Source: iStock/© ValuaVitaly
Source: iStock/© ValuaVitaly

Researchers report that the Harmony prenatal test by Ariosa Diagnostics undertaken between 10 to 14 weeks of pregnancy may be more effective in diagnosing Down syndrome and two other less common chromosomal abnormalities than standard noninvasive screening techniques.

In the study (“Cell-free DNA Analysis for Noninvasive Examination of Trisomy”) published in the New England Journal of Medicine, which followed pregnancy outcomes in close to 16,000 women, the cell-free DNA blood test resulted in correctly identifying all 38 fetuses with Down syndrome. The diagnosis was confirmed by newborn exam, prenatal, or postnatal genetic analysis.

“In this large, routine prenatal-screening population, cfDNA testing for trisomy 21 had higher sensitivity, a lower false positive rate, and higher positive predictive value than did standard screening with the measurement of nuchal translucency and biochemical analytes,” wrote the investigators.

The test focuses on the small percentage of fetal DNA found floating in a pregnant woman’s blood. DNA is amplified via PCR and sequenced so that comparisons can be made between relative amounts of each chromosome’s DNA. A greater quantity of DNA is indicative of some chromosomal conditions, including Down syndrome, which is characterized by an extra copy of chromosome 21.

When the same women underwent standard screening, 30 of the 38 fetuses with Down syndrome were flagged. The screening comprises a blood draw in which hormones and proteins associated with chromosomal defects are identified, together with an ultrasound of the nuchal fold fluid in the back of the neck, an excess of which is suggestive of Down syndrome.

The average age of the pregnant women was 30 and approximately one-quarter were over 35, the age at which women have traditionally been considered high risk and offered prenatal invasive testing with procedures like amniocentesis.

A second advantage of cell-free DNA analysis reported by the researchers, who were led by first author Mary Norton, M.D., professor of clinical obstetrics and gynecology at the University of California-San Francisco, was the relatively low incidence of Down syndrome misdiagnoses. While standard testing is acknowledged to result in a large number of false positives, these were significantly less likely with the cell-free DNA tool. There were nine false positives resulting from this method, vs. 854 with standard  screening.

While far fewer cases of two other less common chromosomal abnormalities were found in the study population, the accuracy of cell-free DNA screening still surpassed the standard screening method, according to Dr. Norton. Among 10 cases of trisomy 18, also known as Edwards syndrome, the cell-free DNA technique pinpointed nine and flagged one false positive. With standard screening, eight were identified and there were 49 false positives.

For trisomy 13, also known as Patau syndrome, the cell-free DNA test identified both cases and flagged one false positive, while standard screening identified one case and flagged 28 false positives.

Dr. Norton said that since use of the cell-free DNA test will result in far fewer false positives than current screening, it can consequently reduce the number of invasive tests and miscarriages attributed to them. However, patients should be made aware of its limitations, she added.

“Providers need to be attuned to patients’ preferences and counsel them about the differences in prenatal screening and diagnostic testing options. 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 said.

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