Noninvasive Prenatal Testing for Down syndrome: 99% malpractice

New Blood Test 99 percentIf you’ve been told you have a 99% chance of having a child with Down syndrome based on a prenatal blood test, your practitioner likely has committed malpractice.

Hyping of 99%

Noninvasive prenatal screening (NIPS) tests have been hyped for being “99% accurate.” This promotion of NIPS’ accuracy comes first from the NIPS laboratories themselves:

  • Sequenom, maker of MaterniT21: “Results from a method validation study demonstrated high performance of the MaterniT21 PLUS test (>99 percent specificity) in accurately detecting these autosomal trisomies and select microdeletions.”
  • Sequenom on its targeted test for Down syndrome and Trisomy 18, VisibiliT: “demonstrated a greater than 99% sensitivity and specificity for trisomies 21 and 18.”
  • Ariosa, maker of Harmony: “the Harmony test can be performed as early as 10 weeks of pregnancy and offers a greater than 99 percent accuracy rate for risk assessment of trisomy 21, which causes Down syndrome.”
  • Natera, maker of Panorama: “Across multiple clinical trials, Panorama has been validated globally for detection of trisomy 21, trisomy 18, trisomy 13, monosomy X, and now triploidy, with a sensitivity of greater than 99 percent for trisomy 21, trisomy 18, trisomy 13, and triploidy, 92 percent for monosomy X, and a less than 0.1% false positive rate for all syndromes tested.”
  • From the website of Illumina, maker of verifi (screenshot taken June 7, 2015):

Illumina 99

Due to the laboratories’ marketing, patients report being told by their obstetrician or their genetic counselor that “the test results are 99% accurate” as though those are the odds of that patient having a child with Down syndrome. Indeed, that is the headline of an article written the week of this blog post (see image at top).

This is a confusion between what is called the test’s “sensitivity” and the test’s “positive predictive value” or “PPV.”

Sensitivity, Specificity, & PPV

Sensitivity is what percentage of pregnancies actually carrying a child with Down syndrome are detected by the test. For the claim of 99%, the laboratories are saying that out of 100 pregnancies carrying a child with Down syndrome, their test detected 99 of them. This also means their test did not detect 1 of the pregnancies actually carrying a child with Down syndrome, who received what is called a “false negative” result.

There is also a test’s “specificity.” Specificity is the percentage of pregnancies not carrying a child with Down syndrome that the test accurately reports are not affected. Referring to Illumina’s claim (above) of 99.94% specificity for its test verifi, that means of 10,000 pregnancies not carrying a child with Down syndrome, verifi accurately reported that 9994 were unaffected.

But that means verifi incorrectly reported that 6 pregnancies were carrying a child with Down syndrome, i.e. 6 “false positives.”

Positive predictive value is the computation taken of a mother’s chance for having a child with Down syndrome, based on her age or a first-level screen result, and then applying NIPS sensitivity and specificity rates to that chance.

For instance, a 30-year old mom has approximately a 1-in-a-1,000 chance for having a child with Down syndrome. If you had 100,000 30-year old expectant moms, then 100 of them would be pregnant with a child with Down syndrome and 99,900 would not.

Applying the sensitivity rate, 99 of the 100 actually pregnant with a child with Down syndrome would be detected. Applying the specificity rate, 60 out of the 99,900 moms not carrying a child with Down syndrome would instead be given a false positive result. For each 30-year old mom, then, when she receives a “positive” verifi result, she could be one of the 99 actually carrying a child with Down syndrome or her test result could be one of the 60 false positives because she is not carrying a child with Down syndrome.

This breakdown means a verifi result for a 30-year old woman has a positive predictive value (PPV) of 62%, i.e. she has a 62% chance that she is actually carrying a child with Down syndrome and a 38% chance that she is not … but not a 99% chance that she is carrying a child with Down syndrome.

Standard of Care

If a provider tells a patient her NIPS test came back “positive” so she has a 99% chance of having a child with Down syndrome, the provider likely has committed malpractice. Not just because the provider is giving his or her patient incorrect information, but it is against the standards of care set by professional medical guidelines:

  • ACOG, the American College of Obstetricians and Gynecologists, advised when reporting screening results: ““it is preferable to provide patients with their numerical risk determined by the screening test, rather than a positive versus negative screening result using an arbitrary cutoff.”
  • The Society for Maternal-Fetal Medicine (SMFM) instructs: “counseling should include a discussion of the predictive value of cfDNA as a screening test (including the possibility that the result is a false positive)”.
  • The National Society for Genetic Counselors (NSGC) states in its 2015 Fact Sheet for NIPS:

A >99% risk score does not mean there is a greater than 99% chance that the pregnancy is affected with a condition.  * * * In order to determine the chance for a high risk result to be a true positive, one must calculate the positive predictive value. * * * Positive predictive value (PPV) is the proportion of positive results that are true positives. In other words, PPV answers the question: “What is the chance an abnormal NIPT means the fetus has this condition?”

Avoid Malpractice

I do not throw around a term like “malpractice” lightly. It immediately puts professionals on the defensive. But women keep being told that based on their MaterniT21/verifi/Harmony/Panorama test result they have a “99% chance” of having a child with Down syndrome, when almost always that is a confusion by the professional of the test’s sensitivity rate and not the test result’s PPV.

If you were told you have a 99% chance that is based on the sensitivity rate and not the PPV, your provider committed malpractice. He or she gave you inaccurate medical information contrary to the standards of care for interpreting NIPS results.

Comments

  1. interesting… so None of these screenings are accurate.

