Comparison of two different protocols of neonatal screening for cystic fibrosis

Abstract

The results of two different protocols of neonatal cystic fibrosis (CF) screening in the Lazio region of Italy are reported. The first study, conducted from 1992 to 2000 on about 200,000 newborns, consisted of an immunoreactive trypsin (IRT) protocol without mutation analysis of the cystic fibrosis transmembrane conductance regulator (CFTR) gene, referred to as the IRT/IRT protocol. Approximately 5% of the newborns with a positive first IRT test were also positive at the second test; approximately 57% of the newborns with a high IRT level at the second test were subsequently found to be affected by CF. In September 1998, a second protocol that included mutation analysis (IRT/DNA/IRT protocol) was started. Comparison of the two different screening protocols in terms of sensitivity in detecting CF patients demonstrated that the IRT/DNA/IRT protocol is more effective because it is able to detect a higher number of CF patients than the IRT/IRT protocol. In the same period, in addition to the overall diagnosis performed on a screening basis, 64 other subjects were identified as being affected by CF on the basis of symptomatic findings. The overall incidence of CF (screening + symptoms) was 1 : 2982, while that for carriers was 1 : 27. The sensitivity of the screening program increased over the period from 1992 to 2000, with the enhanced sensitivity in the past 2 years being due to the introduction of the IRT/DNA/IRT protocol.

Neonatal screening for cystic fibrosis in São Paulo State, Brazil: a pilot study

“…We have used 70.0 ng/mL, as adopted by the 3 regional programs currently active in Brazil (29,31,32). The highest sensitivity previously reported with the IRT/IRT protocol was 86-87% by using either a fixed cut-off point that would permit the recall of 1% of the infants, or a variable cut-off point based on the use of the percentile of the highest values (11,27).…”

“…The original IRT/IRT screening protocol was adopted in the present study in view of the ethnic heterogeneity of the Brazilian population and the need to investigate various mutations, despite the known large number of false-positive results (26,27). This protocol involves two blood collections, with the first ideally to be carried out during the first week of life, and the second, 3-4 weeks later (11).…”

A Genotypic-Oriented View of CFTR Genetics Highlights Specific Mutational Patterns Underlying Clinical Macrocategories of Cystic Fibrosis

“…Their average sweat tests were, respectively, 70 ± 15 and 62 ± 17 mEq/L (both very variable). The enrollment of the male sibling was on the basis of neonatal screening (26,27) at 2 months of age, with no clinical symptoms and no pulmonary bacterial isolates. The enrollment of the female sibling was because of familiarity and neonatal screening at 2 months age, with pulmonary symptoms and bacterial isolates already present.…”

“…The average sweat test was 78 ± 20 mEq/L (very variable). The diagnosis was made at 6 months of age on the basis of neonatal screening (26,27), with no other symptoms. The patient is now 21 years old and displays pulmonary symptoms with chronic bacterial colonization, as well as rhinosinusitis and nasal polyposis.…”

Development and characterization of dried blood spot materials for the measurement of immunoreactive trypsinogen

“…The two most common protocols for CF screening used in Europe, Australia and the US are (a) measuring IRT on one sample and then on a second sample, and (b) IRT testing followed by DNA mutation analysis on the same sample. [16][17][18][19] Trypsinogen is one of the principle components of human pancreatic secretory product. Its concentration in blood is a specific marker of pancreatic function.…”