LAUSR

Background: Newborn screening (NBS) for CF in Wales commenced in December 1996 with a IRT/DNA protocol. All infants with one or two identified mutations proceed to sweat test. Between 1996 and 2001 we screened for 4 CF mutations; between 2001-2006 31 mutations; and 2006-2016 8 mutations. We have a comprehensive network to identify all patients with CF in Wales. Wales has a stable population demographic. Aims: To describe NBS for CF over a 20 year period. Methods: We identified all infants identified through NBS as having CF, and all clinical diagnoses (false +ve screen). Genotype, phenotype and sweat test results were reviewed. We excluded those who presented with meconium ileus. Results: Between December 1996 and December 2016 a total of 673,952 babies in Wales underwent newborn bloodspot screening. Between 1996-2005, 295,247 infants were screened for CF using either the CF4 or CF31 gene panel. 124 infants were diagnosed as having CF (incidence 1:2381), including 5 infants with R117H 7T and normal sweat test. 7 infants were affected but not detected by the screening process in this period (age at diagnosis 0.25-18 years). Screening sensitivity in this period has decreased with time to 94.4%). Between 2006-2016, 378,705 infants were screened for CF using the CF-8 gene panel. 108 infants were diagnosed as having CF in this period (incidence 1:3506), with no subjects with R117H. To date 3 individuals were affected but not detected, sensitivity of screening 97.2%. Conclusions: Changes in the gene panel have changed the incidence of CF in Wales over a 20 year period. We have decreased the number of subjects identified with mutations of variable clinical consequence.