Summary of findings 4. Accuracy of first‐ and second‐trimester ultrasound in detecting anomalies of individual organ systems and 46 selected structural anomalies.
| Accuracy of first‐ and second‐trimester ultrasound in detecting anomalies of individual organ systems and 46 selected structural anomalies | |||||||||
| Two‐stage screening approach | Single‐stage screening approach | ||||||||
| First‐trimester scan (detection < 14 weeks' gestation) |
First + second‐trimester scan (total detection < 24 weeks' gestation) |
Single second‐trimester scan (detection < 24 weeks' gestation) |
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| Studies | Fetuses (cases) | Sensitivity (95% CI) |
Studies | Fetuses (cases) |
Sensitivity (95% CI) |
Studies | Fetuses (cases) |
Sensitivity (95% CI) |
|
| Central nervous system | |||||||||
| Overall (any type) | 23 | 260,409 (843) | 56.6 (47.6 to 65.2) | 19 | 240,786 (779) | 92.9 (85.9 to 96.6) | 10 | 159,170 (663) | 77.5 (65.5 to 86.2) |
| Anencephaly | 30 | 548,041 (445) | 99.5 (90.9 to 100) | 24 | 317,464 (312) | N/A* Range: 0.0 (Taipale 2004) to 100 (remaining 23 studies) |
23 | 1,284,752 (716) |
95.6 (90.6 to 98.0) |
| Spina bifida | 23 | 480,116 (286) | 35.1 (22.0 to 51.1) | 18 | 252,802 (147) | 97.9 (90.0 to 99.6) | 25 | 1,897,018 (946) | 76.3 (65.7 to 84.4) |
| Holoprosencephaly | 15 | 270,372 (99) | 92.4 (71.6 to 98.3) | 11 | 229,181 (90) | N/A* Range: 100 to 100 |
3 | 162,338 (13) | N/A* Range: 77.8 to 100 |
| Hydrocephalus | 14 | 253,796 (99) | 4.2 (0.7 to 21.3) | 10 | 218,872 (81) | 75.4 (53.4 to 89.2) | 8 | 61,812 (154) | 76.0 (45.0 to 92.5) |
| Encephalocele | 15 | 390,064 (84) | 96.3 (62.8 to 99.8) | 12 | 189,661 (47) | N/A* Range: 94.7 to 100 | 5 | 168,263 (37) | 81.8 (49.7 to 95.4) |
| Respiratory | |||||||||
| Overall (any type) | 13 | 239,670 (158) | 14.6 (9.7 to 21.6) | 10 | 222,798 (146) | 83.8 (72.2 to 91.2) | 8 | 157,767 (63) | 83.8 (67.1 to 92.9) |
| CDH | 17 | 2,106,233 (520) |
22.2 (10.1 to 42.2) | 13 | 2,071,309 (513) |
75.8 (44.7 to 92.4) | 9 | 689,973 (243) | 62.9 (56.7 to 68.7) |
| CPAM | 7 | 207,768 (66) | 1.4 (0.1 to 15.6) | 5 | 195,687 (63) | N/A* Range: 92.9 to 100 |
7 | 352,922 (42) | N/A* Range: 50.0 to 100 |
| Cardiac | |||||||||
| Overall (any type) | 28 | 2,719,925 (1543) | 36.7 (27.7 to 46.6) | 24 | 254,349 (1433) | 81.5 (69.8 to 89.4) | 17 | 800,716 (6917) | 33.8 (24.7 to 44.2) |
| Septal defecta | 34 | 301,645 (476) | 32.7 (20.5 to 47.9) | 28 | 275,487 (453) | 73.3 (50.7 to 87.9) | 11 | 1,056,215 (671) | 36.7 (16.0 to 63.9) |
