The New England Journal of Medicine published a paper titled “Cell-free DNA Analysis for Noninvasive Examination of Trisomy” today, suggesting that cfDNA testing for trisomy 21 had higher sensitivity, a lower false positive rate, and higher positive predictive value than did standard screening.

In the study, the authors analyzed data from 15,841 pregnant women who were enrolled at 35 international centers. These pregnant women underwent aneuploidy screening at 10 to 14 weeks of gestation with both standard screening (with measurement of nuchal translucency and biochemical analytes) and cfDNA testing. Determination of the birth outcome was based on diagnostic genetic testing or newborn examination. The study mainly analyzed results for trisomy 21 (Down’s syndrome) with cfDNA testing versus standard screening, but also evaluated cfDNA testing and standard screening to assess the risk of trisomies 18 and 13.

The authors found that the AUC (area under curve) for trisomy 21 was 0.999 for cfDNA testing and 0.958 for standard screening (P=0.001). For example, trisomy 21 was detected in 38 of 38 women (100%) in the cfDNA-testing group, as compared with 30 of 38 women (78.9%) in the standard-screening group (P=0.008). False positive rates were 0.06% in the cfDNA group and 5.4% in the standard-screening group (P<0.001). The positive predictive value for cfDNA testing was 80.9%, as compared with 3.4% for standard screening (P<0.001).

However, we should caution that only standard screening, not amniocentesis, was used in the study, so we cannot tell how cfDNA testing compare with amniocentesis (especially when applied to pregnant women with elevated risk for trisomy 21).

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