Prenatal Screening Quality Assurance Report · BPD Y 1 600 89.5 HC N 0 0.0 LMP N 0 0.0 Maternal weight at test date Y 1 777 99.4 Smoking status (dose if possible, otherwise Y/N) Y

Date: Page 1 of 24 BovenMaas0.0 – March 2011

Prenatal Screening Quality Assurance Report

Laboratory code: BovenMaas 0.0

Report date: March 2011

Andrew Bailey, Paul Newell, and Dave Wright CHES, Tamar Science Park, 1 Davy Road, Derriford, Plymouth, Devon, PL6 8BX

01752 764437 [email protected]

mailto:[email protected]


Summary: BovenMaas0.0 December 2009 – December 2010

Software: ViewPoint (Medians from LifeCycle) Test: First trimester combined test; NT, PAPP-A & Free β-hCG Reagents/equipment: Delfia Xpress

First trimester: Number of pregnancies covered in dataset: 1 788 Number of pregnancies with a risk given:1 1 787 Estimated annual number of pregnancies screened 1 699 Modelled screening performance2 DR 85% FPR 2.6% SPR 2.7% Actual age-standardised lab screening performance3 SPR 2.4%

Data ♦ Maternal weight 99.4%

♦ Gestational age 99.7%

♦ Ultrasound measurements 100%

♦ Smoking status 99.4%

♦ Ethnicity 99.3%

IDDM 0%

Sonographer 100%

♦

Ultrasound measurements

Agreement CRL (100%)

♦ Within 1 day 51%

♦ Within 2 days 75.9%

Within 5 days 99.3%

♦

Algorithm parameters used Risk algorithm parameters have not been provided.

♦

1 Pregnancies for which no risk is given are excluded from all subsequent analyses.

2 This is the modelled performance using MoM values under perfect model assumptions for a cut-off of 1 in 150, based on the

maternal age distribution for England and Wales 2000 – 2002 using FMF parameter estimates. 3 This is the laboratory age-standardised screen positive rate for a cut-off of 1 in 150 in the first trimester and 1 in 200 in the

second trimester, based on the maternal age distribution for England and Wales 2000 – 2002.


Summary: BovenMaas0.0 December 2009 – December 2010

First trimester marker performance

NT: comparison with FMF reference Of the sonographers performing 25 or more scans there the bias is well within the 0.1mm limits. There is little evidence of sonographer effects. The data on NT measurements were exceptionally good.

♦

PAPP-A MoM The estimated median MoM varies from being within 5% of the target to 12%below target.

Recommendations

Updated regression models should be established to remove the trends with gestational age and maternal weight (page 17) so that median MoM levels are at the target level for all gestations and maternal weights.

Adjustments for ethnicity and smoking effects (page 18) should be updated so that median MoM levels by ethnicity and smoking status are on target.

♦

Free β-hCG MoM The estimated median MoM values are within 5% of target for June, August and September. For the remainder of the year they vary from 6% to 15% above target.

Recommendations

A factor update should be applied to remove the general bias seen in the diagnostics on page 19. This should be based on the most recent data for the most recent reagent lot.

Adjustments for smoking effects (page 21) should be updated so that median MoM levels by smoking status are on target.

♦


Previous performance comparison

Comments: No previous data for comparison.


Contents Summary: BovenMaas0.0 ............................................................................................................ 2 Summary: BovenMaas0.0 ............................................................................................................ 3

Previous performance comparison .............................................................................................. 4 Data file ........................................................................................................................................ 6 First trimester screen positive rates ............................................................................................. 7 First trimester maternal age distribution ....................................................................................... 7 Modelled screening performance by maternal age ...................................................................... 8

Modelled screening performance overall ..................................................................................... 8 Maternal weight distribution ......................................................................................................... 9 Gestational age distribution .......................................................................................................... 9

Smoking status .......................................................................................................................... 10 Ethnic origin ............................................................................................................................... 10 Ultrasound dating ....................................................................................................................... 11 NT and CRL measurement characteristics ................................................................................ 12 Sonographer effects ................................................................................................................... 13

Laboratory PAPP-A MoM values: temporal trends ..................................................................... 16 Laboratory PAPP-A MoM values: by gestational week .............................................................. 17 Laboratory PAPP-A MoM values: by maternal weight group ..................................................... 17 Laboratory PAPP-A MoM values: by smoking status ................................................................. 18

Laboratory PAPP-A MoM values: by ethnic status ..................................................................... 18 Laboratory Free β-hCG (T1) MoM values: temporal trends ....................................................... 19

Laboratory Free β-hCG (T1) MoM values: by gestational week ................................................. 20

