Cystic fibrosis newborn screening in a high prevalence population - Ten years' experience in Ireland
Fiona McGuire1, Abigail Collins2, Mohamed Elsammak3
1Department of Public Health - HSE Dublin and Midlands, HSE Area Offices, Arden Road, Tullamore, Count Offaly, R35 TY28, Ireland.
Insights
Ireland's cystic fibrosis newborn screening program effectively identified cases in its first decade. The program demonstrated strong performance, meeting international standards for detecting this rare genetic disorder in newborns.
Area of Science:
- Genetics
- Pediatrics
- Public Health
Background:
- Ireland has a high prevalence of cystic fibrosis (CF).
- Newborn screening (NBS) for CF was implemented in July 2011.
- The screening protocol involves immunoreactive trypsinogen (IRT) and DNA testing.
Purpose of the Study:
- To evaluate the performance of the Irish CF NBS program over its first 10 years.
- To assess key performance metrics against international standards.
Main Methods:
- A review of national birth data and CF NBS laboratory data from 2011 to 2021.
- Analysis of screening results, including IRT levels, mutation identification, and case detection.
Main Results:
- Over 650,000 infants were screened, detecting 284 CF cases with a sensitivity of 97.9%.
- The birth incidence of CF was 1 in 2203 live births.
- The program identified 21 cases of CFSPID, with a CF:CFSPID ratio of 13.2:1.
Conclusions:
- The Irish CF NBS program performed well in its initial decade.
- Screening metrics met or exceeded international benchmarks.
- The program is effective in identifying newborns with cystic fibrosis.
Background:
Ireland has one of the highest birth prevalences of cystic fibrosis (CF) in the world. Newborn screening (NBS) was introduced in July 2011 using an immunoreactive trypsinogen (IRT)/DNA protocol. Tier 1 identifies infants with IRT >99th centile, with samples sent for tier 2 testing against a 38 CF mutation panel (with R117H turned off). A "safety net" system whereby very high IRT values, with no mutations identified, prompt further testing is not employed. Infants with one, or two, CF mutations identified are referred to one of six CF specialist centres for sweat testing.
Methods:
We reviewed the performance of the first 10 years of screening using national birth data and data from the centralised CF NBS laboratory, from where the programme is coordinated nationally.
Results:
From 2011 to 2021, 650,809 infants were screened for CF. IRT was raised in 7424 (1.14 %). Of these, 233 (3.1 %) had two mutations identified and 609 (8.2 %) had one. With 284 cases detected by NBS, and six undetected, the sensitivity was 97.9 %. The positive predictive value was 0.3. The birth incidence was 1 in 2203 live births. Six antenatal diagnoses of CF were confirmed on CF NBS. There were 21 cases of CFSPID resulting in a CF:CFSPID ratio of 13.2:1. The median age of referral to a specialist CF centre was 21 days (range 12-42).
Conclusion:
the Irish CF NBS programme performed well in its first ten years, across all metrics, when compared with international standards and other national programmes.
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