Abstract
In January 2019, CF-NBS was started in Flanders (Belgium) involving 2
screenings labs using an IRT-DNA algorithm with a limited CFTR mutation
panel and an IRT/IRT failsafe. Diagnosis is confirmed by sweat chloride
(SCl) and CFTR mutation analysis.
Methods: IRT was measured in dried blood spots (DBS) collected 72–96
hours after birth. If IRT was above the P99 cut-off, 12 CFTR mutations were
searched for. Screen positive newborns (IRT>P99 and 1 or 2 mutations)
were referred to a CF centre for quantitative pilocarpine iontophoresis
(QPI). For IRT >P99.9 with negative mutation screening, a failsafe is
provided with repeat IRT before day 21 (IRT-D21). For meconium ileus (MI),
CF diagnostics are done irrespective of NBS result. CF centres provided
feedback to the screening labs after diagnostic assessment.
Results: In 2019 and 2020 (analysis of 2021 ongoing), 125,732 newborns
were screened (coverage 99.9%). Sixty-eight (0.056%) had raised IRT plus at
least 1 mutation. Three babies were screen +ve from the failsafe arm (IRTIRT)
and 5 were sent for a QPI after ultra-high IRT, no mutation but missing
the repeat IRT-D2. This resulted in 76 referrals for QPI. CF was confirmed in
24/76 babies (23/68 and in 1/5 newborn after the failsafe net without
repeat IRT-D21; 43 babies were carriers, 3 were CRMS/CFSPID (CF
metabolic syndrome/CF screen positive inconclusive diagnosis), 6 no CF/
no carrier.
Median age at initial visit in the CF centre was 20 days and 23 days at
diagnosis.
CF centres reported no missed cases so far. Only 1 baby with MI had a
negative CF-NBS, however this was not considered as false negative as per
protocol.
Based on these results, sensitivity was 100%, PPV 0.31 (calculated without
CFSPID), and CF/CFSPID ratio was 8.
Discussion: Performance of the program has been in agreement with ECFS
standards. By June 2022, results will be extended to 3 years of screening.
Based on current results, the IRT cut-off will be adapted to P99.2 to further
improve the PPV.
| Original language | English |
|---|---|
| Article number | P001 |
| Pages (from-to) | 65-65 |
| Number of pages | 1 |
| Journal | Journal of Cystic Fibrosis |
| Volume | 21 |
| Issue number | Supplement 1 |
| Publication status | Published - 2022 |
| Event | 45th European cystic fibrosis conference, Rotterdam - Ahoy, Ahoyweg 10 3084 BA Rotterdam, Rotterdam, Netherlands Duration: 8 Jun 2022 → 11 Jun 2022 |