Societe Francaise de la MucoviscidoseJournées annuelles, les 6 et 7 décembre 2007

CF Neonatal Screening in Europe

Carlo CastellaniVerona Cystic Fibrosis Center

years0 5 10 15 20 25 30 35

VenetoLeeds

East AngliaNorthamptonshi

LombardyTuscany

Northern IrelandSouth Yorkshire

MarcheWales

LiguriaSicily

Lazio 1Austria

Lazio 2 UmbriaCastilla-Leon

PolandPiedmontCatalunya

Emilia RomagnaFrance

ScotlandGalice

CalabriaSardinia

Czech Republic

CF NBS duration in Europe (2004)

CFNeonatalScreeningin Europe

6

13

1

3

11

ScreeningServices

(JCF 2007 6:57-65)

Infants screened for PKU and CF in 2004(ISNS data)

PKU 5,886,965

CF 1,622,651

non CFCF

Infants screened for PKU and CF in 2007(predicted)

EUROPE

PKU 6,000,000

CF 3,397,000

non CFCF

bIRTSWEATTEST

2 →

8 rIRT

2 MUT

14 rIRT / MUT

Protocols comparisonScreening

centersbIRT

μg/l

cutoff

(range)

bIRT

Centile

cutoff

(range)

rIRT

μg/l

cutoff

(range)

Mutation panel

detection rate

(range)

- 2 65

(60-70)

- - -

rIRT 8 57.5

(34-70)

99

(90-99)

36

(26-56)

-

MUT 2 65

(60-70)

- - 92.5

(90-95)

rIRT

MUT

14 70

(60-75)

99.1

(95-99.5)

55

(40-60)

82

(54-90)

Mutation panel detection rate

• Median 82%• lower interquartile

76.8%• higher interquartile

86.3%

0

1

2

3

4

5

6

% mutation-negative

76.8detectionrate82detectionrate86.3detectionrate

Protocols comparison

Screening centers

Years of screening

(min-max)

Neonates screened per

year

Incidence False negatives per year

- 2 4.4

(0.8-8)

12,500

(11000-14000)

- -

rIRT 8 5.5

(0.9-21)

29,250

(16000-80000)

1/4450

(1/2850-10500)

0.5

(0.29-0.86)

MUT 2 4

(0-8)

- - -

rIRT

MUT

*

13 9

(2-32)

33,000

(7900-9 2000)

1/2775

(1/2250-5200)

0.3

(0-1)

* France not included

0 5000 10000 15000 20000

carriernewbornsaffectednewbornssweat tests

IRTpositivenewborns

ScreenedNewborns1,659,400

IRTPos

17,223(1.03%)

SweatTests

(24 answers)3,111

(18.06%IRT+)

CF410

(13.17% ST2.38%IRT+)

Carriers(19 answers)

850

EUROPE:CF NBS EPIDEMIOLOGY (per year)

0

2

4

6

8

10

12

0 100

200

300

400

500

600

700

800

900

1000

0

10

20

30

40

50

60

70

80

90

100

0 100

200

300

400

500

600

700

800

900

1000

1100

1200

1300

1400

F508 carrier frequency according to IRT

concentrations

Cumulative frequency distribution of IRT in healthy F508 carriers ()

and F508 non-carriers (O)

F50

8 C

arri

er F

requ

ency

(%

)

IRT (g/L) IRT (g/L)

Cum

ulat

ive

Fre

quen

cy (

%)

adapted from: Lecoq I et al, Acta Pædiatr 88: 338-41, 1999.

10,000neonates

january 1995-

february1998

CFTRtesting

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 controlsCastellani C et al

Am J Med Genet 2005135A:142-4

0

20

40

60

80

100

120

140

IRTcentile 0-49 IRTcentile 50-85 IRTcentile >85

HETEROZYGOTES VS CONTROLSN

UM

BE

R O

F N

EO

NA

TE

S HETEROZYGOTES CONTROLS

Castellani C et al; Am J Med Genet 2005 135A:142-4

2040

6080

100

120

no y es

Tim

e fo

r dia

gnos

is

Mutations 2nd step

p 0.01

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