Summary of findings 2. Performance of other first trimester ultrasound markers alone or in combination with first trimester serum tests.
| Test strategy | Studies | Women (Down's cases) | Sensitivity* (95% CI) | Specificity* (95% CI) | Threshold |
| Without maternal age | |||||
| Ultrasound markers alone | |||||
| Aberrant right subclavian artery | 1 | 425 (51) | 8 (2, 19) | 99 (98, 100) | Feature |
| Frontomaxillary facial angle | 1 | 242 (22) | 18 (5, 40) | 98 (95, 99) | > 95th percentile |
| Presence of mitral gap | 1 | 217 (20) | 20 (6, 44) | 87 (81, 91) | Feature |
| Maxillary bone length | 1 | 927 (88) | 24 (15, 34) | 95 (93, 96) | 5th centile |
| Tricuspid regurgitation | 1 | 312 (20) | 50 (27, 73) | 98 (96, 99) | Feature |
| Iliac angle 90 degrees | 1 | 2032 (52) | 60 (45, 73) | 98 (97, 98) | Feature |
| Ductus venosus a‐wave reversed | 1 | 378 (72) | 68 (56, 79) | 70 (64, 75) | Feature |
| Ductus venosus pulsivity index | 1 | 378 (72) | 81 (70, 89) | 58 (52, 63) | > 95th percentile |
| NT and nasal bone | 1 | 486 (38) | 89 (75, 97) | 93 (91, 95) | Absent nasal bone and NT ≥ 95th centile |
| Ultrasound and double serum markers | |||||
| NT, free ßhCG and PAPP‐A | 1 | 6508 (40) | 90 (76, 97) | 95 (95, 96) | First trimester incidence rate 63.3% |
| With maternal age | |||||
| Ultrasound markers alone | |||||
| NT‐adjusted risk > 1:300 and abnormal ductus venosus flow and absent nasal bones | 1 | 544 (47) | 21 (11, 36) | 100 (99, 100) | 1:300 risk |
| NT and ductus | 3 | 23,697 (177) | 76 to 93 | 73 to 99 | 5% FPR, 1:250 risk, feature |
| NT and tricuspid blood flow | 1 | 19,736 (122) | 85 (78, 91) | 97 (97, 98) | 1:100 risk |
| Ultrasound and single serum markers | |||||
| NT and inhibin A | 2 | 1150 (97) | 61 to 75 | 95 to 96 | 5% FPR, 1:250 risk |
| NT and AFP | 1 | 1110 (85) | 61 (50, 72) | 95 (94, 96) | 5% FPR |
| NT and total hCG | 1 | 1110 (85) | 61 (50, 72) | 95 (94, 96) | 5% FPR |
| NT and ITA | 1 | 278 (54) | 80 (66, 89) | 95 (91, 98) | 5% FPR |
| Ultrasound and double serum markers | |||||
| NT, AFP and free ßhCG | 2 | 2766 (90) | 66 to 100 | 93 to 95 | 5% FPR, 1:250 risk |
| NT, PAPP‐A and inhibin A | 2 | 1150 (97) | 80 to 83 | 95 to 96 | 5% FPR, 1:250 risk |
| NT, total hCG and inhibin A | 1 | 1110 (85) | 62 (51, 73) | 95 (94, 96) | 5% FPR |
| NT, free ßhCG and inhibin A | 1 | 1110 (85) | 66 (55, 76) | 95 (94, 96) | 5% FPR |
| NT, free ßhCG and ADAM 12 | 1 | 351 (31) | 68 (49, 83) | 95 (92, 97) | 5% FPR |
| NT, PAPP‐A and uE3 | 1 | 576 (24) | 79 (58, 93) | 95 (93, 97) | 5% FPR |
| NT, total hCG and PAPP‐A | 1 | 1110 (85) | 80 (70, 88) | 95 (94, 96) | 5% FPR |
| NT, AFP and PAPP‐A | 1 | 1110 (85) | 80 (70, 88) | 95 (94, 96) | 5% FPR |
| NT, PAPP‐A and ITA | 2 | 11,053 (77) | 83 (73, 90) | 95 | 5% FPR |
