First and Second Trimester Serum Tests with and Without First Trimester Ultrasound Tests for Down's Syndrome Screening

Summary

A Cochrane review [Abstract] 1 included 22 studies with a total of 228 615 pregnancies (including 1067 with Down's syndrome). 32 different test combinations were evaluated formed from combinations of 8 different tests and maternal age; first trimester nuchal translucency (NT) and the serum markers AFP, uE3, total hCG, free betahCG (BhCG), Inhibin A, PAPP-A and ADAM 12.

First trimester NT, first trimester PAPP-A, second trimester BhCG, second trimester uE3, second trimester AFP, second trimester Inhibin A, and maternal age(4 studies, 40 348 women with 266 Down's syndrome) yielded sensitivity of 92% (95% CI 88 to 95) at a 5% false positive rate (FPR).

First trimester PAPP-A, second trimester total hCG, uE3, AFP and maternal age (4 studies, 2 474 women with 236 Down's syndrome) with 1:250 risk and at a fixed cut-point of 5% FPR sensitivity of 85% (95% CI 78 to 89).

First trimester nuchal translucency, second trimester total hCG, uE3, AFP and maternal age (4 studies, 13 708 women with 136 Down's syndrome) yielded at a fixed cut-point of 5% FPR sensitivity of 86% (95% CI 78 to 92).

First trimester nuchal translucency, second trimester total hCG, AFP and maternal age (4 studies, 22 793 women with 135 Down's syndrome) yielded with 1:250 risk at a fixed cut-point of 5% FPR sensitivity of 85% (CI 77 to 91).

First trimester NT and PAPP-A, and second trimester total hCG, uE3, AFP and Inhibin A, and maternal age evaluated (3 studies) estimated a sensitivity of 95% (CI 90 to 97) at a cut-point of 5% FPR.

Meta-analysis of the 6 most frequently evaluated test combinations showed that a test strategy involving maternal age and a combination of first trimester NT and PAPP-A, and second trimester total hCG, uE3, AFP and Inhibin A significantly outperformed other test combinations that involved only one serum marker or NT in the first trimester, detecting about nine out of every 10 Down's syndrome pregnancies at a 5% false positive rate.