Newborn screening for cystic fibrosis in Wisconsin: nine-year experience with routine trypsinogen/DNA testing.
OBJECTIVE
To describe the development and follow-up confirmatory results of the routine cystic fibrosis (CF) newborn screening (NBS) program in Wisconsin.


METHODS
CF NBS has been performed on a routine clinical basis in Wisconsin since July 1994. The 2-tiered immunoreactive trypsinogen (IRT)/DNA technique was used on dried blood on filter paper spots. From July 1994 to February 2002, mutation analysis was for the DeltaF508 allele. Beginning in March 2002, multimutation analysis of 25 CF mutations was performed. Infants with a positive result on NBS were seen in certified CF centers for sweat testing by means of quantitative pilocarpine iontophoresis, and families received genetic counseling.


RESULTS
From July 1994 to February 2002, there were 120 cases of CF detected by means of NBS (509,794 infants screened), with 53 DeltaF508 homozygotes and 67 compound heterozygotes. There were 8 clinically diagnosed cases of CF (no DeltaF508 allele). The CF incidence was 1:3983 (95%CI, 1:3373-1:4774). From March 2002 to June 2003, multimutation analysis identified 21 cases of classic CF (90,142 infants screened). Sweat tests were successfully performed in infants younger than 1 month.


CONCLUSIONS
Early diagnosis of CF through NBS was successfully performed, with an estimated sensitivity rate of 99% using the IRT/25 CFTR multimutation assay.
Rock
Michael J
MJ
Department of Pediatrics and State Laboratory of Hygiene, University of Wisconsin, Madison, Wisconsin 53792, USA. mjrock@wisc.edu
Hoffman
Gary
G
Laessig
Ronald H
RH
Kopish
Greg J
GJ
Litsheim
Thomas J
TJ
Farrell
Philip M
PM
D000367:Age Factors; D002712:Chlorides / Q000032:analysis; 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; D042241:Early Diagnosis; D004591:Electrophoresis, Polyacrylamide Gel / Q000379:methods; D015200:Fluoroimmunoassay / Q000379:methods* / Q000592:standards; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D015994:Incidence; D007223:Infant; D007231:Infant, Newborn; D007478:Iontophoresis / Q000379:methods; D018721:Muscarinic Agonists; D015997:Neonatal Screening / Q000379:methods* / Q000592:standards; D010862:Pilocarpine; D016133:Polymerase Chain Reaction / Q000379:methods; D016032:Randomized Controlled Trials as Topic; D012680:Sensitivity and Specificity; D013542:Sweat / Q000737:chemistry; D014362:Trypsinogen / Q000097:blood*; D014922:Wisconsin / Q000453:epidemiology
C505032:CFTR protein, human; D002712:Chlorides; D018721:Muscarinic Agonists; D010862:Pilocarpine; D019005:Cystic Fibrosis Transmembrane Conductance Regulator; D014362:Trypsinogen