Two-tiered immunoreactive trypsinogen-based newborn screening for cystic fibrosis in Colorado: screening efficacy and diagnostic outcomes.
OBJECTIVE
To examine immunoreactive trypsinogen (IRT)-based screening for cystic fibrosis (CF) for recall rate, genotype distribution, and "borderline" sweat test results.


METHODS
CF newborn screening in Colorado began in 1982, and >1,153,000 infants were screened through 2002 with an IRT-based screen (IRT/IRT).


RESULTS
We have identified 313 infants with CF, giving an overall incidence of 1 in 3684 and a Hispanic incidence of 1 in 6495. Fifty-five infants with meconium ileus (17.6%) were excluded from analysis. Fourteen infants with false-negative results were identified (5.4%). The average recall rate was 0.6%, with a positive predictive value of 4.7%. Ninety-three percent of the infants had at least 1 DeltaF508 mutation, and 98% of the infants had at least 1 mutation from the American College of Medical Genetics recommended panel. Six infants had hypertrypsinogenemia and borderline results on sweat tests (30-60 mmol/L). Increased variability in sweat chloride levels were seen in these infants compared with infants with homozygous DeltaF508. Three children with initial borderline results on sweat tests had CF diagnosed.


CONCLUSIONS
The recall and false-negative rates of our IRT/IRT CF screening program are reported. Additionally, genotypes of the patients identified mirror the CF population genotypes, reflecting similar disease severity in the screened population. Finally, infants with persistent hypertrypsinogenemia and borderline sweat test results need long-term follow-up.
Sontag
Marci K
MK
Department of Preventive Medicine and Biometrics and the Department of Pediatrics, University of Colorado Health Sciences Center, Denver, CO 80218, USA. Sontag.Marci@tchden.org
Hammond
Keith B
KB
Zielenski
Julian
J
Wagener
Jeffrey S
JS
Accurso
Frank J
FJ
D002712:Chlorides / Q000032:analysis; D003120:Colorado / Q000453:epidemiology; D003550:Cystic Fibrosis / Q000097:blood / Q000175:diagnosis* / Q000453:epidemiology / Q000235:genetics; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000235:genetics; D004252:DNA Mutational Analysis / Q000379:methods* / Q000592:standards; D005188:False Negative Reactions; D015200:Fluoroimmunoassay / Q000379:methods* / Q000592:standards; D005838:Genotype; D006801:Humans; D015994:Incidence; D007231:Infant, Newborn; D018580:Mandatory Testing; D009154:Mutation / Q000235:genetics; D015997:Neonatal Screening / Q000379:methods* / Q000592:standards; D011237:Predictive Value of Tests; D011863:Radioimmunoassay / Q000379:methods* / Q000592:standards; D012680:Sensitivity and Specificity; D012720:Severity of Illness Index; D013542:Sweat / Q000737:chemistry; D014362:Trypsinogen / Q000097:blood*
C505032:CFTR protein, human; D002712:Chlorides; D019005:Cystic Fibrosis Transmembrane Conductance Regulator; D014362:Trypsinogen