In a study of almost 16,000 pregnant women, researchers found that a cell-free DNA blood test carried out between 10-14 weeks gestation was more effective for diagnosing Down syndrome than standard screening methods.

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The cfDNA test assesses the small amounts of fetal DNA that are circulating in a pregnant woman's blood, searching for extra copies of chromosome 21.

The study - led by Dr. Mary Norton, professor of clinical obstetrics and gynecology at the University of California-San Francisco (UCSF) - also revealed the blood test was more effective for diagnosing two rarer chromosomal abnormalities - Edwards syndrome and Patau syndrome - than conventional techniques.

The team publishes its findings in the New England Journal of Medicine.

Down syndrome is the most common genetic condition in the US, affecting around 1 in every 700 babies born. It occurs when a partial or full additional copy of chromosome 21 is made during embryonic development.

The extra chromosome is then replicated in cells throughout the body, causing the characteristics associated with the condition. These include developmental abnormalities, flattened fatal features, reduced muscle tone, upward slanting eyes and small hands and feet.

All pregnant women, regardless of their age, are offered screening and diagnostic tests for Down syndrome.

These include the first trimester combined test, which involves measuring the levels of proteins and hormones in a pregnant woman's blood that are linked to chromosomal abnormalities. It also involves a nuchal translucency screening test - an ultrasound that measures the amount of fluid accumulating in the baby's neck tissue. Increased fluid buildup may indicate abnormalities.

A clinician uses the blood test and ultrasound results, as well as the mother's age, to estimate their risk of having a baby with Down syndrome.

The cell-free fetal DNA (cfDNA) test is normally recommended for pregnant women who are at high risk of having a baby with Down syndrome. This is a test that assesses the small amounts of fetal DNA that are circulating in a pregnant woman's blood, searching for extra copies of chromosome 21.

According to Dr. Norton and colleagues, the cfDNA test has proved highly accurate in detecting Down syndrome in high-risk pregnant women, but its effectiveness among pregnant women at lower risk is unclear.

100% sensitivity and fewer false-positive results with cfDNA test

For their study, the team enrolled 18,955 pregnant women of an average age of 30 from 35 medical centers over six countries. The researchers note that around 24% of the women were over 35 - an age associated with higher risk for Down syndrome - while the remaining 76% were at lower risk.

Fast facts about Down syndrome
  • The number of babies born with Down syndrome in the US increased by 30% between 1979 and 2003
  • The older a woman is when she becomes pregnant, the higher her risk of having a baby with Down syndrome
  • The medical costs of privately insured children aged 0-4 years with Down syndrome is estimated to be around 12 times higher than those of children of the same age without the condition.

Learn more about Down syndrome

Between 10 and 14 weeks gestation, the women received both the first trimester combined test and the cfDNA test. The team was able to collect the test results and monitor the pregnancy outcomes of 15,841 of the women enrolled.

Among these women, 38 cases of Down syndrome were identified, and they found that the cfDNA test correctly identified all 38 - boasting a sensitivity rate of 100%. The first trimester combined test, however, only correctly identified 30 out of 38 cases.

The researchers also found that the cfDNA test yielded significantly fewer false-positive results; nine compared with 854 with the first trimester combined test.

In addition, the team found the cfDNA test was more accurate than the standard test for identifying Edwards syndrome (trisomy 18) and Patau syndrome (trisomy 13).

The cfDNA test identified nine out of 10 cases of Edwards syndrome and yielded one false-positive result, while eight cases were identified with standard screening and 49 false-positives. While the cfDNA test identified both cases of Patau syndrome and led to one false-positive, standard screening identified one case and led to 28 false-positives.

cfDNA testing should be approached with caution

The researchers say use of the cfDNA test among lower risk women would lead to fewer false-positive results than standard screening, and, as a result, may lead to fewer invasive tests and related miscarriages.

They point out, however, that pregnant women and health care providers should be aware of the potential downfalls with cfDNA testing. They note that standard screening methods capture a much broader range of abnormalities.

For example, 488 women enrolled to the study were excluded because their circulating fetal DNA was immeasurable or their results could not be interpreted. However, 2.7% of these women's fetuses had chromosomal defects that would not have been identified through the cfDNA test. The detection rates of cfDNA testing would have been lower if these women were included in the results, note the researchers.

Dr. Norton adds:

"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."

The team concludes that further studies are warranted to assess the cost utility of cfDNA testing among pregnant women at lower risk of Down syndrome.

In October 2014, a Spotlight feature from Medical News Today investigated whether expectant mothers receive adequate information on Down syndrome.