Cell-Free DNA Screening for Trisomy 21

A cell-free fetal DNA screening test for Down syndrome proved to be more sensitive and have a lower false-positive rate than the standard screening measures for younger, low-risk women, researchers found.

The new study, published in the New England Journal of Medicine, is the largest to show cell-free DNA tests for trisomy 21 are accurate in even low-risk women. Previously, most tests have focused on older women who are at increased risk of having a baby with Down syndrome. For this study, the mean maternal age was 30.7 years, and the mean gestational age at testing was 12.5 weeks.

While the researchers suggested that the test could reduce the need for more invasive testing, such as amniocentesis, they noted that it does not replace diagnostic testing. Instead, because of fewer false-positive results and a higher positive predictive value than the current standard test, they said the test's accuracy should reduce the number of unnecessary follow-up diagnostic tests.

Key Finding:

- Using a cell-free fetal DNA blood test was more accurate in identifying trisomy 21 in younger, low-risk pregnant women than the current standard test.

The investigators compare the performance of standard screening for trisomy 21, which involves the measurement of nuchal translucency and biochemical analytes, with results obtained from cell-free DNA testing in nearly 16,000 pregnancies with well-documented outcomes. All testing occurred between 10 and 14 weeks' gestation. The cell-free DNA test identified all 38 cases of Down syndrome, compared with 30 detected by standard screening.

There were 9 false-positive results from the cell-free DNA screening, but that was significantly better than the standard testing. They found that the cell-free DNA test had a false-positive rate of 0.06%, compared with a false-positive rate of 5.4% for standard screening.

The cell-free DNA test was not accurate in detecting all chromosomal defects, however. For nearly 500 women who underwent cell-free DNA testing, the screening was not able to provide any results because there was not enough fetal DNA in the pregnant women’s blood. Additional testing also showed that 2.7% of fetuses had chromosomal defects, including those that could not have been detected by the new cell-free fetal DNA technique.

The study was funded by Ariosa Diagnostics, which makes the cell-free DNA test. The test is expected to be heavily promoted by Roche, which markets the test under the name Harmony Prenatal Test.

The study abstract is available here.