3. Comparison of integrated, contingent and stepwise strategy for a septuple combination of serum tests and first trimester nuchal translucency.

Test combination	Screening policy	Study	Women (cases)	Sensitivity (95% CI)	Specificity (95% CI)	Threshold
First trimester NT, PAPP‐A and free ßhCG, and second trimester uE3, AFP, total hCG and inhibin A	Integrated	Malone 2005	33,546 (87)	94 (87, 98)	89 (89, 89)	1:150 risk
First trimester NT, PAPP‐A and free ßhCG, if risk <1:30 invasive testing is offered, if risk 1:30‐1:1500, second trimester total hCG, uE3, AFP and inhibin A is performed	Contingent	Cuckle 2008	32,355 (86)	91 (82, 96)	95 (95, 96)	1:270 risk
First trimester NT, PAPP‐A and free ßhCG, if risk <1:30 invasive testing is offered, if ≥ 1:30 second trimester total hCG, uE3, AFP and inhibin A is performed	Stepwise	Cuckle 2008	32,355 (86)	92 (84, 97)	95 (95, 95)	1:270 risk

AFP = alpha‐fetoprotein; ßhCG = beta human chorionic gonadotrophin; FPR = false positive rate; hCG = human chorionic gonadotrophin; NT = nuchal translucency; PAPP‐A = pregnancy‐associated plasma protein‐A; uE3 = unconjugated oestriol.

CI ‐ confidence interval.