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:

IMG_1458

 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.

Comments

  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?

    • Thanks so much for posting this. I just had a horrible experience with a sequenom lab. My wife and I waited three and a half hours for a blood test and ultrasound while they ran around to find a nurse available. They then sit us down and the first thing they say is “you tested positive for DS” ?? – only to backtrack after our shock and state that we have a higher risk factor. I was furious with how it was messaged to us.

  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.

            “http://www.sciencedaily.com/releases/2013/04/130408133754.htm

            http://en.wikipedia.org/wiki/Confined_placental_mosaicism

          • 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?

    • In response to your last question, why don’t the NIPS labs report a positive predictive value, I wish I knew the answer to that one, too.

      • Well, for a couple reasons.
        First, positive predictive value is actually kind of hard to understand. Many clinicians are not entirely clear on what PPV and NPV actually mean so the average patient is even less likely to do so. This makes it a very bad statistic in advertising speak because advertising does not do complicated. “Accuracy” is a very common concept that people latch on to.
        Second, the PPV for NIPS in low-risk populations sucks. Basically if you are already high risk, say a 1/10 risk of an affected pregnancy, then NIPT is 98% likely to detect an affected pregnancy correctly. However, if you are lower risk, say 1/1000, then the PPV is 32%. At 1/10000, it is 4%. (http://www.ajog.org/article/S0002-9378(14)02492-2/abstract. It’s behind a paywall I’m afraid.) This makes sense scientifically, NIPS cannot find what is not there, but is not the kind of thing that a for-profit company with investors really wants to spread around.
        The issue with Turner syndrome has been one of the worst, in terms of false positives. Some providers have reported that every high risk Turner result from NIPS has thus far been a false positive. The other interesting case has been findings of maternal abnormal karyotype. Because the clinical profile of Turner syndrome can be very mild, some women are completely unaware that they may be classified as monosomy. You can imagine the counseling for that one.
        Basically, MCBLINKIE, because it’s bad for business and they have no legal obligation to do so. If the FDA follows through on regulating laboratory developed tests this may change but at the moment, they can basically say what they want.

  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.

  12. This just happened to me but with the nurse at the drs office.. I wish she would have rephrased it because now I have to wait for my ultrasound tomorrow.

  13. I have a question, some one please answer. I am 31 weeks pregnant and 26 years old. I did the Marternity21 test because at one of my ultrasounds it showed my baby girl has only 2 vessels. Other than the two vessel cords all of the scans have been normal and they do not see any abnormalities. I got a call 8 days after taking the m21 and was told that my baby has turners syndrome, and did I want an amino, I said no, if it is in fact turners or any other syndrome I’m still keeping and having my baby, but now I am very stressed out.

    • If you were told that your baby had Turner syndrome based just on a MaterniT21 result, then that is incorrect. MaterniT21 and any other NIPS test is not diagnostic–they can not say for certain whether your child has a condition or not, only whether you have an increased chance for your child having that condition. Given your age, a screen-positive result would still mean more likely than not that your child does not have Turner syndrome. Further, the professional medical organizations do not recognize MaterniT21 or the other NIPS tests as valid for testing for sex conditions, like Turner syndrome. I would ask for a referral to a genetic counselor if you would like to discuss this further with a medical professional.

      • Sir, thank you for both the informative article and for your advice. I have been researching alot and alot of women have been getting false positives. The way the results were given to me, left me speech less and now have me stressing but thank you for the reassurance that everything could possibly turn out okay.I am due January 26th but have a history of preterm labor (last baby was born at 35 weeks) but I will definitely be back to inform you about how everything turned out for me.

        • what ever did happen for you? Im currently going through the something right now.

          • I meant to update. So I had my daughter genetically tested once she was born last month and although I haven’t officially spoken to a genetic specialist, I was told by my Ob that my daughter has what is called mosaic turners. Because they seen normal and abnormal cells. I am still waiting in the referral to the genetic counselor to find out more About her results. So far my baby looks like a normal infant, I’m so nervous.

  14. hi, i’m 44 years old but am pregnant with a 23-year-old donor egg. Does that put me in the category of high-risk 44 or low risk 23?

    • I would think low risk 23, since the “risk” concerns the chromosomes in the egg. I believe some of the labs do not, or have difficulty or lower accuracy, with donor eggs. I would ask your obstetrician, genetic counselor, or maternal-fetal medicine specialist.

  15. Hi I just received results from my M21 testing delivered to me as only negative.The test somewhat put me at ease I will be 24 when I deliver so my age is not high risk. However, I am considered high risk due to a second trimester miscarriage earlier this year with no definitive conclusion or results showing why. Knowing now the way the test actually shows results (it was not explained to me this way) I am going back, and forth with opting for an amino. My last ultrasound showed no physical abnormalities or developmental issues, but my baby has an excess amount of fluid around the heart “most likely” to be in normal range…I don’t like those terms, and an EIF in the heart that is not only associated with heart dysfunction but also Trisomy 21. I am scared to harm my baby going on a fishing expedition for what might not be there but I am also nervous about the false neg/pos results these test provide. Thank you for your time

    • Kristen–As discussed at this post, based on your age, you have a very low chance for having a child with Down syndrome. The MaterniT21 result confirmed this low chance, i.e. meaning your chance of having a child with Down syndrome is very low. We are finding more and more women are relying on MaterniT21’s negative report and avoiding the risk of miscarriage with an amnio. However, if you have to know for certain, an amnio is the diagnostic test. I would encourage you to discuss your concerns with your Maternal-Fetal Medicine specialist or genetic counselor, hoping you have been referred to these specialists. I wish you well with your pregnancy.

      • Thank you Mr. Leach, and yes I will be meeting with a specialist next week to further discuss the screening test results. I will then make known any further testing I desire, and hope for the best. Thank you

      • Hi, I am 39 years old and have 6 healthy children, ages 23-9. I am currently 15 weeks pregnant and had the MaterniT21 test performed during my 13th week. Well, three days ago my doctor called and said he had bad news, that my test results showed my baby has Trisomy 18. I asked if he was sure, and he said the test was 99% accurate. It has always been explained to me that this test is 698% or 99.9% accurate. Now I really don’t know what to do. I have never had a problem pregnancy, and I don’t FEEL like there is anything wrong. I am terrified of having an amnio, partly because I am afraid it will be positive, or it will be negative and I will miscarry. Is there anything that can tell me the risk factor now that my child has this awful condition? Do my results automatically mean I have no chance at having a healthy baby?

        • Tanya–Your doctor is repeating the often misunderstood accuracy rate for MaterniT21 and tests like it. This was the subject of a report just this past Sunday on how false positives remain. I wrote about the report at this post. Also, at a medical conference this year, at one clinic, a screen positive for Trisomy 18 meant more than likely the mom was not having a child with Trisomy 18 (see this post and poster 601). Because MaterniT21 and tests like it are testing DNA passed from the placenta, some theorize that the false positives for Trisomy 18 are due to placental mosaicism of Trisomy 18–where some of the cells of the placenta have Trisomy 18 but not the fetus. According to the Trisomy 18 Foundation, the incidence rate for Trisomy 18 is 1/2,500. Based on a Bayesian analysis (something a genetic counselor could do for you), a 99% accuracy rate really translates into only a 40% chance of having a child with Trisomy 18 (more on this analysis at this post). All this being said, per the guidelines, you should be referred to a genetic counselor to discuss these test results and receive the contact information for the Trisomy 18 Foundation, which can provide you the accurate information on what having a child with Trisomy 18 can mean. Then you can make your decision on whether it is worth risking a miscarriage in order to have a diagnosis from an amnio. I hope you receive the information and support you deserve.

  16. stephanie williams says:

    Thanks for posting this article. I am 30 years old with my first pregnancy at 18 weeks. Yesterday my OB informed me that I had a “positive” quad screen with 1:136 odds for Downs Syndrome. He is sending me for a level 2 ultrasound in a few days. After reading that u/s is not an effective screening tool for Downs, I called and requested the MaterniT21 this morning, awaiting a call back. If the MaterniT21 is “negative” or at least reassuringly low risk level, how necessary would an amnio be? I do not desire to have invasive testing, but who wouldn’t want to know for certain that things are ok? (as “certain” as possible, that is). It is my hope that the u/s coupled with a low MateriT21 will be enough to move forward with this pregnancy without fear.

    • As this article covers, screening tests, be it the quad or the MaterniT21 test, have false positives and false negatives. So, a “screen-negative” is never a true negative. That said, MaterniT21 and tests like it have very low false negatives. More and more women are opting to rely on a screen-negative MaterniT21 and avoid the risk of miscarriage from an amnio. If, however, you must know for certain, then an amnio is the diagnostic test. Professional medical guidelines recommend that you be offered genetic counseling, provided accurate written information about Down syndrome, and the contact information for your local support organization. Fear is largely fear of the unknown and by talking with your genetic counselor, reading about what a life with Down syndrome can be like, and meeting a fellow parent, perhaps your fear will diminish. That said, you still have a relatively low chance for having a child with Down syndrome based on your age and the quad test. I hope you get the information and reassurance you are seeking. More information on accurate information and support resources about Down syndrome can be accessed at the Prenatal Resources tab.

      • Thank you so much for your reply. I will be meeting with a genetic counselor after the U/S and can opt for MaterniT21 at that time. Once again, the OB is stopping short of calling the test diagnostic, saying “it’s a pretty diagnostic test, like 99.9% accurate”. Your article helped me look at this a little more critically. Thanks Mark.

