Post on 21-Jan-2016
description
Conceptual & technical Conceptual & technical advances in Down’s advances in Down’s syndrome screeningsyndrome screening
Howard CuckleHoward Cuckleh.s.cuckle@leeds.ac.ukh.s.cuckle@leeds.ac.uk
Unaffected
Affected
Marker level
1001 100.5 5 500.1
1001 100.5 5 500.1
Separation or Inter-mean SDs
Marker level
0.06 1 160.25 4 64
Unaffected
Spina bifida
Anencephaly
AFP (MoM) UK Collaborative AFP Study, 1977
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
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
15 20 25 30 35 40 45 50 55
Maternal age
Down's syndrome
Unaffected
35
Unaffected
Affected
1001 100.5 5 500.1
Likelihood ratio
Marker level
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
7 8 9 10 11 12 13 14 15 16 17 18 19 20
Gestational age
AFP, uE3, freeß& inhibin
0%
20%
40%
60%
80%
100%
Detection rate
5% false-positives 1% false-positives
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
7 8 9 10 11 12 13 14 15 16 17 18 19 20
Gestational age
PAPP-A & freeß
NT
0%
20%
40%
60%
80%
100%
Detection rate
5% false-positives 1% false-positives
7 8 9 10 11 12 13 14 15 16 17 18 19 20
Gestational age
PAPP-A & hCG
NT
0%
20%
40%
60%
80%
100%
Detection rate
5% false-positives 1% false-positives
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
0%
20%
40%
60%
80%
100%
34 studies 2,400k women
9 studies 77k women
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
7 8 9 10 11 12 13 14 15 16 17 18 19 20
Gestational age
PAPP-A alone
AFP, uE3, freeß& inhibin
0%
20%
40%
60%
80%
100%
Detection rate
5% false-positives 1% false-positives
7 8 9 10 11 12 13 14 15 16 17 18 19 20
Gestational age
PAPP-A & freeß
AFP, uE3, freeß& inhibin
0%
20%
40%
60%
80%
100%
Detection rate
5% false-positives 1% false-positives
7 8 9 10 11 12 13 14 15 16 17 18 19 20
Gestational age
PAPP-A & freeß
AFP, uE3, freeß& inhibin
0%
20%
40%
60%
80%
100%
Detection rate
5% false-positives 1% false-positives
0%
20%
40%
60%
80%
100%
FaSTER
Malone et al, 2005
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
7 8 9 10 11 12 13 14 15 16 17 18 19 20
Gestational age
NF & NBL
0%
20%
40%
60%
80%
100%
Detection rate
5% false-positives 1% false-positives
Even
more
contingent
strategies
are
coming
your
way
soon
7 8 9 10 11 12 13 14 15 16 17 18 19 20
Gestational age
PAPP-A & freeß
0%
20%
40%
60%
80%
100%
Detection rate
5% false-positives 1% false-positives
7 8 9 10 11 12 13 14 15 16 17 18 19 20
Gestational age
DV & TR
NT, NB & FMF
0%
20%
40%
60%
80%
100%
Detection rate
5% false-positives 1% false-positives
7 8 9 10 11 12 13 14 15 16 17 18 19 20
Gestational age
NT
DV & TR
NB & FMF
0%
20%
40%
60%
80%
100%
Fetal Medicine Foundation
Nicolaides et al, 2005
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
7 8 9 10 11 12 13 14 15 16 17 18 19 20
Gestational age
PAPP-A & ADAM12
free ß-hCG
0%
20%
40%
60%
80%
100%
Detection rate
5% false-positives 1% false-positives
7 8 9 10 11 12 13 14 15 16 17 18 19 20
Gestational age
PAPP-A & ADAM12
free ß-hCG
0%
20%
40%
60%
80%
100%
Detection rate
5% false-positives 1% false-positives
7 8 9 10 11 12 13 14 15 16 17 18 19 20
Gestational age
NF & NBL
0%
20%
40%
60%
80%
100%
Detection rate
5% false-positives 1% false-positives
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)
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
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)
100.1 10.05 0.5 50.1
1
0.5
5
10
10 weeks PAPP-A (MoM)
17 weeks PAPP-A (MoM)
Single gene
Heart
NTD
Aneuploidy
0%
20%
40%
60%
80%
100%
Detection rate
5% false-positives10% false-positives