    • More accurately said: too often their claimed accuracy for sensitivity and specificity (99%) is confused for positive predictive value.

      • so what the point of taking these screenings when they are not fetal DNA diagnosis nor FDA approved

        • NIPS remains the most predictive of screening tests, when used as a second-tier screen. As a result, more and more women are choosing to rely on the NIPS result: if it is screen-positive, to prepare for the likelihood of having a child with a condition and if negative to avoid the risk of miscarriage of diagnostic testing, though understanding there’s a chance of a false negative. At least, that would be the clinical utility of the tests, helping women prepare and make decisions about further testing.

          • I got the harmony test done 2 weeks ago and my doctor called to tell me I tested positive for an extra Chromosome 21 and that he was very sorry. I only got the test because I was excited to find out the gender. I’m terrified! I’m 38 and my husband is 41. This would be his first child. I go back in Tuesday for a level 2 ultrasound and a CVS test. Wish me luck that this was a false positive!

          • According to the calculator, you have a 12% chance of a false positive. If you didn’t receive information about Down syndrome with your test result (it sounds like you did not), here’s a link to the online resource recommended by professional guidelines.

  2. Thank you.

  3. I was told my test was positive for Down Syndrome. I did it late at 24 weeks. I then had amino done which was negative. I had my baby and baby does not have Down Syndrome.

    • Which NIPS test?

      • Panorama

        • I took the screening test and the blood work done and it came out that I have 99 percent chance of having a baby with Down syndrome. They told me I still have to take another test with the needle in my belly ,I am only 23 years old .. please tell me if there’s a chance of those results coming out negative and me being able to have a healthy baby …

          • At your age, a screen positive result would mean you have just a 50/50 chance of having a child with Down syndrome, not a 99% chance. You can see for yourself at this calculator where you enter Trisomy 21 and your age to see the chance your test is a true positive is 50% and a false positive is 50%.

          • Mark, me and and wife also took the same test and it came back positive for downs. She is 30 years old. We are getting the Amino test done next week. Can you please tell me the odds of there being a false positive for us?

          • Based on this calculator, you have a 39% chance of a false positive. Resources at the Prenatal Resources Tab share other information to be provided with a prenatal test result about Down syndrome. I hope you find them helpful as well.

  4. This is a very interesting and very informative article. Thank you for this. My sequential screening came back with a 1:5 risk of my child having Down syndrome. They wanted to have an amnio…I refused. They then told me about the Maternit21 test. They wrote me a script. I held on to it. They kept asking me when I was getting it done b/c I could only do it at a certain time. I finally told them to stop asking b/c I wasn’t go thru with further testing. The 1:5 risk was enough of an answer for me and it didn’t matter anyway. He was my child. My son is 2 and he does rock an extra 21st chromosome!

    • Further misinformation: on one of the first investor calls, Sequenom highlighted how MaterniT21 is “trimester independent.” Your sequential screening had to have been performed in the first and second trimester. MaterniT21, on the other hand, can be performed during any trimester of the pregnancy, and, what’s more, it is more accurate the later in the pregnancy because more cfDNA is present as the pregnancy progresses. Suggests something troubling as to why your medical team thought you must have it done before a certain time, no doubt the time allowed for termination in your state.

      • Mark…that was another reason why I didn’t go through with the Maternit21 testing. I know termination is mentioned and suggested, which was not an option for me at all. I would love to know the stats on how many pregnancies where terminated as a result of a “positive” but had no chromosomal anomalies. Fortunately, my son was born without any congenital issues that are common with Down syndrome.

        • Last year it was reported that between 6% and 13% of the pregnancies that ended in termination following a NIPS result did not have diagnostic testing. I’m working on a more recent study that appears to put the number around 10%.

  5. My Maternit21 came back as a Negative for t21 in 2012. According to my GC , the accuracy was at a 99.8 percent and no further testing was necessary . My son was born in 2012 with T21 and was a birth diagnosis . Malpractice is and was NOT an option because it was not guaranteed as 100 percent Accuracy so as someone who has experienced this first hand, yes you ARE throwing the word “malpractice” around too lightly. Your information provided in regards to the NIPT results is appreciated but throwing around the term “malpractice” is not.

    • The post specifically addresses mothers being told, that based on the sensitivity, they have a 99% chance of having a child with Down syndrome. But it works the same for specificity, the ability to rule out unaffected pregnancies. That computation is called the negative predictive value (“NPV“). While few mothers are bringing claims for malpractice based on their PPV not being accurately told, there are malpractice cases being filed by women who received a screen negative and were led to believe it was a true negative. The malpractice is in providing inaccurate information regarding the accuracy of NIPS, which as detailed above, is contrary to medical standards of care.

  6. My Materni21 results came back positive for T21 — which the test has the highest accuracy for. I am 44, will be 45 at delivery. My understanding is that the positive predictive value for my age and T21 for this test is 99.5%. Is that math correct? I feel that for younger women, the 99% number doesn’t hold but at 45 at delivery, the 99% sensitivity does happen to correspond with a 99% positive predictive value, i.e. my baby has a 99% chance of having DS.

    • Helen-see the graph at the center of this post. Based on your baseline chance from your age, a “screen positive” from MaterniT21 would mean you have a 96.7% chance of having a child with Down syndrome. I hope you were provided the recommended resources following a NIPS result. If not, please check them out at the Prenatal Resources tab.