        • Stephanie–I’m glad you’re getting the support you need. So disturbing though that the OB said “pretty diagnostic” and “like 99.9% accurate.” Neither statement even exists factually, i.e. there is no such thing as “pretty diagnostic,” it either is or it isn’t and the 99.9% is the specificity rate, but not the predictive value. See my comment to Tanya above and the links to the posts there which discuss this in greater detail. I wish you well with your pregnancy.

          • Dear Dr. Leach,
            I did NIPT Illumina test and receive positive result for Trisomy 18. I am wondering if you know about the accuracy of this test.

          • Rosie–each non-invasive prenatal screening (NIPS) laboratory claims very high rates for their tests, including Illumina. However, those high rates pertain to their tests’ ability to detect a pregnancy carrying a fetus with the tested-for condition. All of these conditions, trisomy 18 included, are rare conditions. Therefore, there remain false positives and in the case of rarer conditions like Trisomy 18, even with a high rate of detecting affected pregnancies, the tests still report false positives such that a “positive” with a 99% accuracy rate can really only mean a 50/50 or lower chance. In the case of Trisomy 18, false positives have been reported at such a high rate that the practices are changing how they counsel their patients, to ensure they understand it could be a false positive. See poster 421 at this blog post of mine. Professional guidelines recommend that you see a genetic counselor to further explain these results and to refer to the parent support organization for the tested-for condition–for Trisomy 18, one of the organizations is the Trisomy 18 Foundation. I hope this is helpful and that you receive the support and information you deserve. One last post-script, while I have a Juris Doctorate, that makes me a lawyer, not a medical doctor.

          • Dear Mr. Leach,
            Thank you so much for your reply. The info is very helpful. I will hope for the best and prepare for the worst.

          • stephanie williams says:

            Just an update – I opted to have the amnio. Preliminary report and final were all good news. Still awaiting the targeted assay. I appreciate your fast answers to all our questions and comments.

          • Stephanie–thank you for sharing your results. Can you clarify: did you ultimately have the MaterniT21 prior to the amnio?

  17. My maternit21 test came back positive for trisomy 21. I declined an amnio because I will find out at birth either way. I have spent months looking on line for false positive cases. I have only found 1 and have seen hundreds of confirmed cases. That being said it seems to be at least 99% accurate. Is there something I am missing? I hope my test is wrong but I don’t see much hope.

    • Sarah–more and more women are making the choice you have made: to rely on the non-invasive prenatal screening (NIPS) result, in your case MaterniT21, forgo the risk of miscarriage with an amnio, prepare for having a child with Down syndrome, but knowing there’s a possibility of being surprised at birth that MaterniT21 was a false positive. In this series of posts (linked here, here, and here), I covered how the claimed 99% accuracy rate never reaches that high for actually predicting the chances of having a child with Down syndrome. I hope those posts are helpful.
      Having received a screen positive result, professional guidelines recommend you receive genetic counseling to better understand the results, be provided accurate written information, and receive the contact information for your local support organization. The prenatal resources tab (linked here) has the written information approved by the most recent statement on NIPS and links for locating your local support organization. I hope you find those resources helpful as well.

  18. Hello Mark,

    My Panorama screen at 9w6d came back low risk. The OB did not recommend an NT scan, therefore I did not have one. My 16 week ultrasound showed no signs of chromosomal abnormalities. My AFP alone (not the quad) done at 17.9 weeks came back negative. Does a low AFP indicate down syndrome? Although all screens show a low risk or negative, I am still a little nervous due to my age of 38 (will be 39 when I deliver) and that I may have a false negative. I am still considering an amnio but I am scared of the miscarriage risks. I have my 20week ultrasound tomorrow and hoping that will also show no markers. With all my screens being low risk or negative, do you think an amnio is necessary? Why do false negatives occur with the NIPT?

    Amy

    • Amy–False negatives can occur with NIPT for a number of reasons: the tested material was not from the fetus, there was a lab error, there was an insufficient amount of fetal material to be tested. Regardless, it sounds like every screen you have had suggests a low probability of having a child with Down syndrome, which confirms your baseline low chance from just your age (around 99% chance of NOT having a child with Down syndrome). The false negatives with NIPT are more rare than the false positives. Many women are choosing to rely on a screen-negative from NIPT and avoid the chance of miscarriage. Professional guidelines recommend that you receive genetic counseling following your NIPT. Given your multiple screens, I would be curious if a genetic counselor could give a more sophisticated analysis of what all your results mean. That may give you the confidence to rely on the NIPT result and decide the chance of miscarriage isn’t worth the confirmation an amnio could provide. I hope you receive the support and advice you should get.–Mark

      • Thanks for your response Mark. I did speak with a genetic counselor after my 16th week ultrasound, and she laid out the risks of the amnio vs. the low risk of the panorama screen. However, as I am at the halfway mark (20 weeks), I am getting more anxious of the false negative. My fetal fraction was 5.3% and since it was taken before 10 weeks, I am a little apprehensive if the fetal fraction was enough for an accurate result. My OB thinks that an amnio is unnecessary at this point. My 20th week ultrasound appointment showed no signs of abnormalities today so it is a good sign.

        • Amy–“necessary” is a value-driven term in this context. From the beginning of your pregnancy, the only way to know for certain about your fetuses genetic make-up was through either a CVS or amnio, with both risking a miscarriage. So, the screening tests have been done to reassess your likelihood. Every test has come back as unlikely that your pregnancy is affected by a genetic condition. That said, while I doubt it would be reimbursed by insurance, you could pay out of pocket for another NIPS test. The later NIPS is performed in a pregnancy, the more accurate it can be due to more fetal DNA entering the mother’s bloodstream as the pregnancy progresses. I’m not sure that option has been discussed with you. If you do choose to have a another NIPS test, that may give you the reassurance you are seeking, since it would be unlikely to have two false negatives (particularly given it’s unlikely to have a single false negative). I hope this helps.

  19. My sister-in-law is 41 and was just told she received a positive result for Trisomy 18 using the Materni21 test. Her doctor is recommending she undergo amniocentesis to confirm. I have heard you reference the risks of miscarriage from amniocentesis. Do you have any information on how high that risk is? She is really torn. To me, it seems like inviting a very real risk through amniocentesis would be worse than the probabilities associated with these screening tests. So, any information you have on the risks of amniocentesis would be helpful. I do not know her probability or percentage for the Trisomy 18 screening result from the MaterniT test but could probably find out if you think that would influence your response. Thank you.

    • Nicole–the risk for amniocentesis was historically quoted as 1% but in the early 2000’s, a couple of hospitals published studies showing their risk was around 0.7% or lower. The only percentages that matter are the following two: the rate of miscarriage of the specific provider performing the procedure and the rate at the facility where the procedure will be performed. It doesn’t matter if a hospital in St. Louis has a 0.7% miscarriage if your sister-in-law will be at a hospital in Toledo with a 1.8% risk. So, I would have her ask her doctor for his or her rate and the facility’s rate of miscarriage. They likely don’t keep hard data on that, but her doctor should be able to report what his or her own experience has been. I would also have your sister-in-law have her doctor specifically ask Sequenom (the maker of MaterniT21) what her positive predictive value is. If she is told her result means she really has only a 1 in 200 chance of having a child with T21, then she may decide the risk of miscarriage is greater than her risk for having a child with T18 and opt to skip the amnio. At this post are several comments from women getting a screen positive for Trisomy 18 and my responses with links to studies finding false positives happening with Trisomy 18 results. I hope this helps.

      • Sir, thank you so very much for this information. This is exactly what I needed to help her make an informed decision. It is greatly appreciated. Will let you know how it all turns out.

  20. Hi I’m 19 years old and 25weeks pregnant,I did the MaterniT21 and tested positive for trisomy 21 the MSAFP test I did at the begging of my pregnancy was negative for down syndrome but why is this test now positive could this test be wrong I’m to scared to have the amino test done because of the risk, please help I’m a reck

    • Professional guidelines recognize NIPS tests like MaterniT21 as only being accurate in what are considered “high risk” pregnancies. Given your age and screen-negative AFP result, I’m not sure why you were offered the MaterniT21 test. That said, based on your age and with your MaterniT21 result, at best, it means you only have a 40% chance of having a child with Down syndrome–meaning it is more likely than not that you are not carrying a child with Down syndrome (see this post here for more on this). But, the only way to know for certain is with an amnio. I would ask to speak with a genetic counselor to both further discuss your prenatal screening results and so you can make an informed decision about whether you will have an amnio. Having received a screen-positive NIPS result, per the American College of Medical Genetics & Genomics guidelines, you also should have been given a copy of the Lettercase booklet and referred to brightertomorrows.com to learn more about Down syndrome. You can find links to those resources at the Prenatal Resources Tab. Consider this information as well when deciding whether to have an amnio. I wish you well.

      • Hi Jahmeila. First, it is important to stay calm. As Mark (and lots of other people) have repeatedly said, MaterniT21 is just a screen. It doesn’t actually tell you anything for sure, just a suggestion one way or another. The only way to know for sure is to do a diagnostic test like amnio. You should talk to your doctor, but understand that in a large American hospital the ‘risk’ of amnio is very, very, very small. It is considered a completely routine procedure which very rarely has any side effects, let alone a miscarriage. Given your age, if you feel that you need definitive information either way, the amnio is the only way to get it. The only question is whether you feel like you, personally, absolutely need to know one way or another. This is something a genetic counselor can help you think through. The biggest question is whether the information is useful to you in some way. If you think you would consider termination, this information might be relevant. If you would not, some people still find the information useful to help them prepare for the changes in their life going forward. But some people don’t find the information useful at all since they wouldn’t change anything whether the answer was yes or no. So it really comes down to you and your personal needs.

