1. Conceptual & technical advances in Down’s syndrome screening Howard Cuckle h.s.cuckle@leeds.ac.uk

3. Unaffected Affected Marker level 100 1100.5550 0.1

4. 100 1100.5550 0.1 Separation or Inter-mean SDs Marker level

5. 0.06 1160.25464 Unaffected Spina bifida Anencephaly AFP (MoM) UK Collaborative AFP Study, 1977

6. Separation (SD's) Anen- cephaly Spina bifida

7. Separation (SD's) 10 14 11 12

8. 152025303540455055 Maternal age Down's syndrome Unaffected 35

9. Unaffected Affected 100 1100.5550 0.1 Likelihood ratio Marker level

10. Separation (SD's) 10 14 11 12    

11. 7891011121314151617181920 Gestational age  AFP, uE 3, freeß & inhibin

12. Detection rate 5% false-positives1% false-positives  

13. Separation (SD's) 10 14 11 12   

14. 7891011121314151617181920 Gestational age  PAPP-A & freeß NT

15. Detection rate 5% false-positives1% false-positives    

16. 7891011121314151617181920 Gestational age PAPP-A & hCG NT 

17. Detection rate 5% false-positives1% false-positives    

18. Non-viable Insignificant1 in 100,0001 in 10,0001 in 1,0001 in 1001 in 10Certain Down's syndrome Unaffected

19.  34 studies 2,400k women 9 studies 77k women 

21. Separation (SD's) 10 14 11 12       

22. 7891011121314151617181920 Gestational age PAPP-A alone  AFP, uE 3, freeß & inhibin

23. Detection rate 5% false-positives1% false-positives      

24. 7891011121314151617181920 Gestational age PAPP-A & freeß AFP, uE 3, freeß & inhibin  

25. Detection rate 5% false-positives1% false-positives        

26. 7891011121314151617181920 Gestational age    PAPP-A & freeß AFP, uE 3, freeß & inhibin  

27. Detection rate 5% false-positives1% false-positives          

28.    FaSTER Malone et al, 2005

29. Separation (SD's) 10 14 11 12

30. 7891011121314151617181920 Gestational age NF & NBL

31. Detection rate 5% false-positives1% false-positives    

32. Even more contingent strategies are coming your way soon

33. 7891011121314151617181920 Gestational age    PAPP-A & freeß

34. Detection rate 5% false-positives1% false-positives      

35. 7891011121314151617181920 Gestational age DV & TR NT, NB & FMF

36. Detection rate 5% false-positives1% false-positives    

37. 7891011121314151617181920 Gestational age  NT   DV & TR NB & FMF

38.  Fetal Medicine Foundation Nicolaides et al, 2005 

39. Separation (SD's) 8-9 14 10 11-3

40. 7891011121314151617181920 Gestational age PAPP-A & ADAM12 free ß-hCG

41. Detection rate 5% false-positives1% false-positives    

42. 7891011121314151617181920 Gestational age   PAPP-A & ADAM12 free ß-hCG 

43. Detection rate 5% false-positives1% false-positives      

44. 7891011121314151617181920 Gestational age  NF & NBL  

45. Detection rate 5% false-positives1% false-positives        

46. Separation (SD's) Gestation (weeks)

47. Separation (SD's) Gestation (weeks) Mrs B Mrs A

48. 0.01 100.110.050.55 0.1 1 0.5 5 10 Down’s syndromeUnaffected pregnancies 10 weeks PAPP-A (MoM) 17 weeks PAPP-A (MoM)

49. 0.01 100.110.050.55 0.1 1 0.5 5 10 10 weeks PAPP-A (MoM) 17 weeks PAPP-A (MoM)

50. Single gene Heart NTD Aneuploidy

51. Detection rate 5% false-positives10% false-positives