Evaluation in 47,213 neonates of a strategy for neonatal screening of cystic fibrosis coupling pancreatitis-associated protein and immunoreactive trypsinogen assays.

Objectives. - The increasing evidence of the benefits of neonatal screening for cystic fibrosis (CF) indicates that this procedure could soon be imple mented throughout France. The screening strategy currently used involves th e defection of infants with elevated levels of immunoreactive trypsinogen ( IRT) (similar to1% of the population), followed by the detection of CFTR ge ne mutations. However, genetic analysis has certain drawbacks, the most imp ortant of which being the management of heterozygotes, and in France the re quirement by law of previous informed consent. In cases of CF; pancreatic a lterations are already present in utero. A previous study has demonstrated the value of pancreatitis-associated protein (PAP) as a screening test for CF and has indicated that a feasible two-stage strategy could involve the f ollowing: 1) selection of infants with elevated PAP levels; 2) in this grou p of infants, subsequent detection of those with elevated IRT levels for di rect CF diagnosis by the sweat test thereby avoiding the use of genetic ana lysis. The study aim was to evaluate this strategy in a large number of neo nates. Methods and results. - The aforementioned strategy was evaluated in a prosp ective study involving 47,213 infants in the Provence region of France. In infants with a PAP > 7.5 ng/mL (1.28%), 176 had an elevated IRT level > 700 ng/mL (0.37%). In this limited population sample (0.37% of the total), the sweat test diagnosed five cases of CF: A sixth case involving the monozygo us twin of an infant with diagnosed CF remained undetected, probably becaus e of a registration error. Genetic analysis confirmed the diagnosis, and al so defected another case in an infant with two CFTR mutations but with a no rmal phenotype at 20 months of age. As the observed incidence was similar t o that which had previously been reported, and as no further case was subse quently detected two years after the end of the study, this indicated that the sensitivity of this screening strategy was satisfactory. Its specificit y makes the direct diagnosis of CF cases by the sweat test feasible, withou t further selection by genetic analysis. Conclusion. - The PAP/IRT technique for CF detection seems to be suitable f or mass screening, without the drawbacks of genetic testing. (C) 2001 Editi ons scientifiques et medicales Elsevier SAS.