1. Societe Francaise de la Mucoviscidose Journées annuelles, les 6 et 7 décembre 2007 CF Neonatal Screening in Europe Carlo Castellani Verona Cystic Fibrosis Center

3. CF NBS duration in Europe (2004)

4. Screening Services (JCF 2007 6:57-65)

5. Infants screened for PKU and CF in 2004 (ISNS data) PKU 5,886,965 CF 1,622,651 Infants screened for PKU and CF in 2007 (predicted) EUROPE PKU 6,000,000 CF 3,397,000

6. bIRT SWEAT TEST 2 → 8rIRT 2 MUT 14 rIRT / MUT

7. Protocols comparison Screening centers bIRT μg/l cutoff (range) bIRT Centile cutoff (range) rIRT μg/l cutoff (range) Mutation panel detection rate (range) -265 (60-70) --- rIRT857.5 (34-70) 99 (90-99) 36 (26-56) - MUT265 (60-70) --92.5 (90-95) rIRT MUT 1470 (60-75) 99.1 (95-99.5) 55 (40-60) 82 (54-90)

8. Mutation panel detection rate Median 82% lower interquartile 76.8% higher interquartile 86.3%

9. Protocols comparison Screening centers Years of screening (min-max) Neonates screened per year IncidenceFalse negatives per year -24.4 (0.8-8) 12,500 (11000-14000) -- rIRT85.5 (0.9-21) 29,250 (16000-80000) 1/4450 (1/2850-10500) 0.5 (0.29-0.86) MUT24 (0-8) --- rIRT MUT * 139 (2-32) 33,000 (7900-9 2000) 1/2775 (1/2250-5200) 0.3 (0-1) * France not included

10. Screened Newborns 1,659,400 IRT Pos 17,223 (1.03%) Sweat Tests (24 answers) 3,111 (18.06%IRT+) CF 410 (13.17% ST 2.38%IRT+) Carriers (19 answers) 850 EUROPE: CF NBS EPIDEMIOLOGY (per year)

11.  F508 carrier frequency according to IRT concentrations Cumulative frequency distribution of IRT in healthy  F508 carriers ( ) and  F508 non-carriers ( O )  F508 Carrier Frequency (%) IRT (  g/L) Cumulative Frequency (%) adapted from: Lecoq I et al, Acta Pædiatr 88: 338-41, 1999.

12. 10,000 neonates january 1995 - february1998  CFTR testing 1078delT; 1609delCA; 1717-1g/a; 1717-8g/a; 1898+3a/g; 2183aa/g; 2789+5g/a; 3849+10Kb; 394delTT; 457TAT>G; 541delC;621+1g/t; 711+1g/t; 711+5g/a; A559T; deltaF508; deltaI507; G542X;G551D; G85E; N1303K; Q552X; R1158X; R1162X; R117H; R334Q; R334W; R347H; R347P; R352Q; R553X; R709X; S549I; S549I; S549N; S549Ra/c; T338I; W1282X 4 CF (1/2,500) 304 carriers (1/33) 9,692 negative (residual carrier risk 1/180) 304 controls Castellani C et al Am J Med Genet 2005 135A:142-4

13. HETEROZYGOTES VS CONTROLS NUMBER OF NEONATES HETEROZYGOTES CONTROLS Castellani C et al; Am J Med Genet 2005 135A:142-4

14. p 0.01

15. Conclusions CF neonatal screening is growing in Europe CF neonatal screening strategies are heterogeneous CF birth prevalence changes considerably throughout Europe Useful a monitoring system of data and results