1. QA of screening for downs

Probability
Model
Age risk model
Risk
MoM
values
Marker values
(PAPP-A, free  hCG, NT)
Gestational age (from
CRL)
Maternal weight
Smoking
Ethnicity
The process
Standardisation

Standardisation
Ideally markers should be independent of other
variables such as gestation, weight, ethnicity, .. so
that interpretation is easy
The reality is that marker levels depend, to various
degrees, on:
• Gestation
• Maternal weight
• Ethnicity
• Smoking status
• Multiple pregnancy
• IVF
• Machine
• Laboratory
• Reagent lot
• etc.
We standardise into MoM
values to remove the
effects of these
characteristics.
4

PAPP-A
0 5 10 15
PAPP-A
0 5 10 15
PAPP-A
0 5 10 15
Illustration PAPP-A
11w+3d
12w+3d
13w+3d

PAPP-A
0 5 10 15
PAPP-A
0 5 10 15
PAPP-A
0 5 10 15
11w+3d
12w+3d
13w+3d

PAPP-A
0 5 10 15
0.5 1.0 2.0
PAPP-A
0 5 10 15
0.5 1.0 2.0
PAPP-A
0 5 10 15
0.5 1.0 2.0
11w+3d
12w+3d
13w+3d

PAPP-A MoM
0 1 2 3 4 5
PAPP-A MoM
0 1 2 3 4 5
PAPP-A MoM
0 1 2 3 4 5
MoMs
11w+3d
12w+3d
13w+3d

PAPP-A MoM - log scale
0.1 0.5 1.0 2.0 10.0
0.1 0.5 1.0 2.0 10.0
0.1 0.5 1.0 2.0 10.0
Log (MoMs)
11w+3d
12w+3d
13w+3d

11w+3d
12w+3d
13w+3d
0.1 0.5 1.0 2.0 10.0
0.1 0.5 1.0 2.0 10.0
0.1 0.5 1.0 2.0 10.0

PAPP-A
Gestation (days)
PAPP-A(iU/l)
50 60 70 80 90 100
0.1
0.2
0.5
1.0
2.0
5.0
Wk 7 Wk 8 Wk 9 Wk 10 Wk 11 Wk 12 Wk 13
Weight (kg)
PAPP-AMoM
40 50 60 70 80 90 100 110 120 130 140 150
0.2
0.4
0.6
0.8
1.0
1.2
1.4
1.6
1.8
2.0
11

Effects on PAPP-A
MoM PAPP-A
0.1 0.5 1.0 1.5 2.0 3.0
Trisomy 21 - Wk 11-13
Trisomy 18
Trisomy 13
Afro-Caribbean
Asian
Oriental
Smoking
11 12 13
PAPP-A
12

Free β-hCG (T1)
Gestation (days)
hCGbeta
50 60 70 80 90 100
5
10
20
30
40
50
60
80
100
150
200
250
Wk 7 Wk 8 Wk 9 Wk 10 Wk 11 Wk 12 Wk 13
Gestation (days)
FreebetahCG
100 110 120 130 140 150
5
10
15
20
25
30 Wk 15 Wk 16 Wk 17 Wk 18 Wk 19 Wk 20
Weight (kg)
FreebetaMoM
40 50 60 70 80 90 100 110 120 130 140 150
0.2
0.4
0.6
0.8
1.0
1.2
1.4
1.6
1.8
2.0
Gestation (days)
FreebetahCG
100 110 120 130 140 150
5
10
15
20
25
30 Wk 15 Wk 16 Wk 17 Wk 18 Wk 19 Wk 20
13

Free β-hCG (T1)
Effects on Free ß-hCG (T1)
MoM Free ß-hCG (T1)
0.1 0.5 1.0 1.5 2.0 3.0
Trisomy 21
Trisomy 18
Trisomy 13
Afro-Caribbean
Asian
Oriental
Smoking
11 12 13
14

AFP
Weight (kg)
AFPMoM
40 50 60 70 80 90 100 120 140
0.2
0.4
0.6
0.8
1.0
1.2
1.4
1.6
1.8
2.0
Gestation (days)
AFP
100 110 120 130 140 150
20
30
40
50
60
70
80 Wk 15 Wk 16 Wk 17 Wk 18 Wk 19 Wk 20
15

