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.

      • Diagnostic tests all have false positive/negative rates. Nothing is 100% definitive and anything in the hands of humans is subject to error.

        What I’m curious about is the issue you take with this assay. Are you saying that fetal DNA is not in maternal circulation? Or that it cannot be isolated?

        I’m not sure how it’s done either. PCR?

        • My issue is the same as shared by the ISPD, ACMG, ACOG, and NSGC, and an editorial in the NEJM: that we don’t know what any of these tests actual accuracy rate is because none of the labs have been transparent with their data. Specific for this post, my other issue is that some of the labs report their test results in language that lends itself for misunderstanding by both the physician and patient as to the accuracy of the testing. That said, more and more women are relying on these results instead of having a diagnostic test because NIPS results remain more accurate than any other screen and the expectant mothers would prefer to avoid the risk of miscarriage with diagnostic testing.

          • Ok, I thought you might understand how the test works and where the risks lay specifically with the assay itself, which is the actual issue here. I’ll keep looking. Thanks.

          • Feel free to report back what you find as I would be interested as well. Thanks.

          • I did a bit of searching and I ran across an article (linked below), which you have probably seen, that addresses at least one aspect of what I’m looking for as best as I can understand it without a strong background in genetics. Based on what I’m reading it is extraembryonic tissue cells that are tested and apparently the genetics here can differ from genetics of the fetus as far as aneuploidy goes?

            “it is well known that the cells originate from ‘extraembryonic tissues’ around the fetus so aneuploidy status may not always be identical to the genetics of the fetus.”

            I’m not sure why that is the case. Questions that come to mind is how often is it not identical? Knowing the answer to this could contribute to a false/positive risk number I would think. Further, this is the same issue that comes up with some invasive procedures, correct? -Confined placental mosaicism and perhaps other genetic variations that I’m not clued in about that can present as false positives in other testing.

            This does not address assay issues either regarding specificity and sensitivity. For this reason alone of course women should continue to on with standard screens. I can also understand why people are concerned about some of the false advertising here. I get that now.



          • Gina–thank you for sharing this article. My understanding is that because the new blood test is of “extraembryonic tissue” the best accuracy it could ever achieve is that of a CVS, which is the first trimester diagnostic test. But because CVS also takes samples from extraembryonic tissue, it has a higher false positive/negative rate than amniocentesis, which samples actual fetal cells found in the amniotic fluid. Thank you for sharing further information on the new tests.

  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.

  6. My Question is what can be done after you receive the results. The result is not going to change the fact that you are pregnant and you want to have a baby. Those results are going to stress you out and if your body is having down syndrome what are you going to do. Is there any thing offered once I get the results showing down syndrome. My doctor called me and told me that since I am 39 years old and my other blood test came back with some factors showing the need for further testing. Thy offered the test T21 or amniotic. Now I am sitting and thinking about it and I think I will refuse all the tests because those tests are not 100% and they are not going to change the fact that I am pregnant and also that I want to have the baby no matter what the baby has or looks like. Those tests are not going to change enything for me or my baby.

    • This is a common decision process many parents follow: I don’t plan on changing anything about being pregnant so I do not want the added anxiety that comes with testing. That said, many expectant parents do appreciate knowing for certain beforehand so they can prepare themselves and their loved ones. If you do want to know for sure, then tests like MaterniT21 can help in deciding whether to have an amnio, as many mothers are now relying on a negative NIPS result to avoid the risk of miscarriage of an amnio (though as you say NIPS is not 100%). Regardless of what further testing you may or may not pursue, since you’ve already had an early indication from a test, I hope you do receive good prenatal care with heightened ultrasounds and monitoring so that if there is an associated health condition, like a heart defect, that is identified early and plans can be made for delivery and neonatal support.

  7. Dragomira says:

    I took the MaterniT21 – I am an expectant mother, 34 and tested low risk at the Nauchal Translucency Combined first trimester test, however, tested high risk at the second trimester screening. MaterniT21 was negative for DS, with I was told 99.9% accuracy rate, and 5% margin of error. Because of the contradicting results in these screening tests, I am going for amnio. I am curious if you have a possible explanation why results can point in such different directions. I understand those are different tests, but would you give more weight for accuracy to one versus another? My anatomy scan was great, no indications there of DS or any other issues.