  21. BE Informed says:

    A diagnosis of Down syndrome tells you NOTHING about the prognosis of a LIFE. People with DS live, long, healthy productive AMAZING LIVES.

    There is NO medical or other complication that is untreatable and particular to DS. People are treated and helped for conditions that babies with DS have.

    Please educate, not terminate.

  22. If you have been helped by the information shared here or elsewhere on the blog, then in honor of World Down Syndrome Day (March 21), I hope you will support the National Center either through taking advantage of Lettercase’s sale or with a donation. More here at this post.

    • catherine says:

      Hi… I received my harmony test results a few days ago and I am now waiting to have an aminocentesis. The results of the harmony read low risk (less than 1/10,000) for T21, T18 & T13. We are having a boy but the sex chromosome analysis shows a probability of 2/100 = 2% for XXY Klinefelters syndrome. Is the presence of XXY at any % of probability a positive? or is this level of detection being 2% risk anything to worry about? I can’t seem to find much information about intermediate results like mine, just on the high or low ends of the scale..

      Thank you in advance

      Catherine

      • There is little known about the accuracy of NIPS like Harmony for sex chromosomal conditions. So little that the professional organizations do not recognize NIPS as being valid for screening for those conditions. Coincidentally, I’m at a genetics conference and research by Kaiser Permanente found that more often than not a NIPS result for a sex chromosomal condition meant the child did not actually have the condition. I hope your amnio went well.

        • We just received our results and it listed a 29% chance from Klinefelters. What does 30% even mean? I assume that means high-risk? Harmony lists a 99% accuracy rate for Downs etc, so a 29% risk of Klienfelters confuses me.

          • Ryan–I would have your provider ask the lab what “29%” means. As this post details, “99% accuracy” usually does not mean you have a 99% chance of having a child with Down syndrome.

  23. Hi. I’m 35 years old and had the MaterniT21 done at 11 weeks. My OB called me this past Thursday (a week after the test was sent off) and told me that my test came back positive and my baby will have Down Syndrome. She said the test is pretty accurate and has referred me to a genetic counselor. I was not told that this is a screening test. I was told my baby will have Down Syndrome. This is my first child and there is no family history that I know of (I don’t know if that makes a difference). Your article has given me some hope but I truly don’t know what to think.

    • Your OB is mistaken. See the graph at this post. Given the baseline chance from your age, a “screen-positive” results from a test like MaterniT21 means you have around a 75% chance of having a child with Down sydnrome and a 25% chance of a false positive–but that is a pretty significant chance of a false positive, i.e. 1-in-4. I would share this fact sheet about tests like MaterniT21 with your OB which explains they are screening tests. Being referred to a genetic counselor is consistent with professional guidelines and hopefully you’ll get better advice and information from her. Per the guidelines of ACMG, you should also receive the Lettercase booklet and brightertomorrows.org is another resource identified by ACMG for moms receiving a test result for Down syndrome. I hope you find those resources helpful and that your OB learns more about NIPS tests like MaterniT21.

      • Thank you so much for your reply. The information you and your site provided had been extremely helpful. I feel a little more at ease but Friday feels like an eternity away to see the genetic counselor.

        • No doubt it does. Many moms are finding help through on-line support. One such on-site group is the Downsyndromepregnancy board at babycenter (much of the wisdom in Diagnosis to Delivery is from what the moderators of this board learned). There are other boards at babycenter concerning prenatal test results. I cannot vouch for any of the other boards, but know that the Downsyndromepregnancy board is responsibly moderated.

        • Kundra, I had a similar experience in early March. We were told our little girl has a heart defect and because of my age she will have DS. Then we went home and found out not all CAVCD babies have DS. So then we were told that we could take a new test that was 99.9 accurate. We had declined amnio. We took the test and it came back positive for T21. I was never told it was a screening. I recently explained to my doctor that I have come across numerous parents who have gotten false positive results. Much more for T13/T18 & Turners but the T21 false positives are not rare. I reached out to a mom who recently posted in a DS facebook group that her little girl came early and tests confirmed that her free cell dna test was a false positive. Her little girl has no chromosomal abnormalities. Like myself, she reached out to the DS community under the impression it was a diagnosis. I asked her which test but she didn’t know she only said free cell DNA and her little girl was still in the hospital so I didn’t want to keep bothering her. Our most recent heart specialist updated us on our daughters condition and said that she was aware that there was a strong possibility of DS with the heart defect and Panorama test but without amnio we wouldn’t be sure until birth. We would have the test done at that time. I wish we would have her first. She was very compassionate and obviously didn’t regard our Panorama test as a diagnosis. If our results end up being a false positive, I think ours will be the only one with a heart defect. We find more comfort each day with our little girl having DS. I am still shocked at what I am finding. Not only that but when parents reach out looking for information on Baby Center posts regarding free cell DNA accuracy my posts get deleted and one group owner sent me a private message to stop posting links to articles and other feeds having the same discussion. One lady vented that she thought the test reps were trolling the posts. I have relied on Mark’s links and have read everything I can get my hands on but there is no shortage of false positives. You are not alone. Our genetic counselor was awful. I was also told by a local midwife that they don’t encourage the test because women are terminating for GENDER results from free cell DNA. Best to you! I am trying my hardest to enjoy this pregnancy but I still cry a lot. I am terrified of loosing her.

          • The ACMG recommends patients receive resources with a NIPS result. You can find these and other resources at the Prenatal Resources tab. If you weren’t provided with these, I hope you find these helpful.

          • Hello,
            I have an update on my results. I decided against any testing until after my baby was born. All ultrasounds showed no signs of any birth defects, and I had several. When my baby was born he showed no physical signs of Down’s and his echo cardiogram was normal, hearing test, vision, everything has been normal. The pediatrician had a blood test done anyway to be on the safe side due to the results of the MaterniT21. The test came back as positive for Mosaic Down Syndrome so we had an appointment scheduled with a Genetics doctor. He said the blood test showed a small number of cells that had an extra chromosome. He did a physical exam and also stated he saw no signs of Down’s but he wants us to come back in 6 months for a follow up. I know we just have to see as he gets older if he has any type of developmental delays or physical issues of any kind. I’m just staying prayerful and enjoying my little man to the fullest!!

  24. Hi. I’m 41 years old and 14 weeks pregnant. I had NT at 12weeks and my ultrasound doctor said that everything looked good. I had the MaterniT21 Plus after the NT due to the concern of my age and previous 3 consecutive miscarriage (my first child is healthy, and 7 year-old now). I got the MaterniT21 result yesterday, showing positive for trisomy 21. I was very scared and asked for my risk score but my counsellor said that it was not available, only positive or negative. I understand that the test sensitivity for trisomy 21 is 99.1%. Your article has given me some hope but I truly don’t know what to think. Given my age, what could be my chance of carrying a baby with Down syndrome, do you know?

    I will have amniocentesis next week (when I am at 14 weeks and 5 days). My counsellor said that I will know the primary result of the amnio test after 3 days (and she said many people used this primary results to make decisions on their pregnancy), and the final results will be available after 2 weeks. Do you know if the primary result of the amnio test is conclusive enough to make decision?

    Thank you.

    • Jenny–I’m concerned about the advice you’ve been given. The American College of Obstetricians & Gynecologists (ACOG) practice guidelines for screening tests say a screen result should be reported as a positive predictive value, i.e. what you referred to as a “risk score.” From the chart at this post, your positive predictive value is around a 7.5% chance of a false positive and a 92.5% chance that your child has Down syndrome, based on your age and the MaterniT21 results. The information you’ve given about diagnostic testing is concerning. ACOG does not recommend an amnio before the 15th week, yet you are scheduled 2 days before the 15th week. Also, the preliminary results, known as FISH, is not the full test and does not test as many cells as the full amnio. The only way to know for sure is to wait for the full results. I would recommend getting a second opinion. Further, per the ACMG guidelines, you should have received information about Down syndrome with your MaterniT21 results. Those resources are the Lettercase book, Understanding a Down syndrome Diagnosis (available on-line and in hard copy), brightertomorrows.org, a website with information about Down syndrome, and the AAP healthcare guidelines for individuals with Down syndrome. I hope those resources are helpful to you.

      • Thank you so much for your reply. The information you and your site provided is very helpful. I will check the links you suggested. My counsellor did not give me any information about Down syndrome. She just called me to inform that the test is positive with T21 and recommended me to re-schedule the amnio test earlier (originally, she scheduled it for me at my 15weeks and 2 days). I checked with my OB doc. about this change, she said if the result of the amnio would change our decision on the pregnancy, then do it sooner is better. I felt not at ease with their recommendations, and am very glad to find your site.

  25. catherine says:

    Hi Mark,

    I originally posted on March 27th, at thst time I awaited an amniocentesis procedure as I received an abnormal Harmony test result. (XXY detected PPV 2%, low risk for T21, T18, T13). We received a normal amniocentesis result, so just to give hope to anyone else that received abnormal sex chromosome results via Harmony test, Mark you replied to my post and said that this screening is not accurate for sex chromosome conditions, you were right and thank you for your words of wisdom that kept us sane whilst we awaited the results of our amnio. I wish you all well.

