What You Need To Know About New DNA Down Syndrome Tests

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The news recently broke that prenatal testing is entering a new era: DNA tests able to detect Down syndrome in a fetus just by testing the mother's blood are now hitting the market.

Below you'll find a nuts-and-bolts Q&A with a leading researcher on such tests: What's the state of the science? Who should get one? How much are they?

But first, a brief editorial: This is good news for the great many parents-to-be who want the chance to know in advance if a fetus has Down syndrome. As an older mother, I would have been overjoyed to have a near-definitive, non-invasive test. If the women who come after me have that chance, and it looks like they will, I'll consider it quite a boon of the genomic era.

Much of the coverage has struck me as oddly "balanced." If you search on, for example, the headline says the new type of test "raises hopes and questions." Questions? Well, sure, it's a new technology: Will it live up to its initial promise? But the Times story also cites concerns "that use of such tests early will lead to more abortion of fetuses with minor abnormalities, the wrong sex or an undesired father." It quotes Dr. Brian Skotko of the Down syndrome program at Children's Hospital Boston, whose sister has Down syndrome. He "pointed out that these tests could encourage more people to end their pregnancies, causing a decline in the numbers of people with the condition and leading to diminished support for them."

[module align="left" width="half" type="pull-quote"]I remember it as: 'Do I want to avoid Down syndrome badly enough to risk this whole precious pregnancy?'[/module]

We're all entitled to our points of view. But let's look at the tests from the perspective of the parents-to-be.

These DNA tests could bring about the end of the heart-wrenching pregnancy decision on whether to get an invasive test like an amniocentesis despite the small risk of miscarriage. (I remember it as: "Do I want to avoid Down syndrome badly enough to risk this whole precious pregnancy?")

They could mean that women who know they do not want to bear a child with Down syndrome could get reliable testing earlier and, if they choose, terminate their pregnancies earlier and more simply. I know people who've had to grapple with serious amniocentesis complications. My dear friend went through the double agony of a Down syndrome diagnosis and the physical-emotional trauma of a late-term abortion.

The DNA tests could also eventually replace the complex, hard-to-grasp odds ratios of Down syndrome yielded these days by less accurate blood-sample screening. And perhaps best of all, the new tests produce fewer "false positives" that lead to invasive and risky tests like amnios.

Dr. Diana Bianchi
Dr. Diana Bianchi

End of editorial. Now for the facts. Dr. Diana Bianchi, executive director of the Mother Infant Research Institute at Tufts Medical Center has been doing research on non-invasive fetal diagnosis for nigh on a generation; I interviewed her way back in 2004 about her work on fetal cells in a pregnant woman’s blood.

She says that already, the Maternal-Fetal Medicine staff at Tufts Medical Center has been fielding questions from patients about the new tests, and recently held a meeting about how to answer them. I sent over these basic questions, and she, together with the maternal-fetal medicine and genetics staff, generated the crystalline answers below. Financial disclosure: Dr. Bianchi is the chair of the clinical advisory board for Verinata Health, one of the companies making the new tests, and holds equity in it.

Her staff's bottom line: Medicine is advancing very quickly in this area, but for now, the test is considered only “near-diagnostic,” not quite as reliable as an invasive test like an amnio, and is most suitable for women considered at high risk for having a fetus with Down syndrome. Details below.

What exactly is this new "fetal DNA" test? 

The “fetal DNA” test refers to testing of the fetus using fragments of fetal DNA that naturally circulate in the blood of pregnant women. The new test is used to detect Down syndrome and other chromosome abnormalities in the fetus. The test is performed using a blood sample from the pregnant woman in either the first or second trimester.

How does the fetal DNA test work?

In a specialized laboratory, DNA is isolated from the maternal blood sample. This DNA contains a mixture of about 10% fetal and 90% maternal DNA. The DNA is analyzed to see if there is an increased amount of genes present from a specific chromosome. Down syndrome is characterized by the presence of three copies of chromosome 21 instead of the usual two copies. If the fetus has Down syndrome there would be an extra amount of genes from chromosome 21 detected in the sample.

How was the fetal DNA test developed?

Initial research in prenatal diagnosis using DNA in maternal blood started in 1997. Advances in the machines and the computer technology needed to analyze the human genome have made it more affordable and practical to offer this test on a clinical basis to pregnant women. In 2011 there were multiple clinical trials performed and published in the medical literature that validated the technology.

How reliable is the test?

The test is reliable for detecting Down syndrome. Down syndrome accounts for about half of the fetal chromosome conditions that are identified through invasive procedures such as amniocentesis or CVS. While the test may detect other chromosome abnormalities (such as trisomy 13 or trisomy 18), its use for this purpose has not yet been validated.

The test is incorrect only a small percentage of the time. If a fetus truly has Down syndrome there is a greater than 98% chance the test will say that fetus has Down syndrome. If a fetus truly does not have Down syndrome there is a greater than 99% chance the test will say that fetus does not have Down syndrome. Less than 1% of the time the laboratory cannot obtain a result.

