Sequenom’s Whole Genome Sequencing: Reckless Prenatal Care

MaterniT GenomeSequenom, the maker of MaterniT21, has announced a further expansion of its testing: MaterniT Genome. This continues the reckless practice of prenatal genetic testing. 

MaterniT Genome

First off: what is MaterniT GENOME? From Sequenom’s website:

MaterniT Genome webpage

Website image from November 1, 2015

So, Sequenom is promising that MaterniT GENOME will return results on even more genetic conditions beyond the major trisomies (21, 18, and 13), sex aneuploidies (e.g. Turner syndrome), and micro-deletions–all of which Sequenom already tests for.

How is this reckless?

cfDNA screening’s current administration

Cell free DNA screening is becoming an increasingly accepted part of prenatal care. While not recommended for all patients, professional medical organizations recognize that the general population of pregnant women are being offered and are increasingly accepting this testing.

But what is currently known about the challenges with how cfDNA screening is being done?

cfDNA screening beyond recommended conditions

As just detailed, Sequenom (and other labs) are offering cfDNA screening for sex aneuploidies, microdeletions, and even maternal cancer findings. And cfDNA screening isn’t recognized as reliable for any of these conditions.

In the joint statement by the American College of Obstetricians & Gynecologists and the Society for Maternal Fetal Medicine, cfDNA screening is only recognized as a reliable screen for Trisomy 21 (Down syndrome), Trisomy 18 and 13, and y-based testing to indicate the sex of the fetus. That’s it.

Yet, Sequenom presses ahead with offering ever more conditions not recognized as reliable by professional organizations.

ASBH logo

ASBH logo

Physicians do not understand cfDNA screening

At the 2015 American Society for Bioethics & Humanities conference, key findings were reported on how obstetricians understand cfDNA screening.

In an impressive survey of practicing obstetricians (1,101 completing the survey), troubling findings included these:

  • Over 65% admitted their training on prenatal genetic results was only “a little” or “a moderate amount”;
  • A majority were not comfortable communicating prenatal whole genome screening results (PWGS); and
  • They admitted they lacked the resources for interpreting and communicating PWGS results.

In a separate presentation by my colleague Stephanie Allesi with the Prenatal Information Research Consortium (PIRC), she shared results from a qualitative study of obstetricians around the country. Given the above findings, is it any wonder that one of the obstetricians was quoted about cfDNA screening:

it just seems sort of crazy that it works.

The patient experience

Those who have followed this blog know the challenges of cfDNA screening from the perspective of expectant mothers:

  • 2.5-to-1 describe the counseling experience about a Down syndrome diagnosis as negative-to-positive;
  • Mothers are not receiving the rest of the recommended information about the tested-for conditions and referral to support organizations; and,
  • They describe receiving information of uncertain significance–the kind of information PGWS returns–as “toxic.”

A simple review of the comments left on this blog reveals the anxiety, “nightmare”-ish, and lonely experience too many women have with cfDNA screening because they receive results that are inconclusive and for conditions they were not aware they would be screened for.

MaterniT GENOME is akin to driving under the influence

MaterniT GENOME will offer results not recognized by professional guidelines as reliable; will be delivered by obstetricians that admit their training is limited and they lack the resources to counsel their patients; and will be received by patients without any accompanying information, being considered “toxic” information by them.

This is the very definition of reckless.

“Recklessness” is engaging in conduct where the actor does not desire harmful consequence but foresees the possibility and consciously takes the risk.

The classic example is drunk driving: you know you have a higher probability of harming yourself or others if driving under the influence, and yet you still get behind the wheel after a night of drinking.

Sequenom’s MaterniT GENOME is the prenatal genetic testing equivalent of drunk driving. The research shows that it will return results that will be delivered by inadequately trained physicians to inadequately informed and supported patients that will cause them toxic harm.

And, yet, Sequenom MaterniT GENOME will still be offered.

That’s reckless.