      • Aaron reeves says:

        My wife just had a Panorama test that came out as a high risk for Down syndrome. The doctor told us she did have Down syndrome. The risk factor was 99/100. The fetal fraction was low. Only 3.3%. Her prior risk factor was 2/100. She is 39 and will be 40 when she gives birth. The doctor provided no other information other than we need to get a diagnostic test done. My wife doesn’t want to and doesn’t even want to speak with a genetic counselor. We are having the baby and putting it into Gods hands. If we have a child with DS that is what God wants. My question is for reassurance. Based on the info provided is it really a 99/100 chance based on the risk factor we will have A DS baby?

        • No it is not 99/100, as this post covers. However, at your wife’s age, a screen-positive means that she likely does have a 90/100 chance for having a child with Down syndrome, with a 10% chance of the test result being a false positive. Since you have expressed your intent to continue the pregnancy knowing you have a high likelihood of having a child with Down syndrome, professional guidelines recognize the resources at downsyndromepregnancy.org as being helpful for expectant mothers. The website has a book available as a .pdf or for purchase that covers the common issues and questions expectant parents have. Reaching out to your local support organization is another helpful resource professional guidelines recognize. I hope you do find these resources helpful.

          • Thanks Mark! How much does the fetal fraction play into this? Her report only had 3.3% by Panorama. I’ve read where they really need 4% to even be able to accurately report a high or low risk.

          • That is correct: 4% is usually the cut off and incorrect results have been associated with fetal fractions lower than that.

  7. Mark,

    I’m scouring your site and thank you for all of this information. My beautiful daughter Lizzie is blessed with Ds and is 12 months old. I had no testing prior. We learned a few weeks ago via Materni21 that we are expecting another baby with T21. My age (42) certainly is a factor. Lizzie is completely healthy so we know that the NT scan would not offer clarity. We have an amnio (for peace of mind) scheduled after the counselor spoke with Materni21 and came back with info suggesting that “the z-score is not as high as they would expect” and perhaps its mosaicism. I’d really appreciate your comments. Its the first time I’d heard z-score mentioned and the counselor did not give me further #s.

    • Maureen–while not a statistician or formally trained in genetics, the z-score relates to how much chromosome is expressed in the sample taken. Low z-scores have been tied to low fetal fractions (i.e. the amount of cell free DNA in the sample) and low fetal fractions have been related to inaccuracy in results. So, with the z-score not being as high, that why they suggest perhaps its a case of mosaicism, since mosaic Down syndrome has a lower percentage of chromosome 21 as compared to full trisomy 21 like what Lizzie and my daughter Juliet have. Not to give false hope, but with the low z-score, the result simply could be in error, i.e. a false positive, or, if it is mosaic T21 that was detected, then that could be from confined placental mosaicism, meaning the placenta has some cells with mosaic T21, but Lizzie’s sibling does not. However, given you have a child with Down syndrome and your age, it is likely that your child has some form of Down syndrome, mosaic or full Trisomy 21. I’ll be interested in your amnio results if you feel comfortable sharing them and I wish you a safe and simple procedure with immediate recovery.

  8. I’m currently 13 weeks pregnant with my first child. We received a positive panorama test for T21 about a week ago. We met with a genetic couselor yesterday who told us there is a 99% chance our baby has DS (same information we received from my primary OBGYN). A specialist performed an in-depth ultrasound in which he found no physical markers for DS. Ultrasound was completely normal. I’m now 30 (29 when we conceived). How worried should we be at this point? We’re going in for amnio in 2 weeks.

    • Kayla–I would ask your genetic counselor and OB if what they are telling you is the positive predictive value or the specificity of Panorama (I would be they are confusing the latter for the former). Feel free to share with them the NSGC fact sheet which is linked in this post. Also, as this post details, you have a pretty even chance, based on your age and the Panorama result, that your test is either a “true positive” or a “false positive,” hence the need for diagnostic testing through amnio if you want to know for certain. Should you go through with the amnio, I hope the procedure and recovery goes well and that your health care provider provides you better, more accurate information. If the amnio does report a diagnosis of Down syndrome, please visit the Prenatal Resources tab for links to the materials recommended by every major medical organization for you to receive.

  9. Mark- I really appreciate the information. I spoke to my genetic counselor and asked for a copy of my test results. My fetal fraction was 4.2% with a risk score of 99/100. My genetic counselor assured me that the Natera calculates the PPV and enters that as your risk score, instead of just repeating the specificity of Panorama. It sounds like I’m getting incorrect information. Am I correct?

    • I agree that it sounds like you’re getting incorrect information. From other comments on here and my conversations with others in the industry, Counsyl is the only lab regularly reporting PPV.

  10. The Verifi test told me in 2013 that my daughter does not have Down syndrome, but she definitely does!! 🙂

  11. Hello Mark, I had the Harmony test done. My dr then told me test was positive for DS I asked him what was the percentage he said the Harmony test does not give percentages it just gives a positive or negative. He then said this test is so accurate that there is a 99% chance of your baby having DS. I have been stressed out about this. I am 41 yrs old with my second child. My first child is perfectly healthy.

    • Laura–you may want to share this post and this fact sheet from the NSGC with your doctor so he stops saying tests like Harmony give a 99% chance. Based on your age, you instead have around a 90% chance with a 10% chance of the result being a false positive. You can see by the chart at this post, the chances are dependent on your age. I also expect you did not receive the recommended resources to accompany a screen-positive result. You can find those at this tab and I hope you find them helpful during this stressful time.

  12. HI, I had de progenitor test does about 4 weeks ago, it ca,e out inconclusive, they repeated it two weeks ago and just got results today as positive, they are going to refer be to a maternal fetal clinic, I was 30 when got pregnant and 31 right now, what are my chances of. False positive for t21?

