Your MaterniT21 test is NEVER positive

IMG_1457And it’s NEVER negative, either.

A week ago, I attended the American College of Obstetricians & Gynecologists’ (ACOG) Annual Clinical Meeting in Chicago. It was a quick trip, where I met with each of the non-invasive prenatal screening (NIPS) laboratories before getting back on the road to return home. Something I saw there prompted the title of this post.

How accurate are the new blood tests for Down syndrome?

This past weekend was the Kentucky Derby. So, odds have been at the forefront for all us Louisvillians: which horse to bet on, what odds are they going off at, and can we couple them with two or three others for an exotic bet: an exacta, trifecta, or superfecta?

This thinking about odds should also be kept in mind for every woman accepting non-invasive prenatal screening. Be it Sequenom’s MaterniT21, Ariosa’s Harmony, Illumnia/Verinata’s verifi, or Natera’s Panorama, a very critical point needs to be appreciated:

None of the new blood tests provide a definite answer.

None. Of. Them.

No matter how the results are reported, you should understand that if you are pregnant, and you get a non-invasive prenatal test result, it is never positive or negative.

NIPS tests are screening tests. They are a recalculation of the probability that your child may–emphasis on MAY–have Down syndrome (or one of the other conditions they test for). Every one of these tests has false positives and false negatives.

What are patients being told?

But note what Sequenom highlights on its booth for its MaterniT21 test:


 Clear, direct results

+ Positive or negative results

- No risk score!

Sequenom highlights this as though it’s a good thing. In fact, it’s against ACOG’s own professional guidelines.

When ACOG changed the standard to offering prenatal testing for Down syndrome to all women (versus only those over the age of 35), it emphasized that results should never be relayed as a “positive” or “negative.” Instead, results should be presented as a probability calculation (or “risk score”).

But, here is Sequenom, the market-leading NIPS company, highlighting that it reports its results contrary to these professional recommendations, as though it is a selling point for its testing.

Invasive testing is the only option for a definitive answer.

ACOG’s statement on NIPS recommends that patients should be counseled that confirmation is needed with diagnostic testing because no NIPS test is a true positive or true negative. But, what is a mom to think when her test result is reported by the testing lab as a “positive” and not a probability ratio?

Sequenom is not the only lab to suggest its test results are more accurate than they actually are. But if you are receiving these test results, you need to understand that none–NONE–of the new blood tests provide true positives or true negatives. You can only gain that certainty through invasive testing.

NIPS tests remain just screening tests. They are never truly positive or truly negative. Get confirmation through invasive testing if knowing for sure is what you thought you were buying with a NIPS test.


  1. Madeline Levy says:

    I would just like to say say that my Sequenom rep is very clear that MaterniT21 is a SCREENING test. When counseling my patients, I’m confident in saying that MaterniT21 has 2.14% “positive” results, much like the test it will eventually replace, the amniocentesis. The other tests have far more issues with off-base calls, like Verifi with almost 8% of the results “aneuploidy detected” or “aneuploidy suspected”, leading to more invasive screening.

    • What risk score are you able to provide your patients based on your MaterniT21 results? I.e. does Sequenom provide a risk score (it’s marketing booth says it doesn’t). I ask because most would hear a high detection rate and believe that is their personal odds for having a child with Down syndrome, e.g. 99.5%. ACOG PB 77 recommends that when discussing screening results they should be delivered as a probability, e.g. 1-in-1,000, 1-in-250. Can you provide that probability based on the results provided by Sequenom and do you?

  2. Mr Leach, first let me thank you for your website. It seems to be very informative and helpful. My particular comment, or question rather, is related to materniti21 and panorama, both of which my partner has had. She is considered “high risk” at 43 years of age and her first pregnancy. NT scan came back at 1.81, and both tests came back as low risk, or 1:10,000 risk of having down’s syndrome, or any genetic disorders that those tests look for. We seem to be at very low risk for the child being born with down’s etc. which is our biggest fears. My concern is that these tests do not take into account her age. Do you know of or have any data showing the increased risks as age might increase the chances? Or are these tests taking her age into account?

    Thank you for your help on this topic. I’m sure as time goes on, more data will be available for the general public or those not in the industry.

    • Phil–my understanding of MaterniT21 and Panorama is that they do not factor in the mother’s age as they are looking at the genetic material from the pregnancy itself. My understanding of the first trimester nuchal translucency-combined test is that maternal age is factored into the algorithm that reports the probability assessment. As shown in the table at this post, your partner’s baseline chance for having a child with Down syndrome based on her age is between 1:85 and 1:35 (the numbers reported weren’t specifically for age 43, but 40 and 45). Therefore, the NT result of 1:81 likely was for a lower chance than just her baseline chance. With both MaterniT21 and Panorama returning results of 1:10,0000, that is a remarkably lower chance, and the ability of those tests to determine which pregnancies are not carrying a child with Down syndrome is more accurate than their ability to determine which pregnancies are carrying a child with Down syndrome. Given that you have three screen results showing a much lower chance than your partner’s baseline chance according to her age, it would seem more likely than not that the child does not have Down syndrome. I would recommend you discuss your concerns with a genetic counselor.

  3. One thing you’re missing is that maternit21 is only offered to women who are high risk. It is not a general public screen, thus the lack of A risk score result.

    • It is only supposed to be offered to high risk women, but providers admit to doing otherwise. Regardless, it’s a screening test and ACOG practice bulletin 77 says to not report results as “positive” or “negative” but as a risk score. Reporting results as “positive” or “negative” is factually wrong and contrary to professional guidelines.

  4. Hi Mark,

    As an expectant mother will you please explain the issues with these assays and why they are not reliable? I was so excited for it and now am coming across alternative information. thanks

    • The issues with the non-invasive prenatal screening is that they still report out false positives and false negatives. As a result, while they remain the most accurate screening test for patients considered high-risk, their results still hold the potential for being false. Only through diagnostic testing can a patient know to a near certainty whether their child has a genetic condition.

  5. Thank you very much for your work on these new testing procedures.

    How accurate are these test in determining the gender of the baby? Is this aspect of the test also a “screening” or is it more like a positive/negative result (Eg. male or female)?

    • I am not for certain, but my understanding is that the test results for gender, particularly if male, are even more accurate than for aneuploidy. Your physician can check with the lab on the level of certainty.

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