Summary of findings 2. Performance of other first and second trimester serum strategies with or without ultrasound.
| Test | Studies | Women (cases) | Sensitivity* (95% CI) | Specificity* (95% CI) | Threshold |
| Without maternal age and ultrasound | |||||
| Single tests | |||||
| ADAM 12 second trimester to first trimester ratio | 1 | 579 (17) | 53 (28, 77) | 95 (93, 97) | 5% FPR |
| With maternal age and without ultrasound | |||||
| Triple tests | |||||
| First trimester PAPP‐A and second trimester total hCG and AFP | 1 | 1188 (98) | 83 (74, 90) | 95 (93, 96) | 5% FPR |
| First trimester PAPP‐A and second trimester free ßhCG and AFP | 2 | 2197 (94) | 83 to 85 | 94 to 95 | 5% FPR, 1:300 risk |
| Quadruple tests | |||||
| First trimester PAPP‐A and second trimester free ßhCG, uE3 and AFP | 1 | 1188 (98) | 86 (77, 92) | 95 (93, 96) | 5% FPR |
| Quintuple tests | |||||
| First trimester PAPP‐A and second trimester free ßhCG, uE3, AFP and inhibin A | 1 | 1188 (98) | 90 (82, 95) | 95 (93, 96) | 5% FPR |
| First trimester PAPP‐A and second trimester total hCG, uE3, AFP and PAPP‐A | 2 | 707 (121) | 78 (66, 86) | 98 (96, 99) | 1:200 risk |
| First trimester PAPP‐A and total hCG, and second trimester total hCG, uE3 and AFP | 2 | 707 (121) | 80 (68, 88) | 97 (94, 98) | 1:200 risk |
| First trimester PAPP‐A and uE3, and second trimester total hCG, uE3 and AFP | 2 | 707 (121) | 80 (68, 88) | 96 (93, 98) | 1:200 risk |
| Sextuple tests | |||||
| First trimester AFP, free ßhCG and uE3, and second trimester total hCG, uE3 and AFP | 1 | 12,339 (34) | 82 (65, 93) | 94 (93, 94) | 1:250 risk |
| First trimester PAPP‐A and second trimester total hCG, uE3, AFP, inhibin A and PAPP‐A | 1 | 540 (32) | 84 (67, 95) | 96 (94, 98) | 1:250 risk |
| Septuple tests | |||||
| First trimester PAPP‐A, total hCG and uE3, and second trimester total hCG, uE3, AFP and PAPP‐A | 2 | 707 (121) | 49 (36, 61) | 98 (96, 99) | 1:200 risk |
| With maternal age and ultrasound | |||||
| Triple tests | |||||
| First trimester NT and second trimester free ßhCG and AFP | 2 | 6616 (105) | 83 (70, 91) | 95 | 5% FPR |
| Quadruple tests | |||||
| First trimester NT and second trimester free ßhCG, uE3 and AFP | 1 | 1110 (85) | 88 (79, 94) | 95 (94, 96) | 5% FPR |
| First trimester NT and PAPP‐A, and second trimester total hCG and AFP | 1 | 1110 (85) | 91 (82, 96) | 95 (94, 96) | 5% FPR |
| First trimester NT and PAPP‐A, and second trimester free ßhCG and AFP | 2 | 3400 (93) | 88 to 91 | 95 to 98 | 5% FPR, 1:300 risk |
| Quintuple tests | |||||
| First trimester NT and second trimester total hCG, uE3, AFP and inhibin A | 1 | 1110 (85) | 91 (82, 96) | 95 (94, 96) | 5% FPR |
| First trimester NT and second trimester free ßhCG, uE3, AFP and inhibin A | 1 | 1110 (85) | 91 (82, 96) | 95 (94, 96) | 5% FPR |
| First trimester NT and PAPP‐A, and second trimester free ßhCG, uE3 and AFP | 1 | 1100 (85) | 92 (84, 97) | 95 (94, 96) | 5% FPR |
| First trimester NT and PAPP‐A, and second trimester total hCG, uE3 and AFP | 2 | 33,337 (171) | 88 to 92 | 95 to 97 | 5% FPR, 1:200 risk |
| Sextuple tests | |||||
| First trimester NT, PAPP‐A and free ßhCG, and second trimester total hCG, uE3 and AFP | 1 | 5060 (13) | 100 (75, 100) | 97 (96, 97) | 1:250 risk |
| Septuple tests | |||||
| First trimester NT, PAPP‐A and free ßhCG, and second trimester uE3, AFP, total hCG and inhibin A | 1 | 33,546 (87) | 94 (87, 98) | 89 (89, 89) | 1:150 risk |
| Contingent tests | |||||
| First trimester NT, PAPP‐A and free ßhCG, if risk 1:30‐1:1500, second trimester total hCG, uE3, AFP and inhibin A | 1 | 32,355 (86) | 91 (82, 96) | 95 (95, 96) | 1:270 risk |
| First trimester NT, PAPP‐A and free ßhCG, if risk 1:30‐1:1500, second trimester free ßhCG, uE3, AFP and inhibin A | 1 | 7842 (59) | 95 (86, 99) | 95 (94, 95) | 5% FPR |
| Stepwise tests | |||||
| First trimester NT and PAPP‐A, if risk < 1:100, second trimester free ßhCG, uE3 and AFP | 1 | 1507 (12) | 92 (62, 100) | 97 [(96, 98) | 1:250 risk |
| First trimester NT, PAPP‐A and free ßhCG, if risk < 1:30, second trimester total hCG, uE3, AFP and inhibin A | 1 | 32,355 (86) | 92 (84, 97) | 95 (95, 95) | 1:270 risk |
| First trimester NT, PAPP‐A and free ßhCG, if risk < 1:30, second trimester free ßhCG, uE3, AFP and 2T inhibin A | 1 | 7842 (59) | 97 (88, 100) | 95 (94, 95) | 5% FPR |
*Tests evaluated by at least one study are presented in the table. Where there were two studies at the same threshold, estimates of summary sensitivity and summary specificity were obtained by using univariate fixed‐effect logistic regression models to pool sensitivities and specificities separately. if the threshold used was a 5% FPR, then only the sensitivities were pooled. The range of sensitivities and specificities are presented where there were two studies and the thresholds used were different.
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