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Cystic fibrosis
Original article
Novel strategies in newborn screening for cystic fibrosis: a prospective controlled study
  1. Annette M M Vernooij-van Langen1,
  2. J Gerard Loeber2,
  3. Bert Elvers2,
  4. Ralf H Triepels3,
  5. Johan J P Gille4,
  6. Catharina P B Van der Ploeg5,
  7. Sandra Reijntjens1,
  8. Edward Dompeling6,
  9. Jeannette E Dankert-Roelse7 on behalf of the CHOPIN Study Group
  1. 1Department of Research and Innovation, Atrium Medical Centre, Heerlen, The Netherlands
  2. 2Laboratory for Infectious Diseases and Perinatal Screening, National institute for Public Health and the Environment (RIVM), Bilthoven, The Netherlands
  3. 3Clinical Chemistry Laboratory, St Elisabeth Hospital, Tilburg, The Netherlands
  4. 4Department of Clinical Genetics, VU Medical Centre, Amsterdam, The Netherlands
  5. 5Department Public Health and Prevention, TNO Quality of Life, Leiden, The Netherlands
  6. 6Department of Paediatric Pulmonology, Maastricht University Medical Centre, Maastricht, The Netherlands
  7. 7Department of Paediatrics, Atrium Medical Centre, Heerlen, The Netherlands
  1. Correspondence to Dr Annette M M Vernooij-van Langen, RIVM-LIS, P.O. Box 1, 3720 BA Bilthoven, The Netherlands; amm.vernooij+chopin{at}gmail.com

Abstract

Context Newborn screening for cystic fibrosis (CF) is included in many routine programmes but current strategies have considerable drawbacks, such as false-positive tests, equivocal diagnosis and detection of carriers.

Objective To assess the test performance of two newborn screening strategies for CF.

Design, setting and participants In 2008 and 2009, CF screening was added to the routine screening programme as a prospective study in part of the Netherlands.

Interventions Two strategies were performed in all newborns. In the first strategy, concentrations of immunoreactive trypsinogen (IRT) and pancreatitis-associated protein (PAP) were measured. In the second method, samples with IRT ≥60 μg/litre were analysed for 36 CFTR mutations, followed by sequencing when a single mutation was detected. Tests were positive only with two identified CFTR mutations.

Main outcome Sensitivity, specificity and positive predictive value (PPV) of both screening strategies.

Results 145 499 infants were screened. The IRT/PAP approach showed a sensitivity of 95.0%, a specificity of 99.897% and a PPV of 12.3%. Test properties for the IRT/DNA/sequencing strategy were respectively 100%, 100% and 64.9%. Combining both strategies (IRT/PAP/DNA/sequencing) led to a sensitivity of 95.0%, a specificity of 100% and a PPV of 87.5%.

Conclusion In conclusion, all strategies performed well. Although there was no statistically significant difference in test performance, the IRT/DNA/sequencing strategy detected one infant that was missed by IRT/PAP (/DNA/sequencing). IRT/PAP may be the optimal choice if the use of DNA technology must be avoided. If identification of carriers and equivocal diagnosis is considered an important disadvantage, IRT/PAP/DNA/sequencing may be the best choice.

  • Cystic fibrosis newborn screening
  • immunoreactive trypsinogen
  • pancreatitis-associated protein
  • mutation analysis
  • sequencing
  • sensitivity
  • specificity
  • clinical epidemiology
  • cystic fibrosis
  • infection control
  • alpha1 antitrypsin deficiency
  • lung cancer
  • lung proteases
  • macrophage biology
  • respiratory infection
  • cystic fibrosis
  • oxidative stress
  • asthma
  • exhaled airway markers
  • paediatric asthma
  • paediatric physician
  • respiratory infection

https://doi.org/10.1136/thoraxjnl-2011-200730

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    Footnotes

    • See Editorial, p 281

    • CHOPIN Study Group J E Dankert-Roelse, MD, PhD, A M M Vernooij-van Langen, MD (Atrium Medical Centre); J G Loeber, PhD, L H Elvers (RIVM); R H Triepels, PhD (St Elisabeth Hospital); J J P Gille, PhD (VUmc); C P B Van der Ploeg, PhD (TNO Quality of Life); E Dompeling, MD, PhD (MUMC); G Pals, PhD (VU Medical Centre), S M van der Pal, PhD, M E van den Akker van Marle, PhD (TNO Quality of Life); V A M Gulmans, PhD (NCFS, Dutch CF Foundation), M J W Oey-Spauwen, MD, Y H H M Wijnands, MD, L M Castricum, MD (RIVM); H G M Arets, MD, PhD, Professor C K van der Ent, MD, PhD (University Medical Centre Utrecht); Professor H A W M Tiddens, MD, PhD, Y B de Rijke, PhD (Erasmus Medical Centre Rotterdam); J B Yntema, MD, PhD (Radboud University Nijmegen Medical Centre).

    • Funding ZonMw, the Dutch Organization for Health Research Development, financed the study at the request of the Dutch Health Council. ZonMw in no way influenced the data collection, analysis or interpretation of the results, and they did not comment about the writing of this article or the decision for submission.

    • Competing interests None.

    • Ethics approval The Medical Ethical Committee of the Atrium Medical Centre approved the performance of the CHOPIN study according to the Good Clinical Practice guidelines and privacy statements.

    • Provenance and peer review Not commissioned; externally peer reviewed

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