  1. Hi Mark – I think that you are placing too much blame on the lab and test rather than on the providers ordering the test. In any medical specialty the person ordering the test should be able to appropriately explain both the test and the results to the patient. If you don’t know how to interpret the result then you shouldn’t order the test. Appropriate pre-test and post-test counseling is necessary. The MaterniT Genome test is targeted to women who are considered to be at an increased risk for having a pregnancy with a chromosome abnormality. All patients in our practice who have this testing are counseled by a genetic counselor or an MFM physician – We have told our local rep not to promote their tests to the local OB’s offices because we would prefer to order the testing. And she has always respected that. You are correct in that the professional organizations are not currently supporting screening for more rare chromosomal conditions. However, the more information that we can give to patients through blood work, the better. There is so much focus on screening for Down syndrome, but there are so many other conditions that families might want to know about before birth. And the majority of our patients decline amniocentesis (at least initially) due to concerns about the risk of miscarriage, so this testing is a good option for them.

    Using your analogy above – I would say that the MaterniT Genome test is like alcohol. Alcohol in moderation (not during a pregnancy) is not necessarily a problem (I realize that the harmfulness of alcohol is debatable, but that’s not the purpose of the post). It’s the person who chooses to drink too much and then drive – that’s the problem. So the test itself isn’t the problem. It’s the physician/provider who chooses to offer it when he/she doesn’t understand it – that’s the problem. Sequenom also has genetic counselors available to providers (and patients too, I think) to help explain any abnormal results.

    So I agree that providers offering the test without an understanding of it is reckless. But I disagree with your characterization of the test itself as reckless.

    • I appreciate your thoughtful reply, but would caution to not fall victim of having a sample size of one, i.e. your practice, to impute how all other practices are administering this testing. That you felt the need to caution Sequenom’s rep not to market GENOME to OB offices suggests there is a chance that other reps are already doing so. Even accepting your analogy of physicians being the middlemen akin to bartenders and Sequenom being a distillery, that simply spreads those who are culpable for the reckless way prenatal testing is administered, but does not absolve Sequenom. The beverage industry invests substantially in drunk driving prevention programs and “drink responsibly” public awareness campaigns. Conversely, the amount Sequenom has invested in providing professionally-recommended patient support resources is de minimis, approaching $0.00.

      • Hi Mark – I wanted to clarify a few things. First, we did not “caution” our Sequenom rep not to market Genome to OB’s offices. We’ve asked her not to approach the OB’s offices regarding their test for “low-risk patients.” Many of the other labs are marketing their test (Harmony, Panorama) to OB practices for use as a general population screening test. Again, the Genome test is designed for patients who meet specific criteria for testing and to my knowledge they are promoting it at MFM offices, not OB practices. The issue of providers ordering testing that they cannot properly explain is also not new – Unfortunately, even traditional maternal serum screening tests are not always explained properly. Also, Sequenom, as well as the other labs, have genetic counselors who help provide education to the practices who are ordering the testing.

        Is it a lab’s responsibility to provide patient information for the conditions that it tests for? Diagnostic testing and maternal serum screening has been routinely performed by many labs for years. I wonder if any of those labs invest in patient support resources. I honestly don’t know if they do. It seems as though you are holding the labs that offer cell-free DNA testing to a higher standard than the labs that perform other testing. In my opinion, it is the provider’s responsibility to provide appropriate information regarding Down syndrome or any other condition that a baby is diagnosed with (or is at a high risk of).

        Prenatal screening and testing is only going to get more and more complicated as additional conditions are included. Again, it is up to the providers to make sure that they understand the testing that they are offering. We can agree to disagree, but I do not think that just the act of offering the test or the test itself is reckless.

        • Thank you again for your respectful reply and I hope my messages are received in the same way. Whether labs provided patient resource materials with earlier prenatal tests or not does not address whether they should have or should start doing so now. The ACMG, NSGC, and ACOG statements on cfDNA screening all recommend patients be provided identified educational resources–the NSGC has even boiled it down to an easy two-page fact sheet. Unlike those other testing laboratories, many of which are at academic centers and not for-profit companies, with cfDNA there is a finite number of labs conducting the testing so they know every positive result that is being returned. And, yet, they won’t even share the NSGC fact sheet much less the recommended materials–even when they have been offered to them for free.