    Thank you

    Catherine

  26. Cheryl says:

    I’m 39 and expecting my second child. I had an NT scan and blood draw for MaterniT21 at 13 weeks, 3 days. The NT measured 2.9 and the perinatalogist told me there was a 1:75 chance of a possible heart defect based on the measurement. I met with a genetic counselor to go over family history and discuss the NIPT options. A few days later I get a call from the GC saying my M21 test came back positive for T21 and that false positives are extremely rare. Needless to say, I was really shocked. No warning, just bam, your baby has downs syndrome. The GC asked if I even wanted to know the gender and said she was really sorry. I’ve been doing a ton of research looking for hope, but getting very mixed information. I have an amino scheduled, but feeling pretty hopeless. I am a scientist and know a little about statistics, so just want to know what a positive M21 result really means. Thanks!

    • Cheryl–See the graph on NIPS PPV at this post. Based on your age, a screen positive with MaterniT21 would mean you have approximately a 90% chance of having a child with Down syndrome and a 10% chance of a false positive. It sounds like your GC is unaware of these helpful resources published this year by the National Society of Genetic Counselors: a fact sheet on NIPS and a fact sheet on Down syndrome. Per guidelines of the American College of Medical Genetics, you should have also received a copy of the Lettercase book, Understanding a Down Syndrome Diagnosis, and you can find helpful information at brightertomorrows.org. I hope these resources and information are helpful.

      • Cheryl says:

        Thank you for the response. Still not great odds, but better than the 99% I was originally told. I did not get any resources from my genetic counselor, so I will review the ones you listed.

  27. Misty White says:

    We just had this testing done. I am older so I figured it would be a smart idea. The results came back the baby has Trisomy 18. I am so conflicted. Do I ask for further testing? I am reading some things that suggest they could be wrong, is this the case? Could they indeed be wrong?

    • Whether you need further testing depends on you. As this post explains, MaterniT21 and tests like it (Harmony, verifi, Panorama, etc.) are screening tests, having false positives and false negatives. Search elsewhere on this blog and you’ll find research papers reporting a screen positive result for Trisomy 18 more often than not turned out to be a false positive at certain clinics. So, yes, the test can indeed be wrong. The only way to know for certain whether your child has a genetic condition is through an amnio, which has a risk of miscarriage. Whether you should ask for further testing depends on what decisions about your pregnancy you would make based on a diagnosis and whether you need that level of certainty. For instance, if you would terminate if you knew prenatally your child had Trisomy 18, the only way to know that is with an amnio. On the other hand, if you would not terminate no matter the diagnosis, then you could prepare for having a child with Trisomy 18 knowing there’s a chance your child does not have Trisomy 18 and then find out at delivery.

      • Misty White says:

        Well, we met with a genetic counselor and based on the ultrasound they took they do suspect T18. The NT was 9.2mm and add the fact that we had the Materni21 test they are pretty certain the baby has T18 or worse. We went ahead with the CVS testing to determine exactly what is wrong with the baby. We did have hope that they were wrong, but didn’t want to look too much into that hope. I have run across so many people who’ve had this testing and it was either a false negative or a false positive. I believe that this lab is very generous with the numbers they offer.

        • Thank you for sharing the follow up testing. While false positives and false negatives do occur, the tests also do detect affected pregnancies. Regardless of the results, I hope you receive the compassionate care and support you and your baby deserve.

  28. TorontoResident says:

    I can relate personally that my wife’s brother’s family was put through an agonizing 2 months of grief and suffering when a doctor in Hong Kong performed this test and told them that with 99.99% certainty their child had Down’s Syndrome. The mental anguish they suffered was beyond description.

    They came very close to following the doctor’s advice and terminating the pregnancy, but something made them stop and wait for an amniocentesis. I want to be explicitly clear. This one doctor told them that there is 99.99% certainty that the baby they were carrying had Down’s Syndrome. It’s not phrased as asking them to further test because of a potential risk, but virtual certainty that the test was conclusive.

    Today, they finally received the result of the amniocentesis and the results came back as 100% normal. IE: no down’s syndrome. The joy they felt gave way to anger and fear of what would have happened if they had followed the initial advice and terminated the baby. If I were them, I’d seek legal counsel.

    This misinformation has to stop.

    • I’m not sure what recourse they may have in Hong Kong, but in the United States and likely Canada there are certain measures they can take to file their complaint to change the practitioner’s behavior.

  29. I’m 39 and currently pregnant with Twins at 11 weeks and this is my 3rd pregnancy. My doc has suggested that I go for the MaterniT 21 test as she said this is the only test that can be down for twins with a higher accuracy rate. Right now I am in a dilemma whether I should go ahead as I read from the comments here, seems that if test is positive, the other alternative is to go for Amnio. I would like to know if this test really have a higher accuracy rate for twins. And also what are the chances of mis-carrying twins with Amnio, my doc said its higher, is this true? I have previously done an amnio on my 2nd pregnancy and the whole process now scares me alot. My 2nd baby turns out fine so my husband is now against all these testing and screening, afraid of it being a false positive resuit.

    • Joelyn: I believe most of the testing laboratories claim to be accurate for twins now, however, to my knowledge, their tests have not been recognized for twins by the American professional societies. Regarding risk of miscarrying with twins being higher, I have no knowledge of that, but it would make sense simply due to twins being a higher risk pregnancy automatically and there being less room in the womb. To know for certain, only amnio will provide that information. A negative result from NIPS has a very low chance of being a false negative, but a positive result, particularly with twins, could be a false positive. I would discuss your concerns with a genetic counselor and your MFM (if you are being seen by one). I hope you get the information and support you need in making this decision.

  30. Hello,
    I am 45 years old and I am 16 weeks pregnant with my 10th baby. I have had 9 healthy, full term babies previous, ranges in ages 22 to 2 years old. I had an ultrasound with this baby for the first time at 11.4 weeks and the ultrasound tech check the nuchal fold and said it was think and looked normal. I didn’t have the blood work that goes with that. Then last week at 15 weeks along, I had my blood drawn for the MaterniT21 test. Today my OB called to tell me that I tested positive for Trisomy 13. Of course I’m devastated, but because of my AMA I knew a chromosomal abnormality was a possibility. So my OB said that I should have further testing to just to be sure it’s not a false positive, but then he added that, “It’s highly unlikely that it’s a false positive. I’m so sorry.” — My question to you is this: is it true that out of the 3 Trisomies, that the T13 one has the highest rate of false positives? I’m just trying to cling to some hope, you know. The lab down in San Diego “Sequenom” is the one who performed my test, and they also did my last baby’s test (which was negative) — their website seems pretty adamant that they are 99.9% and 98.9% accurate but is it just as accurate for the Trisomy 13?
    I’ve been reading this thread and don’t see much discussion about T13 so I was just curious what you know about that specific Trisomy’s “false positive” rate for MaterniT21 testing. Thank you,

    • Katrina: see this post on what “99% accurate” really means (usually not 99% accurate). In the largest known clinical study of tests like MaterniT21, it reported a 50% false positive rate for Trisomy 13 (albeit, there were only 2 total cases of a NIPS positive, with one being a true positive and the other being a false positive). Trisomy 13 the rarest of the major trisomies, so it will also have the highest false positives. With T13, there can be anatomical signs shown on an ultrasound consistent with T13. If those aren’t present, I would find that reason to hope for a false positive. Ultimately, an amnio is the only way to know for sure. I wish you the best, and hope your medical team becomes better informed on what “99% accurate” really means.

      • Katrina says:

        Thank you for your prompt reply to my post.

        Do you think the results are more likely to be accurate with an maternal age of 45? or does that matter in the test at all? (not talking statistics of that AMA, but just within the test’s accuracy) I seem to read the false positives happen with women in their 30’s….

        Also, the blood draw was done in the 15th week — would that make it more likely to be accurate?

        Last, when the extra chromosomes are only present in the placenta and not the fetus, what can be the cause of that? would that only be in the case of a disappearing twin? or can something else cause that? Because I know this was a single pregnancy, and I don’t have any kind of cancer that would cause that, and I myself do not have Trisomy 13. Is there any other way that the extra chromosome would show up up in a placenta if it were not from the baby?

        Thank you again,

        • Katrina says:

          Or can the mother’s AMA product a placenta with extra chromosomes? (sorry, I forgot to add that to my post)

        • Katrina–within the 99% post I referenced in my previous reply are links to other posts here that explain how maternal age does affect the positive predictive value. As women age, they have a greater chance for conceiving a child with an aneuploidy, like Trisomy 21 (Down syndrome) or Trisomy 13. So, yes, being 45 means you had an increased baseline chance for having a child with Trisomy 13 and therefore the chance of a false positive is less than that of a younger mother–since the younger mother had a lower baseline chance. Likewise, the later the blood test is taken in the pregnancy, the more accurate it is because there is more cell free DNA in the mother’s blood from the pregnancy. Lastly, confined placental mosaicism (CPM) is a phenomena associated with the placenta, an incredibly unique organ in the human body. Why it happens, I’m not exactly sure, but disappearing twin is unrelated to CPM. The reason why disappearing twin can result in false positives is because the cell free DNA could have come from that placenta-based cell line. Having a singleton pregnancy, you can still have CPM. As far as a mother’s AMA producing a placenta with an extra chromosome, I’m unaware of CPM being correlated to maternal age. These are all good questions and ones a genetic counselor, MFM, or medical geneticist may be able to answer with greater clarity and certainty.

