Is Prenatal Cell-Free DNA Aneuploidy Screening Useful for All?

Summary and Comment |
February 26, 2014

Is Prenatal Cell-Free DNA Aneuploidy Screening Useful for All?

  1. Allison Bryant, MD, MPH

Compared with standard screening, cell-free DNA screening had lower false-positive rates for trisomies 21 and 18 in a general obstetric population; but this technology's performance must be replicated before it can be routinely used in low-risk women.

  1. Allison Bryant, MD, MPH

The use of cell-free DNA (cfDNA) testing as a primary screen for aneuploidy has greatly changed obstetric practice as applied to high-risk women (typically defined as those older than 35 at delivery). Women who screen negative are less likely to proceed with invasive diagnostic testing, thus averting the risk for procedure-related miscarriage. However, because the cfDNA screen's utility has been documented only in women at highest risk for aneuploidy, low-risk populations have often been excluded from the test in clinical practice. In an industry-supported study, investigators enrolled women at 21 general prenatal care centers to evaluate the performance of cfDNA compared with standard aneuploidy screens (whether first-trimester combined, sequential, or integrated), primarily in detecting trisomies 21 and 18.

Cell-free DNA testing had significantly lower false-positive rates than did standard screening (0.3% vs. 3.6% for trisomy 21 and 0.2% vs. 0.6% for trisomy 18) in 1914 women. Positive predictive values (PPVs) of cfDNA testing for trisomies 21 and 18 were 45.5% and 40.0%, respectively — 10 and 5 times higher than PPVs of standard screens. The overall negative predictive value of either test was 100%.


The field of prenatal screening for aneuploidy is evolving rapidly, and clinicians must be cautious about the generalizability of a given study's results before introducing new technologies into clinical practice. These authors are to be applauded for devoting the time, effort, and funds to demonstrate the efficacy of the cell-free DNA screen in an unselected population. Still, we must be wary of the temptation to market these tests as diagnostic: The false-positive rates, while vastly improved over those of traditional screens, are still not trivial — and other (albeit less common) genetic abnormalities are not detectable with cfDNA technology. In addition, these data were derived from one of several companies that offer cfDNA screening. Because methodologies differ, the performance of each should be replicated before this screening is made available to all low-risk women.

Editor Disclosures at Time of Publication

  • Disclosures for Allison Bryant, MD, MPH at time of publication Nothing to disclose


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