Epidemiological Monitoring and

Quality Control of Nuchal Translucency

Jack Canick

Intensive Course on Screening for Down’s SyndromeWolfson Institute of Preventive Medicine

London

May 2013

BROWNWomen & Infants’

NT Training Programs

Fetal Medicine Foundation

Less formalized systems

Overview

Epidemiological monitoring is the study of the measurements made on the population being tested

Application of serum marker experience to nuchal translucency monitoring

Examples of monitoring activities for nuchal translucency

New sonographer data

The Level of Maternal Serum AFP Increases

with Increasing Gestation

Palomaki GE, unpublished data

log-linear increaseslope = +15% per week

Nuchal Translucency Thickness Increases

with Increasing Gestation

Schuchter et al, Prenat Diagn 1998; 18: 281-4

log-linear increase

slope = +20% per week

MS AFP (MoM)

NT (MoM)

NT

AFPSD of log MoM = 0.15

SD of log MoM = 0.10

The Distribution of AFP and NT MoM

in Unaffected Pregnancies

Why is NT such a good marker?

0.2 0.5 1 2 5 10NT (MoM)

0.2 0.5 1 2 5 10hCG (MoM)

unaffected

unaffected DS

DS

NT: 0.11 SD50% DR 1% FPR

hCG: 0.24 SD

50% DR 8% FPR

NT parameters that are monitored:

Rate of increase with CRL log-linear over 10,3 - 13,6 weeksshould go up by ~ 20% per week

Median calculated MoM values should be stable at 1.0 MoM

SD of the distribution calculated SD of the log MoM values expected to be about 0.1

Nuchal Translucency (NT)Epidemiological monitoring

NT medians by CRL: All Centers

NT change with gestation

NT medians by CRL: All Centers

median MoM

Distribution width

Epidemiologic Monitoring of Nuchal Translucency: Monthly Medians - A

Epidemiologic Monitoring of Nuchal Translucency:Monthly Medians - B

NT data monitoring

Use objective criteria as guide

Partially subjective process Look for trends Sample volume must be considered What to do with very small volume sonographers?

Sonographer feedback has been minimally useful

Getting started:Newly trained sonographers

Provide paired CRL and NT measurements to the laboratory

If more than one sonographer within a center, identify each person within the database

Expect data to conform to parameters defined in literature

New sonographer A

30 40 50 60 70 80

1

NT

(m

m)

CRL (mm)

Reference (slope +20% per week)New sonographer A

+14%

CRL (mm)

30 40 50 60 70 80

NT

(m

m)

1

Sonographer variation:New sonographer B

Reference (slope +20% per week)New sonographer B

+48%

Reference (slope +20% per week)New sonographer C

CRL (mm)

30 40 50 60 70 80

NT

(m

m)

1

3

Sonographer challenges:New sonographer C

?

Reference (slope +20% per week)New sonographer B

Schielen PC et al., Prenat Diagn 2006;26:711-8

Published Literature:Variation in NT median measurement

FMF-certified centers

Non-FMF certified

Crossley JA et al. BJOG 2002;109:667-76.

Inter-operator variation at one hospital

Range of NT measurements (in MoM) between hospitals

Published Literature:Variation in NT median measurement

0.3

3.0

NT

(m

m)

10 11 12 13 14G.A. (week)

0.6

0.9

1.2

1.5

1.8

2.1

2.72.4

NT Epidemiologic MonitoringNT Medians (mm) at 15 FASTER Centers

NT Epidemiologic MonitoringImpact of Using A Single Population Median

risk: 1 in 230

Center A is routinely high: result 1.3mm median 0.8mm

Center B is routinely average: result 0.8mm median 0.8mm

Center C is routinely low: result 0.6mm median 0.8mm

= = 1.67 MoM

= = 0.75 MoM

= = 1.00 MoM

Example of a 30 year old who has the most typical result at 12 wks

risk: 1 in 2400

risk: 1 in 3500

Patient-specific risk varies 15 fold.

0.3

3.0

NT

(m

m)

10 11 12 13 14G.A. (week)

0.6

0.9

1.2

1.5

1.82.1

2.72.4

14

NT Epidemiologic MonitoringImpact of Using Center-Specific Medians

Patient-specific risk is the same at each center.

Center A is routinely high: result 1.3mm median 1.3mm

Center B is routinely average: result 0.8mm median 0.8mm

Center C is routinely low: result 0.6mm median 0.6mm

= = 1.00 MoM

= = 1.00 MoM

= = 1.00 MoM

Example of a 30 year old who has the most typical result at 12 wks

risk: 1 in 2400

risk: 1 in 2400

risk: 1 in 2400

0.3

3.0

NT

(m

m)

10 11 12 13G.A. (week)

0.6

0.9

1.2

1.5

1.82.1

2.72.4

Palomaki GE et al. Genet Med 2008;10(2):131-138