Summary of findings'. 'Performance of urine tests with or without maternal age.
| Review Question | What is the accuracy of urine based markers for screening for Down's syndrome? | ||||
| Population | Pregnant women at less than 24 weeks' gestation confirmed by ultrasound, who had not undergone previous testing for Down’s syndrome. Most studies were undertaken in women identified to be high risk based on maternal age | ||||
| Settings | All settings | ||||
| Numbers of studies, pregnancies and Down's syndrome cases | 19 studies (reported in 29 publications) involving 18,013 pregnancies of which 527 were Down's syndrome pregnancies. | ||||
| Index tests | Risk scores computed using maternal age and first and second trimester urine markers for AFP; ITA; ß‐core fragment; free ßhCG; total hCG; oestriol (also termed as uE3); gonadotropin peptide. | ||||
| Reference standards | Chromosomal verification (amniocentesis and CVS undertaken during pregnancy, and postnatal karyotyping) and postnatal macroscopic inspection. | ||||
| Study limitations | Seven studies only used selective chromosomal verification during pregnancy, and were at risk of under‐ascertainment of Down's syndrome cases due loss of the pregnancy to miscarriage between the serum test and the reference standard. | ||||
| Test | Studies | Women (Cases) | Sensitivity* (95% CI) | Specificity* (95% CI) | Threshold |
| Test without maternal age | |||||
| Single tests | |||||
| First trimester free ßhCG | 1 | 516 (86) | 5 (1 to 11) | 95 (92 to 97) | 5% FPR |
| First trimester ß‐core fragment | 1 | 516 (86) | 10 (5 to 19) | 95 (92 to 97) | 5% FPR |
| First trimester ITA | 2 | 579 (94) | 15 (2 to 62) | 95 | 5% FPR |
| First trimester total hCG | 1 | 516 (86) | 17 (10 to 27) | 95 (92 to 97) | 5% FPR |
| Second trimester oestriol | 2 | 1472 (47) | 23 (8 to 49) | 95 | 5% FPR |
| Second trimester total hCG | 1 | 390 (65) | 31 (20 to 43) | 95 (92 to 97) | 5% FPR |
| Second trimester free ßhCG | 3 | 1517 (107) | 32 (12 to 63) | 95 | 5% FPR |
| Second trimester ß‐core fragment | 6 | 9613 (193) | 41 (20 to 66) | 95 | 5% FPR |
| Second trimester ITA | 3 | 2748 (131) | 43 (35 to 51) | 95 | 5% FPR |
| Second trimester ß‐core fragment to oestriol ratio | 2 | 1649 (35) | 74 (58 to 86) | 95 | 5% FPR |
| Second trimester gonadotropin test | 1 | 105 (14) | 93 (66 to 100) | 95 (88 to 98) | 1:384 risk |
| Double tests | |||||
| Second trimester AFP and ITA | 1 | 524 (24) | 79 (58 to 93) | 95 (93 to 97) | 5% FPR |
| Second trimester ß‐core fragment and oestriol | 1 | 315 (24) | 83 (63 to 95) | 95 (92 to 97) | 5% FPR |
| Triple tests | |||||
| Second trimester AFP, uE3 and ITA | 1 | 524 (24) | 79 (58 to 93) | 95 (93 to 97) | 5% FPR |
| Test with maternal age | |||||
| Single tests | |||||
| Second trimester oestriol | 1 | 474 (69) | 49 (37 to 62) | 95 (92 to 97) | 5% FPR |
| Second trimester ß‐core fragment | 5 | 3419 (155) | 56 (45 to 66) | 95 | 5% FPR |
| Second trimester free ßhCG | 2 | 879 (98) | 57 (47 to 67) | 95 | 5% FPR |
| Second trimester free ßhCG to oestriol ratio | 1 | 474 (69) | 64 (51 to 75) | 95 (92 to 97) | 5% FPR |
| Second trimester ß‐core fragment to free ßhCG | 1 | 474 (69) | 67 (54 to 78) | 95 (92 to 97) | 5% FPR |
| Second trimester ITA | 1 | 1016 (23) | 70 (47 to 87) | 95 (93 to 96) | 5% FPR |
| Second trimester ß‐core fragment to oestriol ratio | 3 | 2088 (105) | 71 (51 to 86) | 95 | 5% FPR |
| Double tests | |||||
| Second trimester oestriol and free ßhCG | 1 | 474 (69) | 68 (56 to 79) | 95 (92 to 97) | 5% FPR |
| Second trimester ß‐core fragment and oestriol | 2 | 1631 (92) | 73 (57 to 85) | 95 | 5% FPR |
| Second trimester AFP and ß‐core fragment to oestriol ratio | 1 | 356 (10) | 90 (55 to 100) | 95 (93 to 97) | 1:58 risk |
*Tests evaluated by at least one study are presented in the table. Where two studies reported the same threshold, estimates of summary sensitivity and summary specificity were obtained by using univariate fixed effects logistic regression models to pool sensitivities and specificities separately. if the threshold used was a 5% FPR, then only the sensitivities were pooled.
AFP: alpha‐fetoprotein; ßhCG: beta human chorionic gonadotrophin;CI: confidence interval; CVS: chorionic villus sampling; FPR: false positive rate; hCG: beta human chorionic gonadotrophin;ITA: invasive trophoblast antigen; uE3: unconjugated oestriol