| Valvular anomaly (biventricular heart)b | 17 | 247,073 (99) | 26.8 (11.6 to 50.5) | 14 | 229,673 (85) | 99.7 (10.5 to 100) | 10 | 1,056,169 (173) | 38.6 (30.8 to 47.0) |
| Venous return anomalyc | 6 | 74,351 (27) | N/A*
Range: 0.0 to 100;
0.0 (Becker 2012; Kenkhuis 2018); 57.1 to 100 (remaining 4 studies) |
4 | 66,388 (25) | N/A* Range: 0.0 to 100; 0.0 (Becker 2012; Kenkhuis 2018); 85.7 to 100 (Gireada 2022; Liao 2021) | 2 | 723,265 (49) | N/A* Range: 25.0 (Ingale 2017) to 33.3 (van Velzen 2016) |
| Aortic arch anomalyd | 18 | 242,677 (185) | 24.8 (16.1 to 36.2) | 13 | 219,782 (167) | 69.4 (38.8 to 89.1) | 8 | 1,047,246 (263) |
31.6 (26.1 to 37.6) |
| Conotruncal anomalye | 31 | 291,090 (284) | 34.5 (21.1 to 50.9) | 25 | 264,931 (255) | 90.0 (76.5 to 96.2) | 12 | 1,066,551 (606) | 66.4 (38.8 to 86.1) |
| HRHSf | 7 | 86,642 (25) | 92.7 (0.0 to 100) | 5 | 72,992 (23) | N/A* Range: 0.0 to 100; 0.0 (Gireada 2022); 100 (remaining 4 studies) | 5 | 1,009,708 (40) | 55.7 (35.3 to 74.4) |
| HLHSg | 24 | 260,805 (155) | 79.0 (45.2 to 94.5) | 21 | 247,473 (147) | 98.2 (75.8 to 99.9) | 12 | 1,579,434 (392) | 87.5 (79.1 to 92.8) |
| Other single ventricle defectsh | 14 | 242,246 (67) | 100 (58.8 to 100) | 12 | 232,136 (63) | N/A* Range: 0 (Hernadi 1997) to 100 (remaining 11 studies) | 7 | 1,328,100 (255) |
85.6 (79.6 to 90.1) |
| Complex defects with atrial isomerismi | 10 | 207,098 (28) | N/A* Range: 0.0 to 100; 0.0 (Vellamkondu 2017); 57.1 to 100 (remaining 9 studies) | 8 | 203,174 (26) | N/A* Range: 91.7 to 100 | 4 | 1,011,866 (130) | 75.1 (62.0 to 84.7) |
| Miscellaneous major cardiac defectsj | 18 | 249,653 (166) | 20.1 (2.1 to 75.1) | 12 | 212,983 (74) | 87.9 (69.6 to 95.8) | 10 | 1,391,739 (978) | 38.8 (23.3 to 56.9) |
| Minor cardiac defectsk | 11 | 89,679 (198) | 9.7 (2.9 to 27.8) | 10 | 87,776 (181) | 83.8 (52.8 to 96.0) | 3 | 24,043 (78) | N/A* Range: 0 to 4.2 |
| Thoracic and abdominal wall | |||||||||
| Overall (any type) | 17 | 251,923 (358) | 95.6 (89.1 to 98.3) | 14 | 235,051 (335) | 99.0 (87.3 to 99.9) | 7 | 58,014 (31) | 90.8 (54.7 to 98.8) |
| Gastroschisis | 17 | 276,233 (99) | 100 (74.8 to 100) | 13 | 241,309 (91) | 100 (99.1 to 100) | 10 | 811,149 (368) | N/A* Range: 0.0 to 100; 0.0 (Ingale 2017); 93.5 to 100 (remaining 9 studies) |
| Omphalocele | 23 | 288,522 (273) | 98.0 (90.4 to 99.6) | 18 | 250,335 (247) | 99.2 (98.5 to 99.6) | 9 | 827,508 (330) | N/A* Range: 79.3 to 100 |
| Gastrointestinal | |||||||||
| Overall (any type) | 13 | 238,447 (155) | 8.3 (4.9 to 13.8) | 10 | 221,575 (138) | 46.5 (39.0 to 54.1) | 9 | 157,923 (197) | 33.3 (14.8 to 59.0) |
