02/27/2012 05:38 pm ET Updated Apr 28, 2012

Non-Invasive Tests for Down Syndrome Are Here -- Now What?

Science can be as dramatic as television, and in the 15 years since fetal DNA was first extracted from maternal serum, the quest to develop a reliable, non-invasive test for Down syndrome and other chromosomal abnormalities has at times resembled a soap opera. Laboratories competed to publish first, a scandal erupted over a test for fetal gender (that was sometimes wrong), and in the biggest scandal of all, industry leader Sequenom announced impressive results (that unfortunately turned out to be fraudulent).

But legitimate science caught up, and in recent months two companies have launched non-invasive tests for Down syndrome (trisomy 21) that also diagnose the other common chromosomal abnormalities, trisomy 13 and trisomy 18. Each published impressive data prior to commercial launch, demonstrating that the tests are highly accurate, with false positive and false negative rates below one percent for trisomies 21 and 18. (They are somewhat less accurate for the very rare trisomy 13.) Two other companies are poised to launch competitive tests in the coming months.

A friend called me up this week from the waiting room of a hospital where he had gone with his wife to have a CVS (chorionic villus samping) because she is over 35 and they wanted to be more certain than a screening test could make them that their fetus was normal. He wanted to see what I thought about skipping the CVS in favor of the Sequenom assay, and after a discussion, they went home without the CVS.

(I love doing CVS procedures, so the idea that these tests are going to make me shelve my needle does bring a tear to my eye, but enough about that.)

The next part of my conversation with my friend had to do with the cost of the test. For some reason his insurance wasn't going to cover it, so he was worried he would have to pay the $1,900 cost out of pocket.

It struck me that we are moving into the mundane part of the process of adopting a new diagnostic technology: Will insurance cover it? How do we integrate this test into the way we think about prenatal diagnosis of chromosomal abnormalities? Which populations of patients -- high-risk for abnormalities, low-risk, or both? How do we deal with abnormal results? (I'll skip the ethical issues, because they aren't new -- anti-choice zealots are predictably opposed to these tests.)

Although it depends a lot on the insurance company, many are paying for these tests for women at high risk of having an abnormal pregnancy -- women over 35 or women with other risk factors. This is the typical, incremental, reactive approach that insurance companies tend to take, but I suspect in time they will cover this test for all women, because in time it will probably replace three tests (two blood tests and an ultrasound) with a single test -- and the cost of the single test will come down to the point that it's cheaper than the combined test.

"The availability of non-invasive prenatal diagnosis is very exciting," said Lauren Lichten, a genetic counselor at Tufts Medical Center, where I work. "Our discussions with patients often center on the risk of amniocentesis and CVS and whether the information is worth the risk of losing the pregnancy. These tests may completely revolutionize what we do as genetic counselors. However, at this time, the main barrier for many of our patients is cost."

It will take my colleagues a while to figure out how to integrate this test into the way we counsel women and do prenatal diagnosis. Unanswered questions include whether we are willing to trust an abnormal result (not yet, but maybe in the future), what do we do if the test result is normal but the patient has an ultrasound finding that is concerning (for now, do an amniocentesis), what do we do if a patient has multiple types of testing that give different results (probably respond to the most concerning result). From an academic perspective, this will be a very interesting process.

Most critically, what do we do about low-risk women, who constitute the overwhelming majority of moms? These test were all developed on high-risk women, because it takes fewer test subjects to prove accuracy in this population. Will these tests work on low-risk women? Figuring this out will take time, big studies, and probably a good deal of prescribing the tests "off-label."

The last mundane part of the arrival of these tests is the lawsuits, as the four companies with similar tests start suing each other. Sequenom announced on Feb. 22 that it was suing Aria, and Verinata announced the next day that it was suing Sequenom. But I'll leave this dramatic chapter for a future post.

For more by Adam Wolfberg, M.D., click here.

For more on healthy living health news, click here.