New contingent sequential screening model for Down syndrome based on the combined test associated with modified genetic sonography

Abstract

Objective: The aim of this study is to evaluate the possibility of implementing a contingent sequential screening test for Down syndrome (DS) based on the combined test (CT) associated with modified genetic sonography (MGS). We evaluate sensitivity (Sen), false positive rate (FPR), and economic costs.

Method: We compiled data from the results of a prospective screening programme for DS during a 5-year study period (July 2005–December 2011). Pregnancies were offered the CT as the first step in the contingent sequential test. We identified an intermediate risk group (1/101–1/1000) using CT results, and offered these individuals a MGS (major malformation and nuchal fold).

Results: A total of 19 440 pregnancies (103 chromosome abnormalities and 66 cases of DS) were administered the CT. We performed a MGS on 99.6% of individuals in the intermediate risk group (2188/2197); in this group, we observed 22 chromosome abnormalities (17 DS). The CT provided a Sen for DS of 80.30% (95%CI: 68.68–89.07) (53/66), and a Sen for all chromosome abnormalities of 76.70% (95%CI: 67.34–84.46) (79/103), with a FPR of 3.79% (95%CI: 3.52–4.05) (732/19 374). The contingent sequential strategy produced a Sen for DS of 81.82% (95%CI: 70.39–90.24) (54/66) and a Sen for all chromosome abnormalities of 79.61% (95%CI: 70.54–86.91) (82/103), with a FPR of 1.16% (95%CI: 1.02–1.33) (224/19 457). The economic costs of the CT and the contingent sequential model were 9 70 275 Euros and 9 41 716 Euros, respectively.

Conclusions: We present a new sequential contingent strategy for DS screening and demonstrate its usefulness for reducing FPR while maintaining a high level of Sen for DS, without requiring an increase in economic costs.

• Combined test
• contingent test
• down syndrome
• genetic sonography