  31. About a month ago I took the Verifi test through my HMO’s genetics department. This test could only be ordered through a genetic counselor and only to patients above 35 at delivery. At the time I was not worried about my chances of chromosomal defects since I’ve had 2 normal children already, and would just turn 35 two months before delivery. However a week later my NIPT results came back as “aneuploidy detected” for T21.

    I had to wait 3 weeks to take the amnio test, during which I researched online and learned the differences between PPV and accuracy and hoped dearly that I’d be the lucky 1 in 5 whose positive results were wrong for T21. I’ve also grappled with what I would do if the baby truly did have Ds, all while a baby grew inside.

    Unfortunately my amnio results do confirm the NIPT screen. I’m still unsure what the best course is for me and my family but for anyone else going through a similar ordeal, I’m very sorry

    • Sher: thank you for sharing your experience. It tracks what professional guidelines recommend: offering NIPS to “high risk” moms, receiving pre-test counseling, and that results can only be confirmed through amnio. The guidelines further recommend that you receive the Lettercase book, Understanding a Down syndrome diagnosis (which your provider can order a copy for free and is available on-line) and receive the contact information for your local Down syndrome support organization. The National Society for Genetic Counselors has a comprehensive and helpful fact sheet on the basics about Down syndrome, a list of approved resources, and advice for moms considering all three options, continuation, adoption, and termination. I hope you will find these resources helpful.

  32. Im 25 with a daughter who has down syndrome but is smart and very healthy. No heart problems no surgeries. I will be 26 when my second is born. Im getting my m21 test tomorrow. Does already having a child with ds affect m21 results?

    I do understand statistically it does raise my chances but does it affect m21?

    • Donna–a good question. Until the most recent updates to professional guidelines, tests like MaterniT21 typically were limited in being offered only to moms considered “high risk,” one of those factors being if you already had a child with Down syndrome. However, I don’t recall reading any reports that having a child with Down syndrome affected the accuracy of the test, though it could. Tests like MaterniT21 test the cell free DNA (cfDNA) floating in the mother’s blood from her pregnancy, but cfDNA from previous pregnancies remain in the blood as well. Therefore, there is a chance that should your MaterniT21 be “screen-positive” it could be because MaterniT21 tested cfDNA from your pregnancy with your daughter with Down syndrome and not cfDNA from your current pregnancy. Having had a child with Down syndrome, and being 26 years old, your baseline chance for having another child with Down syndrome is approximately 1-in-400. With that revised incidence rate, a screen-positive MaterniT21 would mean you have approximately a 70% chance of having a child with Down syndrome. I would have a genetic counselor or medical geneticist check my math, however, and ask them about the impact of your previous pregnancy. I’m glad to hear your daughter is doing well and I wish you a healthy pregnancy.

  33. Dear Mark-Firstly thank you so much for this site and article which was a great help during me recent pregnancy. Just to share-when I was 13 weeks pregnant I had the harmony test. I understood that the test would give results for the three trisomies, but was not aware that the test gave result of sex chromosome disorders. I was phoned the results a couple of weeks later whilst at work. I was told over the phone ( I am a GP) that the results showed Kleinfelter’s XXY ‘HIGH RISK’-at 5%. This was on a friday. I was offered no counselling and the clinic did not seem to understand what the results meant. After a v stressful 2 weeks we decided not to have an amniocentesis. I understand this result (5%) could have reflected a vanishing twin (picking up some Xs from the lost twin), mosaic XXY or placental XXY/mosaicism. Following birth we had karyotyping which showed a NORMAL KARYOTYPE no XXY.

  34. Hi Mark, I am 29 years old and around 34 weeks pregnant. At around 13 weeks , I was told baby’s nasal bone is not visible and NT 1.6 mm. I was called next day, next day doc said it is there probably but told to come after a week so that she can give me correct measurements. I went to another radiologist suggested by my gynae next day only instead of waiting and NB was 1.3 or 1.4 mm. My gynae suggested Nipt which was negative and my gynae was relaxed but I was still worried, may be because I am a worrier.At 17 weeks I again went for a scan and NB was 2.4 mm (after a gap of 4 weeks). All other markers were fine. At 20 weeks radiologist took different measurements of NB, highest being 5.29 mm and least one as 4.7 mm.She wrote both the measurements. If 5.29 was OK which I think was what was the need to write 4.7 mm ( hypo plastic) in the report. Do they play safe or make us fear??Other markers were fine again. To be noted after a gap of 3 weeks, NB raised to 5.29 mm from 2.4 mm and in the previous scans it raised only to 2.4 mm from 1.3 mm. I got so many scans done because this is my ivf pregnancy and precious to me. I want my baby to be healthy and fine. It is my first pregnancy. I have gone through so much and now this worry. My fetal echo at 23 weeks was fine too. I know all markers are fine but this NB thing is some how not completely going off my mind. I have been worrying but my gynae is relaxed she says it’s a baby with small nosy and nothing else which I wish is the case. At 24 weeks I got a private scan done which said NB was 8 mm (normal).At 30 weeks growth scan I asked my radiologist to scan, he said at this stage it’s difficult to measure. He said NB is little small but all other things are on track. This is. H entire story Mark. You must think of me as mad but I am a too be mommy who is anxious and worried or rather confused. Sometimes I feel so confident that all is fine and other days I fear. Please throw some light.

    • I’m sorry to hear of your anxiety, but you should not feel “mad” as it is a common feeling going through prenatal testing due to the imprecise nature of screening tests. Nasal bone measurements are far from indicative of any particular condition. Instead it is considered a soft marker that when coupled with other screening methods can then be a factor in calculating the odds of having a child with Down syndrome. However, in your case, your other screens have all suggested a low chance for having a child with Down syndrome. Your screen-negative NIPT result is far more indicative of the health of your child than your subsequent nasal bone measurements. Of course, the only way to know for sure is with an amnio, but I understand your desire to avoid any risk of miscarriage. I would feel more confident based on the NIPT measurements and I hope that will provide some calm for you.

      • Thanks for replying. I appreciate the way you are so prompt and help people out there. Thanks for presenting nasal bone facts in such a way that it makes me feel calm and positive. Regards

  35. I am 34 years old and 12 weeks pregnant. I had the panorama test at 11 weeks and my NP called today with the results. I am very low risk for everything except Turner’s syndrome, which she said I was high risk for. The results came back with a 1:255 chance of a positive result. My NP also said that there is a 50% chance of a false positive for Turner’s syndrome with this test. She made an emergency referral to a genetic counselor for my husband and I. With these odds, am I really considered high risk enough to consider an amnio? I’m very concerned but also quite skeptical.

    • Panorama reports you as “high risk” because its results show you have a chance for Turner syndrome that is higher than your baseline chance based just on your age. That said, the incidence for Turner is relatively low and there have not been enough clinical studies for the professional organizations to recognize cfDNA screening as accurate for detecting Turner syndrome or other sex based aneuploidies. I’m glad your NP shared the 50% chance for a false positive–it may be actually higher than that. I would talk through with your genetic counselor your decision about whether to have an amnio. Amnio was always the only way to know for certain, but after discussing your values, what information you are seeking, and what risk you’re willing to accept–both in having a child with the condition versus the risk of miscarriage from amnio–then I hope you’ll arrive at a decision you are satisfied with.

  36. Hi…
    NACE Test (non-invasive prenatal test) test is 100% safe for you and your baby. It is as simple as a routine blood analysis. A small blood sample taken from the arm that is sufficient to run the test. NACE test is a new type of genetic test that screens for birth defects and inherited diseases. The NACE is to detect birth defects such as neural tube defects, Down syndrome, chromosome abnormalities, genetic disorders.

    • I find it laughable that this comment was left by someone apparently affiliated with Igenomix, the maker of the NACE test, is basically a cut-and-paste from the Igenomix NACE website, AND YET the commenter inaccurately says what NACE will test for. NACE DOES NOT test for neural tube defects. If they can’t even represent what their test actually tests for, how accurate can the results be for what NACE does actually test for, hmm?

      • Ok, sorry. Just figured it out.
        Im 46 with 34 year old donor eggs and was told I have a 99% chance of having a baby with DS based on the M21. Is it possible its incorrect because of MY age as the determining factor and not the donors?

        • That could be the possibility, basing it on your age and not on your donor’s age. As this post covers, I’d ask your provider if 99% is your test results’ positive predictive value (PPV) or if they are mistakenly taking a “positive” as meaning “99% accurate.”

          • The genetic counselor said it was 94% PPV. Could you explain that? We had our amnio done today and should have FISH results by Wednesday

          • I wonder where the genetic counselor is getting that figure from, i.e. did he or she come up based on their own computation or was that provided by the testing company. If it’s their own computation, I wonder if they were using your age and not your donor’s age, since at your age, possibly the PPV could be 94% but not at the donor’s age. If it was from the laboratory, that would be rare, since most labs don’t report out PPV. Regardless, I hope you get accurate information with your amnio results (understanding that FISH is still preliminary and the full report is what should be relied upon).

          • I guess I’m confusing things. When I asked her what my PPV was she said 94%. Then I said no an actual ratio, as in 1:200, etc. She said the lab doesn’t give those results. She said my risk is 94% with the specificity being 99.9%.