    • My explanation is that all three–nuchal, quad, & MaterniT21–are screening tests, meaning they have false negatives and false positives. However, the false negatives are far fewer than the false positives, and particularly so with MaterniT21–meaning, it is more likely that a “positive” is false than a “negative” is false. Based on your screen results, the statistics would say you are far more likely to not be carrying a child with Down syndrome. Please share your amnio results as I’m sure others are curious about the outcome. And, regardless of the outcome, I hope the procedure goes well and that you receive counseling and support.

      • dragomira says:

        Thank you, Mark. I will share. It will be grueling several days before we know but I am trying hard to stay calm and strong.

        • I did amnio after much deliberation – the genetic specialists at my hospital didn’t seem to think it is necessary due to previous reassuring result from Maternit21. The good news is my baby is totally normal. Largely, they thought of the quad test as being the most unreliable of all screening tests.. To sum up, I guess I am part of the stats where the non invasive blood testing seems to have been accurate..

          • I’m glad your procedure went well. Many women are choosing to rely on a negative NIPS result to avoid the stress of a diagnostic procedure, the result being that the number of diagnostic procedures are plummeting. I hope the remainder of your pregnancy goes well and you enjoy it!

  8. Mcblinkie says:

    There are also quite a few women that have screened positive for their baby having Turner Syndrome (me included) through NIPT such as Maternit21, and amnio results or tests after delivery have shown the baby to be completely normal.

    As women age we can lose an X chromosome due to age related drop off so women over 35 taking these tests should understand that the false positive rate for sex chromosome aneuploidys is actually much higher than the percentage the laboratories report. Once I realized that these tests have not had any independant studies but use their own lab results to determine sensitivity and specificity I became much more sceptical of the use of these as an ‘almost’ diagnostic screening test. My test results through Verifi only showed a negative or positive result, when I asked for the specific numbers the lab would not release that information to me. It seems clear to all us women that the labs should be adjusting their false positive rate but they are steadfast in stating that it is 2% since the original sensitivity was 98%. This seems a little too neat and tidy for me. Why don’t the labs have positive predictive value rates which would give a much better indication of the chances of a positive being a true positive?

  9. Interesting article! Please allow me to share my story. I am hoping that I can help save other women from what I went through.

    Just in case you are all wondering: My husband and I are well educated with career backgrounds in the clinical laboratory sciences. I am a professor with a PhD in science. However, when you’re the patient, things are a bit different..

    I was pregnant in 2012 at age 37 due to give birth in 2013 at age 38. The results of my quad screen was a 1:10 risk/ probability of my baby girl having Downs Syndrome. I was strongly advised by my OB that I needed to get tested because of my age. We also had a Level II ultrasound to check for any early signs of DS – none were found. After both results, we were seen by the Genetics Counselor who, for lack of a better description, put the fear of God in both my husband and me. She was for sure that the baby will have DS. We were pushed to have the MaterniT-21 test — we politely refused. For each and every single visit to the OB we were reminded that our baby will most likely have DS and we needed to do this blood test or the Sequenom one. We kept refusing.

    Our OB (from a reputable teaching hospital in Los Angeles) insisted that my baby’s head was too small (at 5% range) and she was for sure that this is an indication of DS or a genetic disorder and she had to induce my labor. Because of the 1:10 screen, we leaned towards the strong possibility that the baby will have a genetic disorder and most likely DS. She was sure that we needed to induce to save the baby’s life as she was no longer growing appropriately in the womb.

    We listened to her advice and went through with the induction (even though I was only a few days late and got to the hospital 2cm dilated already).

    Long story short, I suffered placental abruption (which I suspect is because of the overdose of pitocin) as they kept telling me that the baby had IUGR or intrauterine growth restriction. I underwent emergency C-section, lost almost all of my blood, went into what I think were early stages of DIC (in laymen’s terms some say this stands for Death is Coming) or disseminated intravascular coagulation, and was transfused with at 8 bags of packed RBCs.

    My baby? She’s a beautiful baby girl, 6 lbs, 12 oz, 21″ long, a beautiful head, and no Down Syndrome. I was in the ICU for 3 days and only got to see text message photos of her. But I am a happy mom! She is now 16 months and I am grateful to be alive. Grateful for my surgeon who saved my life and my uterus!

    Am I angry? You betcha! But my focus is on the gratefulness that I am alive. I am compelled to share my story because I am wondering if I can help other women make decisions about these types of tests. I worried my ENTIRE pregnancy that something was wrong with my baby. I owe all of this worrying to my wonderful medical team (you should sense the sarcasm).

