LAUSR

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. Newborn screening programmes for cystic fibrosis (CF) are based on levels of immuno-reactive trypsinogen (IRT). This study highlights the importance of gestational age and day of sampling in interpreting these results and emphasises the importance of a second IRT for inconclusive diagnoses.