1. Epidemiological Monitoring and Quality Control of Nuchal Translucency Jack Canick Intensive Course on Screening for Down’s Syndrome Wolfson Institute of Preventive Medicine London May 2013 BROWN Women & Infants ’

2. NT Training Programs Fetal Medicine Foundation Less formalized systems

3. 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

4. The Level of Maternal Serum AFP Increases with Increasing Gestation Palomaki GE, unpublished data log-linear increase slope = +15% per week

5. Nuchal Translucency Thickness Increases with Increasing Gestation Schuchter et al, Prenat Diagn 1998; 18: 281-4 log-linear increase slope = +20% per week

6. MS AFP (MoM) NT (MoM) NT AFP SD of log MoM = 0.15 SD of log MoM = 0.10 The Distribution of AFP and NT MoM in Unaffected Pregnancies

7. Why is NT such a good marker? 0.20.512510 NT (MoM) 0.20.512510 hCG (MoM) unaffected DS NT: 0.11 SD 50% DR 1% FPR hCG: 0.24 SD 50% DR 8% FPR

8. NT parameters that are monitored: Rate of increase with CRLlog-linear over 10,3 - 13,6 weeks should go up by ~ 20% per week Mediancalculated MoM values should be stable at 1.0 MoM SD of the distributioncalculated SD of the log MoM values expected to be about 0.1 Nuchal Translucency (NT) Epidemiological monitoring

9. NT medians by CRL: All Centers NT change with gestation

10. NT medians by CRL: All Centers median MoM Distribution width

11. Epidemiologic Monitoring of Nuchal Translucency: Monthly Medians - A

12. Epidemiologic Monitoring of Nuchal Translucency: Monthly Medians - B

13. 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

14. 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

15. New sonographer A 304050607080 1 NT (mm) CRL (mm) Reference (slope +20% per week) New sonographer A +14%

16. Sonographer variation: New sonographer B Reference (slope +20% per week) New sonographer B +48%

17. Reference (slope +20% per week) New sonographer C CRL (mm) 304050607080 NT (mm) 1 3 Sonographer challenges: New sonographer C ? Reference (slope +20% per week) New sonographer B

18. Schielen PC et al., Prenat Diagn 2006;26:711-8 Published Literature: Variation in NT median measurement FMF-certified centers Non-FMF certified

19. 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

21. NT Epidemiologic Monitoring Impact 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.

22. 14 NT Epidemiologic Monitoring Impact 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 = = Example of a 30 year old who has the most typical result at 12 wks risk: 1 in 2400

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