| Oesophageal atresia | 8 | 202,606 (26) | N/A* Range: 0.0 to 50.0; 0.0 (7 studies); 50.0 (Iliescu 2013) | 5 | 170,904 (18) | N/A* Range: 0.0 to 50.0; 0.0 to 0.25 (4 studies); 50.0 (Syngelaki 2019) | 6 | 63,913 (19) |
N/A* Range: 0.0 to 100; 0.0 to 16.7 (5 studies); 100 (Drukker 2020) |
| Duodenal atresia | 7 | 202,562 (23) | N/A* Range: 0.0 to 12.5 | 5 | 194,508 (21) | 98.2 (0.0 to 100) | 6 | 47,284 (45) | 52.3 (18.2 to 84.4) |
| Small bowel obstruction | 3 | 165,978 (18) | N/A* Range: 0.0 to 0.0 | 2 | 147,926 (12) | N/A* Range: 0.0 (Syngelaki 2019) to 33.3 (Liao 2021) | 2 | 19,528 (3) | N/A* Range: 0.0 (Rydberg 2017) to 50.0 (Jacobsen 2011) |
| Urinary tract | |||||||||
| Overall (any type) | 19 | 253,523 (906) | 23.5 (17.0 to 31.6) | 16 | 236,649 (843) | 87.1 (67.9 to 95.6) | 9 | 158,415 (972) | 60.6 (30.9 to 84.0) |
| Renal agenesis | 15 | 210,855 (46) | N/A*
Range: 0.0 to 100;
0.0 (10 studies); 15.3 to 50.0 (4 studies); 100 (Sainz 2020) |
11 | 175,931 (39) | 90.3 (45.5 to 99.1) | 8 | 72,038 (31) | N/A* Range: 66.7 (Drukker 2020) to 100 (7 remaining studies) |
|
7 | 74,458 (17) | N/A* Range: 0.0 (6 studies) to 100 (Brown 2021) | 5 | 62,377 (15) | 73.4 (38.0 to 92.5) | 4 | 35,300 (16) | N/A* Range: 50.0 (Drukker 2020) to 100 (remaining 3 studies) |
|
12 | 203,506 (30) | 16.6 (6.5 to 36.2) | 8 | 168,582 (24) | 100 (57.8 to 100) | 9 | 698,237 (103) | 91.4 (68.9 to 98.1) |
| MCDK | 15 | 238,157 (129) | 6.8 (0.0 to 36.2) | 13 | 230,144 (124) | 80.3 (54.5 to 93.3) | 5 | 38,486 (39) | 82.1 (34.1 to 97.6) |
|
6 | 153,637 (79) | N/A* Range: 0.0 (5 studies) to 100 (Whitlow 1999) | 5 | 148,846 (78) | 88.4 (79.6 to 93.7) | 0 | ‐ | ‐ |
|
5 | 149,834 (10) | N/A* Range: 0.0 to 0.0 | 4 | 145,044 (9) | N/A* Range: 100 to 100 | 0 | ‐ | ‐ |
| Other renal dysplasias | 12 | 252,838 (87) | 16.2 (9.9 to 25.4) | 10 | 225,927 (77) | N/A* Range: 78.6 to 100 | 4 | 34,481 (18) | 71.7 (16.9 to 96.9) |
|
1 | 13,639 (2) | N/A* Range: 0.0 to 0.0 (Grande 2012) | 1 | 13,639 (2) | N/A* Range: 100 to 100 (Grande 2012) | 2 | 23,216 (11) | N/A* Range: 20.0 (Hildebrand 2010) to 100 (Jacobsen 2011) |
|
8 | 222,602 (40) | 22.4 (11.5 to 39.3) | 8 | 222,602 (40) | N/A* Range: 78.6 to 100 | 2 | 10,121 (2) | N/A* Range: 100 to 100 (Johnson 1997; Leiroz 2021) |
| Upper urinary tract obstruction | 17 | 268,687 (225) | 0.9 (0.0 to 10.8) | 13 | 233.763 (188) | 68.2 (38.7 to 87.9) | 5 | 40,990 (85) | 33.9 (2.3 to 91.8) |
| Lower urinary tract obstruction | 18 | 262,135 (167) | 94.0 (82.6 to 98.1) | 16 | 250,018 (157) | 99.0 (70.0 to 100) | 7 | 194,823 (27) | N/A* Range: 83.3 to 100 |
| Genital | |||||||||
