Markedly elevated neonatal immunoreactive trypsinogen levels in the absence of cystic fibrosis gene mutations is not an indication for further testing.
OBJECTIVE
To investigate the immunoreactive trypsinogen (IRT) values above the usual 99th centile laboratory cut-off and determine the value of offering further testing to those infants with a markedly elevated IRT but no cystic fibrosis transmembrane regulator (CFTR) gene mutation identified by the screening programme.


METHODS
All babies born in Victoria, Australia, between 1991 and 2003, were screened by IRT followed by CF gene mutation analysis.


RESULTS
Of the 806,520 babies born, 9268 with the highest IRT levels had CFTR mutation analysis. There were 123 DeltaF508 homozygotes and 703 heterozygotes (86 with CF, 617 carriers). A total of 8442 babies had no CFTR gene mutation, of whom 18 (0.21%) had CF. The total number of CF babies with IRT greater than the laboratory cut-off was 227 (2.4%). The IRT results of the CF patients were distributed normally, with the majority above the laboratory cut-off of newborn IRT results. There was no evidence of an excess of babies with CF in the very highest levels of IRT above the 99th centile.


CONCLUSIONS
Only a small proportion of babies with a neonatal IRT >99th centile have CF. Additional CF testing for infants with an elevated IRT but no CFTR gene mutation has an extremely low yield, no matter how high the IRT result.
Massie
J
J
Department of Respiratory Medicine, Royal Children's Hospital, Parkville, Victoria, Australia. john.massie@rch.org.au
Curnow
L
L
Tzanakos
N
N
Francis
I
I
Robertson
C F
CF
D015415:Biomarkers / Q000097:blood; D003550:Cystic Fibrosis / Q000175:diagnosis* / Q000201:enzymology; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000235:genetics*; D004252:DNA Mutational Analysis; D005189:False Positive Reactions; D005260:Female; D005820:Genetic Testing; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D007231:Infant, Newborn; D008297:Male; D009154:Mutation; D015997:Neonatal Screening; D012016:Reference Values; D014362:Trypsinogen / Q000097:blood*
D015415:Biomarkers; C505032:CFTR protein, human; D019005:Cystic Fibrosis Transmembrane Conductance Regulator; D014362:Trypsinogen