          • I wonder then what she is basing her statement that your risk if 94%–that is just another way of representing a ratio, e.g. 94% = 94-out-of-100 or greater than 9-out-of-10 or 94:100 or 9.4:10. So, if she believes the lab does not provide a ratio, then what is she basing her statement that your risk is 94% on? Weird.

          • Thank you for your responses. I really wish I didn’t have the M21 test done although what precipitated all of this was an abnormal nt blood test. The NT itself was normal 2.2, normal crl and present nose bone but my lab work put me at a 1:83 risk for DS because of a low PAPP-A, which is placental. I am still perplexed with the M21 results but I guess we will have definitive answers with our Amnio results. I called Sequenom to see if they could give me a better answer but I was told my doctor needs to call.

          • Ok, WONDERFUL WONDERFUL news!!!!! I received my FISH results from my amnio and they’re negative!!! I do realize the final results are the ones to ultimately go by but this is such a relief.
            Basically is all is well in 2 weeks, I has a false positive for DS.

          • Thank you for sharing your results. I hope you have a healthy remainder of your pregnancy and that you enjoy it!

          • I’ll be curious what your doctor finds out.

          • Hello. I have nine healthy children (all with my husband) and we had our tenth child on November 4th. He passed away 6 days later due to complications from having Full T13. My doctors and geneticist all assumed his T13 was random, due to an unhealthy egg (I was 45 when he was conceived) — I did not have an amino when the MaterniT21 test came back positive for T13. We just assumed it was correct based on our 17 week ultrasound which showed many markers. Anyway, once he was born his blood was tested to confirm his suspected T13. It came back showing he was Full Trisomy 13 which was no surprise, but we were surprised to know his was a translocation T13. So to my understanding this means either myself or my husband is a carrier for Trisomy 13? yet we produced 9 healthy children before our T13 son. Is this unusual? Or do you think it could still be due to my age at conception? Also, my other nine children could possibly be carriers, too?

          • Katrina–my condolences on your loss and I hope you and your child received good care. Translocation is something I am less familiar with. Intuitively, I would have thought that, yes, if your child had a translocation, then either you or your husband had a balanced translocation, making one of you a carrier. However, it turns out that only a 1/3 of those children with a translocation inherited from a parent who was a carrier, meaning that translocation uniquely occurs in 2/3 of all cases. This is based on my reading of Table 1 in the NSGC guidelines for delivering a Down syndrome diagnosis (available here). But, as I am less familiar with Translocation, I would encourage you to consult with an MFM, medical geneticist, or genetic counselor. And, because 1/3 of translocation cases are due to an inheritable form, I suppose the only way you could know for sure is for you to have a karyotype done on yourself and if that did not show balanced translocation, then have your husband have a karyotype. But, again, consult with a medical professional trained in genetics.

  37. This website has given me slight bits of hope over the last few days. Reading about the false positives some other women got and the fact that it’s not so clear cut with this test. I’m pregnant with my 4th child, and got a positive for t21 on this test. I was told by the doctor and genetics team that this is 99% chance correct. I had a CVS test done and will receive the results in a few days. I’m a wreck………, however, my NT scan and the finger prick test that goes along with it showed no problems whatsoever. In fact my results from that testing came back as 1:10000. But the doctors tell me that the Maternity test is more accurate, etc. Nothing shows on the ultrasound, everything looks perfect. Please tell me what my real chances are in numbers and if there is hope.

    thank you

    • MaterniT21 has been shown to be more accurate than conventional screening, e.g. the NT scan, when the mother being tested is already considered “high risk,” i.e. she has a “positive” conventional screen result or she had a previous pregnancy with a child with an aneuploidy like Down syndrome. Your conventional screen results would put you at low risk, therefore it is not accurate to say definitively that MaterniT21 is more accurate. To know your actual chance I would need to know your age. And, in the end, MaterniT21 has false negatives and false positives. I’ll be curious to hear what the CVS reports.

      • thank you so much for your prompt response, I am 40 years old. I’m still waiting for my cvs results, and hoping for a miracle

        • I got the fish results. 75% down’s 25% normal. Now we need to wait for the longer results to come back in 10 days. Please help me make sense of all of this.

          thank you

          • Based on your age and your MaterniT21 result, you would have had around a 10% chance of a false positive. Based on the FISH results, Down syndrome has been confirmed as present, but it could be mosaic Down syndrome, a form where the extra 21st Chromosome is only in some of the cells, or it could be confined mosaicism to those cells sampled (though this is unlikely). You’ll need to wait for the full amnio results.

  38. Thank you so much for this helpful website. I’m 11 weeks pregnant + two days, age 41 and just got a high risk result from Harmony for T21. I realize given my age and reading prior comments that this puts my PPV at approximately 92.5%. The only unusual thing is that the report states that the probability of T21 is 2/100 (anything at 1/100 or greater is high risk). That’s only slightly higher than the 1/70 risk for my age. The comments in the report indicate false positive statistics apply to any high risk result, regardless of probability. Do you know if the PPV is lower if the risk is lower than 99.9%? I wonder what would cause the probability to come out lower? I had 22.4% fetal fraction so not having enough fetal cells is not an issue. I saw someone early on this page with a 15% probability given, but she didn’t report her outcome. I don’t want false hope but 2% seems much lower than 99%. My doctor thinks this is an accurate result and is recommending CVS asap. Wouldn’t this test the same placental cells and give the same result? I don’t want to wait until 15 weeks for an amnio. I’m scheduled for an NT scan in a few days but it seems like a normal result would not be reassuring anyway. Any thoughts or feedback would be much appreciated. Thank you for your time.

    • The PPV would change if the sensitivity/specificity of the test changed. I’m not sure how to interpret the report of “2/100.” I’d suggest having your provider call Ariosa for clarification. If that is your PPV, then that is obviously much lower than 92.5%. The National Society of Genetic Counselors have recognized what you note that a CVS has the chance of being less accurate because it tests DNA from the same source as screening tests like Harmony, and therefore an amnio is recognized that the more definitive of diagnostic tests. Harmony has been provided copies of the Lettercase booklet, Understanding a Down Syndrome Diagnosis, which despite the title is recommended by the ACMG and NSGC for providing to patients receiving a positive screen result. If you did not receive a copy, your provider can order one for free (or he or she could ask Ariosa for a copy). Here’s the link to that resource.

      • I am divested, I am 35, just turn 35 last October. I am 4 months 3 days pregnant. I did the ultrasound where they check the back of the baby neck. That results were normal. I was given a 1in 121 of having a baby with down syndrome. I did the nips blood test, all my doctor told me is that this test is 99 % accurate.
        My test came back positive. All my doctor said I am so sorry that your baby is tested positive for down syndrome. I wasn’t given any info.
        On Monday January 25 th 2016, I have my amnio schedule. ( LONG ISLAND JEWISH MEDICAL CENTER IN LONG ISLAND NY)
        My question is should I be worried? What are my chances of having a DS baby. My other 2 kids are perfectly healty.
        Thank you looking forward for a response.
        Thanks a million

        • Based solely on your age, a screen positive NIPS result would mean you had about a 25% chance of it being a false positive. With the probability of 1-in-121, that would mean your chance of a false positive would be about 15%. The reasons for this are explained in a series of posts beginning with this one; the rest in the series are linked at the end. I hope you find these helpful, that your amnio procedure goes wells, and that you actually get the information and support you are looking for with the amnio results. Check out the prenatal resources tab for more information on Down syndrome recommended by professional medical organizations.

          • Hi Mark, thank you for your response. So it’s more likely that I will have the same results, (positive) as the Nips test ?
            Is the nips test actually 99.9 % accurate, or it’s just a screening (meaning).?
            I am so confused and heart broken.
            Don’t know what to think, both of my other 2 kids were born healthy and no trace of down syndrome in both side of the family.

          • NIPS is a screening test. As the posts explain, if it claims to be 99.9% accurate, that means out of 100 women actually having a child with Down syndrome, it will correctly detect 99.9% of them. Equally, out of 99,900 women that are NOT having a child with Down syndrome, that 0.1% means that still a significant number will receive false positives–in the case of a 30 year old, it would be 100 out of 99,900 would get a false positive. But for the 30-year old mom getting a “positive” nips, she has no way of knowing if she’s in the population of those actually having a child with DS or the 99,900 that are not having a child with DS. In your case, your baseline odds were higher than a 30 year, hence why you have about a 15% chance of a false positive. More is explained by the National Society for Genetic Counselors fact sheet on NIPS which it sounds like your doctor could benefit from reviewing.

          • Hi mark, my fish and amnio test both came back positive for down syndrome.
            So heart broken.

          • I appreciate you sharing your amnio result, though I understand how tough they are to hear. There is more information out there and more support, if you would like to access it. The Prenatal Resources Tab has the resources recommended when a mom receives a diagnosis. Given you have reached out on-line, I would also point you to the Down Syndrome Pregnancy board at babycenter.com. It is moderated by wise, compassionate moms who have walked in your shoes. I hope these are helpful.

