
authors.lastname: Dvořáková
authors.forename: Dana
authors.initials: D
authors.lastname: Zemková
authors.forename: Petr
authors.initials: P
authors.lastname: Kračmar
authors.forename: Blanka
authors.initials: B
authors.lastname: Chovancová
authors.forename: Věra
authors.initials: V
authors.lastname: Vávrová
authors.forename: Alexandra
authors.initials: A
authors.lastname: Stambergová
authors.forename: Felix
authors.initials: F
authors.lastname: Votava
authors.forename: Milan
authors.initials: M
authors.lastname: Macek
mesh_terms: D000951:Antigens, Neoplasm / Q000097:blood; D015415:Biomarkers / Q000097:blood; D014408:Biomarkers, Tumor / Q000097:blood; D002985:Clinical Protocols; D003550:Cystic Fibrosis / Q000097:blood / Q000175:diagnosis* / Q000235:genetics; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000235:genetics; D018153:Czech Republic; D004252:DNA Mutational Analysis; D059788:Dried Blood Spot Testing; D005188:False Negative Reactions; D005189:False Positive Reactions; D005819:Genetic Markers; D006801:Humans; D007231:Infant, Newborn; D037181:Lectins, C-Type / Q000097:blood; D015997:Neonatal Screening / Q000379:methods*; D000073718:Pancreatitis-Associated Proteins; D011446:Prospective Studies; D012680:Sensitivity and Specificity; D013542:Sweat / Q000737:chemistry; D014362:Trypsinogen / Q000097:blood
chemical_list: D000951:Antigens, Neoplasm; D015415:Biomarkers; D014408:Biomarkers, Tumor; C505032:CFTR protein, human; D005819:Genetic Markers; D037181:Lectins, C-Type; D000073718:Pancreatitis-Associated Proteins; C000612141:REG3A protein, human; D019005:Cystic Fibrosis Transmembrane Conductance Regulator; D014362:Trypsinogen