A product of immunoreactive trypsinogen and pancreatitis-associated protein as second-tier strategy in cystic fibrosis newborn screening

J Cyst Fibros. 2016 Nov;15(6):752-758. doi: 10.1016/j.jcf.2016.07.002. Epub 2016 Jul 22.


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.

Keywords: Cutoff; Cystic fibrosis; Immunoreactive trypsinogen; Newborn screening; Pancreatitis-associated protein.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Chemistry Techniques, Analytical
  • Cystic Fibrosis* / blood
  • Cystic Fibrosis* / diagnosis
  • Female
  • Humans
  • Infant, Newborn
  • Male
  • Neonatal Screening / methods*
  • Pancreatitis-Associated Proteins / analysis*
  • Retrospective Studies
  • Sensitivity and Specificity
  • Trypsinogen* / analysis
  • Trypsinogen* / immunology


  • Pancreatitis-Associated Proteins
  • Trypsinogen