Cell-free DNA blood test more accurately detects down syndrome

by Bruce Sylvester: A blood test administered between weeks 10 and 14 weeks of pregnancy appears to be a more accurate diagnostic tool for Down syndrome and two other less common chromosomal abnormalities than standard non-invasive screening techniques, researchers reported in The New England Journal of Medicine/NEJM on April 1, 2015.

The investigators tracked outcomes for about 16,000 pregnancies. The cell-free DNA blood test  correctly identified all fetuses with Down syndrome, which was confirmed by a series of other post-natal tests.

The blood test uses fetal DNA found floating in a pregnant woman’s blood, amplifies it with a  polymerase chain reaction, and sequences it to enable comparisons between relative amounts of each chromosome’s DNA.

More DNA is indicative of chromosomal conditions, including Down Syndrome, which shows an extra copy of chromosome 21.

The same group of women received standard screening, which identified 30 of the 38 fetuses with Down syndrome. Standard screening involves a study of blood which identifies hormones and proteins associated with chromosomal defects, and an ultrasound of the nuchal fold fluid in the back of the neck. Excess fluid suggests the presence of fetal Down syndrome.

Average age of the subjects was 30, with about one-quarter being over 35.

There were nine false positives resulting from cell-free DNA screening, compared with 854 with standard screening.

The accuracy of cell-free DNA screening for two other less common chromosomal abnormalities also surpassed standard screening methods. For 10 cases of trisomy 18, also known as Edwards syndrome, the cell-free DNA technique flagged 9 cases and one false positive. With standard screening, eight cases were flagged plus 49 false positives. For trisomy 13, known as Patau syndrome, cell-free DNA testing flagged 2 cases and one false positive, and standard screening flagged one case and 28 false positives.

Encouraging caution, the authors noted that standard screening, “can identify risk for a broad array of abnormalities that are not detectable on cell-free DNA testing.”  Cases of Down syndrome comprise just over 50 percent of aneuploidies, disorders deriving from an abnormal number of chromosomes, they said.

“Providers need to be attuned to patients’ preferences and counsel them about the differences in prenatal screening and diagnostic testing options,” said lead author Mary E. Norton, MD, Professor and Vice Chair, Clinical and Translational Genetics at the University of California in San Francisco. “Those women who do opt for cell-free DNA testing should be informed that it is highly accurate for Down syndrome, but it focuses on a small number of chromosomal abnormalities and does not provide the comprehensive assessment available with other approaches….Counseling should also include information about the risks associated with failed tests and the pros and cons of pursuing invasive testing if no results are obtained,” she added.