Cystic fibrosis newborn screening in Switzerland - evaluation and scenarios for improvement after 11 years of follow-up.

Pedersen, ESL; de Jong, Carmen C M; Jurca, M; Berger, D O; Sanz, J; Sluka, Shm; Poms, M; Baumgartner, M R; Regamey, N; Kuehni, C E; Barben, J; Rueegg, C S (2024). Cystic fibrosis newborn screening in Switzerland - evaluation and scenarios for improvement after 11 years of follow-up. Journal of cystic fibrosis, 23(4), pp. 796-803. Elsevier 10.1016/j.jcf.2024.04.008

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BACKGROUND

Newborn bloodspot screening (NBS) for cystic fibrosis (CF) is important for early diagnosis and treatment. However, screening can lead to false-positive results leading to unnecessary follow-up tests and distress. This study evaluated the 11-year performance of the Swiss CF-NBS programme, estimated optimal cut-offs for immunoreactive trypsinogen (IRT), and examined how simulated algorithms would change performance.

METHODS

The Swiss CF-NBS is based on an IRT-DNA algorithm with a second IRT (IRT-2) as safety net. We analysed data from 2011 to 2021, covering 959,006 IRT-1 analyses and 282 children with CF. We studied performance based on European Cystic Fibrosis Society (ECFS) standards including sensitivity, specificity, positive predictive value (PPV), false negative rate, and second heel-prick tests; identified optimal IRT cut-offs using receiver operating characteristics (ROC) curves; and calculated performance for simulated algorithms with different cut-offs for IRT-1, IRT-2, and safety net.

RESULTS

The Swiss CF-NBS showed excellent sensitivity (96 %, 10 false negative cases) but moderate PPV (25 %). Optimal IRT-1 and IRT-2 cut-offs were identified at 2.7 (>99th percentile) and 5.9 (>99.8th percentile) z-scores, respectively. Analysis of simulated algorithms showed that removing the safety net from the current algorithm could increase PPV to 30 % and eliminate >200 second heel-prick tests per year, while keeping sensitivity at 95 %.

CONCLUSION

The Swiss CF-NBS program performed well over 11 years but did not achieve the ECFS standards for PPV (≥30 %). Modifying or removing the safety net could improve PPV and reduce unnecessary follow-up tests while maintaining the ECFS standards for sensitivity.

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