NEONATAL SCREENING FOR CYSTIC-FIBROSIS USING IMMUNOREACTIVE TRYPSINOGEN AND DIRECT GENE ANALYSIS - 4 YEARS EXPERIENCE

Objective-To assess the performance and impact of a two tier neonatal screening programme for cystic fibrosis based on an initial estimation of immunoreactive trypsinogen followed by direct gene analysis. Desig n-Four year prospective study of two tier screening strategy. First ti er: immunoreactive trypsinogen measured in dried blood spot samples fr om neonates aged 3-5 days. Second tier: direct gene analysis of cystic fibrosis mutations (Delta F-508, Delta I-506, G(551)D, G(542)X, and R (553)X) in samples with immunoreactive trypsinogen concentrations in h ighest 1% and in all neonates with meconium ileus or family history of cystic fibrosis. Setting-South Australian Neonatal Screening Programm e, Adelaide. Subjects-All 88752 neonates born in South Australia betwe en December 1989 and December 1993. Interventions-Neonates with two id entifiable mutations were referred directly for clinical assessment an d confirmatory sweat test; infants with only one identifiable mutation were recalled for sweat test at age 3-4 weeks. Parents of neonates id entified as carriers of cystic fibrosis mutation were counselled and o ffered genetic testing. Main outcome measures-Identification of all ch ildren with cystic fibrosis in the screened population. Results-Of 100 4 (1.13%) neonates with immunoreactive trypsinogen greater than or equ al to 99th centile, 912 (90.8%) had no identifiable mutation. 23 neona tes were homozygotes or compound heterozygotes; 69 carried one identif iable mutation, of whom six had positive sweat tests. Median age at cl inical assessment for the 29 neonates with cystic fibrosis was 3 weeks ; six had meconium ileus and two had affected siblings. 63 neonates we re identified as carriers of a cystic fibrosis mutation. Extra laborat ory costs for measuring immunoreactive trypsinogen and direct gene ana lysis were $A1.50 per neonate screened. Conclusion-This strategy resul ts in early and accurate diagnosis of cystic fibrosis and performs bet ter than screening strategies based on immunoreactive trypsinogen meas urement alone.