    • Based on the calculator linked at this post, you have a 39% chance that your result is a false positive. Professional guidelines recommend (and laws in certain states) require patients to receive written information and referral to support resources with a screen positive result. You can find these recommended resources at this tab on this website.

  13. Cynthia says:

    I did the 1st trimester screen cane back positive and went in at 15 wks 4 days had another sono baby looks fine and was referred ti genetics becauae i was at a 1:5 i went to genetics was told that sono put me at a 1:24 for ds but nipt was necessary. I got results a few days ago and was told i tested positive again for t21 at a 75% chance baby will have ds. My husband and i are scared. Sonos look great no soft or hard markers what are the chances baby doea have ds. Im 17wks2 days and i have an anatomy scan 4.19.16.

    • Based on your screen results, your chances that your child has Down syndrome appears to be 75%. Usually, when reporting an NIPT result, the number “99%” is inaccurately reported; therefore, that they said 75% suggests to me that was your NIPT’s “positive predictive value” or “PPV.” You could confirm that by asking them whether 75% is your PPV.

  14. Andrea Foster says:

    I too had this test done by verifi. I’m 28 years old and all my Dr. told me was “it’s positive, he has it. Trisomy 21. Down syndrome.” She didnt say what my ratio was either. Just “it’s positive.” They did find 2 hard markers in my 2nd trimester ultrasound which I did at 19 weeks 5 days, but no birth defects like with the heart or bowels. I’m waiting on my appointment with the ultrasound specialist hopefully that will shed more light. Thank you for this article!

    • It’s unfortunate to hear that even with cell free DNA being used since 2011, practitioners remain ignorant about its results. The post at this link has links to helpful fact sheets for patients and practitioners on what cell free DNA results mean and how they should be delivered along with links to the resources also recommended to accompany a screen-positive result. I hope you find the post helpful (and that your practitioner visits the link).

      • Andrea Foster says:

        I went to my Dr.’s office and got the copy of the results and it literally has “POSITIVE” all over it. I have no clue how to read the test results. From what I’m looking at the chances are pretty high for him to be positive which I’m okay with. This is what it says:
        Test: Chromosome 21
        N: 500 (what does “N” stand for?)
        Sensitivity: >99.9% 90/90
        95% CI: 96.0-100.0
        Specificity: 99.8% 409/410
        95% CI: 98.7-100.0
        Accuracy: –
        95% CI: –

        The markers that were found were a cystic hygroma and a LT Choroid Cyst that measures 5x3mm

        I am 28 years old and the blood was drawn at 19w5d

        Any help or input or advice would be greatly appreciated.

        Thank you!

        • Andrea–Thank you for sharing the results from the lab. Unfortunately, ACOG with its most recent recommendations say that results, even screen results, should be reported as positive or negative, but that there should also be a risk assessment provided as well–so ACOG has endorsed the confusing way screen results are reported because screen results, by definition, are never positive. Based on what you’ve shared, while the ultrasound findings are considered “soft markers” they do not result in a reassessment of your baseline chance based on your age. Being 28, a screen-positive cell free DNA result means that it has a 56% chance of being a true positive and a 44% chance of it being a false positive–so, again, far. from. “positive!” In order to know for certain, the two options are to have an amnio or to find out at delivery. Regardless of which choice you make, professional guidelines recommend that you receive accurate, written information, with every U.S. professional medical association recognizing the Lettercase booklet as the resource to be provided about Down syndrome. I hope all of this is somewhat helpful.

  15. Hi, Mark. I’m probably grasping at straws but I ran across your article tonight. I’m 38 yrs old and am 15 weeks pregnant. I had the progenity test and my baby tested positive for Down’s. I was told by my dr that this was 99% accurate. I didn’t completely understand all the statistics in the article so I was hoping you might be able to give me a bit of a breakdown. I’m so wore that my baby has this. I go for an amnio on Tuesday. Thanks for your help.

    • Click through the links at this post and provide your doctor with the fact sheet on cfDNA screening to help him understand how the “99%” accuracy claim is not what is known as the test’s “positive predictive value” or “PPV.” Then click the link for the PPV calculator where you can enter Trisomy 21 and your age and see that the chances that your test result is a true positive is approximately 88% and the chance that it is a false positive is 12%–meaning you have a greater than 1-in-10 chance that your baby does not have Down syndrome. Click this link for a further breakdown on the math that goes into determining the PPV. Then, to learn more about Down syndrome, click the final link for the Prenatal Resources tab where you can find the professionally recommended materials for expectant moms seeking to know more about Down syndrome. I hope this helps.

      • Thank you so much for your response. I had an amnio yesterday. I’m still not getting my hopes up but a 12% false positive rate is much better than 1%. I couldn’t find the link that broke down the statistics. I had a miscarriage and partial molar pregnancy in January, 2016. I’m wondering if there could be any residual markers from that baby (who also had Down’s syndrome).
        Thanks!

        • See the middle of this post which breaks down the math using a 30-year old mom as an example. Cell free DNA leaves the mother’s bloodstream relatively soon after a pregnancy ends so your prior pregnancies should not affect your cfDNA screen result.

  16. Hi Mark, I am 34 weeks pregnant and two weeks ago we found out that my unborn baby has trisomy 13 according to blood test. I am 29 years old. They said we have a high risk for T13 from the ultrasound and the blood test I’ve done. How accurate are these tests since I am so close to my due date? Thank you for the article.

    • The detection rates for Trisomy 13 are lower than that for Trisomy 21 (Down syndrome). Based on the positive predictive value calculator (linked at this post), your cell free DNA result for Trisomy 13 has only a 7% chance of being a true positive and a 93% chance of being a false positive. Given that you are into your third trimester, a condition like Trisomy 13 would likely have anatomical characteristics that can be seen by ultrasound. You should have received written information about Trisomy 13 with your test result. Professionally recommended information about Trisomy 13 can be found at this link.

