A New Cystic Fibrosis Newborn Screening Algorithm: IRT/IRT1↑/DNA

Objective

To evaluate an immunoreactive trypsinogen (IRT) IRT/IRT1↑/DNA algorithm, aimed at improving sensitivity while decreasing cystic fibrosis (CF) carrier identification.

Study design

New technologies allow the measurement of the second IRT level solely in infants with an elevated first IRT level. Specimens with an elevated second IRT level undergo mutation analysis. We tested the projected efficacy with retrospective data from Colorado.

Results

All known infants with CF would have been identified with our proposed IRT cutoff points, and 3 would have been missed with our mutation panel. Two of 3 missed cases would have been identified by using a failsafe method (IRT >99.9th percentile), yielding a sensitivity rate of 99.7% (95% CI, 98.4-99.9). Estimated reduction in carrier detection was 80% compared with IRT/DNA.

Conclusion

IRT/IRT1↑/DNA appears to improve cystic fibrosis newborn screen sensitivity while decreasing carrier identification, providing an alternative to IRT/IRT in states that obtain 2 blood spots.

ACMG, American College of Medical Genetics, CF, Cystic fibrosis, CFTR, Cystic fibrosis transmembrane conductance regulator, IRT, Immunoreactive trypsinogen, NBS, Newborn screening