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Immunoreactive trypsinogen in healthy newborns and infants with cystic fibrosis
  1. Ralph Fingerhut1,
  2. Corina Rueegg2,
  3. Orell Imahorn3,
  4. Eva Sophie Lunde Pedersen4,
  5. Claudia Kuehni4,5,
  6. Sabina Gallati6,
  7. Nicolas Regamey7,
  8. Jürg Barben3
  1. 1 Swiss Newborn Screening Laboratory, University Children's Hospital Zürich, Zurich, Zürich, Switzerland
  2. 2 Oslo Centre for Biostatistics and Epidemiology, Oslo University Hospital, Oslo, Norway
  3. 3 Division of Pediatric Pulmonology, Ostschweizer Kinderspital, St Gallen, St Gallen, Switzerland
  4. 4 Institute of Social and Preventive Medicine, University of Bern, Bern, Bern, Switzerland
  5. 5 Children's Hospital, Division of Pediatric Pulmonology, University of Bern, Bern, Bern, Switzerland
  6. 6 Children's Hospital, Division of Human Genetics, Inselspital University Hospital Bern, Bern, Bern, Switzerland
  7. 7 Children's Hospital, Division of Paediatric Pulmonology, Luzerner Kantonsspital, Luzern, Luzern, Switzerland
  1. Correspondence to Dr Ralph Fingerhut, Swiss Newborn Screening Laboratory, University Children's Hospital Zürich, Zurich, Zürich, Switzerland; ralph.fingerhut{at}synlab.com

Abstract

Objective Newborn screening (NBS) for cystic fibrosis (CF) was introduced in Switzerland in 2011 based on an immunoreactive trypsinogen (IRT)-DNA-IRT protocol. CF diagnosis was confirmed by sweat test and/or genetics but remained inconclusive for some newborns (cystic fibrosis transmembrane conductance regulator related metabolic syndrome (CRMS)/CF screen positive, inconclusive diagnosis (CFSPID)). We aimed to (1) Describe IRT levels in healthy newborns in the first year of life and by gestational age (GA), and (2) Compare IRT at two time points between healthy newborns and newborns with CF and CRMS/CFSPID.

Design Retrospective study.

Setting National NBS database.

Patients All children with an IRT measurement by heel prick test from 2011 to 2019.

Interventions None.

Main outcome measures IRT values were extracted from the National NBS Laboratory, and clinical characteristics of positively screened children from the CF-NBS database. Second IRT assessment in positively screened children was usually performed after 18–24 days. We calculated internal IRT Z-Scores and multiples of the median to compare our results across different laboratory tools.

Results Among 815 899 children; 232 were diagnosed with CF, of whom 36 had meconium ileus (MI); 27 had CRMS/CFSPID. Among all samples analysed, mean IRT Z-Scores were higher for newborns with GA <33 weeks and ≥43 weeks (all Z-Scores >0.11) compared with term babies (all Z-Scores ≤0.06). Repeated IRT Z-Scores after a median (IQR) of 19 (17–22) days remained high for infants with CF with or without MI but decreased for infants with CRMS/CFSPID.

Conclusions Measurement of a second IRT value can help distinguish between children with CRMS/CFSPID and CF, early in life.

  • Cystic Fibrosis
  • Neonatology

Data availability statement

Data are available upon reasonable request.

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Data availability statement

Data are available upon reasonable request.

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Footnotes

  • RF and CR equally shared first-authorship.

  • Contributors Study conception and design: RF, CR, JB. Data acquisition and analysis: RF, CR, ESLP, CK, SG. Interpretation and supervision: RF, CR, OI, ESLP, CK, SG, NR, JB. RF is the author acting as guarantor.

  • Funding This work was supported by the Swiss CF Society, the Telethon Foundation, and the Cantonal Lung Leagues of Bern, Solothurn, St.Gallen, Ticino, Vaud and Zurich. CEK received funding from the Federal Office of Public Health Bern, for the evaluation of CF newborn screening 2011–2020.

  • Competing interests None declared.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Supplemental material This content has been supplied by the author(s). It has not been vetted by BMJ Publishing Group Limited (BMJ) and may not have been peer-reviewed. Any opinions or recommendations discussed are solely those of the author(s) and are not endorsed by BMJ. BMJ disclaims all liability and responsibility arising from any reliance placed on the content. Where the content includes any translated material, BMJ does not warrant the accuracy and reliability of the translations (including but not limited to local regulations, clinical guidelines, terminology, drug names and drug dosages), and is not responsible for any error and/or omissions arising from translation and adaptation or otherwise.