  17. Angie A. says:

    Hello Mark,

    I had my NT scan at 14 weeks 2 days pregnant with a result of 3.8mm. I had the NIPT test done that same day and the results came back at 91% positive for Down syndorme. The genetic counselor is convinced based on my age of 41 and my percentage that my baby has Down syndrome. No nasal bone was seen during the ultrasound, but no other markers were mentioned. I was wondering what your thoughts are regarding my stats. Thank you.

    • It sounds as though your genetic counselor has counseled you correctly, reporting the positive predictive value (PPV) at 91%, which means there remains an 8% chance of your result being a false positive. NT scan alone is not recognized as a valid screen for Down syndrome, only when it is combined with a test of your blood for different factors than what NIPT tests for. Professional recommendations recognize NIPT as a first tier screening test for women of your age and further do not recommend another screening test for chromosomal conditions. The next step to consider is whether to have confirmation through an amniocentesis which can be performed after 15 weeks. Lastly, you should have been provided information regarding Down syndrome with your test result. If you weren’t, you can access the recommended resources via the Prenatal Resources Tab.

  18. Hi Mark,

    This information is so helpful. I took the Harmony test and results showed 99% chance for T21. Genetic counselor said it was impossible to determine PPV because I am off the charts- this was an unplanned pregnancy- I just turned 47. She could only go with the PPV for a 45 year old. She encouraged us to do a CVS, though counseled us that the results would almost certainly confirm the NIPT. She assured us that any potential mosaicism (sp) would be ruled out even though only placental cells are being tested. We are 12w4d.

    I’m glad to know that our practitioner insisted that any decisions should be done only after a diagnostic. I just want to know that the CVS is just as accurate as the amnio would be, knowing the potential for placental mosaicism for T21. We are not grasping- we’ve accepted the results- but want to make sure we are being as thorough as possible before our final decision.

    Thanks for your time.

    Polly

    • Due to your age, your PPV is actually 99% with a 1% chance of a false positive. I’m not sure what “chart” your GC is referencing, but you can find your PPV based on your age at the link for the PPV calculator in this post. In that same post are links to fact sheets about cell free DNA screening by the National Society of Genetic Counselors. In those fact sheets, you’ll see where CVS is not as accurate as amnio since both cell free DNA screening and CVS test DNA derived from the placenta and not necessarily from the fetus; amnio tests fetal cells. Feel free to share the fact sheets in the post with your GC and if you weren’t given information (as you should have been) about Down syndrome, the Prenatal Resources Tab shares the ones recommended for expectant mothers. The recognized resource, the Lettercase booklet, just launched a webapp that can be viewed here.

  19. Hi Mark. I just got my panorama results with a 99% high risk for T21. I am 38. My husband and I are so confused about this test. Fetal fract trying 7.9% what does that mean?

    • See the links in this post, specifically the link to the PPV calculator. Based on your age, your positive predictive value, i.e. the chance that your child has Down syndrome (T21) is about 88% with a 12% chance of the test being a false positive. Please also see the link for Down syndrome resources as you should have received that information as well with your test result.

      • Hi my name is Kimberly. I’m 21 years old and 14 weeks pregnant. Almost 2 weeks ago I had an ultrasound done showing a NT measurement of 4 mm I then had blood drawn my doctor and genetic counselor told me not to worry about it because there are plenty of healthy babies born with 4mm reading. I recieved the test results by phone yesterday for the panorama screening the genetic counselor told me my baby boy is very high risk for T18. I just don’t understand how this happened I’m going in for a amnio This Friday and should get the results in 2 weeks. My question is have you
        Heard a story like Mine? I thought I was low risk considering my age and my family history they told me everything would be fine. I’m so scared to get the results the genetic counselor also told me my baby would be born with severe birth defects and mental retardation. Is my risk really as high as she said? I’d love your input Mark. Please everyone keep my baby boy in your prayers.

        • See the links in this post here, particularly the one for the positive predictive value calculator. Based on your age and a screen-positive result for Trisomy 18, the chances that your son actually has Trisomy 18 is only 14%–you have an 86% chance that your result is a false positive. As this post covers, scaring patients based on a misunderstanding of the accuracy of cell free DNA screening like Panorama is malpractice. Please share the fact sheets on cfDNA screening with your providers which are linked in the post with the calculator. And, yes, if you search the blog for Trisomy 18 or T18, you’ll find several comments where moms were told their cfDNA screen was “positive” for T18 but it ended up being a false positive.

          • Thank you so much for your feedback Mark I am getting an aminocentisis this Thursday doctor called me to move it up. I will be 15 weeks this week. I don’t understand why the genetic counselor would tell me I’m at such a high risk. I feel helpless for the the time I don’t know if it’s a positive T18. When I first met with the genetic counselor she told me I’m considered low risk for T18 because of my age. I have a question for you Mark I’ve been doing a lot of reach and I found that the Panorama testing is the “most accurate” of all the non invasive testing is this true? Do you think it’s still possible that my baby will be born healthy even with a NT scan of 4mm and a “positive” testing for T18? Also why would I get a reading like this could it be an different birth defect?

          • Per my previous comment, the odds are far greater that the Panorama test is a false positive than a true positive, so yes it’s possible that your child will be born without Trisomy 18. False positives can be attributed to any number of factors: simple lab error, an error in the algorithm used by the lab, human error in handling the sample, and, particularly with T18, the fact that what is being tested is DNA from the placenta, which can have “confined placenta mosaicism” for conditions like T18–so your placenta could have cells that have Trisomy 18 but your baby would be completely unaffected. No one knows which lab offers the most accurate results because none of the labs are transparent about their lab performance.