How much does the test cost?

Currently only one company (Sequenom) offers this testing on a clinical (commercial) basis. The information in this section only pertains to that company. For women with Medicaid and Commercial HMO health insurance, your health care provider can request prior authorization for this test. The insurance company may deny authorization for this test. For women who choose the self-pay option, there is a discounted price of $1933.00 (paid by credit card). For patients with commercial PPO health insurance, the additional (out of pocket) cost to patients is currently $235.00. There is an option to contact the laboratory’s billing department to request an application for the company’s financial hardship program. The cost to the patient may change over time, so consult the company or your insurance company before choosing this test.

Which pregnant women may find the test most useful? 

Currently the test is only recommended for women who are at increased risk to have a pregnancy affected by Down syndrome. High risk women should meet at least one of the following criteria:

• Be age 35 or older at the time of delivery

• Have a “screen positive” result on a first or second trimester serum screen

• Have a previous pregnancy affected with Down syndrome

• Have an abnormal ultrasound finding in the fetus that is known to be associated with Down syndrome.

The test may be useful to “high risk” women who would like to know if their fetus has Down syndrome without having a diagnostic test like amniocentesis or chorionic villus sampling (CVS). Amniocentesis and CVS are tests that require a needle to be placed in the uterine cavity. Both are associated with a small chance of miscarriage. Some women may still need to consider an amniocentesis or CVS even after having the fetal DNA test. Your obstetrician can refer you to a genetic counselor to help you determine if the DNA blood test is right for you.

Which pregnant women may not be interested or eligible for the test?

Women in the general population who are not at increased risk to have a pregnancy with Down syndrome probably should not consider this test at this time, as there is no information as to how this test performs in a low risk population. Women who do not want to know if their fetus has Down syndrome will not be interested in the test, nor are they required to take the test. Women who want prenatal testing because they are at increased risk for other genetic conditions (such as cystic fibrosis) will still need to have an amniocentesis or CVS.

The performance of the test has not yet been validated in women carrying multiple fetuses (i.e. twins, triplets) and in women carrying fetuses with other major chromosome abnormalities such as trisomy 13 and 18. Also, one study has suggested that maternal weight influences the way the test performs, so in obese pregnant women, the test results may not be as accurate as they are in women who are of average weight. Further research may clarify these issues.

If I get the test and it indicates my fetus does have Down syndrome, what happens then?

You should meet with a genetic counselor to discuss the results. Diagnostic tests, such as amniocentesis or CVS will be recommended to confirm the result.

If I get the test and it indicates my fetus does not have Down syndrome, what happens then? What if I still want a diagnostic test like amniocentesis or CVS?

Although a negative result is very reassuring, false negatives can occur in a very small percentage of patients (less than 1%).  Your results will be reported to you by a genetic counselor. A diagnostic test (amniocentesis) can be performed in the second or third trimester if you want definitive confirmation that the fetus does not have Down syndrome.

More broadly, what are the overall pros and cons of the test?

The pros of the test are that it detects over 98% of fetuses with Down syndrome and does not involve a needle being placed in the uterus.

It performs better than the currently available serum screening tests, which detect between 80-92% of fetuses with Down syndrome. As more experience develops with the DNA test it is anticipated that fewer women will need tests like amniocentesis and CVS, which have a risk of miscarriage. This makes the overall screening process safer.

Currently, the cons are:
The test is not able to detect Down syndrome in 100% of women carrying fetuses with Down syndrome. A small percentage of women may test negative but have a fetus with Down syndrome.

A small percentage of women may test positive but have a fetus that does not have Down syndrome.

Even if the test is positive for Down syndrome, a diagnostic test like amniocentesis or CVS will still be recommended to confirm the results.

The cost of the test is high and may not be covered by insurance.

At present women have to go to specific centers to get their blood drawn, which may be inconvenient.

The test is currently only validated to detect Down syndrome and is not validated detect other chromosome abnormalities, for which the woman may also be at risk.

Having the test may delay getting a confirmatory result during a time-sensitive period (if termination of pregnancy is being considered).

The test has not yet been validated for use in twin pregnancies or IVF donor pregnancies.

Note that this is a very rapidly advancing area of medicine, and some of the information presented here will change over the next few months as a result of further research.

A final editorial note: Diana Bianchi's lab is performing research — still in very early stages — on the possibility of not just diagnosing Down syndrome prenatally but treating it as well.

The new DNA tests raise concerns among some that there will be more "seek and terminate" of fetuses with Down syndrome. But, she says, "currently another option is 'diagnose and prepare (for an affected child)' and the hope is that in the future a third option will be 'diagnose and treat.'”

This program aired on December 5, 2011. The audio for this program is not available.

Carey Goldberg Twitter Editor, CommonHealth
Carey Goldberg is the editor of WBUR's CommonHealth section.