Cell-free DNA (cfDNA) testing for fetal trisomy is highly effective among high-risk women. However, there have been few direct, well-powered studies comparing cfDNA testing with standard screening during the first trimester in routine pre- natal populations.


In this prospective, multicenter, blinded study conducted at 35 international cen- ters, we assigned pregnant women presenting for aneuploidy screening at 10 to 14 weeks of gestation to undergo both standard screening (with measurement of nu- chal translucency and biochemical analytes) and cfDNA testing. Participants re- ceived the results of standard screening; the results of cfDNA testing were blinded. Determinationofthebirthoutcomewasbasedondiagnosticgenetictestingornew- born examination. The primary outcome was the area under the receiver-operating- characteristic curve (AUC) for trisomy 21 (Down’s syndrome) with cfDNA testing versus standard screening. We also evaluated cfDNA testing and standard screen- ing to assess the risk of trisomies 18 and 13.


Of 18,955 women who were enrolled, results from 15,841 were available for analysis. The mean maternal age was 30.7 years, and the mean gestational age at testing was 12.5 weeks. The AUC for trisomy 21 was 0.999 for cfDNA testing and 0.958 for standard screening (P=0.001). Trisomy 21 was detected in 38 of 38 women (100%; 95% confidence interval [CI], 90.7 to 100) in the cfDNA-testing group, as compared with 30 of 38 women (78.9%; 95% CI, 62.7 to 90.4) in the standard-screening group (P=0.008). False positive rates were 0.06% (95% CI, 0.03 to 0.11) in the cfDNA group and 5.4% (95% CI, 5.1 to 5.8) in the standard-screening group (P<0.001). The positive predictive value for cfDNA testing was 80.9% (95% CI, 66.7 to 90.9), as compared with 3.4% (95% CI, 2.3 to 4.8) for standard screening (P<0.001).

Fonte : The New England Journal of Medicine


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