| Overall (any type) | 8 | 177,556 (145) | N/A* Range: 0.0 to 0.0 | 6 | 169,543 (137) | NA* Range: 0.0 to 8.1 | 6 | 149,642 (107) | N/A* Range: 0.0 to 33.3; 0.0 to 3.0 (5 studies); 33.3 (Chen 2009) |
| Ambiguous genitalia | 2 | 99,504 (6) | N/A* Range: 0.0 to 0.0 (Iliescu 2013; Syngelaki 2019) | 1 | 94,713 (5) | N/A* Range: 80.0 to 80.0 (Syngelaki 2019) | 1 | 13,516 (1) | N/A* Range: 0.0 to 0.0 (Drukker 2020) |
| Musculoskeletal | |||||||||
| Overall (any type) | 21 | 257,229 (696) | 25.4 (18.2 to 34.3) | 18 | 240,357 (635) | 77.5 (59.9 to 88.8) | 10 | 158,988 (536) | 43.8 (29.3 to 59.5) |
| Skeletal dysplasias | 16 | 269,236 (83) | 54.1 (39.9 to 67.7) | 14 | 246,393 (77) | N/A* Range: 50.0 to 100 | 8 | 670,352 (102) | NA* Range: 0.0 to 100; 0.0 (Jacobsen 2011); 50.0 to 100 (remaining 7 studies) |
|
10 | 229,873 (32) | 56.5 (30.7 to 79.2) | 9 | 224,819 (30) | N/A* Range: 100 to 100 | 4 | 189,617 (26) | N/A* Range: 75.0 to 100 |
|
7 | 146,455 (26) | 37.2 (9.8 to 76.3) | 5 | 123,612 (20) | N/A* Range: 0.0 to 100; 0 (Taipale 2004); 50.0 to 100 (remaining 4 studies) | 4 | 40,383 (9) |
N/A* Range: 0.0 to 66.7; 0.0 to 25.0 (3 studies); 66.7 (Stefos 1999) |
| Limb reduction defect | 18 | 273,864 (144) |
62.0 (43.3 to 77.7) | 13 | 233,886 (107) | 100 (67.4 to 100) | 9 | 211,781 (66) | 46.3 (24.7 to 96.4) |
| Talipes | 17 | 244,832 (266) | 6.0 (2.2 to 15.6) | 13 | 222,906 (241) | 72.1 (46.4 to 88.5) | 8 | 72,151 (133) | 42.6 (24.0 to 63.5) |
| Ear, face and neck | |||||||||
| Overall (any type) | 16 | 247,420 (334) | NA* Range: 0.0 to 50.0; 0.0 to 22.2 (14 studies); 50.0 (Becker 2012; Iliescu 2013) | 14 | 233,770 (321) | 59.6 (37.8 to 78.1) | 7 | 144,251 (117) | 32.3 (14.8 to 56.7) |
| Orofacial clefts | 19 | 276,776 (264) | 13.5 (5.1 to 31.4) | 15 | 241,811 (216) | N/A*
Range: 0.0 to 100;
0.0 (Carvalho 2002; Hernadi 1997; Souka 2006); 57.1 to 100 (remaining 12 studies) |
12 | 737,082 (786) | 44.1 (26.9 to 62.9) |
|
9 | 181,324 (48) | 0.7 (0.0 to 8.1) | 8 | 176,533 (47) | 68.4 (40.9 to 87.1) | 5 | 109,843 (43) | 76.7 (65.1 to 85.3) |
|
8 | 176,319 (126) | 31.7 (24.4 to 40.1) | 6 | 162,669 (118) | 100 (81.5 to 100) | 8 | 324,854 (261) | 81.9 (77.7 to 85.5) |
|
4 | 170,424 (26) | N/A* Range: 0.0 to 0.0 | 3 | 161,565 (23) | 11.7 (1.8 to 49.4) | 5 | 93,865 (34) | 2.9 (0.1 to 53.4) |
| Multisystem anomalies | |||||||||
| Overall (any type) | 21 | 256,603 (413) | 69.6 (59.0 to 78.5) | 18 | 239,731 (386) | 94.7 (85.2 to 98.2) | 7 | 58,014 (73) | 40.6 (4.5 to 90.9) |
| Fetal hydrops | 20 | 252,415 (196) | 72.4 (38.7 to 91.6) | 18 | 240,293 (188) | 96.6 (76.1 to 99.6) | 3 | 26,856 (8) | N/A* Range: 0.0 to 100; 0.0 (Rydberg 2017); 80.0 (Drukker 2020); 100 (Lee 1998) |
