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Cystic fibrosis newborn screening: the importance of bloodspot sample quality
  1. Iolo Doull1,
  2. Christopher William Course1,
  3. Ruth E Hanks1,
  4. Kevin W Southern2,
  5. Julian T Forton1,
  6. Lena P Thia1,
  7. Stuart J Moat3,4
  1. 1Department of Paediatric Respiratory Medicine and Paediatric Cystic Fibrosis Centre, Children's Hospital for Wales, Cardiff, UK
  2. 2Department of Women's and Children's Health, University of Liverpool, Liverpool, UK
  3. 3Department of Medical Biochemistry, Immunology & Toxicology, University Hospital of Wales, Cardiff, UK
  4. 4School of Medicine, Cardiff University, Cardiff, UK
  1. Correspondence to Prof Iolo Doull, Department of Paediatric Respiratory Medicine and Paediatric Cystic Fibrosis Centre, Children's Hospital for Wales, Cardiff CF14 4XN, UK; doullij{at}cf.ac.uk

Abstract

Objective Wales has an immunoreactive trypsin (IRT)-DNA cystic fibrosis (CF) newborn screening (NBS) programme. Most CF NBS false negative cases are due to an IRT concentration below the screening threshold. The accuracy of IRT results is dependent on the quality of the dried bloodspot (DBS) sample. The aim of this study was to determine the cause of false negative cases in CF NBS and their relationship to DBS quality.

Design Longitudinal birth cohort.

Setting Wales 1996–2016.

Patients Children with CF.

Interventions Identification of all CF patients with triangulation of multiple data sources to detect false negative cases.

Main outcome measures False negative cases.

Results Over 20 years, 673 952 infants were screened and 239 were diagnosed with CF (incidence 1:2819). The sensitivity of the programme was 0.958, and positive predictive value was 0.476. Eighteen potential false negatives were identified, of whom eight were excluded: four screened outside Wales, two had complex comorbidities, no identified cystic fibrosis transmembrane conductance regulator (CFTR) variants on extended analysis and thus not considered to have CF and two were diagnosed after their 16th birthday. Of the 10 false negatives, 9 had a low DBS IRT and at least one common CFTR variant and thus should have received a sweat test under the programme. DBS cards were available for inspection for five of the nine false negative cases—all were classified as small/insufficient or poor quality.

Conclusions The majority of false negatives had a low bloodspot IRT, and this was associated with poor quality DBS. The optimal means to improve the sensitivity of our CF NBS programme would be to improve DBS sample quality.

  • cystic Fibrosis
  • screening
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Footnotes

  • Twitter @chriscourse

  • Contributors ID and SJM conceived the paper and its design and wrote the first draft. CWC, RH and KWS collated the data and amended and contributed to the paper. JF and LT amended and contributed to the paper.

  • Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.

  • Competing interests None declared.

  • Patient consent for publication Not required.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Data availability statement Data are available on reasonable request. The identified clinical data is held on password-protected computers at the Children’s Hospital for Wales.

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