  39. Thank you for your response.

  40. Darlene BIelich says:

    Hi Mark,
    My daughter is 22, has one healthy baby girl that is 2, and is currently pregnant. She had an ultrasound at about 13 weeks, and , the NT measurement was 6.9. We met with a genetics counselor and Dr. and were directed to have the Maternity 21 test due to the measurement. The test came back positive for Turner’s Syndrome. She is now 15 weeks and, has decided to have the amnio at 16 plus weeks. What do you think her chances are of the baby actually having a chromosomal abnormality?
    Thank you SO much for taking the time to reply to all of these questions. I am sure that you’re giving much hope to many who have been directed toward abortion. God bless you!

    • Tests like MaterniT21, while they list Turner syndrome as one of the conditions they test for, have far less precision in actually detecting it. Studies I’ve seen at conferences report that a screen-positive result for Turner syndrome is just as often a false positive as it is a true positive. Due to this uncertainty, the American College of Obstetricians & Gynecologists do not recognize tests like MaterniT21 for detecting Turner syndrome. That said, the nuchal measurement and the screen result still suggest that a chromosomal condition may be present. The only way to know for sure is with the amnio. I hope you get accurate information and compassionate care and that the procedure goes well.

      • Darlene BIelich says:

        Hi Mark,
        Thanks for the quick response! When you say the result could suggest a chromosomal condition could be present, do you mean it could be Trisomy 13, 18 or 21. Or, could it even be a different chromosomal condition? What do you think the odds are for Turners or something else based on the NT scan and the Maternity 21 at her age? Also, have you ever heard of instances where the NT level went back down to normal after testing higher than the norm? We are steadfast in prayer! Thank you!

        • The MaterniT21 screen result means that Turner syndrome is a possibility. The nuchal measurement could be associated with a number of chromosomal conditions. I have heard (and commenters on this blog have reported) that nuchal measurements have decreased to the normal range on a later scan.

          • Darlene BIelich says:

            Thank you Mark! I will post an update after the amnio.

          • Darlene BIelich says:

            Hi Mark,
            I wanted to follow up in regard to my daughter. We were scheduled to have the amnio done today, but, the Dr. couldn’t hear a heartbeat at the monthly appointment yesterday. We went today for a sonogram to see if it could be detected, but, it was not. My daughter will be having a D&C on Thursday. Thanks for doing what you do by giving so much needed insight to us all!
            We are saddened, but, have faith that this is God’s will and we take comfort in that.
            Many blessings to you!

          • My condolences on your loss, but I appreciate you sharing your experience here for others. I wish you and your family well.

  41. Mark – I just have to say that the information you give on this page provides so much detailed and personalized information that is invaluable to women who are faced with a lot of information at a potentially very upsetting and confusing time. You are truly one in a million and most definitely ‘statistically significant’ :)

  42. Mark – Do these NIPS tests consider ethnicity? I had the Verifi test done and was given a negative result. When I was given a copy of the lab report, I noticed that the ethnicity reported by my my doctor is not correct. I had called the nurse and asked about it. The lab indicated that the result would not change but will re-run to make sure. Now I’m waiting to hear back. Thanks!

    • I have not heard that these tests test for ethnicity. Instead, it seems like an entry error on either your doctor’s or the lab’s part. But, if you do find out that they do test for ethnicity, please share here!

  43. Hello Mark, thank you for your work in sharing this info! There’s far too much misinformation in the medical field. It’s frightening.. My sister-in-law had the MaterniT21 test & it just came back saying there is 99% chance the baby has Down Syndrome. Fortunately, I had read your article recently & have told my brother to make sure to get an amnio done before making any decisions, since M21 is only a screening test & not diagnostic like amnio is. My sister-in-law is almost 42 & they are already blessed with 3 healthy children. My question is, what do you think the likeliness is of the baby actually having DS? Any other advice would also be most welcome. Thank you.

    • I’m glad the info here was helpful. In your sister’s case, due to her age, the positive predictive value is around 96%, meaning a 4% chance that her result was a false positive. You can use this PPV calculator at this link to see for yourself. Also, per the guidelines of ACOG, ACMG, and NSGC, your sister should’ve received written information about Down syndrome with her test result; the Lettercase booklet is recognized by all three organizations. Her provider may already have a copy, or order one for free, or she can view it online. Here’s the link for that resource.

      • Thank you for your reply and the info.. It’s a sad situation :(

        • I hope the resources help. We were sad, too, when we got the diagnosis, but ours was a postnatal, so we were also happy holding our new little girl. The feelings of sadness about the diagnosis faded over time and now, if I am sad, it almost always is due to how people pre-judge Juliet because of the diagnosis before taking the time to get to know who she is.

  44. Hi Mark, I’m 44 years old and this is our pregnancy. I did the Harmony NIPT. Results came as positive, 99.99% high risk with Down syndrome. I’m advised to do CVS, does it mean we are likely to get the same result or the result may tell a different one? Hoping to get more hope.

    • While generally the claimed 99.9% accuracy does not mean your chance for having a child with Down syndrome (more on that here), due to your age, your positive predictive value (PPV), i.e. the chance based on a screen-positive Harmony result that you are having a child with Down syndrome, is 98% (you can calculate that yourself here). CVS is recognized as a diagnostic test, however, because it, like Harmony, tests DNA derived from the placenta, there remains a chance that if your screen-positive result was due to placental mosaicism, then the CVS would be no more definitive than the screening test of Harmony. This is why amnio remains considered the “gold standard” of diagnostic testing, because it tests actual cells from the fetus. (more on this and PPV here). With a screen-positive result, professional medical organizations recommend that you should have been provided written materials on Down syndrome, with the Lettercase booklet on Down syndrome being the recognized resource. Harmony received thousands of these booklets and your physician can order one for free (or preferrably order several in order to provide to other patients) and you can view it on-line at this link. Should you have diagnostic testing that confirms your result, professional guidelines also recommend providing patients with helpful resources, which you can find at the Prenatal Resources Tab.

      • Hi Mark, thank you. Your explanation has been most helpful. We received FISH results today, is positive. We decide to terminate the pregnancy. Very devastated, but we wish we don’t have to face bad news like these in future miracle pregnancy if we ever going to have.

  45. I am 34 and was offered the Qnatal advanced because I turn 35 next month, I am also a lab tech and we drew my blood at my facility and sent it off. I received a call this last Monday that “my baby tested positive for trisomy 13” I asked my ob how accurate this was and she said 1 in 10000 chance of it not being correct. She told me she did not want me getting my hopes up that it is a false positive. I had it drawn at 10 weeks and 5 days pregnant. Our world has shattered as I have suffered 3 losses and we have no living children. This is the worst of the trisomys that are on the test. I have been offered no hope, was asked if I wanted to terminate. I am almost 13 weeks and am being seen at maternal fetal medical in Denver, CO for an early ultrasound. The incomprehensible devastation we now feel has made me angry that I ever got the test.

    • How aggravating that your OB is simply repeating the marketing claim of the labs that it is 99% accurate to tell you that you have a 1-in-10000 chance of it not being correct. I’d want to know how she arrived at that number and what it was based on. Because it’s wrong (and I’ve argued malpractice). According to the Perinatal Quality Foundation’s positive predictive value (PPV) calculator, you actually have a 79% chance that the test result is a FALSE POSITIVE, a far more likely occurrence than 1/10,0000 that your OB mistakenly believes and incorrectly told you. I’d ask your OB to follow up with QNatal and see what they say your PPV is based on your test result, since every lab has different levels of sensitivity/specificity for each particular condition. You can read more on what these terms mean at this fact sheet by the National Society of Genetic Counselors. I hope your OB will read these same links and better advise future patients so they are spared the heart-wrenching experience you are going through due in no small part to being told inaccurate information and not being given any further information. More can be learned about Trisomy 13 at this link.

      • My issue with all of this, is in our laboratory we have validation studies. Qnatal is the newest testing, I can find very little information regarding clinical studies, validation studies. Yet it is touted as being highly accurate. What are they basing this claim on??!! Trisomy 13 is the rarest condition of the three, but I am feeling as if my world is ending. These tests are not even FDA approved. I’m hoping the specialists in Denver will provide me with more hope than my ob did. I will never do this testing again. Never. Ignorance is bliss in a way. I have read journal article after journal article, all by legitimate sources stating that false positives occur especially the less prevalent a condition.

        • Additionally I had a miscarriage at 8 weeks 6 months prior to this pregnancy. I had wondered if the additional representation of chromosome 13 might in fact be from that pregnancy.

          • I, too, thought of that in regards to previous commenters who had had a recent miscarriage. However, I’ve since been informed that the cfDNA that is tested clears the maternal blood stream relatively soon after the pregnancy ends. Fetal cells may persist in the maternal bloodstream from previous pregnancies, but cell free DNA does not.

          • In my molecular genetics class as I have been pursuing my BS in clinical laboratory science, it is stated that so much regarding DNA is unknown, and the rate at which information is being uncovered is faster than research can keep up with. I am just hoping the test is wrong, with all of my being.

          • I empathize and wish you well.

        • Again, something for your OB to ask QNatal about, ie “where’s the evidence to support your claimed accuracy?” And, if they can’t provide a response, then perhaps something for your state’s office of consumer affairs to hear a complaint about.

          • If my test turns out to be false as I pray it will, I actually have hundreds of people praying it is wrong….you can bet I will be addressing these questions. I can’t eat or sleep, I’ve lost 12 pounds when I am supposed to be gaining weight…,this week has been the most difficult of my life. This is not fair to women and it is almost criminal if these tests are being so highly touted as accurate

      • Update, I saw a fetal maternal specialist in Denver, Co, and they did a 13 week scan, she looks normal. None of the significant anomalies were noted, and he recommended another ultrasound there on March 28. He also discussed that T13 does have false positives and went into detail regarding confined placental mosaicism. He said labs should NOT be reporting results as positives and negatives and that providers are giving grave news to so many women. I told him how I was told by my ob, and he said it happens all the time. So glad I got in at 13 weeks, it helped me keep hope.