| NT, PAPP‐A and ADAM 12 | 2 | 1042 (77) | 83 (73, 90) | 95 | 5% FPR |
| Free ßhCG and PAPP‐A, if risk between 1:42 and 1:1000 (intermediate risk), NToffered, final composite risk !:250 | 1 | 10,189 (44) | 89 (75, 96) | 94 (94, 95) | 1:250 risk |
| NT, ductus, free ßhCG and PAPP‐A | 3 | 30,061 (212) | 83 to 96 | 97 to 99 | 1:100 risk, 1:250 risk |
| NT, nasal bone, free ßhCG and PAPP‐A | 3 | 41,842 (271) | 89 to 94 | 95 to 98 | 5% FPR, 1:100 risk, 1:300 risk |
| NT, PAPP‐A, free ßhCG and ductus venosus pulsivity index | 1 | 7,250 (66) | 89 (79, 96) | 95 (94, 95) | 5% FPR |
| NT, tricuspid blood flow, free ßhCG and PAPP‐A | 1 | 19,736 (122) | 91 (84, 95) | 97 (97, 98) | 1:100 risk |
| NT, fetal heart rate, free ßhCG and PAPP‐A | 2 | 76,385 (517) | 92 (89, 94) | 95 | 5% FPR |
| NT, fetal heart rate, nasal bone, free ßhCG and PAPP‐A | 1 | 19,736 (122) | 95 (90, 98) | 96 (95, 96) | 1:200 risk |
| NT, fetal heart rate, tricuspid blood flow, free ßhCG and PAPP‐A | 1 | 19,736 (122) | 96 (91, 99) | 95 (95, 95) | 5% FPR |
| NT, fetal heart rate, ductus, free ßhCG and PAPP‐A | 1 | 19,614 (122) | 97 (92, 99) | 95 (95, 95) | 5% FPR |
| Ultrasound and triple serum markers | |||||
| NT, AFP, free ßhCG and PAPP‐A | 3 | 6789 (135) | 73 to 84 | 95 | 5% FPR, 1:250 risk |
| NT, PAPP‐A, free ßhCG and PP13 | 1 | 998 (151) | 77 (69, 83) | 95 (93, 96) | 5% FPR |
| NT, PAPP‐A, free ßhCG and total hCG | 1 | 998 (151) | 77 (69, 83) | 95 (93, 96) | 5% FPR |
| NT, total hCG, inhibin A and PAPP‐A | 1 | 1110 (85) | 81 (71, 89) | 95 (94, 96) | 5% FPR |
| NT, free ßhCG, inhibin A and PAPP‐A | 1 | 1110 (85) | 84 (74, 91) | 95 (94, 96) | 5% FPR |
| NT, PAPP‐A, free ßhCG and PGH | 1 | 335 (74) | 86 (77, 93) | 95 (92, 97) | 5% FPR |
| NT, PAPP‐A, free ßhCG and PIGF | 2 | 1443 (221) | 88 (70, 95) | 95 | 5% FPR |
| NT, PAPP‐A, free ßhCG and GHBP | 1 | 335 (74) | 91 (81, 96) | 95 (92, 97) | 5% FPR |
| Ultrasound and quadruple serum markers | |||||
| NT, PAPP‐A, free ßhCG, ADAM 12 and PlGF | 1 | 998 (151) | 79 (72, 86) | 95 (93, 96) | 5% FPR |
| Ultrasound and quintuple serum markers | |||||
| NT, PAPP‐A, free ßhCG, ADAM 12, total hCG and PlGF | 1 | 998 (151) | 79 (72, 86) | 95 (93, 96) | 5% FPR |
| NT, total hCG, inhibin A, PAPP‐A, AFP and uE3 | 1 | 1110 (85) | 84 (74, 91) | 95 (94, 96) | 5% FPR |
| NT, free ßhCG, inhibin A, PAPP‐A, AFP and uE3 | 1 | 1110 (85) | 86 (77, 92) | 95 (94, 96) | 5% FPR |
| Ultrasound and sextuple serum markers | |||||
| NT, PAPP‐A, free ßhCG, ADAM 12, total hCG, PlGF and PP13 | 1 | 998 (151) | 80 (73, 86) | 95 (93, 96) | 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 meta‐analysis was not performed because there were only two or three studies and no common threshold.