Validation of the Cobas/Ssdw system
for trisomy 21 screening in the first
trimester of pregnancy:
Comparison with the Kryptor/
FastScreen combination
MF Rossier, N Beloeil, J Hediger-Bonfantini, S Dahoun,
R Stricker, E Dayer, O Irion, DF Hochstrasser, and I Kern
Dr M.F. Rossier Institut Central (ICHV)
Service de Chimie
clinique & Toxicologie
|
Introduction
June 12 2 Swiss MedLab 2012
Source: Merck Manual of Medical Information
0
1
2
3
4
5
6
7
Ris
k o
f D
ow
n s
yn
dro
me i
n
live b
irth
s (
%)
20 24 28 32 36 40 44 48
Maternal age (years)
Risk assessment
1 in
1667
1 in
769
1 in 14
1 in 38
1 in
1061 in
1250
1 in
1053
1 in
294
0
1
2
3
4
5
6
7
Ris
k o
f D
ow
n s
yn
dro
me i
n
live b
irth
s (
%)
20 24 28 32 36 40 44 48
Maternal age (years)
Risk assessment
1 in
1667
1 in
769
1 in 14
1 in 38
1 in
1061 in
1250
1 in
1053
1 in
294
Prenatal Screening Increasing Down syndrome risk with increasing maternal age
|
Introduction
June 12 3 Swiss MedLab 2012
Nuchal Translucency
(NT)
|
Introduction
June 12 4 Swiss MedLab 2012
Snijders et al.,Lancet 1998;351:343.
Sensitivity
False positives
(5 %)
Nuchal Translucency (NT) is
increased in case of Down
Syndrome, congenital heart
defects, other syndromes and
conditions.
Sens = 77 % at Spec = 95 %
(NT + maternal age, medians
according to gestational age and
embryo size)
|
Introduction
June 12 5 Swiss MedLab 2012
Risk Assessment Comparison of detection rates of different screening methods
Comparison of the detection
rates (DR), for a false
positive rate (FPR) of 5% of different screening
methods for trisomy 21 in
prenatal screening.
Source: FMF, London 2004
|
Instruments for free b-hCG and PAPP-A determination
Cobas 6000 <e601> (Roche)
(FMF certified since 2010)
Kryptor (Brahms/Thermo)
(reference method)
Program Furnisher Ref Instrument Statistics Calculated
risk
Certification
required
Recommendation
*FastScreen (2009 - V.1.1.3.2)
Brahms Kryptor DoE At sampling FMF (D) Recommended in
Switzerland
Prisca (2004 – V.4.0.20.4)
Siemens Kryptor or
Immulite
MoM At term or at
sampling
no Alternative to
FastScreen
Astraia (2009)
Astraia MoM At term FMF (UK) Recommended in
Switzerland
*Ssdw Lab
(2007 – V.5)
Roche Cobas MoM At sampling
or at term
no In process
June 12 6 Swiss MedLab 2012
Softwares for risk assessment
|
0 5000 10000 15000
0
5000
10000
15000
Passing-Bablok
regression anal.
y=0.915x+60.7
r=0.973, n=209
PAPP-A vs Lab1
vs Lab2
Co
ba
s 6
00
0 P
AP
P-A
(m
UI/L
)
Kryptor PAPP-A (mUI/L)
June 12 7 Swiss MedLab 2012
Instrument comparisons
|
1000 10000
1000
10000
Passing-Bablok
regression anal.
y=0.915x+60.7
r=0.973, n=209
PAPP-A vs Lab1
vs Lab2
Co
ba
s 6
00
0 P
AP
P-A
(m
UI/L
)
Kryptor PAPP-A (mUI/L)
June 12 8 Swiss MedLab 2012
Instrument comparisons
|
10 100
10
100
vs Lab1
vs Lab2
Co
ba
s 6
00
0 fre
e b
-hC
G (
ng
/ml)
Kryptor free b-hCG (ng/ml)
free b-hCG
Passing-Bablok
regression anal.
