conceptual & technical advances in down’s syndrome screening howard cuckle...
TRANSCRIPT
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Conceptual & technical Conceptual & technical advances in Down’s advances in Down’s syndrome screeningsyndrome screening
Howard CuckleHoward [email protected]@leeds.ac.uk
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Unaffected
Affected
Marker level
1001 100.5 5 500.1
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1001 100.5 5 500.1
Separation or Inter-mean SDs
Marker level
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0.06 1 160.25 4 64
Unaffected
Spina bifida
Anencephaly
AFP (MoM) UK Collaborative AFP Study, 1977
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0 0.5 1 1.5 2 2.5 3 3.5
PAPP-A
freeß
NT
hCG
AFP
uE3
freeß
hCG
Inhibin
Separation (SD's)
Anen-cephaly
Spina bifida
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0 0.5 1 1.5 2 2.5 3 3.5
PAPP-A
freeß
NT
hCG
AFP
uE3
freeß
hCG
Inhibin
Separation (SD's)
10
14
11
12
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15 20 25 30 35 40 45 50 55
Maternal age
Down's syndrome
Unaffected
35
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Unaffected
Affected
1001 100.5 5 500.1
Likelihood ratio
Marker level
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0 0.5 1 1.5 2 2.5 3 3.5
PAPP-A
freeß
NT
hCG
AFP
uE3
freeß
hCG
Inhibin
Separation (SD's)
10
14
11
12
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7 8 9 10 11 12 13 14 15 16 17 18 19 20
Gestational age
AFP, uE3, freeß& inhibin
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0%
20%
40%
60%
80%
100%
Detection rate
5% false-positives 1% false-positives
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0 0.5 1 1.5 2 2.5 3 3.5
PAPP-A
freeß
NT
hCG
AFP
uE3
freeß
hCG
Inhibin
Separation (SD's)
10
14
11
12
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7 8 9 10 11 12 13 14 15 16 17 18 19 20
Gestational age
PAPP-A & freeß
NT
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0%
20%
40%
60%
80%
100%
Detection rate
5% false-positives 1% false-positives
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7 8 9 10 11 12 13 14 15 16 17 18 19 20
Gestational age
PAPP-A & hCG
NT
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0%
20%
40%
60%
80%
100%
Detection rate
5% false-positives 1% false-positives
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Non-viable
Insignificant 1 in 100,000 1 in 10,000 1 in 1,000 1 in 100 1 in 10 Certain
Down's syndrome
Unaffected
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0%
20%
40%
60%
80%
100%
34 studies 2,400k women
9 studies 77k women
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0 0.5 1 1.5 2 2.5 3 3.5
PAPP-A
freeß
NT
hCG
AFP
uE3
freeß
hCG
Inhibin
Separation (SD's)
10
14
11
12
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7 8 9 10 11 12 13 14 15 16 17 18 19 20
Gestational age
PAPP-A alone
AFP, uE3, freeß& inhibin
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0%
20%
40%
60%
80%
100%
Detection rate
5% false-positives 1% false-positives
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7 8 9 10 11 12 13 14 15 16 17 18 19 20
Gestational age
PAPP-A & freeß
AFP, uE3, freeß& inhibin
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0%
20%
40%
60%
80%
100%
Detection rate
5% false-positives 1% false-positives
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7 8 9 10 11 12 13 14 15 16 17 18 19 20
Gestational age
PAPP-A & freeß
AFP, uE3, freeß& inhibin
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0%
20%
40%
60%
80%
100%
Detection rate
5% false-positives 1% false-positives
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0%
20%
40%
60%
80%
100%
FaSTER
Malone et al, 2005
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0 0.5 1 1.5 2 2.5 3 3.5
PAPP-A
freeß
NT
hCG
AFP
uE3
freeß
hCG
Inhibin
NF
NBL
Separation (SD's)
10
14
11
12
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7 8 9 10 11 12 13 14 15 16 17 18 19 20
Gestational age
NF & NBL
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0%
20%
40%
60%
80%
100%
Detection rate
5% false-positives 1% false-positives
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Even
more
contingent
strategies
are
coming
your
way
soon
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7 8 9 10 11 12 13 14 15 16 17 18 19 20
Gestational age
PAPP-A & freeß
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0%
20%
40%
60%
80%
100%
Detection rate
5% false-positives 1% false-positives
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7 8 9 10 11 12 13 14 15 16 17 18 19 20
Gestational age
DV & TR
NT, NB & FMF
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0%
20%
40%
60%
80%
100%
Detection rate
5% false-positives 1% false-positives
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7 8 9 10 11 12 13 14 15 16 17 18 19 20
Gestational age
NT
DV & TR
NB & FMF
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0%
20%
40%
60%
80%
100%
Fetal Medicine Foundation
Nicolaides et al, 2005
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0 0.5 1 1.5 2 2.5 3 3.5
ADAM12
PAPP-A
PAPP-A
freeß
NT
hCG
AFP
uE3
freeß
hCG
Inhibin
Separation (SD's)
8-9
14
10
11-3
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7 8 9 10 11 12 13 14 15 16 17 18 19 20
Gestational age
PAPP-A & ADAM12
free ß-hCG
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0%
20%
40%
60%
80%
100%
Detection rate
5% false-positives 1% false-positives
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7 8 9 10 11 12 13 14 15 16 17 18 19 20
Gestational age
PAPP-A & ADAM12
free ß-hCG
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0%
20%
40%
60%
80%
100%
Detection rate
5% false-positives 1% false-positives
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7 8 9 10 11 12 13 14 15 16 17 18 19 20
Gestational age
NF & NBL
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0%
20%
40%
60%
80%
100%
Detection rate
5% false-positives 1% false-positives
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0 0.5 1 1.5 2 2.5 3 3.5
9
10
11
12
13
14
15
16
17
Separation (SD's)
Gestation (weeks)
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0 0.5 1 1.5 2 2.5 3 3.5
9
10
11
12
13
14
15
16
17
Separation (SD's)
Gestation (weeks)
Mrs BMrs A
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100.1 10.05 0.5 50.1
1
0.5
5
10Down’s syndrome Unaffected pregnancies
10 weeks PAPP-A (MoM)
17 weeks PAPP-A (MoM)
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100.1 10.05 0.5 50.1
1
0.5
5
10
10 weeks PAPP-A (MoM)
17 weeks PAPP-A (MoM)
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Single gene
Heart
NTD
Aneuploidy
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0%
20%
40%
60%
80%
100%
Detection rate
5% false-positives10% false-positives