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.
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
Data availability statement
Data are available upon reasonable request.
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RF and CR equally shared first-authorship.
Correction notice This article has been corrected since it was first published. In figure 3, panel C was duplicated and this has now been changed.
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.
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