Laboratory Free β-hCG (T1) MoM values: by maternal weight group ........................................ 20

Laboratory Free β-hCG (T1) MoM values: by smoking status ................................................... 21 Laboratory Free β-hCG (T1) MoM values: by ethnic status ....................................................... 21

Parameter estimates for log MoM values ................................................................................... 22 Standard deviations ................................................................................................................... 23 Correlations ................................................................................................................................ 24


Data file

Data field Supplied

(Y/N)

Number of records received

Percentage of records received

Pseudo-patient ID Y 1 787 100.0

Maternal date of birth Y 1 787 100.0

Scan date Y 1 787 100.0

Sonographer ID Y 1 787 100.0

Test date, first trimester Y 1 782 99.7

Test date, second trimester N 0 0.0

Maternal age at expected date of delivery Y 1 787 100.0

Gestational age (days) at test date, first trimester Y 1 782 99.7

Gestational age (days) at test date, second trimester N 0 0.0

CRL Y 1 787 100.0

BPD Y 1 600 89.5

HC N 0 0.0

LMP N 0 0.0

Maternal weight at test date Y 1 777 99.4

Smoking status (dose if possible, otherwise Y/N) Y 1 777 99.4

Ethnicity Y 1 774 99.3

Previous Down's pregnancy Y 1 0.1

Outcome data Y 8 0.5

NT Y 1 787 100.0

PAPP-A Y 1 703 95.3

Free β-hCG, first trimester Y 1 703 95.3

AFP N 0 0.0

uE3 N 0 0.0

ThCG N 0 0.0

Free β-hCG, second trimester N 0 0.0

Inhibin N 0 0.0

MoM NT N 0 0.0

MoM PAPP-A Y 1 781 99.7

MoM Free β-hCG, first trimester Y 1 781 99.7

MoM AFP N 0 0.0

MoM uE3 N 0 0.0

MoM ThCG N 0 0.0

MoM Free β-hCG, second trimester N 0 0.0

MoM Inhibin N 0 0.0

Calculated risk Y 1 787 100.0

Calculated prior age risk Y 1 787 100.0

IDDM N 0 0.0

Twins Y 1 787 100.0


First trimester screen positive rates

First trimester maternal age distribution

The reference maternal age distribution shown in blue is the maternal age distribution for England and Wales for the three years from 2000 to 2002.

Comments: The laboratory maternal age distribution is older than the reference population; this is likely to be because of differences between to the countries. The standardised SPR is therefore lower than the crude SPR.


Modelled screening performance by maternal age

Maternal Age

First trimester4 Second trimester

5

FPR (%) DR (%) FPR (%) DR (%)

20 and under 1.1 73 1.8 55

21 1.1 73 1.8 56

22 1.1 73 1.8 56

23 1.2 73 1.9 56

24 1.2 74 1.9 57

25 1.2 74 2 57

26 1.3 75 2.1 58

27 1.4 75 2.3 59

28 1.5 76 2.5 61

29 1.6 77 2.8 62

30 1.8 78 3.2 64

31 2 79 3.6 66

32 2.3 80 4.2 68

33 2.7 82 5.1 71

34 3.2 83 6.1 74

35 3.8 85 7.5 77

36 4.6 86 9.2 80

37 5.6 88 11.3 83

38 7 89 13.9 85

39 8.7 91 16.9 88

40 10.8 92 20.5 90

41 13.3 93 24.6 92

42 16.4 95 29.3 94

43 20.2 96 34.4 95

44 24.6 96 40 97

45 29.6 97 45.8 98

Modelled screening performance overall

Detection rate False positive rate

Laboratory maternal age distribution

First trimester 86% 3.6%

Second trimester 76% 4.6%

4 This is the modelled performance using MoM values under perfect model assumptions for a cut-off of 1 in 150, based on the

maternal age distribution for England and Wales 2000 – 2002 using FMF parameter estimates. 5 This is the modelled performance using MoM values under perfect model assumptions for a cut-off of 1 in 200, based on the

maternal age distribution for England and Wales 2000 – 2002 using SURUSS parameter estimates, unless local parameters provided.


Maternal weight distribution

The red dashed line indicates the mean maternal weight.

Gestational age distribution

The red dashed line indicates the mean gestational age. First trimester

Comments:


Smoking status

Ethnic origin

Comments: The ethnic categories only show the first name from each group given in the data file.