  20. I went to my doctor yesterday to have a consult with him about the lab results and he said he would not be surprised if my amniocentesis came back abnormal he pretty much said the odds are against me even at my age. He also vouched for the panorama testing saying it’s pretty accurate. This left me extremely discouraged. After I get my lab results from the amniocentesis I’m thinking about switching OB/GYN’s and I will opt out of doing the panorama testing in my next pregnancy. I’m having an amniocentesis done today and will get the results in two weeks I will keep you updated on the results. I would not recommend any woman get the panorama testing done you were put in agony for weeks and left questioning whether or not your child will be healthy. Thank you for your feedback Mark you are giving me hope that my baby boy will be born healthy!

    • The doctor said he is leaning more to the abnormal results because of the NT scan coming back at 4mm but I also read online that the NT scans are extremely unreliable is that true? What factors contribute to the NT scan coming back at a higher number than it actually is?

      • NT measurement alone is not recognized as a valid screening method for conditions like Trisomy 18. Only when combined with analysis of proteins in the mothers blood (a separate blood-based test than those like Panorama) is the NT-combined screen recognized as accurate. Still, even when combined with a maternal serum analysis, the false positives outweigh the positives for a mother your age.

    • I hope the procedure and recovery goes well. Feel free to email your OB the fact sheets on cfDNA screening.

      • Just wanted to give an update FISH results came in positive for T18. I really thought this was going to be a false positive.

        • While FISH are still screening results, these multiple screening results make the possibility of them being a false positive extremely unlikely. I hope your care givers are providing you compassionate support with accurate information about the condition and references to support organizations.

  21. Charlotte Safrit says:

    I was told by my genetic councilor last week that my panorama score was 1:5 for 22q microdeletion. My genetic cousilor did not use her own calculator but simply stated that was the risk. We asked her about the ppv but she just stated that the score is what the company’s algorithm assigned me. I’ve been reading everything I can find since hearing this heartbreaking news. I don’t understand how they can be so certain in my case. Every person I’ve seen post on every site I’ve seen had better statistics than I do. I did read in the investor’s Natera conference call of August 7, 2016 that they were going into the 3rd phase of testing in a week from the call date, which is expected to result in more accurate testing for microdeletions. Natera received my test 8/16/2016, so I suppose it could mean that 1:5 is actually a good indication rather than a bad one considering the new improved testing is supposed to be more reliable? In your experience eith this company do you think my councilor is correct in her assumption that the panorama score is indeed including all variables? If they are changing the way they score microdeletions when will these new statistics become public?

    • Cell free screening like that of Panorama has not been recognized by professional guidelines as accurate for microdeletions like 22q. Where results are reported, it is recommended that the laboratory provide several pieces of data. If Natera, the lab offering Panorama, provided its specificity and sensitivity, then you can calculate your PPV using this calculator by entering 22q as the condition, your age, and the specificity and sensitivity numbers. If Natera did not report those numbers, then your GC could request them.

  22. Hello how are you , hope everything well , I am 12 weeks pregnant, at week 10 I did the blood test visibilit studying t21 and t 18 and sex, high risk my result was as follows
    High risk
    Trisomy21 : > 99/100
    Age related risk . Post- NIPT Trisomy21. 1/278 . 99/100
    Trisomy18 . 1 / 2,826 . 1 / 10,000

    performance
    This study was blinded analytical validation designed to be representative of pregnancy general population cohort , ten weeks of gestation or greater.2
    Chromosome
    performance confidence Interval ( 95 % CI)

    Trisomy 21.performarce confidenc interv
    Sensitivity : > 99 %. 80.8-100 %
    Specificity : > 99.9 %. 99.5-100 %
    Trisomy 18
    Sensitivity : > 99 %. 65.6-100 %
    Specificity : > 99.9 %. 99.5-100 %
    Y chromosome
    Accuracy : 99.3 %. 98.6-99.7 %
    As I do the calculation to know what is the probability that the result is false , thank you very much Mark for your cooperation and help. Thank you very much and sorry for my little English

    • It looks like the test is reporting a positive predictive value of 1-in-278, meaning only a 0.35% chance of being a true positive. I believe these numbers are reporting a screen negative, but I would confirm that with your provider. You can also plug the numbers into this calculator to find out for yourself.

  23. Hi,
    I am 33 years old pregnant with my 3rd child. I had the blood test Harmony done a couple of weeks ago. Last week we found out I am at an increased risk for T13. My results say the PPV =18%. I have seen a lot on here about T21, but not as much for T13. I feel like 18% is a lower chance than most, but I wanted to see if I am accurate in my thoughts. I know the sensitivity is lower for 13 so I did not know if that meant I have a higher chance of the test being positive. My OB has set me up with a high risk genetic OB, but could not get in me in until next week. This waiting is awful and I am trying to be more hopeful, but am not sure if I should. The results can be confusing and the more I read the more confused I get. Thank you for your article and any information is appreciated. Thank you1

    • If Harmony is reporting the PPV as 18%, then that means you have an 82% chance that the result is a false positive. Put another way, odds are the test is a false positive. The lower sensitivity would mean the test is less accurate at detecting pregnancies carrying a child with T13, but there is also lower specificity, which means the test returns more false positives, too.

