Optimal cut-offs for down syndrome contingent screening in a population of 10156 pregnant women

Study design A population of 10156 pregnant women with singleton pregnancies were screened by the integrated test. Risks were retrospectively recalculated for contingent test strategies with first step intermediate risk groups defined by first trimester upper cut-offs of 1:10, 1:30, 1:50, and 1:70 and lower cut-offs 1:1500, 1:1200, 1:1100, and 1:900. The second trimester high risk group was based on a single cut-off of 1:250. Results In the first trimester, the detection rate (DR) ranged from 21% (6/29) to 52% (15/29) as the high risk first trimester cut-off was changed from 1:10 to 1:70. The corresponding first trimester false positive rate (FPR) increased from 0.2% to 1.4%. In the second trimester, an additional 21/29 (72%) to 12/29 (41%) affected pregnancies could be detected with an additional 1.6% to 2.7% false positives when lower first trimester cut-offs of 1:900 to 1:1500 were used. The best results were obtained with the upper first trimester cut-off of 1:30 and lower first trimester cut-off of 1:900, which yielded a rate of women requiring a second trimester test of only 12%, with overall DR and FPR of 93% and 2.8%, respectively. Conclusions Although the study population was relatively small, the results confirm the advantage of using contingent screening and suggest optimal first trimester cut-offs of 1:30 (lower cut-off) and 1:900 (upper cut-off). © 2012 John Wiley & Sons, Ltd. [PUBLICATION ABSTRACT]