As National Down Syndrome Awareness Month has come to an end, the introduction of a new prenatal test risks ending the births of babies with Down syndrome. While promoted as being safer, the current administration of the testing is reckless.
On October 17, 2011, Sequenom, a San Diego–based testing company, rolled out “MaterniT21” in twenty major cities across the United States. Using a technique called “massively parallel shotgun sequencing,” the test identifies fetal DNA in a sample of the mother’s blood and sequences it. The test detects whether the fetal DNA is positive for Trisomy 21, the most common cause of Down syndrome, with the lowest false positives and false negatives of current screening tests.
In 2007, the American Congress of Obstetricians and Gynecologists (ACOG) recommended that all women be offered screening and diagnostic prenatal testing for Down syndrome. Noninvasive screening tests for Down syndrome have existed since the 1980s. Like MaterniT21, they use a mother’s blood sample and are just as safe, though less accurate in assessing a fetus’s likelihood of having Down syndrome. In this initial roll-out, Sequenom is only offering its testing to those mothers considered “high risk” due to advanced maternal age, having a family member with Down syndrome, or having already received a “positive” screen result from the existing screening tests. The only way to know for certain whether a pregnancy is positive for Down syndrome, even after receiving a MaterniT21 result, is through invasive testing, usually an amniocentesis or chorionic villus sampling (CVS). Because invasive testing involves inserting a needle into the womb, it has a risk of miscarriage. MaterniT21 does not make invasive testing any safer—if anything, it might increase the risk.
The journal Genetics in Medicine published a Sequenom-funded study on the eve of the new test’s launching. Jacob Canick, one of the study’s leaders, explains how the test is “safer”: “It is possible that with the availability of this new DNA-based test, more women will opt for screening because of the increased safety resulting from far fewer amniocentesis and CVS procedures being performed.” This is the clinical reason cited as justification for introducing the new test: that it will drastically reduce miscarriages from invasive testing. As Dr. Glenn Palomaki, the study’s lead author, put it, “nearly all women with a normal pregnancy could avoid an invasive diagnostic procedure and its associated anxiety, cost and potential for fetal loss.” This quote deserves to be unpacked.
First, “nearly all” pregnancies currently do avoid invasive diagnostic testing. There are millions of pregnancies each year, with 750,000 being considered high risk for Down syndrome, but only 200,000 invasive procedures each year. ACOG made its 2007 recommendations because studies had found that the risk for miscarriage was lower than historically reported when invasive testing was performed at experienced facilities by experienced practitioners. If Sequenom’s goal of reducing the number of invasive tests is achieved, there also will be fewer experienced facilities and practitioners, thereby potentially increasing the risk of miscarriage for those undergoing invasive testing.
Dr. Palomaki’s assurance that “nearly all women with a normal pregnancy could avoid an invasive diagnostic procedure” also deserves consideration. Most parents of children with Down syndrome would object to the crass labeling of their sons and daughters as abnormal. Putting that aside, Down syndrome is but a small fraction of the baseline risk every pregnancy has for what is commonly considered a birth defect. Further, Down syndrome represents only about half of chromosomal conditions identified through invasive testing. This means that for each woman who opts for invasive testing following a positive MaterniT21 result, there could be another woman falsely reassured by a negative result that her child will not have a chromosomal condition.
Sequenom’s test has also been called safer because it can be performed earlier than ever in a pregnancy, as soon as ten weeks. This, however, is another reason for concern.
MaterniT21 can be performed any time from ten weeks forward in a pregnancy. In the research study, half of the samples were from the second trimester, but the test is offered earlier in the pregnancy specifically because it allows for earlier termination. Matthew Rabinowitz is CEO of Gene Security Network, a company developing its own noninvasive prenatal test for Down syndrome. Commenting on Sequenom’s new test, he clinically and candidly stated, “If a couple finds an abnormality, and chooses to terminate the pregnancy, it’s better to do it earlier.” Considering that the majority of women currently receiving a prenatal diagnosis of Down syndrome do opt to terminate, Sequenom’s new test is definitively not safer for the fetus.
