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New Study: Genetic Blood Test Better than Standard Prenatal Screening, Still Not Perfect

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May 21, 2015


A new study published in the New England Journal of Medicine found that a relatively new, non-invasive prenatal blood test that screens for Down syndrome in unborn babies is more accurate than standard screening methods, even in low-risk pregnancies. However, a small percentage of the new tests detected abnormalities when, in fact, none existed (called false positives). The new screening method still requires pregnant women to have follow-up diagnostic testing after positive results.

The new test is called cell free fetal DNA testing (cffDNA) or non-invasive prenatal test (NIPT) because it uses a blood sample drawn from an expectant mother's arm to analyze for pieces of fetal DNA that shed from cells in the placenta and circulate freely in the mother's blood. While the test has proven to be highly accurate, it does have limitations and it is not yet known how it will fit in with current prenatal testing.

"If one is thinking about screening for Down syndrome — about screening options for that one condition — it is very clear that DNA testing is the best for that," said Dr. Mary Norton, a UCSF obstetrician and lead author of the study, in the San Francisco Chronicle. "But this test, while very exciting, tests for a very narrow group of disorders. For a given woman thinking about her test options, what should be our first-line test is still not so clear."

Standard first trimester prenatal screening consists of a combination of two blood tests that measure pregnancy-associated plasma protein A (PAPP-A) and human chorionic gonadotropin (hCG) plus a special ultrasound procedure called nuchal translucency. If results from these tests cause concern, a woman may undergo diagnostic testing such as amniocentesis or chorionic villus sampling (CVS). These require a needle to be inserted into the mother's abdomen to collect fetal cells and carry a small risk of miscarriage. Alternatively, for CVS, a needle may be inserted through the cervix to collect cells, but the risk of miscarriage with this method is even slightly higher.

Currently, the American College of Obstetricians and Gynecologists recommends the newer cffDNA only for women at risk of having a baby with Down syndrome because it has not been sufficiently tested in low-risk women. The recent NEJM study compared a specific test for cffDNA to the standard method of screening and included both low and high-risk women. The study involved over 15,000 pregnant women with an average age of 31 and was conducted at 35 medical centers in 6 countries. Testing was done when the mothers were 10 to 14 weeks pregnant.

Even though about a quarter of the women were at low risk for having a baby with Down syndrome because of their young age, the specific cffDNA test accurately detected all cases of Down syndrome — 38 cases — among the women in the study. Standard screening detected 30 of the 38 cases of Down syndrome. The improved detection rate by cffDNA would mean that a woman could have more confidence that a negative result rules out Down syndrome.

In addition, there were only 9 cases of false positives among the women who had cffDNA screening, compared with 854 for standard screening. The substantially lower false-positive rate for cffDNA means that fewer women would have unnecessary follow-up diagnostic testing or experience the anxiety that usually accompanies a positive screen. A brief report in the same issue of the New England Journal of Medicine suggests that the false positives from the cffDNA test may be linked to the mothers' chromosomal abnormalities.

Though the primary focus of the study was Down syndrome, researchers found that accuracy of cffDNA for screening for two other rare chromosome disorders, Edwards syndrome (trisomy 18) and Patau syndrome (trisomy 13), was similar to that for Down syndrome.

Since the study showed that the new test is more accurate than standard screening, even in younger, low-risk women, it could lead to wider use. However, an editorial in the same journal issue as the new study urges caution for now.

Although the rate of false positives was far below that of standard screening, positive cffDNA screens would still require follow-up with tests such as amniocentesis or CVS. And since the test is currently limited to screening mainly for Down syndrome and a few other disorders, standard prenatal screening methods would still be needed to detect other defects. The study revealed another important drawback of the test: it could not be done for 500 women in the study because they had no, or too little, DNA from the fetus in their bloodstreams.

As noted in the editorial, additional studies like this current one are needed to better understand the usefulness of this test and how it might be implemented. Expectant mothers who are considering the test should talk to their healthcare providers and get pre-test genetic counseling so that a trained genetic counselor can explain what the test is able to detect and about the need for follow-up testing if the cffDNA screen is positive.

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NOTE: This article is based on research that utilizes the sources cited here as well as the collective experience of the Lab Tests Online Editorial Review Board. This article is periodically reviewed by the Editorial Board and may be updated as a result of the review. Any new sources cited will be added to the list and distinguished from the original sources used. To access online sources, copy and paste the URL into your browser.

Norton, Mary E. MD, Jacobsson, Bo MD, PhD, et al. Cell-free DNA Analysis for Noninvasive Examination of Trisomy. New England Journal of Medicine. 2015. April 23, 372:1589-1597. Available online at http://www.nejm.org/doi/full/10.1056/NEJMoa1407349#t=article through http://www.nejm.org. Accessed May 19, 2015.

Chitty, Lyn S. PhD, MB, BS. Cell-free DNA Analysis for Noninvasive Examination of Trisomy. New England Journal of Medicine. 2015, April 372:1666-1667. Available online at http://www.nejm.org/doi/full/10.1056/NEJMe1502441 through http://www.nejm.org. Accessed May 19, 2015.

(April 2, 2015) Walker, Molly. Fetal DNA in Mom's Blood Signals Down Syndrome. Medpage Today. Available online at http://www.medpagetoday.com/Genetics/GeneticTesting/50791 through http://www.medpagetoday.com. Accessed May 19, 2015.

April 1, 2015. Allday, Erin. New DNA tests highly accurate in detecting Down syndrome. San Francisco Chronicle. Available online at http://www.sfgate.com/health/article/New-DNA-tests-highly-accurate-in-detecting-Down-6173524.php through http://www.sfgate.com. Accessed May 19, 2015.