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Conceptual & technical advances in Down’s syndrome screening Howard Cuckle h.s.cuckle@leeds.ac.uk. 100. 0.5. 1. 5. 10. 50. 0.1. Unaffected. Affected. Marker level. 100. 0.5. 1. 5. 10. 50. 0.1. Separation or Inter-mean SDs. Marker level. 0.06. 0.25. 1. 4. 16. 64.
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Conceptual & technical advances in Down’s syndrome screening Howard Cuckle h.s.cuckle@leeds.ac.uk
100 0.5 1 5 10 50 0.1 Unaffected Affected Marker level
100 0.5 1 5 10 50 0.1 Separation or Inter-mean SDs Marker level
0.06 0.25 1 4 16 64 Unaffected Spina bifida Anencephaly AFP (MoM) UK Collaborative AFP Study, 1977
Spina bifida Anen-cephaly Separation(SD's)
10 11 12 14 Separation(SD's)
Unaffected 35 Down'ssyndrome 15 20 25 30 35 40 45 50 55 Maternal age
100 0.5 1 5 10 50 0.1 Unaffected Affected Likelihood ratio Marker level
10 11 12 14 Separation(SD's)
7 8 9 10 11 12 13 14 15 16 17 18 19 20 Gestational age AFP, uE3, freeß & inhibin
Detection rate 5% false-positives 1% false-positives
10 11 12 14 Separation(SD's)
7 8 9 10 11 12 13 14 15 16 17 18 19 20 Gestational age PAPP-A & freeß NT
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
Detection rate 5% false-positives 1% false-positives
Insignificant 1 in 100,000 1 in 10,000 1 in 1,000 1 in 100 1 in 10 Certain Unaffected Down'ssyndrome Non-viable
9 studies 77k women 34 studies 2,400k women
10 11 12 14 Separation(SD's)
7 8 9 10 11 12 13 14 15 16 17 18 19 20 Gestational age PAPP-A alone AFP, uE3, freeß & inhibin
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
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
Detection rate 5% false-positives 1% false-positives
FaSTER Malone et al, 2005
10 11 12 14 Separation(SD's)
7 8 9 10 11 12 13 14 15 16 17 18 19 20 Gestational age NF & NBL
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
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, NB & FMF DV & TR
Detection rate 5% false-positives 1% false-positives
7 8 9 10 11 12 13 14 15 16 17 18 19 20 Gestational age NB & FMF NT DV & TR
Fetal Medicine Foundation Nicolaides et al, 2005
8-9 10 11-3 14 Separation(SD's)
7 8 9 10 11 12 13 14 15 16 17 18 19 20 Gestational age free ß-hCG PAPP-A & ADAM12
Detection rate 5% false-positives 1% false-positives
7 8 9 10 11 12 13 14 15 16 17 18 19 20 Gestational age free ß-hCG PAPP-A & ADAM12
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
Detection rate 5% false-positives 1% false-positives
Gestation (weeks) Separation(SD's)
Gestation (weeks) Mrs B Mrs A Separation(SD's)
0.01 10 5 1 0.5 0.1 0.05 0.1 0.5 1 5 10 17 weeksPAPP-A (MoM) Down’s syndrome Unaffected pregnancies 10 weeksPAPP-A (MoM)
0.01 10 5 1 0.5 0.1 0.05 0.1 0.5 1 5 10 17 weeksPAPP-A (MoM) 10 weeksPAPP-A (MoM)
Single gene Aneuploidy Heart NTD