Neonatal screening for cystic fibrosis: comparing the performances of IRT/DNA and IRT/PAP

J Cyst Fibros. 2014 Jul;13(4):384-90. doi: 10.1016/j.jcf.2014.01.004. Epub 2014 Feb 7.

Abstract

Background: French health authorities promoted a study on 553,167 newborns comparing the performances of IRT/DNA and IRT/PAP for CF newborn screening.

Methods: In parallel to IRT/DNA, PAP was assayed in newborns with IRT>50 μg/L. Provisional PAP cutoffs at 3.0 μg/L when 50<IRT<100 μg/L and 1.7 μg/L when IRT>100 were used. Positive newborns were subjected to sweat test. Optimal cutoffs were established by a non-inferiority method.

Results: 95 CF newborns were identified (83 classical forms (ClF), including 9 meconium ileus (MI), and 12 atypical (mild) forms (AF) Of them, IRT/DNA identified 85 (73 ClF including 5 MI and 12 AF). PAP cutoffs at 1.8 μg/L when 50< IRT<100 μg/L and 0.6 μg/L when IRT>100 μg/L would identify 82 CF: 77 ClF, including 8 MI, and 5 AF. The number of sweat tests was 314 and 1039 in the IRT/DNA and IRT/PAP strategies, respectively.

Conclusions: Using the optimal cutoffs, the sensitivity of the IRT/PAP strategy would not be inferior to that of IRT/DNA if identification of MF is not required.

Keywords: CFTR; Cystic fibrosis; IRT; Neonatal screening; Non-inferiority; PAP.

Publication types

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

MeSH terms

  • Antigens, Neoplasm / blood*
  • Biomarkers, Tumor / blood*
  • Biomarkers, Tumor / genetics
  • Cystic Fibrosis / blood
  • Cystic Fibrosis / diagnosis*
  • Cystic Fibrosis / genetics
  • Cystic Fibrosis Transmembrane Conductance Regulator / genetics
  • Cystic Fibrosis Transmembrane Conductance Regulator / metabolism
  • DNA / genetics*
  • DNA Mutational Analysis
  • Female
  • Follow-Up Studies
  • Genetic Testing
  • Humans
  • Infant, Newborn
  • Lectins, C-Type / blood*
  • Male
  • Mutation*
  • Neonatal Screening / methods*
  • Pancreatitis-Associated Proteins
  • Retrospective Studies
  • Trypsinogen / blood
  • Trypsinogen / genetics*

Substances

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