  24. 'A worried sister' says:

    Hi Mark, I have been reading some of the comments on here and I am looking for some reassurance for my little sister who is currently 22 weeks pregnant. She had the down syndrome screening at her 12 week scan and that came back as low risk ( she is only 22 years old). So all was thought to be fine until she went to her 20 week scan where they discovered some fluid around the heart and couldn’t get the baby to look face on so they could see nasal bone and so gave her two options of amniocentesis or having private blood test that is non intrusive. She opted for the latter and had that test done on Thursday 15th September. She recieved the results this Thursday just gone (22nd september) and she has been told it is 99% positive that she will have a child with DS. How accurate really is this result? I’m looking to give her a little reassurance as she is very upset at the moment? She also had amniocentesis booked in for tomorrow, but any help in the meantime would be greatly appreciated.
    Thanks

    • See this post here and the links in it. Click on the calculator and you can see that her actual chances of having a child with Down syndrome are just 49%, meaning she has a greater chance that her test result is a false positive. The fact sheets on cfDNA should be shared with her providers so they’ll stop saying the incorrect “99% positive.”

  25. Christina Dixon says:

    Hi Mark! I am 32 years old. Ny Michael scan came back fine but my panorama test came back 38/100 for Down syndrome. I looked at support groups and there were ladies that had weird numbers like 78%, 32% just like mine and all came back normal after cvs or amino. I had cvs so I am waiting on results. Your thoughts?

    • I’m sorry I meant Nuchal scan! Damn autocorrect

    • Every pregnancy has it’s own “positive predictive value” or actual chance for having a child with Down syndrome. From what you share, it sounds as though your Panorama test reported at 38% chance of having a child with Down syndrome, meaning you had a 62% chance that the Panorama test result was a false positive. Saying it another way, your Panorama test result means it is more likely that you are not having a child with Down syndrome than the chances that you are. Every result like Panorama’s (e.g. MaterniT21, verifi) has a chance of being a false positive and diagnostic tests, like CVS and amnio, confirm whether the screening result is a true positive or a false positive.

  26. Maegan roliczek says:

    I’m 25 years old and had the maternit21 test done and my Dr said it came back positive for down syndrome. She said it’s 99% accurate and it’s my decision to do further testing or to terminate my pregnancy. I feel as if I need to do further testing. What are the odds that this was a false positive?

    • Your doctor has advised you incorrectly. See this post and the calculator linked therein. Based on your age and y our MaterniT21 result, you have a 51% chance that the result is a true positive and a 49% chance of it being a false positive. I wonder if your OB would advise a mom to terminate based on essentially a coin flips chance of the test being at true positive. Please share the post and the links on the cfDNA screening fact sheet with your OB–it sounds like she could benefit from reviewing them. You may also wish to point her to my post, linked in the same post, of how saying it is “99% accurate” is tantamount to malpractice.

  27. Mark,
    I recently had the harmony test done and tested high risk for T13. Went to the doctor and had an ultrasound done at 13.5 weeks where the doctor said that ultrasound was normal. However, went on to say that the test was 97% accurate. I’m 31, will be 32 when I deliver. I am scheduled for another ultrasound at 18 weeks and amnio. What are my chances of having a false positive reading

    • According to this calculator, you have an 11% chance that your test is a true positive and an 89% chance that it is a false positive. Sounds like your doctor needs to read this post–feel free to share it with him or her.

  28. Hello, I’m 18 weeks pregnant and will be 38 when I deliver. I had the panorama test done which came back with a PPV of 99/100 and they said that others that scored in that range had a 91% chance of DS T21. The fetal fraction was 11.3%. But they also had my ultrasound listed as abnormal but the DR office told me it was normal.

    I previously had progenity done and that came back as 1:35.

    I’m considering the Amino just so I know for sure but my DR is saying that he believes that with the two results that we are going to have a DS baby and that we should not do any further diagnostics testing.

    I’m just not sure what to do and how much the number may be skewed by Panorama having the wrong ultrasound result.

    • I’m not sure whether the ultrasound result was factored into Panorama’s reporting of its positive predictive value (PPV). To be clear, since Panorama reported a 91% chance of having a child with DS, that is the PPV; the “99%” cited by Panorama pertains to its specificity and sensitivity, but not the actual chance of having a child with DS. Based just on your age and a screen positive cfDNA test result, your PPV would be 81% according to this calculator. Whether to have diagnostic testing should factor in whether the result would change the course of your pregnancy and, if not, whether the value of simply knowing for sure is greater than the risk of procedure-related miscarriage.

    • Hello KERRIM79… I am curious if you proceeded with diagnostic testing. If you are sharing, what were the results?

  29. Hello,
    I recently found this site after I was given a positive result for t21 on the maternit21 test. I will be 37 years old at the time of delivery with my third child. On my first trimester screening, I had a 1:121 risk due to a low Papp- a score of .27 and my age (at least that is what my obgyn told me). My hCG was good at 1.25 MoM as well as the NT measurement at 1.5 MM. While the maternit21 results stated that an increased amount of that they found an increased amount of t21 material was found, the lab director comments stated that the amount was below which is usually detected on a full trisomy. He also stated that this suggests a possibility of mosaicism in either the fetus or placenta. Finally he states that trisomy 21 is a common finding that is often confined to the placenta (CPM). The genetic counselor that I have been working with didn’t great job of explaining all of this to me. I asked her if the low Papp-a could be related to the possibility of CPM and she said that yes, the two could be related. Has anyone ever had similar results ( low Papp-a and then finding of CPM from an amnio result)? I go for my amnio on 11/1 so it’s really just a waiting game and wondering and hoping that it is just CPM. I know that is going to offer a whole other set of hurdles but that is what I am hoping for at this point.

