History of Newborn Screening for Cystic Fibrosis-The Early Years.

This review summarises the trajectory of neonatal screening strategies for the detection of cystic fibrosis (CF) using the measurement of Immunoreactive Trypsin (IRT) in dried blood spots (DBS) from 1979 until the beginning of the 21st century when newborn screening (NBS) programmes started to spread throughout many countries, using IRT measurement combined with a CF genotype analysis of DBS.

European best practice guidelines for cystic fibrosis neonatal screening.

There is wide agreement on the benefits of NBS for CF in terms of lowered disease severity, decreased burden of care, and reduced costs. Risks are mainly associated with disclosure of carrier status and diagnostic uncertainty. When starting a NBS programme for CF it is important to take precautions in order to minimise avoidable risks and maximise benefits. In Europe more than 25 screening programmes have been developed, with quite marked variation in protocol design. However, given the wide geographic, ethnic, and economic variations, complete harmonisation of protocols is not appropriate. There is little evidence to support the use of IRT alone as a second tier, without involving DNA mutation analysis. However, if IRT/DNA testing does not lead to the desired specificity/sensitivity ratio in a population, a screening programme based on IRT/IRT may be used. Sweat chloride concentration remains the gold standard for discriminating between NBS false and true positives, but age-related changes in sweat chloride should be taken into account. CF phenotypes associated with less severe disease often have intermediate or normal sweat chloride concentrations. Programmes should include arrangements for counselling and management of infants where the diagnosis is not clear-cut. All newborns identified by NBS should be managed according to internationally accepted guidelines. CF centre care and the availability of necessary medication are essential prerequisites before the introduction of NBS programmes. Clear explanation to families of the process of screening and of implications of normal and abnormal results is central to the success of CF NBS programmes. Effective communication is especially important when parents are told that their child is affected or is a carrier. When establishing a NBS programme for CF, attention should be given to ensuring timely and appropriate processing of results, to minimise potential stress for families.

A survey of newborn screening for cystic fibrosis in Europe.

BACKGROUND: Cystic fibrosis (CF) is a recessively inherited condition caused by mutation of the CFTR gene. Newborn infants with CF have raised levels of immuno-reactive trypsinogen (IRT) in their serum. Measurement of IRT in the first week of life has enabled CF to be incorporated into existing newborn screening (NBS) blood spot protocols. However, IRT is not a specific test for CF and NBS therefore requires a further tier of tests to avoid unnecessary referral for diagnostic testing. Following identification of the CFTR gene, DNA analysis for common CF-associated mutations has been increasingly used as a second tier test. The aim of this study was to survey the current practice of CF NBS programmes in Europe. METHOD: A questionnaire was sent to 26 regional and national CF NBS programmes in Europe. RESULTS: All programmes responded. The programmes varied in number of infants screened and in the protocols employed, ranging from sweat testing all infants with a raised first IRT to protocols with up to four tiers of testing. Three different assays for IRT were used; in the majority (24) this was a commercially available kit (Delfia). A number of programmes employed a second IRT measurement in the 4th week of life (as the IRT is more specific at this point). Nineteen programmes used DNA analysis for common CFTR mutations on samples with a raised first IRT. Three programmes used a second IRT measurement on infants with just one recognised mutation to reduce the number of infants referred for sweat testing. Referral to clinical services was prompt and diagnosis was confirmed by sweat testing, even in infants with two recognised mutations in most programmes. Subsequent clinical pathways were less uniform. Multivariate analysis demonstrated a relationship between the age of diagnosis and the timing of the first IRT. More sweat tests were undertaken if the first IRT was earlier and the diagnosis was later. CONCLUSIONS: Annually these programmes screen approximately 1,600,000 newborns for CF and over 400 affected infants are recognised. The findings of this survey will guide the development of European evidence based guidelines and may help new regions or nations in the development and implementation of NBS for cystic fibrosis.