AFP
Effects on AFP
MoM AFP
0.1 0.5 1.0 1.5 2.0 3.0
Trisomy 21
Trisomy 18
Trisomy 13
African
Caribbean
Chinese
Oriental
Asian
Bangladeshi
Indian
Pakistani
Smoking
16

uE3
Weight (kg)
uE3MoM
40 50 60 70 80 90 110 130 150
0.2
0.4
0.6
0.8
1.0
1.2
1.4
1.6
1.8
2.0
Gestation (days)
uE3
100 110 120 130 140 150
1
2
3
4
5
6
7
8
10
15
20 Wk 15 Wk 16 Wk 17 Wk 18 Wk 19 Wk 20
17

Effects on uE3
MoM uE3
0.1 0.5 1.0 1.5 2.0 3.0
Trisomy 21
Trisomy 18
Trisomy 13
African
Caribbean
Chinese
Oriental
Asian
Bangladeshi
Indian
Pakistani
Smoking
uE3
18

hCG
Weight (kg)
hCGMoM
40 50 60 70 80 90 100 120 140
0.2
0.4
0.6
0.8
1.0
1.2
1.4
1.6
1.8
2.0
Gestation (days)
hCG
100 110 120 130 140 150
10
20
30
40
50 Wk 15 Wk 16 Wk 17 Wk 18 Wk 19 Wk 20
19

hCG
Effects on hCG
MoM hCG
0.1 0.5 1.0 1.5 2.0 3.0
Trisomy 21
Trisomy 18
Trisomy 13
African
Caribbean
Chinese
Asian
Indian
Pakistani
Smoking
20

Free β-hCG (T2)
Weight (kg)
FreebetahCGMoM
40 50 60 70 80 90 100 120 140
0.2
0.4
0.6
0.8
1.0
1.2
1.4
1.6
1.8
2.0
Gestation (days)
FreebetahCG
100 110 120 130 140 150
5
10
15
20
25
30 Wk 15 Wk 16 Wk 17 Wk 18 Wk 19 Wk 20
21

Free β-hCG (T2)
0.1 0.5 1.0 1.5 2.0 3.0
Trisomy 21
African
Caribbean
Black Other
Asian
Bangladeshi
Indian
Pakistani
Other Asian
Chinese
Oriental
Smoking
22

Gestation (days)
Inhibin
100 110 120 130 140 150
100
150
200
250
300
Weight (kg)
InhibinMoM
40 50 60 70 80 90 100 120 140
0.2
0.4
0.6
0.8
1.0
1.2
1.4
1.6
1.8
2.0
Inhibin
23

Effects on Inhibin
MoM Inhibin
0.1 0.5 1.0 1.5 2.0 3.0
Trisomy 21
Asian
Caribbean
Smoking
Inhibin
24

NT
Crown-rump length (mm)
Nuchaltranslucency(mm)
45 50 55 60 65 70 75 80 85
0.5
1
2
3
4
5
6
7
8

WHY : the effect of
errors on the
screening program

Standardisation
• MoM values should be centred on 1.0 when viewed
together, by gestation, by weight, by smoking status,
by ethnicity …
• What if this is not true?
28

Inputs and
parameter
estimates
Risk
DR/FPR/SPR
Process
Amplification of errors

Effects of bias – biochemistry
(NT and biochemistry at 12 weeks risk cut-off 1 in 150 at term)
A 27% increase in SPR with 70 more ‘positive’ results per 10,000
screening tests than expected.
PAPP-A hCG β
1 1 2.6% 85%
0.9 1 3.3% 87%
1 0.9 2.0% 83%
1.1 1 2.0% 83%
1 1.1 3.1% 86%
0.9 0.9 2.7% 85%
1.1 1.1 2.4% 84%
0.9 1.1 4.0% 88%
1.1 0.9 1.7% 81%
Median MoM
FPR (%) DR (%)

