cfDNA is More Accurate Than Standard Methods in Indentifying Down Syndrome

In a research of nearly 16,000 pregnant ladies, investigators identified that a cell-free DNA blood test performed between 10-14 weeks gestation was more helpful for identifying Down syndrome than standard testing methods.

The research – lead by Dr. Mary Norton, professor of clinical obstetrics and gynecology at the University of California-San Francisco (UCSF) – also unveiled the blood test was more successful for diagnosing two more rare chromosomal abnormalities – Edwards syndrome and Patau syndrome – than standard techniques.

The team reported its results in the New England Journal of Medicine.

Down syndrome is the very common genetic problem in the US, impacting about 1 in every 700 babies born. It happens when a partial or full additional copy of chromosome 21 is made while in embryonic development.

The extra chromosome is then replicated in cells all over the body, causing the characteristics connected with the problem. These consist of developmental abnormalities, flattened fatal features, decreased muscle tone, upward slanting eyes and small hands and feet.

All pregnant women, no matter of their age, are provided screening and diagnostic assessments for Down syndrome.

These consist of the initial trimester combined test, which includes calculating the levels of necessary protein and hormones in a pregnant woman’s blood that are connected to chromosomal irregularities. It also includes a nuchal translucency screening test – an ultrasound that measures the quantity of fluid accumulating in the baby’s neck tissue. Enhanced fluid buildup may suggest irregularities.

A clinician uses the blood examine and ultrasound outcomes, along with the mother’s age, to calculate their danger of having a baby with Down syndrome.

The cell-free fetal DNA (cfDNA) examine is generally suggested for pregnant women who are at great risk of having a child with Down syndrome. This is a test that analyzes the small quantities of fetal DNA that are circulating in a pregnant woman’s blood, looking for extra copies of chromosome 21.

With respect to Dr. Norton and co-workers, the cfDNA test has proved extremely accurate in discovering Down syndrome in high-risk pregnant women, but its effectiveness among pregnant women at reduced risk is unclear.

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

For their research, the team registered 18,955 pregnant ladies of an average age of 30 from 35 medical centers more than six nations. The scientists note that about 24% of the women were over 35 – an age connected with greater risk for Down syndrome – while the remaining 76% were at reduced risk.

etween 10 and 14 weeks gestation, the women obtained both the first trimester combined test and the cfDNA test. The team was capable to obtain the test outcomes and monitor the pregnancy results of 15,841 of the women enrolled.

Among these women, 38 cases of Down syndrome were recognized, and they identified that the cfDNA test properly recognized all 38 – boasting a sensitivity rate of 100%. The first trimester combined test, on the other hand, only correctly determined 30 out of 38 cases.

The investigators also identified that the cfDNA test yielded considerably fewer false-positive outcomes; nine compared with 854 with the initial trimester combined test.

In add-on, the team identified the cfDNA test was more appropriate than the standard test for determining Edwards syndrome (trisomy 18) and Patau syndrome (trisomy 13).

The cfDNA test identified 9 out of 10 cases of Edwards syndrome and yielded one false-positive outcome, while 8 cases were determined with standard testing and 49 false-positives. While the cfDNA test recognized both cases of Patau syndrome and led to one false-positive, standard screening recognized one case and led to 28 false-positives.

cfDNA testing must be approached with caution

The scientists say use of the cfDNA test among reduced risk women would result in fewer false-positive outcomes than standard screening, and, as a outcome, may lead to fewer invasive tests and relevant miscarriages.

They point out, however, that pregnant women and health care providers must be conscious of the potential downfalls with cfDNA testing. They note that standard screening approaches capture a much broader range of irregularities.

For instance, 488 women registered to the research were excluded because their circulating fetal DNA was immeasurable or their outcomes could not be interpreted. On the other hand, 2.7% of these women’s fetuses had chromosomal problems that would not have been recognized through the cfDNA test. The detection rates of cfDNA testing would have been reduced if these women were included in the outcomes, note the investigators.

Dr. Norton adds:

“Providers have to be attuned to patients’ choices and counsel them about the distinctions in prenatal screening and diagnostic testing choices. Those women who do opt for cell-free DNA examining must be informed that it is extremely accurate for Down syndrome, but it concentrates on a small number of chromosomal irregularities and does not offer the comprehensive evaluation available with other techniques.

Counseling must also include information about the risks connected with failed tests and the pros and cons of pursuing invasive examining if no outcomes are obtained.”

The team concludes that additional researches are warranted to evaluate the cost utility of cfDNA examining among pregnant women at reduced risk of Down syndrome.