Ultrasound dating

Ultrasound scanning Count Percent

CRL 1 787 100.0

Head circumference 0 0.0

CRL and head circumference 0 0.0

Total pregnancies dated by USS 1 787 100.0

Gestational ages given 1 782 99.7

Dated by CRL

Gestation obtained from CRL using Robinson & Fleming’s formula,

CRLdaysGA 037.1052.873.23)( , agrees to within 1 day for 51% of records.

Lines indicate agreement within 1, 2 and 5 days.


NT and CRL measurement characteristics

Histogram of NT (mm).

Scatter plot of NT by CRL, with FMF reference curve shown in red.

Comments:

The NT measurements evenly distributed around the FMF reference curve.


Median deviation (mm) from FMF reference by month with 95% confidence intervals

Sonographer effects

Median NT by sonographer† with 95% confidence intervals.

Comments:


Median CRL by sonographer † with 95% confidence intervals.

Estimated bias relative to FMF reference curve with 95% confidence intervals.

Comments: Of the sonographers performing 25 or more scans there the bias is well within the 0.1mm limits.


Number of scans by sonographer.

Number of scans Number (%) of sonographers

≥100 5 (71.4)

50-99 1 (14.3)

25-49 0 (0)

1-24 1 (14.3)

Total 7

BovenMaas prenataal

Sonographer ID

Number of scans

Median CRL

Median NT

Bias* Spread† Trend‡

♦ 35782 595 60.9 1.6 -0.01

♦ 19349 408 60.6 1.6 -0.02

♦ 19468 280 58.2 1.7 0.06

♦ 42364 233 60.5 1.7 -0.01

♦ 19498 206 58.6 1.6 0.04

♦ 70202 51 61.3 1.7 0.05

◊ 19450 12 61.2 1.5 -0.38

1. These flags are based on statistical summaries from the NT & CRL measurements supplied. They do not provide any assurance of the quality of the images on which the results are based nor on the positioning of callipers. 2. These diagnostics should be read in conjunction with the individual sonographer outputs (which are also available as a pdf file). ◊ The minimum required 25 paired measurements have not been provided in this QA cycle and a flag cannot be assigned * The bias above is the median deviation from the FMF reference curve. † A flag appears in this column if there is evidence of increased spread in NT measurements. ‡ A flag appears in this column if there is evidence of a difference in trend (slope) relative to the FMF reference.

Comments: Of the sonographers performing 25 or more scans all have been given green flags for being within the 0.1mm limits.


Laboratory PAPP-A MoM values: temporal trends

Estimated monthly median MoMs with 95% confidence intervals.

CUSUM chart with 20 simulated series (blue).

Comments: Throughout the year, the estimated median MoM vary from within the 5% target to around 12% from target for April and May.


Laboratory PAPP-A MoM values: by gestational week

Estimated medians with 95% confidence intervals.

Laboratory PAPP-A MoM values: by maternal weight group


Comments: There is clear evidence of a non-linear trend with gestational age. The estimated median MoM at 11 weeks is around 15% below target. There is some evidence of an increasing trend with maternal weight.


Laboratory PAPP-A MoM values: by smoking status


Laboratory PAPP-A MoM values: by ethnic status


Comments: There is evidence that adjustments for smoking and ethnicity are not suitable for the screened population.


Laboratory Free β-hCG (T1) MoM values: temporal trends

Estimated monthly median MoMs with 95% confidence intervals.

CUSUM chart with 20 simulated series (blue).

Comments: The estimated median MoM values are within 5% of target for June, August and September. For the remainder of the year they vary from 6% to 15% above target.


Laboratory Free β-hCG (T1) MoM values: by gestational week


Laboratory Free β-hCG (T1) MoM values: by maternal weight group


Comments: The estimated median MoM values show the general tendency for MoM values to be above target. There is little evidence of any substantive trend with gestation or with maternal weight.


Laboratory Free β-hCG (T1) MoM values: by smoking status


Laboratory Free β-hCG (T1) MoM values: by ethnic status


Comments: There is evidence that the adjustments for smoking status are not suitable for the screened population.


Parameter estimates for log MoM values

First trimester parameter estimates

Correlation

Standard deviation NT PAPP-A Free β-hCG

NT * * * *

PAPP-A 0.2401 1 0.2495

(n = 1401) (n = 1400)

Free β-hCG 0.2636 1

(n = 1403)


Standard deviations

PAPP-A

Free β-hCG

The red dashed lines represent the reference value.


Correlations

PAPP-A, Free β-hCG

The red dashed lines represent the reference value.

Documents

Prenatal Screening Quality Assurance Report · BPD Y 1 600 89.5 HC N 0 0.0 LMP N 0 0.0 Maternal weight at test date Y 1 777 99.4 Smoking status (dose if possible, otherwise Y/N) Y