The importance
of crown rump
length

The (near) perfect world of biochemistry
Cyprus
Gestation (weeks)
PAPP-AMoM
7 8 9 10 11 12 13
0.8
0.9
1.0
1.1
1.2
1.3
1.4
1.5
n= 812
n= 4787 n= 4231
n= 1426
n= 311
n= 72
n= 2
Median Standard
The median MoM
value for any sub-
population defined by
time period, gestational
age, maternal weight,
smoking status and
ethnicity should lie
within 5% of the target
value of 1.
Median MoM by
gestation

Operator
hCGbetaMoM
###
###
###
###
###
###
###
###
###
###
###
###
###
###
###
###
###
###
###
###
###
0.8
1.0
1.2
n = 2 7
n = 2 9
n = 3 3n = 3 4
n = 3 5
n = 3 7
n = 3 8
n = 4 7
n = 6 6
n = 6 8
n = 7 0
n = 7 5
n = 7 7
n = 7 9
n = 8 0
n = 9 9
n = 1 0 4
n = 1 0 4
n = 1 0 9
n = 1 5 3
n = 1 8 6
OperatorPAPP-AMoM
###
###
###
###
###
###
###
###
###
###
###
###
###
###
###
###
###
###
###
###
###
0.8
1.0
1.2 n = 2 7
n = 2 9
n = 3 3
n = 3 4
n = 3 5
n = 3 7
n = 3 8
n = 4 7
n = 6 6
n = 6 8
n = 7 0
n = 7 5
n = 7 7
n = 7 9
n = 8 0
n = 9 9
n = 1 0 4
n = 1 0 4
n = 1 0 9
n = 1 5 3
n = 1 8 6
PAPP-AMoMhCGβMoM
Operator
Operator

Why operator effects on biochemistry?
• Causes include
– case mix
– sample preparation
– storage
– transportation
– CRL measurement

PAPP-A by gestation
Gestation (days)
PAPP-A
50 60 70 80 90 100
0.1
0.2
0.5
1.0
2.0
5.0
Wk 7 Wk 8 Wk 9 Wk 10 Wk 11 Wk 12 Wk 13

PAPP-A by gestation
Gestation (days)
PAPP-A
50 60 70 80 90 100
0.1
0.2
0.5
1.0
2.0
5.0
Wk 7 Wk 8 Wk 9 Wk 10 Wk 11 Wk 12 Wk 13

MoM = 1

PAPP-A by gestation
Gestation (days)
PAPP-A
50 60 70 80 90 100
0.1
0.2
0.5
1.0
2.0
5.0
Wk 7 Wk 8 Wk 9 Wk 10 Wk 11 Wk 12 Wk 13

MoM = 1

MoM = 0.57

Free β-hCG by gestation
Gestation (days)
hCGbeta
50 60 70 80 90 100
5
10
20
30
40
50
60
80
100
150
200
250
Wk 7 Wk 8 Wk 9 Wk 10 Wk 11 Wk 12 Wk 13

MoM = 1
MoM =1.2


Effects of Crown Rump Length (CRL) biases on
biochemistry MoM values
(NT and biochemistry at 12 weeks risk cut-off 1 in 150 at term)
CRL Error Error in GA Median MoM
(mm) (days) PAPP-A hCG beta DR FPR
-5 -2.7 1.17 0.93 80% 1.4%
-4 -2.2 1.13 0.94 81% 1.6%
-3 -1.6 1.10 0.96 82% 1.9%
-2 -1.1 1.06 0.97 83% 2.0%
-1 -0.5 1.03 0.99 84% 2.4%
0 0.0 1.00 1.00 85% 2.7%
1 0.5 0.97 1.01 86% 3.1%
2 1.0 0.94 1.03 86% 3.7%
3 1.6 0.92 1.04 87% 4.1%
4 2.1 0.89 1.06 88% 4.8%
5 2.6 0.87 1.07 89% 5.5%
Down’s syndrome presents as biochemical immaturity so effects of errors on PAPP-A
and free β-hCG combine.

45 50 55 60 65 70 75 80 85
0.5
1
2
3
4
5
6
7
8
Impact of NT on risks

Impact of NT on risks
45 50 55 60 65 70 75 80 85
0.5
1
2
3
4
5
6
7
8

DQASS
• The aim is to monitor and support the quality and
effectiveness of screening
• Provide feedback on all aspects of the test to laboratories,
ultrasound departments and commercial suppliers.
• Through meta-analyses DQASS provides information on
effects of factors such a smoking that can be used to
improve screening performance.

