Newborn bloodspot screening for cystic fibrosis in Scotland
Purpose: In February 2003, newborn bloodspot screening for cystic fibrosis (CF), based on the measurement of immunoreactive trypsinogen (IRT) in dried bloodspots, was added to the existing national newborn screening programme for phenylketonuria and congenital hypothyroidism in Scotland. The aim of screening for CF is to shorten the time to diagnosis thus allowing earlier initiation of treatment with possible improved outcome.
Methods: An initial mean bloodspot IRT ≥70ng/ml, measured using the Perkin Elmer Delfia fluoroimmunoassay method, was considered elevated. Mutation analysis was carried out on DNA eluted from the same blood spot card using the Applied Biosystems OLA method. Subsequently, the Elucigene fluorescence ARMS assay was used. Babies with 2 mutations are referred to a specialist CF physician. Babies with 1 mutation and babies from minority ethnic groups with an initial raised IRT are followed up through IRT testing of a second specimen obtained at 27 days. Babies with a second raised IRT are referred to a specialist CF physician and are sweat tested.
Results: Between February 2003 and December 2005, 157,000 babies were screened. There were 1041 with an elevated IRT (0.66%) and 56 of these were found to have 2 mutations. A further 9 cases were identified with a single mutation and a positive sweat test. Two cases, both with normal IRT, were missed by screening (sensitivity 97%). The incidence of CF in the screened population was 1:2345. Eighty two probable carriers (initial raised IRT and one mutation) were identified.
Conclusions: Newborn screening for CF using an IRT-DNA protocol can identify affected infants as early as two weeks after birth. Additional reporting and genetic counselling work is generated by the incidental detection of a small number of carriers.