For this reason, Sequenom’s product name for the test is rather Orwellian. “MaterniT21” recognizes that the test is for a mother, but provides the opportunity for most women to end their maternal status through abortion.
Sequenom’s justification for its testing is as misleading as the test’s name. In a press release, Harry F. Hixson, Jr., Sequenom’s CEO, said, “We believe that the MaterniT21 LDT will provide physicians and their patients with critical new information to help them make better informed decisions about the patients’ healthcare and pregnancies.” In the study Sequenom funded, however, it noted as an implementation issue that “educational materials for both patients and providers need to be developed and validated to help ensure informed decision making.” This long has been recognized, based on the current administration of prenatal testing.
Study after study has found that a significant number of expectant mothers and their partners do not understand the probability assessments of screening tests, did not expect they would have to make a decision about invasive testing, and, after a positive diagnosis, often are unexpectedly counseled about termination for the first time and rarely informed of the option of adoption. This has led one researcher to conclude that the current administration of prenatal testing does not respect a woman’s right to choose because so many make uninformed decisions. In response, just this summer, both the National Society of Genetics Counselors (NSGC) and the American Academy of Pediatrics (AAP) published new guidelines specifically calling for the delivery of accurate, up-to-date written materials about Down syndrome and referral to parent support organizations when a patient receives a prenatal diagnosis. The NSGC even listed the educational materials that should be provided to patients, but Sequenom has yet to invest in these equally important information resources for expectant mothers undergoing its testing.
Now, other prenatal testing companies have launched testing without providing the balancing resources, but Sequenom has recognized that these resources are needed from the outset of its testing and still does not provide them. Dr. Hixson’s statement simply makes Sequenom one more purveyor of the “prenatal testing sham” that I wrote about earlier this year—justifying prenatal testing as simply providing information while failing to provide all of the needed information. But Sequenom’s motivation for rolling its tests out without the accompanying educational materials makes its actions particularly unconscionable.
Sequenom had intended to launch its test in 2009, when it was being promised as a diagnostic test. On the eve of going to market, however, it had to admit it had manipulated its data. Its stock price plummeted, a shareholder lawsuit followed alongside an SEC investigation, and its research official pled guilty to conspiracy to commit securities fraud. Competitors, such as Gene Security, also are promising similar testing as soon as next year. Sequenom patented its methodology, promising patent battles should these competitors try to roll their tests out. With the launch of its new test, Sequenom’s stock price increased by 4.5 percent.
So, Sequenom having suffered a hit to its reputation and finances, with competitors poised to offer similar testing, pushed MaterniT21 to be the first available test, justifying it on the premise that it was “safer” and would help mothers make informed decisions, but implementing it without the needed educational resources called for by its own paid-for study.
With a potential market of up to 750,000 “clients” initially, and millions if its testing can be shown to be reliable for even low-probability pregnancies, Sequenom stands to reap billions of dollars in revenue. Yet it has not invested even a small fraction of this revenue into the educational materials it recognizes are needed for physicians and patients to make informed decisions about prenatal testing and following a prenatal diagnosis. In offering its testing with the business interest of most women accepting it, and knowing that most will choose to abort, without having been properly informed, Sequenom is participating in the reckless elimination of Down syndrome.
As a laboratory-developed test, MaterniT21 currently is not regulated by the Food and Drug Administration. Therefore, absent public pressure, a lawsuit, or shareholder demands, there is no compulsion for Sequenom to fund the educational resources it recognizes are needed to inform expectant mothers’ decisions. One hopes its leadership will recognize that its current offering of MaterniT21 is reckless, and that investing in the educational resources is a small price to pay for a clear conscience.
Mark W. Leach is an attorney from Louisville, Kentucky, and a Master of Arts in bioethics candidate.