Report
production
Feedback
& advice
Improvements
Data
submissions
Lab reports ~40
per year
Cycle reports
A Two Day Workshop
Thursday 17 and Friday 18 January 2008
DQASS Workshop on
Standardisation, Monitoring and
Updating Medians: Why, When
and How?
Presented by:
Amy Baker
Barry Nix
Dave Worthington
Dave Wright
Workshops
Individualised feedback to
all sonographers on all
scan measurements
~20002
(from April 2010)
NuchalTranslucency(mm)
ID: 49057 (n = 184)
Cycle 5
From: 16/05/2008
To: 31/10/2008
40 45 50 55 60 65 70 75 80 85 90
0.0
0.5
1.0
1.5
2.0
2.5
3.0
3.5
4.0
68(37%)
116(63%)
Bias =0.08mm
4NTvalues greaterthan4mmshownas 4mm
ID: 49057 (n = 184)
Cycle 5
From: 16/05/2008
To: 31/10/2008
40 45 50 55 60 65 70 75 80 85 90
0.0
0.5
1.0
1.5
2.0
2.5
3.0
3.5
4.0
68(37%)
116(63%)
Bias =0.08mm
ID: 49057 (n = 184)
Cycle 5
From: 16/05/2008
To: 31/10/2008
40 45 50 55 60 65 70 75 80 85 90
0.0
0.5
1.0
1.5
2.0
2.5
3.0
3.5
4.0
68(37%)
116(63%)
Bias =0.08mm
ID: 49057 (n = 184)
Cycle 5
From: 16/05/2008
To: 31/10/2008
40 45 50 55 60 65 70 75 80 85 90
0.0
0.5
1.0
1.5
2.0
2.5
3.0
3.5
4.0
68(37%)
116(63%)
Bias =0.08mm
DQASS

DQASS diagnostics for
biochemistry
• MoM values should be centred on 1.0
when viewed together, by gestation,
by weight, by smoking status, by
ethnicity …
• Small deviations from this target can
have important implications for
screening

Gestational age
Gestation (weeks)
MoMPAPP-A
10 11 12 13 14
0.7
0.8
0.9
1.0
1.1
1.2
1.3
1.4
1.5
1.6
1.7
n= 28
n= 227
n= 1137
n= 3710 n= 2539
n= 11
Gestation (weeks)
MoMPAPP-A
10 11 12 13 14
0.7
0.8
0.9
1.0
1.1
1.2
1.3
1.4
1.5
1.6
1.7
n= 2066
n= 6793 n= 3234
n= 25
Cycle 2
Cycle 7
48

Maternal weight
Weight group
MoMFreebeta-hCG
<50kg
50-60kg
60-70kg
70-80kg
80-90kg
90-100kg
100-110kg
110-120kg
>120kg
0.7
0.8
0.9
1.0
1.1
1.2
1.3
n= 368
n= 1818 n= 2404
n= 1409
n= 706
n= 385
n= 170
n= 88
n= 46
Weight group
MoMFreebeta-hCG
<50kg
50-60kg
60-70kg
70-80kg
80-90kg
90-100kg
100-110kg
110-120kg
>120kg
0.7
0.8
0.9
1.0
1.1
1.2
1.3
1.4
1.5
n=638
n=3043
n=3870 n=2326 n=1211
n=614 n=273
n=136
n=88
Cycle 2
Cycle 7
49

Smoking status
Cycle 2
Cycle 7
Smoking status
MoMInhibin
No Yes
0.7
0.8
0.9
1.0
1.1
1.2
1.3
1.4
1.5
n= 4729
n= 1119
Smoking status
MoMInhibin
Non-Smoker Smoker
0.7
0.8
0.9
1.0
1.1
1.2
1.3
1.4
1.5
n= 2821
n= 563
50

