First Trimester Ultrasound Tests in Combination with First Trimester Serum Tests for Down's Syndrome Screening

Summary

A Cochrane review [Abstract] 1 included 126 studies with a total of 1604 040 fetuses (including 8 454 Down's syndrome cases. 60 combinations were evaluated formed from combinations of 11 different ultrasound markers as nuchal translucency (NT) and nasal bose and 12 serum tests. The most frequently evaluated serum markers in combination with ultrasound markers were PAPP-A and free betahCG (BhCG). Test strategies that combine ultrasound markers with serum markers, especially PAPP-A and free ßhCG, and maternal age were significantly better than those involving only ultrasound markers (with or without maternal age) except nasal bone. They detect about nine out of 10 Down's affected pregnancies for a fixed 5% false positive rate (FPR).

NT, PAPP-A, free ßhCG and maternal age (69 studies, 1173 853 women including 6 010 Down's syndrome cases): At a cut-point of 5% FPR (24 studies, 391 874 women including 2 521 Down's syndromes), the estimated sensitivity was 87% (95% CI 84 to 89); at a cut-point of 1:250 risk (25 studies, 174712 women including 1 032 Down's syndromes), the estimated sensitivity was 85% (95% CI 81 to 87) and the specificity was 95% (95% CI 95 to 96).

NT, PAPP-A, BhCG, ADAM 12 and maternal age (4 studies, 2 571 women including 256 Down's syndrome cases): At a cut-point of 5% FPR (4 studies, 2571 women), the estimated sensitivity was 85% (95% CI 75 to 91); at a cut-point of 1:250 risk (2 studies; 1 222 women with 74 Down's syndromes), the estimated sensitivity was 86% (95% CI 77 to 93) and the specificity was 97% (95% CI 96 to 98).

NT, PAPP-A and maternal age (5 studies, 9 814 women including 372 Down's syndrome cases): At cut-point 1:100 risk the sensitivity was 67% (95% CI 35 to 90) and specificity 98% (95% CI 97 to 98) (1 study, 1507 women with12 Down's syndromes). At cut-point of 1:185 risk the sensitivity was 82% (95% CI 65 to 93) and specificity 95% (95% CI 94 to 96) (1 study, 5809 women with 33 Down's syndromes). At a 5% FPR, the estimated sensitivity was 80% (95% CI 75 to 84) (3 studies, 2498 women with 327 Down's syndromes).

NT, nasal bone and maternal age (5 studies, 29 699 women including 221 Down's syndrome cases): At cut-point of 1:100 risk the sensitivity was 83% (95% CI 75 to 89) and specificity of 97% (95% CI 97 to 97) (1 study, 19 736 women with 122 Down's syndromes). At a cut-point of 1:300 risk the estimated sensitivity was 61% (95% CI 22 to 89) and the specificity was 97% (95% CI 90 to 99) (4 studies; 9 963 women with 99 Down's syndromes).

NT, BhCG and maternal age (5 studies, 10 975 women with 421 Down's syndromes): At a cut-point of 5% FPR (4 studies, 4986 women wtih 388 Down's syndromes), the estimated sensitivity was 77% (95% CI 68 to 84). At a cut-point of 1:240 risk (1 study; 5 799 women with 33 Down's syndromes) the sensitivity was 79% (95% CI 61 to 91) and specificity 95% (95% CI 94 to 96).

NT and maternal age (50 studies, 530 874women with 2701 Down's syndromes): At a cut-point of 5% FPR (22 studies, 288 853 women with 1784 Down's syndrome cases), the estimated sensitivity was 71% (95% CI 67 to 75); at a cut-point of 1:250 risk (10 studies, 79 412 women with 247 Down's syndromes), the estimated sensitivity was 72% (95% CI 62 to 80) and specificity was 94% (95% CI 90 to 96).