Neonatal Screening for Cystic Fibrosis in the Trent Region (UK): Two-Stage Immunoreactive Trypsin Screening Compared with a Three-Stage Protocol with DNA Analysis as an Intermediate Step

Abstract

Objectives— To assess neonatal screening for cystic fibrosis using immunoreactive trypsin, either alone or in conjunction with DNA analysis for the AF508 mutation. A novel three-stage screening protocol was compared with the previously introduced two-stage immunoreactive trypsin-DNA protocol. Design— (a) Collection of data from a 41/2 year period (phase 1) of two-stage immunoreactive trypsin screening. The initial dried blood samples were obtained at 6 days of age and repeat samples at 27 days of age from babies with results above the 99.5th centile. Babies with persistent hypertrypsinaemia were referred for a diagnostic sweat test. (b) Retrospective DNA analysis: Patients with cystic fibrosis diagnosed in phase 1 were genotyped and most samples from babies with increased initial immunoreactive trypsin but normal results in the second sample were analysed for the δF508 mutation, (c) Phase 2, a prospective study of a three-stage neonatal screening protocol, in which only babies heterozygous for the δF508 cystic fibrosis mutation progressed to the second immunoreactive trypsin test. Setting— The Trent neonatal screening programme. Subjects— 437 859 babies born between August 1989 and March 1996. Main outcome measures— Proportions of unaffected babies requiring a second blood sample or a sweat test. Overall sensitivity for the detection of cystic fibrosis. Results— The two-stage screen failed to identify six out of 94 cases of cystic fibrosis (without meconium ileus). The introduction of the DNA analysis step would have resulted in one additional case being missed. With the three-stage screen there was a 92% reduction in babies requiring a second blood sample and an 80% reduction in negative sweat tests, results close to the predictions of the retrospective study. Conclusions— The three-stage screening protocol is a marked improvement on the two-stage immunoreactive trypsin strategy and on the two-stage immunoreactive trypsin-DNA strategy recently introduced in some other screening programmes.

Communication of carrier status information following universal newborn screening for sickle cell disorders and cystic fibrosis: qualitative study of experience and practice

“…While research in relation to newborn CF screening may suggest little evidence of enduring adverse psychosocial effects, 7,59,73 parents may be distressed or depressed during the process of newborn screening, 14,60,[74][75][76][77][78][79][80] which may relate to difficulties in understanding relatively complex information. 15,58 Health professional communication may also shape parents responses to newborn CF screening results, 81 which can include shock and anxiety, 14,58,59,82,83 with health professional communication following newborn carrier identification sometimes found wanting by parents in relation to both CF and SC.…”

Demographics of the UK cystic fibrosis population: implications for neonatal screening

“…It is envisaged that the proposed screening programme will be based on a three-stage protocol. 6 In Table 4 but not in the 31 mutation panel; 1154insTC, E60X, P67L, Y569D, L218X, 1161delC and R709X. the first stage, a confirmed raised immunoreactive trypsinogen (IRT) level on a day 4 -6 blood spot sample would be followed by a second stage DNA analysis for CFTR mutations from the same blood spot card.…”

Cystic fibrosis and neonatal screening

“…Pollitt et al 44 , using this methodology, observed a reduction of 92% in the number of recalls for a second IRT test, as compared to the IRT/IRT protocol, and a reduction of 80% in recalls for the sweat test.…”

“…Pancreatitis-associated protein (PAP) is elevated in the blood of children with cystic fibrosis 44 . Sarles et al 45 studied the combined use of measuring PAP and IRT.…”

“…These services have been working with CF neonatal screening for an average of ten years (varying from nine months to 31 years), screening 1,600,000 children/year and detecting some 400 cases/year. Median age at diagnosis is reported at 37 days (32)(33)(34)(35)(36)(37)(38)(39)(40)(41)(42)(43)(44)(45)(46)(47)(48)(49)(50). This was the first detailed report on CF screening in Europe, and the results showed heterogeneous protocols, varying from the sweat test after the first IRT to those involving IRT1/IRT2/DNA, IRT1/DNA/IRT2, IRT1/ protein in meconium/IRT2, IRT1/sweat chloride test.…”