Ethnicity
Cycle 2
Cycle 7
Ethnic origin
MoMPAPP-A
Caucasian
Afro-Caribbean
Asian
Mixed
Oriental
0.7
0.8
0.9
1.0
1.1
1.2
1.3
1.4
1.5
1.6
1.7
n= 7907
n= 2054
n= 563
n= 373
n= 176
Ethnic origin
MoMPAPP-A
Caucasian
Afro-Caribbean
Asian
Oriental
Other
0.7
0.8
0.9
1.0
1.1
1.2
1.3
1.4
1.5
n=7881
n=1979
n=1608 n=263
n=469
51

CUSUM
52
Time 1 2 3 4 5 6 7 8 9 10
Deviation from target 0 0 0 0 0.5 0.5 0.5 0.5 0.5 0.5
Cumulative sum 0 0 0 0 0.5 1 1.5 2 2.5 3
0
0.5
1
1.5
2
2.5
3
3.5
0 2 4 6 8 10 12
CUSUM
Time

Change points
A change of -10% was
introduced around the
middle of September.
This is detected
relatively quickly.
A change of -5% was
introduced around the
middle of September.
This takes longer to
detect.
53

CUSUM charts for detecting change
points

ID: 49057 (n = 184)
40 45 50 55 60 65 70 75 80 85 90
0.0
0.5
1.0
1.5
2.0
2.5
3.0
3.5
4.0
68 (37%)
116 (63%)
4 NTvalues greaterthan 4mmshownas 4mm
Expected relationship
with CRL
Expected degree of
scatter about the curve
DQASS Diagnostics: Nuchal Translucency

ID: Sample (n = 300)
Cycle
From: NA
To: NA
40 45 50 55 60 65 70 75 80 85 90
0.0
0.5
1.0
1.5
2.0
2.5
3.0
3.5
4.0
152 (51%)
148 (49%)
Bias = 0mm

Cycle
From: NA
To: NA
40 45 50 55 60 65 70 75 80 85 90
0.0
0.5
1.0
1.5
2.0
2.5
3.0
3.5
4.0
152 (51%)
148 (49%)
Bias = 0mm
Cycle
From: NA
To: NA
40 45 50 55 60 65 70 75 80 85 90
0.0
0.5
1.0
1.5
2.0
2.5
3.0
3.5
4.0
287 (96%)
13 (4%)
Bias = -0.58mm
Bias

Cycle
From: NA
To: NA
40 45 50 55 60 65 70 75 80 85 90
0.0
0.5
1.0
1.5
2.0
2.5
3.0
3.5
4.0
152 (51%)
148 (49%)
Bias = 0mm
Bias
Cycle
From: NA
To: NA
40 45 50 55 60 65 70 75 80 85 90
0.0
0.5
1.0
1.5
2.0
2.5
3.0
3.5
4.0
12 (4%)
288 (96%)
Bias = 0.55mm
1 NT value greater than 4mm shown as 4mm

0.0 0.1 0.2 0.3 0.4 0.5 0.6
020406080100
Bias
(mm)
Proportionoftests
10% of all scans,
bias of 0.60mm
Illustration (n = 4 sonographers)

0.0 0.1 0.2 0.3 0.4 0.5 0.6
Bias
(mm)
Proportionoftests
30% of all
scans, bias of
0.34mm
020406080100

0.0 0.1 0.2 0.3 0.4 0.5 0.6
020406080100
Bias
(mm)
Proportionoftests
Area = Average bias

0.0 0.1 0.2 0.3 0.4 0.5 0.6
Bias
(mm)
Proportionoftests
020406080100

0.0 0.1 0.2 0.3 0.4 0.5 0.6
020406080100
Bias
(mm)
Proportionoftests

Other outputs from DQASS
Parameter estimates for configuring
the screening program.
Example: Twin effect for Inhibin-A.
MoM
1.4 1.6 1.8 2 2.2 2.4 2.6 2.8 3 3.2 3.4
Cycle 18
Cycle 19
Pooled

Cycle
From: NA
To: NA
40 45 50 55 60 65 70 75 80 85 90
0.0
0.5
1.0
1.5
2.0
2.5
3.0
3.5
4.0
152 (51%)
148 (49%)
Bias = 0mm
Spread
Cycle
From: NA
To: NA
40 45 50 55 60 65 70 75 80 85 90
0.0
0.5
1.0
1.5
2.0
2.5
3.0
3.5
4.0
159(53%)
141(47%)
Bias =-0.01mm
Spreaddecreased: 0.43

