Summary of findings 2. Performance of other first trimester serum test strategies with or without maternal age.
| Test strategy | Studies | Women (cases) | Sensitivity (95% CI) | Specificity (95% CI) | Threshold |
| Without maternal age | |||||
| Single tests | |||||
| AFP | 2 | 2248 (104) | 10 (4 to 21) | 95 | 5% FPR |
| ADAM 12 | 1 | 579 (17) | 41 (18 to 67) | 95 (93 to 97) | 5% FPR |
| Free ßhCG to AFP ratio | 1 | 476 (9) | 11 (0 to 48) | 98 (96 to 99) | 0.25 MoM |
| Inhibin | 3 | 2098 (184) | 19 (4 to 58) | 95 | 5% FPR |
| PlGF | 1 | 699 (90) | 28 (19 to 38) | 95 (93 to 97) | 5% FPR |
| Total hCG | 3 | 2098 (184) | 19 (4 to 58) | 95 | 5% FPR |
| SP1 | 3 | 1080 (53) | 32 (1 to 96) | 95 | 5% FPR |
| uE3 | 1 | 1110 (85) | 13 (7 to 22) | 95 (94 to 96) | 5% FPR |
| Double tests | |||||
| Free ßhCG and AFP | 1 | 1138 (19) | 16 (3 to 40) | 95 (94 to 96) | 5% FPR |
| Free ßhCG and Inhibin | 1 | 876 (76) | 30 (20 to 42) | 95 (93 to 96) | 5% FPR |
| PAPP‐A and free ßhCG | 2 | 795 (106) | 64 (50 to 76) | 95 | 5% FPR |
| Triple tests | |||||
| Total hCG, free αhCG and progesterone | 1 | 129 (17) | 53 (28 to 77) | 96 (90 to 99) | 0.34 MoM |
| With maternal age | |||||
| Single tests | |||||
| ADAM 12 | 2 | 703 (46) | 67 (46 to 83) | 91 (87 to 94) | 1:400 risk |
| AFP | 2 | 1397 (126) | 33 (23 to 46) | 95 | 5% FPR |
| Free αhCG | 1 | 512 (12) | 25 (5 to 57) | 89 (86 to 91) | 1:384 risk |
| GHBP | 1 | 335 (74) | 27 (17 to 39) | 95 (91 to 97) | 1:250 risk |
| hPL | 1 | 183 (47) | 45 (30 to 60) | 93 (88 to 97) | 1:250 risk |
| Inhibin | 1 | 1110 (85) | 32 (22 to 43) | 95 (94 to 96) | 5% FPR |
| ITA | 1 | 278 (54) | 48 (34 to 62) | 95 (91 to 98) | 5% FPR |
| PGH | 1 | 335 (74) | 41 (29 to 53) | 94 (91 to 97) | 1:250 risk |
| PlGF | 1 | 699 (90) | 43 (33 to 54) | 95 (93 to 97) | 5% FPR |
| ProMBP | 1 | 181 (25) | 36 (18 to 57) | 94 (89 to 97) | 1:250 risk |
| SP1 | 2 | 804 (29) | 38 (22 to 56) | 95 | 5% FPR |
| Total hCG | 1 | 512 (12) | 33 (10 to 65) | 94 (92 to 96) | 1:384 risk |
| uE3 | 1 | 512 (12) | 33 (10 to 65) | 86 (83 to 89) | 1:384 risk |
| Double tests | |||||
| ADAM 12 and PAPP‐A | 1 | 691 (46) | 61 (45 to 75) | 95 (93 to 97) | 5% FPR |
| AFP and free αhCG | 1 | 512 (12) | 33 (10 to 65) | 87 (83 to 89) | 1:384 risk |
| AFP and total hCG | 1 | 512 (12) | 33 (10 to 65) | 93 (90 to 95) | 1:384 risk |
| AFP and uE3 | 1 | 512 (12) | 42 (15 to 72) | 87 (84 to 90) | 1:384 risk |
| Free ßhCG and free αhCG | 1 | 512 (12) | 42 (15 to 72) | 94 (91 to 96) | 1:384 risk |
| Free ßhCG and Inhibin | 1 | 1110 (85) | 44 (33 to 55) | 95 (94 to 96) | 5% FPR |
| Free ßhCG and total hCG | 1 | 512 (12) | 25 (5 to 57) | 93 (90 to 95) | 1:384 risk |