| MCA or syndrome | 28 | 298,117 (268) | 70.4 (53.0 to 83.3) | 23 | 259,930 (232) | 96.0 (82.3 to 99.2) | 9 | 301,085 (1119) | 69.6 (24.9 to 94.0) |
| *N/A: meta‐analysis was not possible because of failure of the random‐effects models to converge due to a lack of variation between studies, or was not performed due to a lack of data (i.e. two or fewer studies available). | |||||||||
|
a‐kCardiac anomalies were grouped according to their anatomical classification as proposed by van Velzen 2016.
Examples of anomalies that were included in each category: aSeptal defects: e.g. major VSD, balanced AVSD. bValvular anomalies (biventricular heart): e.g. significant pulmonary or aortic valve stenosis, Ebstein’s anomaly, significant tricuspid dysplasia or regurgitation. cVenous return anomalies: e.g. total anomalous pulmonary venous return, partial anomalous pulmonary venous return. dAortic arch anomalies: e.g. aortic coarctation, hypoplastic or interrupted aortic arch, double aortic arch, right aortic arch with left ductus arteriosus. eConotruncal anomalies: e.g. Tetralogy of Fallot, double outlet right ventricle, transposition of the great arteries, truncus arteriosus, pulmonary atresia with VSD. fHypoplastic right heart syndrome (HRHS): HRHS or hypoplastic right heart, pulmonary atresia with intact ventricular septum, critical pulmonary valve stenosis with right ventricular hypoplasia. gHypoplastic left heart syndrome (HLHS): HLHS or hypoplastic left heart, aortic valve atresia or critical aortic valve stenosis with left ventricular hypoplasia. hOther single ventricle defects: e.g. unbalanced AVSD, tricuspid atresia, pulmonary atresia without VSD, unspecified single ventricle defect. iComplex defects with atrial isomerism: e.g. left or right atrial isomerism, heterotaxy syndromes. jMiscellaneous major cardiac defects: e.g. unspecified major or complex heart defects, myocardial abnormalities, rhabdomyomas. kMinor cardiac defects: e.g. minor or insignificant septal defects, minor or insignificant isolated valvular anomalies, isolated right aortic arch with right ductus arteriosus, isolated persistent left vena cava superior. | |||||||||
| AVSD: atrioventricular septal defect; CI: confidence interval; CDH: congenital diaphragmatic hernia; CPAM: congenital pulmonary airway malformation; FN: false negative; FP: false positive; HRHS: hypoplastic right heart syndrome; HLHS: hypoplastic left heart syndrome; MCA: multiple congenital anomalies; MCDK: multicystic dysplastic kidney; TN: true negative; TP: true positive; VSD: ventricular septal defect | |||||||||