y=0.970x-1.251
r=0.983, n=209
June 12 9 Swiss MedLab 2012
Instrument comparisons
|
Cohort: 143 pregnancies including
- 40 cases of trisomy 21, plus
- 103 consecutive controls
Analysis: ROC curve characteristics
Sensitivity and specificity
Illegitimate combinations
Influence of nuchal translucency
June 12 10 Swiss MedLab 2012
Performance evaluation
|
0.0 0.2 0.4 0.6 0.8 1.0
0.0
0.2
0.4
0.6
0.8
1.0
S
en
sit
ivit
y
1 - Specificity (FPR)
Kryptor / FastScreen
AUC = 99%
Se = 95% at 5% FPR
Cobas / Ssdw
AUC = 99%
Se = 95% at 5% FPR
Analysis on
- 40 T21 cases
- 103 controls
ROC curve analysis
June 12 11 Swiss MedLab 2012
| June 12 12 Swiss MedLab 2012
Comparison Kryptor/FastScreen and Cobas/Ssdw
1 10 100 1000 10000
10
100
1000
10000
Sen : 88% (35/40)
Spe : 98% (101/103)
Sen : 90% (36/40)
Spe : 98% (101/103)
Controls (103)
Affected (40)
Cobas /
Ssdw
ris
k a
t sam
plin
g (
odds r
atio)
Kryptor / FastScreen risk at sampling (odds ratio)
| June 12 13 Swiss MedLab 2012
1 10 100 1000 10000
1
10
100
1000
10000
Sen : 88% (35/40)
Spe : 100% (103/103)
Sen : 88% (35/40)
Spe : 98% (101/103)
Controls (103)
Affected (40)
juillet 2011
Co
ba
s / F
astS
cre
en
ris
k a
t sa
mp
ling
(o
dd
s r
atio
)
Kryptor / FastScreen risk at sampling (odds ratio)
Comparison of instruments using FastScreen
| June 12 14 Swiss MedLab 2012
10 100 1000 10000
10
100
1000
10000Sen : 90% (36/40)
Spe : 100% (103/103)
Sen : 88% (35/40)
Spe : 100% (103/103)
Controls (103)
Affected (40)
Cobas /
Ssdw
ris
k a
t te
rm (
odds r
atio)
Kryptor / Ssdw risk at term (odds ratio)
Comparison of instruments using Ssdw
| 15 June 12 Swiss MedLab 2012
Comparison of softwares using Cobas
1 10 100 1000 10000
10
100
1000
10000
Sen : 90% (36/40)
Spe : 98% (101/103)
Sen : 88% (35/40)
Spe : 100% (103/103)
Controls (103)
Affected (40)
Co
ba
s /
Ssd
w r
isk a
t sa
mp
ling
(o
dd
s r
atio
)
Cobas / FastScreen risk at sampling (odds ratio)
|
1.0 1.5 2.0 2.5 3.0 3.5 4.0
1
10
100
1000
10000
odd
s r
atio
NT (mm)
Ssdw
FastScreen
Prisca
Cisline
1.0 1.5 2.0 2.5 3.0 3.5 4.0
1
10
100
1000
10000
NT (mm)
Cobas
Kryptor
June 12 16 Swiss MedLab 2012
Weight of nuchal translucency in risk assessment
|
Case 1 Case 3 Case 2
June 12 17 Swiss MedLab 2012
1.0 1.5 2.0 2.5 3.0 3.5 4.0
10
100
1000
10000
odd
s r
atio
NT (mm)
Ssdw
FastScreen
Prisca
Cisline
1.0 1.5 2.0 2.5 3.0 3.5 4.0
1
10
100
1000
10000
NT (mm)
1.0 1.5 2.0 2.5 3.0 3.5 4.0
1
10
100
1000
10000
NT (mm)
Weight of nuchal translucency in risk assessment
|
Conclusion
In our limited cohort, the Cobas/Ssdw system performed as well as
the Kryptor/FastScreen system and therefore could be considered as
a new alternative in Switzerland for risk assessment in the first
trimester of pregnancy
PAPP-A and free b-hCG determinations in biological
samples were similar with the Kryptor and the Cobas e-601
In our cohort, both systems predicted the presence of
trisomy 21 with similar sensitivity and specificity
Variability between systems was mostly due to the software,
not to the analytical instrument
The weight of the nuchal translucency in the risk assessment
was similar in the four tested softwares
June 12 18 Swiss MedLab 2012
|
Acknowledgements
Central Institute (ICHV)
Nicole Beloeil*
Eric Dayer
Univ. Hosp. Geneva (HUG)
Jocelyne Hediger*
Sophie Dahoun
Olivier Irion
Denis Hochstrasser
Ilse Kern*
Dianalabs
Reto Stricker
Disclosure: Cobas reagents were provided by Roche
June 12 19 Swiss MedLab 2012