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Arch Dis Child 97:1043-1047 doi:10.1136/archdischild-2012-301968
  • Original articles

Thirty-years of screening for cystic fibrosis in East Anglia

  1. Written on behalf of the Norfolk, Suffolk and Cambridgeshire Paediatric Cystic Fibrosis Network
  1. 1Biochemical Genetics Unit, Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK
  2. 2Department of Paediatrics, Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK
  3. 3Medical School, St George's University of London, London UK
  4. 4Formerly Biochemical Genetics Diagnostic Unit, Peterborough District Hospital, Peterborough, UK
  1. Correspondence to Dr Jacqui Calvin, Biochemical Genetics Unit, Cambridge University Hospitals NHS Foundation Trust, Box 247, Hills Road, Cambridge CB2 0QQ, UK;.jacqui.calvin{at}addenbrookes.nhs.uk
  • Received 23 March 2012
  • Accepted 4 September 2012
  • Published Online First 16 October 2012

Abstract

Background Newborn screening for cystic fibrosis (CF) relies on the measurement of immunoreactive trypsinogen (IRT) originating from the pancreas. The Norfolk, Suffolk and Cambridgeshire screening programme initially exploited the persistent increase in IRT seen in CF (IRT-IRT protocol) and later changed to include mutation analysis as a second tier test (IRT-DNA-IRT protocol).

Results During a 30 year period 582 966 babies have been screened by IRT-IRT and 147 764 by IRT-DNA-IRT (total 730730), resulting in 296 screen positive cases of CF and 29 false negatives (including 10 false negatives with meconium ileus). Ten missed CF cases were pancreatic insufficient, however all were diagnosed before their first birthday, suggesting that a false negative result did not forestall appropriate clinical investigation. The IRT-DNA-IRT protocol had a much improved positive predictive value (PPV) of 85.9% compared to 67.3% for IRT-IRT, excluding CF babies with meconium ileus. The PPVs increased to 82.2% and 98.2% respectively if only well, term babies were considered. The main factor to account for this improvement in PPV has probably been the incorporation of DNA analysis in the second tier testing.

Conclusions The diagnosis of screen-positive babies proved difficult in a minority of cases with the classification of some patients changing with evolving phenotype. Our results illustrate the importance of collecting outcome data over a long time period for accurate assessment of the screening programme. This study provides evidence that newborn screening for CF is a valid undertaking that detects 95% of unsuspected CF cases presenting before 3 years of age.

Footnotes

  • Contributors All authors contributed to the collection and analysis of the screening outcome data and to the writing of the report.

  • Competing interests None.

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