    • Hi Tessa
      I gave birth to a sweet baby boy last November who had full T13. I actually wrote on this thread back when I was first diagnosed. I was just as frightened as you are. I did the MaterniT21 blood test at 15 weeks, and a week later it came back positive for Trisomy 13. A week after that, we had an ultrasound done to check for T13 markers. We saw a perfectly formed little baby boy from the neck down. But he had a bilateral cleft lip and palate, and he was missing the vermis in his cerebellum. I prayed and prayed that the test was wrong. I refused an amnio because it wouldn’t change anything. I knew he was my baby, trisomy or not, and I loved him just as he was. He grew on target, never measured small. He was born at 36 weeks and was 7 pounds 1 ounce. He was a beautiful baby, and I had hopes that he would survive. By that time I had made many friends in the Trisomy 13 community and knew of many children who were surviving and thriving with Trisomy 13. I had hopes for my little guy. He was beautiful. Unfortunately, when he was born he was unable to breathe on his own, despite his efforts. He really tried to breathe but he had some sort of obstruction. I chose for him to be put on a ventilator until they could figure out what the obstruction was. The night he was born they did an echo on his heart and found that he had a stenosis in his aortic arch. They also did an MRI to confirm his missing vermis, and they also found he was missing his corpus colosseum. Still, I was willing to take care of and love a child with disabilities. What my husband and I didn’t want for our child was a life on a ventilator, so his breathing issues was the major for us. But before we could find out what was causing his breathing issues, we were told that no operation to fix his stenosis would be granted to him due to his T13 status. Without an operation, his heart could not pump blood correctly and he would die. On day five we took him off the ventilator and he passed away. I don’t regret carrying him to term. He did not suffer, we made sure of his comfort at all times, and we got the chance to love on him and show him love. I got to hold him and rock him and examine every sweet inch of him. I will forever miss my little guy. I am so glad that I chose to carry him to term. He was given the chance at life. His body wasn’t strong enough to live very long, but that was HIS life to live. I honored that life.

      I really hope that your test is wrong. I will keep you in my prayers. If your baby does in fact have T13, and should you choose to carry your baby to term please know that there is a lot of support out there. Also, know that the medical community deems these little ones as no value and will likely not support any life saving efforts. You have to be strong and advocate for treatments and operations. With medical intervention, these little ones can survive. Yes, they have varying degrees of disabilities. But they are happy children. I have met quite a few during my pregnancy with my son. They are happy and loved and bring joy to their families. Even in my son’s short life, he brought us much joy. He was loved. We are blessed that he was brought to us.

      Had my son not had T13, they would have operated on his stenosis and he would have lived. If I had to do it over again I would have demanded he be treated as a typical newborn. They waited until his DNA tests came back before they told us they would not operate, and that was 4 days after he was born. In the meantime, they only did comfort feeds for him…just sugar water instead of a life sustaining substance that every other baby in the NICU was getting. Looking back now it’s obvious to me that they were letting him get weaker by the day. It makes me so angry. Total discrimination due to his trisomy. I wish we had fought harder for him. I was on a lot of pain killers and anxiety meds due to my high blood pressure and I believe I was not in my right mind. I have regrets about that…but NOT about carrying him to term. He was a beautiful baby. I’m glad I got to meet him, and he got to meet me.

  46. 39, NT was 1.8mm, first maternal screening was normal, risk was 1:87. Second screening, my hcg was 2.7, AFP was 0.5, risk now 1:36. Did my materniT21 today and have to wait it out. I have one healthy 4 year old, then a molar pregnancy, plus 3 miscarriages to follow. Had all testings done possible and everything looked well. The only problem my Dr and Gyno said that I have age and bad luck working against me. We were not going to try for a second child at this point. I am now 18 weeks and waiting on results from MaterniT21.

  47. Heather Chastain says:

    I did a Verifi test, which came back negative for everything. I had a NT scan done, and scan was normal with normal measurements. I am awaiting the serum reading though, and I have read it will likely come back positive due to my age (will be 39 at delivery). What are the probabilities of DS if the serum tests comes back positive despite the negative Verifi test? I am contemplating amnio at this point. Thank you!

    • New guidelines by ACOG have stated that multiple screens run independent of each other should not be done precisely because those with lower sensitivity/specificity will report more false positives, injecting confusion into the mix. According to the negative predictive value calculator at this site, the chance that your verifi is a false negative is less than 1%–you’re not going to get any more accurate with screening tests. The only way to know for certain from the beginning is with an amnio. But, more and more women are relying on a negative cfDNA screen result like your verifi result to avoid the risk of miscarriage associated with an amnio, accepting the very slight chance that the verifi result may be a false negative.

      • Heather Chastain says:

        Thank you for your quick reply, I really appreciate it! Am I correct in assuming my serum test from the nt scan will come back positive based on my age despite the normal scan? And I read your message to state that I should rely on the verifi results rather than this? It looks as though my negative result in verifi has a .8% chance of being incorrect. Based on this should I forego an amnio in your opinion? Thank you so much in advance!!!!

        • You are correct that your verifi screen result should be relied upon moreso than your serum or NT result. You could receive a negative result from your serum test, but that still would not be as accurate as the verifi result. Your risk of having a miscarriage exceeds your risk that your verifi result is a false negative. However, if you need to know for certain, an amnio is the only way.

          • Heather Chastain says:

            Thank you again for your quick reply. I called the office to inquire as to serum results, and they said that they would only call me if something came back bad-and would have known within 3 days. It has been a week since my test and the OB does NOT recommend I get an amnio at this point bc like you said the risk is greater than the false negative risk. She said the second trimester screenings would also alert me to a problem and it is safer to wait for that….

          • Your doctor is correct, I should’ve clarified my earlier reply: multiple serum screens run independently for conditions like Down syndrome are not recommended; however, 2nd Trimester screening is still recommended to be offered for the reason your doctor noted as it can also detect conditions like spina bifida which NT cannot.

          • Heather Chastain says:

            So after I wrote my last reply, the doctor called and said the NT scan ultrasound was normal but the serum test came back positive for high risk downs. I already anticipated this due to being 39. She said most people would NOW opt for the NIPT but I have already done that ( seems I did things backwards) and mine was normal. She said its up to me now to get an amnio or not. I guess I want to know how much weight I should give the high risk serum result. Am I correct to assume it’s mostly high risk based on my age? Should I just rely on my negative NIPT result? Sorry if I sound redundant I’m just confused. Thank you so much.

          • Your confusion is exactly what ACOG cites as why multiple screening tests should not be done independent of one another. Your serum test came back positive because those tests have a higher positive rate and therefore a higher false positive rate, i.e. simply more women receive a “positive” result with serum screening than with NIPT. As I said before, your NIPT is what you should rely on and then you need to determine whether knowing for sure is what you need to know or whether you’re willing to avoid the risk of miscarriage relying on the chances of your NIPT being a false negative being lower than the chance of miscarriage.

  48. Fern Dapper says:

    Hello Mark, thank you so much for answering so many questions. Your comments have really helped me but at the same time I am still confused and worried. (who would not be). I am 38 years old and had the MaterniT21 done on May 5th. I will be 12 weeks at the end of May. My Dr. called about 2 days ago and informed me that I received a positive result of 40%. My question is, what do you think the likeliness is of the baby actually having DS? How strange this sounds but does the 40% mean… that this is the chance that the Baby could have DS or the baby will have DS and that the 40% is how serious the DS will be in our baby. (I hope this Question makes since). I have never been so scared and worried in all my life. You have said that there is a chart to look at and that they should not give a positive or a negative but should give us a ratio of the results. So what does 40% mean? High or Low risk of having a child with DS? I do know that no matter what happens my husband, I and our families will love and care for this child no mater what. I do not think I want to get anymore testing done b/c no matter what I do the outcome will be the same and I can not change anything about it. I just need to enjoy every minute of being pregnant and be ready for anything. thank you again and I hope to hear form you soon.
    Fern

    • I’m puzzled to by the “40%” figure. If the MaterniT21 result had come back screen positive, at your age that would mean you would have an 88% chance that your child had Down syndrome and a 12% chance that the result was a false positive. So when your doctor says “40%” it doesn’t match up with what a screen positive result would mean. I would ask to see the report your doctor received from Sequenom (the maker of MaterniT21) and see if the report explains what “40%” means. Please see this post and the links in it for more helpful information on what these results mean, fact sheets that can help you and your physician, and the link to the prenatal resources tab where you can find more helpful resources about Down syndrome.

Trackbacks

  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 […]

  3. […] accurate as NIPS may be, it remains a screening test and never definitively detects a chromosomal condition. And, the method of preventing the birth of children […]

  4. […] and does not have the diagnostic accuracy of amniocentesis.  By its very nature, a screening test does not tell with 100% certainty whether or not a fetus will be affected by a given disorder. Unfortunately, in […]

  5. […] that cell-free DNA screens like Sequenom’s MaterniT21 or Illumina’s verifi are never positive, and linking to this post on why saying those results are “99% accurate” amounts to […]

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