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Screening for Cystic Fibrosis

  • Review Article
  • Epidemiology
  • Published:
Disease Management and Health Outcomes

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Abstract

Cystic fibrosis (CF) is an autosomal recessive genetic disorder; it is most common in the Caucasian populations, with a prevalence of about 1 per 2500 births. The disorder is associated with progressive lung disease and pancreatic enzyme deficiency, leading to considerable morbidity and mortality. The burden of disease might be reduced by either genetic screening or neonatal screening.

The aim of genetic screening is to identify carrier couples and avoid affected births. The gene responsible for CF was cloned in 1989 and includes over 700 mutations. However, about 85% of carriers or 72% of carrier couples in most countries are accounted for by just a few mutations. There have been 11 prospective intervention studies of antenatal screening, and of 57 147 women offered the test, 75% accepted. Among carrier couples 90% accepted prenatal diagnosis and 94% of affected pregnancies were terminated. The cost per case detected is considerably less than the cost of treatment. Preconceptual screening would provide more reproductive choices but would be more difficult to organise.

An alternative, although less efficient, approach is general population screening to identify individual carriers. Four studies in general practice compared actively sending invitations with opportunistic testing, and in each case only the latter achieved acceptance rates approaching those in pregnancy. Systematic ‘cascade’ screening within CF families has a high yield of carriers which falls off beyond second cousin testing, and ultimately only a small fraction of all carriers is detected.

The aim of neonatal screening is to ensure an early diagnosis, usually by immunoreactive trypsin testing of neonatal heelprick samples. The overall results from 16 studies is a 0.1% false-positive rate and 89% detection rate. The acceptance rate is very high and the cost is low, but there is little direct proof of improved prognosis. There have been 2 randomised trials of which one showed a considerable reduction in malnutrition, although the long term consequences are unknown. Malnutrition is a common consequence of CF due to the gastrointestinal disorder. The second trial was analysed as a case-control study with an apparent benefit similar to that seen in 4 geographical or historical control studies, but such studies are biased. We conclude that antenatal genetic screening has been sufficiently evaluated to recommend a routine service. And while a long term morbidity and mortality benefit of neonatal screening is difficult to demonstrate directly, the known natural history and the low cost of screening may be justification enough.

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Authors and Affiliations

  1. Department of Reproductive Epidemiology, Centre for Reproduction, Growth and Development Research, School of Medicine, University of Leeds, 26 Clarendon Road, Leeds, LS2 9NZ, England

    Howard Cuckle (Professor) & Jenni Murray

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  1. Howard Cuckle
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  2. Jenni Murray
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Correspondence to Howard Cuckle.

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Cuckle, H., Murray, J. Screening for Cystic Fibrosis. Dis-Manage-Health-Outcomes 3, 161–172 (1998). https://doi.org/10.2165/00115677-199803040-00001

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  • DOI: https://doi.org/10.2165/00115677-199803040-00001

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