Cycle
From: NA
To: NA
40 45 50 55 60 65 70 75 80 85 90
0.0
0.5
1.0
1.5
2.0
2.5
3.0
3.5
4.0
152 (51%)
148 (49%)
Bias = 0mm
Trend
Cycle
From: NA
To: NA
40 45 50 55 60 65 70 75 80 85 90
0.0
0.5
1.0
1.5
2.0
2.5
3.0
3.5
4.0
130(43%)
170(57%)
Bias =0.09mm
Trenddeviation

Cycle
From: NA
To: NA
40 45 50 55 60 65 70 75 80 85 90
0.0
0.5
1.0
1.5
2.0
2.5
3.0
3.5
4.0
152 (51%)
148 (49%)
Bias = 0mm
Trend
Cycle
From: NA
To: NA
40 45 50 55 60 65 70 75 80 85 90
0.0
0.5
1.0
1.5
2.0
2.5
3.0
3.5
4.0
168 (56%)
132 (44%)
Bias = -0.07mm
Trend deviation
1 NT value greater than 4mm shown as 4mm

Hospital Summary Report
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End of cycle reports
Cycle 14 report
April 2013 to September 2013

Cycle reports for biochemistry-
PAPP-A
Estimated proportion of median MoMs outside 5%
Best
Worst
DQASS 88
DQASS 99

Cycle reports for NT - National

Cycle reports for NT - Region x

Rationale
• Need for sufficient precision to estimate
performance (standardised SPR)
• To enable monitoring of laboratory
medians and early detection of change
points
• For proficiency/expertise

log(MoM)
-50
-40
-30
-20
-10
0
10
20
log(MoM)
-50
-40
-30
-20
-10
0
10
20
log(MoM)
-50
-40
-30
-20
-10
0
10
20
log(MoM)
-50
-40
-30
-20
-10
0
10
20
Sample
log(MoM)
-50
-40
-30
-20
-10
0
10
20
0 200 400 600 800 1000
Sample
log(MoM) -250
-200
-150
-100
-50
0
50
0 2500 5000
5 labs 1,000 samples
1 lab5,000 samples

DQASS
• Feedback and support to sonographers
laboratories, hospitals and suppliers
• Monitoring at the local and national level
• A national database: evidence on
screening parameters, effects of smoking
ethnicity etc

MONITORING PROGRESS
REGIONALLY AND
NATIONALLY

Cycle by cycle feedback to individual
laboratories
0
10
20
30
40
50
60
AFP hCG uE3 Inhibin
Estimatedproportion(%)ofMoMvalues
outside5%
Cycle 1 Cycle 2 Cycle 3

0.0 0.1 0.2 0.3 0.4 0.5 0.6 0.7
0
10
20
30
40
50
60
70
80
90
100
Bias (mm)
ProportionofWomenScreened
National
Cycle 8: Reference
Cycle 12:
Cycle 11:
Cycle 10:
Cycle 12:
1841 Sonographers
203601 Scans
1.24% < 25 scans
Cycle 11:
1759 Sonographers
188472 Scans
1.37% < 25 scans
Cycle 10:
1599 Sonographers
167944 Scans
1.91% < 25 scans
46.92% 42.38% 6.91% 3.79%
57.55% 38.40% 3.29% 0.77%
60.94% 36.39% 2.08% 0.59%
DQASS NT-QA

Highlights
• Consistency of provision
• Evidenced improvement is quality
• Improved outcomes

Consistent provision
March 2007: SPR 5.9% September 2012: SPR 2.5%
Combined
15%
Quadruple
9%
Triple
48%
Double
27%
Integrated
1%
Combined
Quadruple
Triple
Double
Integrated
Combined
80%
Quadruple
19%
Integrated
1%

Cycle Scans (000,s) Sonograhers (n) Green (%)
8 (Apr-Sep 2010) 102 884 35
9 128 1,160 39
10 168 1,599 47
11 188 1,759 58
12 (Apr-Sep 2012) 204 1,841 61
Improving Quality

