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

J Cyst Fibros. 2014 Jan;13(1):15-23. doi: 10.1016/j.jcf.2013.06.003. Epub 2013 Jul 25.

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.

Keywords: Biochemical screening; CF; CFNBS; Cystic fibrosis; DBS; FS; IRT; Immunoreactive trypsinogen; MI; NBS; Newborn screening; PAP; PI; PS; Pancreatitis associated protein; cystic fibrosis; cystic fibrosis newborn screening; dried blot spot; failsafe strategy; immunoreactive trypsinogen; meconium ileus; newborn screening; pancreatic insufficient; pancreatic sufficient; pancreatitis associated protein.

Publication types

  • Comparative Study
  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antigens, Neoplasm / analysis
  • Antigens, Neoplasm / blood*
  • Antigens, Neoplasm / genetics
  • Biomarkers, Tumor / analysis
  • Biomarkers, Tumor / blood*
  • Biomarkers, Tumor / genetics
  • Chemistry, Clinical / methods
  • Chemistry, Clinical / standards
  • 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
  • Infant, Newborn
  • Lectins, C-Type / analysis
  • Lectins, C-Type / blood*
  • Lectins, C-Type / genetics
  • Neonatal Screening / methods*
  • Neonatal Screening / standards
  • Pancreatitis-Associated Proteins
  • Prospective Studies
  • Retrospective Studies
  • Sensitivity and Specificity
  • Trypsinogen / analysis
  • Trypsinogen / blood*
  • Trypsinogen / genetics

Substances

  • Antigens, Neoplasm
  • Biomarkers, Tumor
  • CFTR protein, human
  • Lectins, C-Type
  • Pancreatitis-Associated Proteins
  • REG3A protein, human
  • Cystic Fibrosis Transmembrane Conductance Regulator
  • Trypsinogen