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Prospective and parallel assessments of cystic fibrosis newborn screening protocols in the Czech Republic: IRT/DNA/IRT versus IRT/PAP and IRT/PAP/DNA

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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. Conclusion: 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.

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Abbreviations

CF:

Cystic fibrosis

CFTR:

Cystic fibrosis transmembrane conductance regulator gene

DBS:

Dried blood spot

DNA:

Deoxyribonucleic acid

IRT:

Immunoreactive trypsinogen

NBS:

Newborn screening

PAP:

Pancreatitis-associated protein

PSP:

Population-specific percentile

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Acknowledgments

This study was supported by a grant from the Czech Ministry of Health: IGA NS 9986-3/2008 to FV. We would like to acknowledge all collaborating primary care physicians and clinicians from neonatal units who we could not list individually. We would like to thank Mr Thomas Secrest for linguistic proofreading of the final manuscript. Finally, we would like to thank all participants of the parallel CF NBS research protocols.

Conflict of interest

The authors declare that they have no conflict of interest.

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Authors and Affiliations

  1. 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

    Veronika Krulišová, Miroslava Balaščaková, Tereza Piskáčková, Andrea Holubová, Jana Paděrová, Petra Křenková, Lenka Dvořáková, Alexandra Štambergová & Milan Macek Jr.

  2. Department of Pediatrics, University Hospital Motol and the 2nd Faculty of Medicine, Charles University, Prague, Czech Republic

    Veronika Skalická, Dana Zemková & Věra Vávrová

  3. Department of Pediatrics, University Hospital Královské Vinohrady and the 3rd Faculty of Medicine, Charles University, Prague, Czech Republic

    Petr Kračmar, Blanka Chovancová & Felix Votava

Authors
  1. Veronika Krulišová
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  2. Miroslava Balaščaková
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  3. Veronika Skalická
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  8. Lenka Dvořáková
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  9. Dana Zemková
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  10. Petr Kračmar
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  11. Blanka Chovancová
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  12. Věra Vávrová
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  13. Alexandra Štambergová
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  14. Felix Votava
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  15. Milan Macek Jr.
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Corresponding author

Correspondence to Milan Macek Jr..

Additional information

Veronika Krulišová and Miroslava Balaščaková contributed equally to this paper. Senior authors, Felix Votava and Milan Macek Jr., also contributed equally to this paper.

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Krulišová, V., Balaščaková, M., Skalická, V. et al. Prospective and parallel assessments of cystic fibrosis newborn screening protocols in the Czech Republic: IRT/DNA/IRT versus IRT/PAP and IRT/PAP/DNA. Eur J Pediatr 171, 1223–1229 (2012). https://doi.org/10.1007/s00431-012-1747-z

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  • DOI: https://doi.org/10.1007/s00431-012-1747-z

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