0
10
20
30
40
50
60
70
80
90
100
8 9 10 11 12
Proportiongreen(%)
Cycle
Improving Quality
All
regions

What Next
• Choice of screening test
• Choice of risk cut-off
• QA of screening (what, why, how)
• DQASS Reports
• Monitoring program performance

CHOICE OF
SCREENING TEST
AND RISK CUT-OFF

Double Test: AFP + hCG
False Positive Rate (%)
DetectionRate(%)
0 2 4 6 8 10
020406080100
1 in 100
1 in 150
1 in 200
1 in 250

Double Test: AFP + free beta hCG
DetectionRate(%)
0 2 4 6 8 10
020406080100
1 in 100
1 in 150
1 in 200
1 in 250

Triple Test: AFP + hCG + uE3
DetectionRate(%)
0 2 4 6 8 10
020406080100
1 in 100
1 in 150
1 in 200
1 in 250

Triple Test: AFP + free beta hCG + uE3
DetectionRate(%)
0 2 4 6 8 10
020406080100
1 in 100
1 in 150
1 in 200
1 in 250

Combined Test: NT + free beta hCG + PAPP-A
Week 11
DetectionRate(%)
0 2 4 6 8 10
020406080100
1 in 100
1 in 150
1 in 200
1 in 250

Week 12
DetectionRate(%)
0 2 4 6 8 10
020406080100
1 in 100
1 in 150
1 in 200
1 in 250

Week 13
DetectionRate(%)
0 2 4 6 8 10
020406080100
1 in 100
1 in 150
1 in 200
1 in 250

Quad test (hCG)
DetectionRate(%)
0 2 4 6 8 10
020406080100
1 in 100
1 in 150
1 in 200
1 in 250

Quad test (free beta hCG)
DetectionRate(%)
0 2 4 6 8 10
020406080100
1 in 100
1 in 150
1 in 200
1 in 250

Integrated Test
Week 11
DetectionRate(%)
0 2 4 6 8 10
020406080100
1 in 100
1 in 150
1 in 200
1 in 250

Integrated Test
Week 12
DetectionRate(%)
0 2 4 6 8 10
020406080100
1 in 100
1 in 150
1 in 200
1 in 250

Integrated Test
Week 13
DetectionRate(%)
0 2 4 6 8 10
020406080100
1 in 100
1 in 150
1 in 200
1 in 250

QA OF SCREENING
WHAT, WHY, HOW

Overview
• What
– Quick overview of first and second trimester
screening
• Why
– The effects of errors from different sources
• How
– The DQASS process

DQASS
A service, funded by the NHS, to
support the improvement of quality
and effectiveness of prenatal
screening in the UK
Based in Plymouth, Devon
Louise Armitage
Amy Baker
Andy Baker*
Nathan Eastwood*
Barry Nix
Paul Newell*
Dave Worthington
Dave Wright
Jade

Report
production
FeedbackImprovements
Data
submissions
Quality Assurance Support Service
People (2.8 full time equivalents):
Louise Armitage (admin)
Amy Baker
Andy Bailey
Paul Newell
Dave Wright
Dave Worthington (Biochemist)
Barry Nix (Statistician)
Statisticians
DQASS
Cycle 1 Cycle 2 Cycle 3 Cycle 4 Cycle 5 Cycle 6 Cycle 7 Cycle 8 Cycle 9
Oct-06 Mar 07 Apr 07 Sep-07 Oct-07 Mar-08 Apr 08 Sep-08 Oct-08 Mar-09 Apr 09Sep-09 Oct-09 Mar-10 Apr 10 Sep-10 Oct-10 Mar-11

20082011
PND
type
Number
2003/2004
Number
2004/2005
Number
2005/2006
Number
2006/2007
Number
2007/2008
Number
2008/2009
Number
2009/2010
Amnio
28,700 24,349 22,625 14,733 12,932 12,145 9,894
CVS 8,268 7,980 7,819 4, 781 4,681 3,520 3,701
*TOTA
L
36,968 32,329 30,444 19,514 17,613 15,665 13,595
Total screening tests
PND as % of screening tests
Total births
Percentage acceptance
365,775
4.81%
409,346
3.83%
427,527
3.18%
690,721 708, 711 706,248
52.95% 57.76% 60.53%
Improved Outcomes: Invasive Tests