    • Thank you for sharing your story, Lane. I’m glad your daughter and you are both doing well. Your experience supports this study’s finding that too many medical professionals are administering prenatal testing incorrectly.

      • Thank you so much for allowing me to share my story. I hope that other women do the research about these tests and be vigilant about “firing” medical professionals who administer these types of testing incorrectly. We need to be educated consumers. Thank you for this article as well.

  10. Thank you all for your comments, this is very helpful.

    I am a little panicked right now and read a ton of information but still don’t know what to do. I am 13 weeks and 39 years old with my 3rd pregnancy. My doctor pushed Maternit21 at our first visit. I struggled for over a week and then decided to proceed with the NT test as usual. My first pregnancy I was 36 so I was already high risk by age but had beautiful numbers coming back, that of a 20 something year old so I was not concerned this time. However I got the call last week, the scan showed a “slight” because the doctor kept emphasizing that increase in the neck 2.4 and my results were 1:36 for downs only. The other tri’s came back with results of that of a 19 year old. I had a bad sinus infection and was sick when I took the tests. I also had a possibility of a UTI since my urine test came back compromised? I was assured that infection in my system would not alter the tests. Do you know if it would?

    Anyway my doctor said I already wrote the lab work up, come and pick it up and go take the Maternit21 test, my lab just started offering it so no need to go to a genetics counsler. I got up and ran to the doctor’s office shaking the whole way. I didn’t even think about it. If I did maybe I would have said no schedule a CVS now. I think I’m too late to take it and have to wait for an amnio?

    I took the test on Friday and am still waiting for my results. My doctor said although it is a screening test it will be close to positive tell me if the baby has downs and we can trust it. However this was weird, I said what if we get a positive result and I don’t want to proceed with this pregnancy, he said well then I would suggest you go to a genetics counsler to help you understand the results bettter. What? That confused me, wouldn’t he trust and understand the results. He just told me it would be very close to being right? I’m not saying I would terminate, I just wanted to see what the options were.

    Is this true? What can I expect to get back? I’m torn because I do respect and think my doctor is great but I don’t feel comfortable with any of this. I’m not sure if I should still do an amnio, I think I am too late for a CVS.

    Thank you for letting me vent and any thoughts you have would be helpful.

    • As this post explains, MaterniT21 and all the other tests like it, remain screening tests, with false positives and false negatives. Given your age, a screen-positive result from MaterniT21 would likely mean you had close to a 90% chance for having a child with Down syndrome–but that means you would have 10% chance of not having a child with Down syndrome (see this post here). Before making any decision to terminate, professional guidelines and medical ethics instructs that you should confirm your screening test with a diagnostic test. You are beyond the window for CVS, but can have an amnio after 15 weeks. I hope this helps, and I agree with your OB, that ultimately, you should meet with your genetic counselor to discuss this further.

  11. Dear doctor Leach, I am an expecting mother, AMA, I will be 40 at child birth. Do you know if a Maternit21 Plus taken at 10w+1 is just as reliable (having clear that we talk about odds, and not positive/negative results) as the same taken at, say 11 w?
    These few days may make a big difference to me.
    I’m Italian and live in Italy. Blood samples are shipped to California it takes 3 calendar weeks to get results. While I wait for Maternit21 Plus, I will of course get NT scan and, if such scan is worrying, will opt for CVS without further waiting. However, if NT is borderline Maternit21 may eìbe very relevant in deciding about invasive tests. Given the long time needed to get the results back in Italy I’d rather go for Maternit21 sooner than later, however, only if the exam is still reliable.
    Thank you very much for your excellent website.

    • Claudia–Sequenom’s website says its test is “indicated for use as early as 10 weeks gestation.” However, the later any NIPS test is done in a pregnancy, the more accurate it is, due to more DNA from the pregnancy being present in the mother’s blood stream. That said, if you’re AMA, then a screen-positive result from MaterniT21 would mean more likely than not you’re having a child with Down syndrome (or one of the other conditions the screen tests for) (see the chart at this post for the positive predictive value of NIPS tests). A correction and an appreciation: I am a lawyer with a master’s in bioethics, but I am not a doctor; and, thank you for your compliment of the website–I’m glad you found it helpful.


  1. […] tests, NIPS, most of the labs do not report their test results in a 1-in-N format. Sequenom even touts as though it’s a good thing that it reports a “positive” or […]

  2. […] in this practice’s experience, if you received a “positive” NIPS (which there is no such thing), you actually had a 75% chance for a false […]

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