          All that being said, that you are reading this blog and thoughtfully commenting shows that you share some concern and probably agree that prenatal genetic testing can be administered better by more practitioners. I hope that if my tone is argumentative (forgive me, I am a lawyer after all), that it is not off-putting as I would much rather have you working to improve patient care by providing the recommended materials with each test result and encourage your other colleagues to do so likewise. Indeed, it is what they are charged to do by the professional guidelines (and increasingly state laws) and clearly the cfDNA labs, though they appeal to patients by marketing their tests’ ability to provide information, have shown they are not willing to share all the information recommended for patients.

  2. These are all screening tests, not diagnostic tests. They all generate false positives and false negatives and the literature around them adds to the confusion when trying to compare the various screening tests accuracy. Therefore, why do you take exception with Sequenom’s test and not the others, do you have a financial or personal interest in doing so?

    • Read the whole blog. I take issue with how all of prenatal genetic testing is being administered. But Sequenom is at the forefront of its reckless administration.

  3. I rather find this article to be toxic and reckless. Once you enter the group of mothers at high risk, less information is not better than more. Your issue seems to be the management of expectations in regards to inconclusive results or any kind or results?. Welcome to navigating the world of probabilities or improbabilities. Education is crucial to lessening anxieties. There’s only so much that you can assimilate in a 15 min meeting with a genetic counselor unless you prepare yourself before hand. But even if you are not prepared is not like you’re left in limbo. On the other hand I read this and I learned nothing….

    • Re-read the closing paragraphs and perhaps that will explain the idea of recklessness and how Sequenom proceeding ahead with whole genome sequencing in the face of professional guidelines and research showing both trained practitioners and patients are not prepared for it qualifies as being described as “reckless.”

  4. Hello Mark. I am 43 years old and had a negative Maternit21 screening test. A week later I retested because I wanted to do the Maternit Genome, My results were again negative. I just did the NT ultrasound and all looks good. The Negative Predictive Value (NPV) for the Genome test Is more than .999 for the major chromosomal abnormalities so I am confident that my results are a true negative. But I believe the PPV is not as high. I know it’s only a screening test but I think it is highly accurate for those who tested negative. Do you agree with my statement? My questions to you are: What genetic disorders does the Genome not look at that the CVS does? Given that the additional disorders that the Genome looks at are uncommon, how accurate is the test (what is the NPV)? Thank you for your post.

    • Unfortunately, I cannot offer any more information regarding Maternit Genome. Cell free DNA screens, like MaterniT21, verifi, etc., are only recognized for the major aneuploidies (Trisomy 21, 18, 13) and for sex of the fetus. Because the other conditions are so rare, there aren’t studies of a significant enough sample size to know what the relative accuracy cfDNA screening is for them. Unlike Maternit genome, diagnostic tests like CVS and amnio have been recognized as valid for chromosomal microarry analysis, which is a comprehensive genetic analysis, however the information it reports can be of unknown significance, causing more anxiety.

  5. Thank you for your response Mark. I agree that the sample size would need to be very large since the conditions the Genome looks at are rare. I can’t find the website where I read that the rare conditions had a very high NPV but I don’s see how that is possible since the sensitivity for the test (other than Tri 21,18,13) has a very wide confidence interval with a low lower limit. My report shows the sensitivity of the tests along with confidence intervals but no PPV or NPV. I am trying to decide whether to do amnio. I would have done CVS with a very experienced doctor but now it is too late because I took too much time with the screening tests. There are so many rare conditions that I wonder what the additive probability is. Again, thank you for sharing your knowledge on this topic.

    • For what it’s worth, while it’s true that no one knows how accurate genome is, I would expect most medical professionals would look at a screen negative MaterniT21 and Genome as making it highly unlikely for a genetic condition to be present. Whatever your decision regarding further testing, I hope it brings you some peace to enjoy your pregnancy.

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