0 1000 2000 3000 4000 5000
-100-50050
Sample
log(MoM)

Second trimester triple and
quadruple test

AFP
Weight (kg)
AFPMoM
40 50 60 70 80 90 100 120 140
0.2
0.4
0.6
0.8
1.0
1.2
1.4
1.6
1.8
2.0
Gestation (days)
AFP
100 110 120 130 140 150
20
30
40
50
60
70
80 Wk 15 Wk 16 Wk 17 Wk 18 Wk 19 Wk 20
123

AFP
Effects on AFP
MoM AFP
0.1 0.5 1.0 1.5 2.0 3.0
Trisomy 21
Trisomy 18
Trisomy 13
African
Caribbean
Chinese
Oriental
Asian
Bangladeshi
Indian
Pakistani
Smoking
124

uE3
Weight (kg)
uE3MoM
40 50 60 70 80 90 110 130 150
0.2
0.4
0.6
0.8
1.0
1.2
1.4
1.6
1.8
2.0
Gestation (days)
uE3
100 110 120 130 140 150
1
2
3
4
5
6
7
8
10
15
20 Wk 15 Wk 16 Wk 17 Wk 18 Wk 19 Wk 20
125

Effects on uE3
MoM uE3
0.1 0.5 1.0 1.5 2.0 3.0
Trisomy 21
Trisomy 18
Trisomy 13
African
Caribbean
Chinese
Oriental
Asian
Bangladeshi
Indian
Pakistani
Smoking
uE3
126

hCG
Weight (kg)
hCGMoM
40 50 60 70 80 90 100 120 140
0.2
0.4
0.6
0.8
1.0
1.2
1.4
1.6
1.8
2.0
Gestation (days)
hCG
100 110 120 130 140 150
10
20
30
40
50 Wk 15 Wk 16 Wk 17 Wk 18 Wk 19 Wk 20
127

hCG
Effects on hCG
MoM hCG
0.1 0.5 1.0 1.5 2.0 3.0
Trisomy 21
Trisomy 18
Trisomy 13
African
Caribbean
Chinese
Asian
Indian
Pakistani
Smoking
128

Free β-hCG (T2)
Weight (kg)
FreebetahCGMoM
40 50 60 70 80 90 100 120 140
0.2
0.4
0.6
0.8
1.0
1.2
1.4
1.6
1.8
2.0
Gestation (days)
FreebetahCG
100 110 120 130 140 150
5
10
15
20
25
30 Wk 15 Wk 16 Wk 17 Wk 18 Wk 19 Wk 20
129

Free β-hCG (T2)
0.1 0.5 1.0 1.5 2.0 3.0
Trisomy 21
African
Caribbean
Black Other
Asian
Bangladeshi
Indian
Pakistani
Other Asian
Chinese
Oriental
Smoking
130

Gestation (days)
Inhibin
100 110 120 130 140 150
100
150
200
250
300
Weight (kg)
InhibinMoM
40 50 60 70 80 90 100 120 140
0.2
0.4
0.6
0.8
1.0
1.2
1.4
1.6
1.8
2.0
Inhibin
131

Effects on Inhibin
MoM Inhibin
0.1 0.5 1.0 1.5 2.0 3.0
Trisomy 21
Asian
Caribbean
Smoking
Inhibin
132

The (near) perfect world of biochemistry
Cyprus
Gestation (weeks)
PAPP-AMoM
7 8 9 10 11 12 13
0.8
0.9
1.0
1.1
1.2
1.3
1.4
1.5
n= 812
n= 4787 n= 4231
n= 1426
n= 311
n= 72
n
Median Standard
The median MoM value
for any sub-population
defined by time period,
gestational age, maternal
weight, smoking status
and ethnicity should lie
within 5% of the target
value of 1.
Median MoM by gestation

Communication with sonographers
DQASS
Screening support
sonographers (165)
Sonographers (1,950)
Sonographer reports
Hospital reports
Cycle reports
Regional reports
Training
Regional meeting
Annual meetings

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