A new cystic fibrosis newborn screening algorithm: IRT/IRT1 upward arrow/DNA.
OBJECTIVE
To evaluate an immunoreactive trypsinogen (IRT) IRT/IRT1 upward arrow/DNA algorithm, aimed at improving sensitivity while decreasing cystic fibrosis (CF) carrier identification.


METHODS
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.


CONCLUSIONS
IRT/IRT1 upward arrow/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.
Sontag
Marci K
MK
Department of Epidemiology, Colorado School of Public Health, University of Colorado Denver, Aurora, CO, USA. sontag.marci@tchden.org
Wright
Dan
D
Beebe
James
J
Accurso
Frank J
FJ
Sagel
Scott D
SD
D000465:Algorithms; D015331:Cohort Studies; D003120:Colorado / Q000453:epidemiology; D016001:Confidence Intervals; D003550:Cystic Fibrosis / Q000097:blood / Q000175:diagnosis* / Q000453:epidemiology / Q000235:genetics*; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000235:genetics; D004252:DNA Mutational Analysis; D005260:Female; D020022:Genetic Predisposition to Disease / Q000453:epidemiology; D005820:Genetic Testing / Q000379:methods*; D006579:Heterozygote; D006801:Humans; D007231:Infant, Newborn; D008297:Male; D015997:Neonatal Screening / Q000379:methods; D011336:Probability; D012189:Retrospective Studies; D012680:Sensitivity and Specificity; D013997:Time Factors; D014362:Trypsinogen / Q000235:genetics* / Q000276:immunology
D019005:Cystic Fibrosis Transmembrane Conductance Regulator; D014362:Trypsinogen