Summary of findings 1. Performance of the six most evaluated first and second trimester serum test strategies with or without ultrasound.

Test strategy (with maternal age)	Studies	Women (cases)	Sensitivity (95% CI) at a 5% FPR	Test*
First trimester PAPP‐A and second trimester total hCG, uE3 and AFP	4	2474 (236)	85 (78, 89)	P = 0.014
First trimester PAPP‐A and second trimester total hCG, uE3, AFP and inhibin A	3	35,361 (217)	87 (81, 91)
First trimester NT and second trimester total hCG and AFP	4	22,793 (135)	85 (77, 91)
First trimester NT and second trimester total hCG, uE3 and AFP	4	13,708 (136)	86 (78, 92)
First trimester NT and PAPP‐A, and second trimester total hCG, uE3, AFP and inhibin A	3	39,670 (184)	95 (90, 97)
First trimester NT and PAPP‐A, and second trimester free ßhCG, uE3, AFP and inhibin A	4	40,348 (266)	92 (88, 95)

*Likelihood ratio test for the difference in accuracy between the six test strategies compared in a single meta‐analytic model

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