| Free ßhCG and uE3 | 1 | 287 (41) | 61 (45 to 76) | 95 (92 to 97) | 5% FPR |
| GHBP and free ßhCG | 1 | 335 (74) | 61 (49 to 72) | 92 (88 to 95) | 1:250 risk |
| GHBP and PAPP‐A | 1 | 335 (74) | 66 (54 to 77) | 93 (89 to 96) | 1:250 risk |
| GHBP and PGH | 1 | 335 (74) | 47 (36 to 59) | 93 (90 to 96) | 1:250 risk |
| hPL and free ßhCG | 1 | 183 (47) | 68 (53 to 81) | 94 (89 to 97) | 1:250 risk |
| hPL and PAPP‐A | 1 | 183 (47) | 55 (40 to 70) | 94 (89 to 97) | 1:250 risk |
| PAPP‐A and AFP | 2 | 2705 (116) | 63 (50 to 74) | 95 | 5% FPR |
| PAPP‐A and Inhibin | 1 | 1110 (85) | 68 (57 to 78) | 95 (94 to 96) | 5% FPR |
| PAPP‐A and ITA | 2 | 622 (78) | 62 (46 to 75) | 95 | 5% FPR |
| PGH and free ßhCG | 1 | 335 (74) | 64 (52 to 74) | 93 (89 to 96) | 1:250 risk |
| PGH and PAPP‐A | 1 | 335 (74) | 65 (53 to 76) | 93 (89 to 96) | 1:250 risk |
| Total hCG and free αhCG | 1 | 512 (12) | 42 (15 to 72) | 92 (89 to 94) | 1:384 risk |
| Total hCG and Inhibin | 1 | 1110 (85) | 34 (24 to 45) | 95 (94 to 96) | 5% FPR |
| Total hCG and PAPP‐A | 2 | 4327 (133) | 66 (54 to 76) | 95 | 5% FPR |
| Total hCG and uE3 | 1 | 512 (12) | 42 (15 to 72) | 92 (89 to 94) | 1:384 risk |
| uE3 and free αhCG | 1 | 512 (12) | 33 (10 to 65) | 89 (86 to 91) | 1:384 risk |
| Triple tests | |||||
| AFP, free αhCG and uE3 | 1 | 512 (12) | 58 (28 to 85) | 82 (79 to 85) | 1:384 risk |
| Free ßhCG, AFP and uE3 | 1 | 287 (41) | 66 (49 to 80) | 95 (92 to 97) | 5% FPR |
| GHBP, PAPP‐A and free ßhCG | 1 | 335 (74) | 76 (64 to 85) | 94 (91 to 97) | 1:250 risk |
| PAPP‐A, total hCG and Inhibin | 1 | 1110 (85) | 69 (58 to 79) | 95 (94 to 96) | 5% FPR |
| PGH, PAPP‐A and free ßhCG | 1 | 335 (74) | 76 (64 to 85) | 94 (91 to 97) | 1:250 risk |
| Total hCG, AFP and uE3 | 1 | 512 (12) | 42 (15 to 72) | 91 (88 to 94) | 1:384 risk |
| Quadruple tests | |||||
| Free ßhCG, total hCG, AFP and uE3 | 1 | 512 (12) | 50 (21 to 79) | 92 (89 to 94) | 1:384 risk |
| Total hCG, AFP, uE3 and free αhCG | 1 | 512 (12) | 50 (21 to 79) | 90 (87 to 92) | 1:384 risk |
| Quintuple tests | |||||
| Free ßhCG, total hCG, AFP, uE3 and free αhCG | 1 | 512 (12) | 33 (10 to 65) | 90 (87 to 92) | 1:384 risk |
AFP: alpha‐fetoprotein; αhCG: alpha human chorionic gonadotrophin; ßhCG: beta human chorionic gonadotrophin; CI: confidence interval; FPR: false positive rate; GHBP: growth hormone binding protein; hCG: human chorionic gonadotrophin; hPL: human placental lactogen; ITA: invasive trophoblast antigen; PAPP‐A: pregnancy‐associated plasma protein A; PGH: placental growth hormone; PIGF: placental growth factor; PROMBP: proform of eosinophil major basic protein; SPI: Schwangerschafts protein 1; uE3: unconjugated oestriol