Screening for cystic fibrosis in newborn infants: results of a pilot programme based on a two tier protocol (IRT/DNA/IRT) in the Italian population.
OBJECTIVE
To assess the performance of a two tier neonatal screening programme (IRT/DNA/IRT) for cystic fibrosis, based on immunoreactive trypsinogen (IRT) followed by direct cystic fibrosis transmembrane conductance regulator (CFTR) gene analysis (based on a panel of up to 31 mutations) in hypertrypsinaemic newborn infants and to compare it with a previous screening protocol.


METHODS
The study comprised all the newborn infants in the period 1 October 1998 to 31 December 1999 in the Lombardia region, north western Italy.


METHODS
The screening strategy consisted of an immunoreactive trypsinogen assay from dried blood spots, a polymerase chain reaction (PCR) followed by an oligonucleotide ligation assay (PCR-OLA), and a sequence code separation.


RESULTS
104 609 newborn infants were screened. 1457 hypertrypsinaemic infants (1.39%) were analysed with the PCR-OLA assay. 18 newborn homozygotes or compound heterozygotes for CFTR mutations were identified and referred to the cystic fibrosis (CF) centre at a mean age of 3 weeks. 125 infants presenting only one mutation were recalled for a sweat test: a diagnosis of CF was made in 13 infants, and parents of 112 neonates identified as carriers (1:13) received genetic counselling. The remaining 1314 hypertrypsinaemic newborn infants were recalled for IRT retesting and 177 were referred for a sweat test because the second IRT measurement was above the cut off value. Among this group a further two infants were diagnosed with CF (1.1%) leading to a CF prevalence of 1:3170.


CONCLUSIONS
This strategy resulted in an early and accurate diagnosis of CF. The IRT/DNA/IRT protocol with an OLA assay was shown to be useful in an Italian population with a genetic heterogeneity, leading to the identification of 94% of infants with CF.
Corbetta
C
C
Neonatal Screening Centre, AO Istituti Clinici di Perfezionamento, Milano, Italy.
Seia
M
M
Bassotti
A
A
Ambrosioni
A
A
Giunta
A
A
Padoan
R
R
D003550:Cystic Fibrosis / Q000175:diagnosis* / Q000453:epidemiology; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000032:analysis / Q000235:genetics; D004252:DNA Mutational Analysis; D006580:Genetic Carrier Screening; D018740:Genetic Heterogeneity; D005838:Genotype; D006801:Humans; D007231:Infant, Newborn; D007558:Italy / Q000453:epidemiology; D015997:Neonatal Screening / Q000191:economics / Q000379:methods; D010865:Pilot Projects; D015995:Prevalence; D015397:Program Evaluation; D012680:Sensitivity and Specificity; D017384:Sequence Deletion; D013542:Sweat / Q000737:chemistry; D014362:Trypsinogen / Q000097:blood
C505032:CFTR protein, human; D019005:Cystic Fibrosis Transmembrane Conductance Regulator; D014362:Trypsinogen