    • I welcome other commenters to share if they have had similar results of low Papp-a and a finding of confined placental mosaicism. I wish you the best for your procedure and recovery.

  30. Hi mark , I recently got the cell free DNA test results. I was told I was high risk for my baby having downs. I’m 13 weeks, i have a cvs schedule in a few days. I was told I have a 90-95 % chance that this baby has downs. I’m 36 this is my second baby, first baby is completely fine. How much does my age play into the probability? I’m really scared and anxious. I called my geneticist asking the difference between the cvs and amnio because I read that the cvs only tests the placenta and not the fetal cells. She told me that if she sees 3 lines that make up downs it’s accurate, if less than that then we will do the amnio…. it’s just all so confusing and all providers are basically telling me the baby has downs. Please help and clarify thank you!!!

    • Your age establishes your baseline chance for having a child with Down syndrome, which is then adjusted based on the cfDNA screen results. That baseline chance, then, goes into calculating your “positive predictive value” (PPV), since cfDNA screens have false positives and false negatives. The Perinatal Quality Foundation has a helpful PPV calculator where you can see for yourself that your actual chance for having a child with Down syndrome based on your cfDNA results is not 90-95% but 82%, with an 18% that your result is a false positive. The National Society of Genetic Counselors has recognized that because CVS tests DNA from the same source as cfDNA screening, CVS shares the risk, like cfDNA screening, of reporting results based on confined placental mosaicism (where there are cells in the placenta with a 3d copy of chromosome 21 but the fetus does not have a 3d copy). Therefore, amnio is recognized as the more definitive diagnostic test. See this post that has links to fact sheets on cfDNA and PPV, the calculator, and links to learn more about Down syndrome.

  31. Hi Mark, I am currently involved in the discussion around justification of introducing NIPT into the UK National Health Service as a second tier screen. Not very keen. One of my objections (apart from the massive amount of ethical issues) is that it is being sold as reducing the numbers of amniocenteses necessary, thereby reducing costs to the NHS. The proposal, as I am sure you are aware, is that NIPT be offered to women with high chance (over 1:150) from one of the current blood tests, and only those who come out with a high likelihood of having DS from NIPT will be offered an amnio (hence the cost saving).

    My feeling is, that with NIPT having 1:1054 chance of false negative in high chance women :
    a) if they wish to know for sure, all women would need an amnio following NIPT as well (costs increase, not decrease).
    b) If they are happy to continue with such a low chance as 1:1054 then no need for amnio- but
    i) are they understanding the statistics, ie. they could be that one or
    ii) they wouldnt have had an amnio anyway, (NIPT will increase cost) or
    iii) there is a ‘real’ difference between the results of the two screening tests, and 1:1054 is a result produced by statistics rather than real life, therefore women are right to trust the negative NIPT
    iv) human nature says that with a 1:1054 chance of a baby with DS then women will happily take that tiny chance, and be fine (not sue) if they are that 1.

    Basically I am not sure if I am unhealthily obsessing over that 1:1054, and that it wont cost save, and should rather focus on ethics of offering testing, and forget about false negatives….
    Thanks

    • I think they’re two issues that need to be uncoupled. I’ve made the bioethical case that can justify offering NIPT as a second-tier screen precisely because it drastically reduces the number of invasive procedures, thereby sparing pregnancies that would miscarry from the procedure. But whether it should be part of a nationally-funded public health care measure, there are eugenic motivations for even offering the testing as it is justified by “saving” society the “cost” of lives with Down syndrome which are detected through prenatal testing and “prevented” through abortion. That should not be a statement of public policy. (Links herein are to posts on these subjects).

  32. Hello Mark… I am 38 years old (39 at EDD). My ultrasound at 13 weeks indicated no soft markers. However, my Harmony test was positive with a 91% PPV. It appears the location of my genetic counselor uses the same PPV calculator that you provide the link to. My question with this is the results say “The prevalence of Trisomy 21 at 16 weeks gestation for a woman who is 39 at EDD is 1 in 112”. Where does the 16 weeks come from and how much affect does it have? I was only 13 weeks and 2 days when the blood was drawn. Btw… I am scheduled for amnio in about 10 days.

    • I expect that Ariosa, Harmony’s lab, bases its PPV calculation off of published prevalence rates for women at certain ages and gestational weeks. There might not be a published prevalence rate for a 38 y/o at 13 weeks, so the lab uses the one that is published for 16 weeks. Ariosa had been provided copies of the Lettercase booklet recommended by all professional medical organizations for expectant mothers with a positive prenatal result. If you did not receive a copy, you can access it for free online at this link to learn more.

  33. Hi Mark at 10 weeks 6 days I had a cell free Dna blood work done, I believe Verifi. The results came back : screen result Abnormal aneuploidy detected, chromosome 21 result abnormal aneuploidy detected, chromosome 21 interpretation abnormal and fetal fraction 16.5 %
    My doctor basically told us the baby had Down’s syndrome and that was it, we went to have an ultrasound which was fine baby looked great according to tech and specialist and talked to a specialist who was as bad as the ob and my husband and I are so confused. If possible what does these results mean.

    • Please see this post and the links in it. It shares facts sheets on cell free DNA screening and a calculator where you can enter your age and find out what your positive predictive value is, i.e. what is the chance that your child has Down syndrome. No matter the age, there is also the chance of a false positive. I hope you find the post and calculator helpful.

  34. Crystal Cotto says:

    Hello Mark,
    Here is my story. I am 26 years old. This is my 3rd child. My 2nd child had TGA which required immediate open heart surgery and put me at a higher risk for heart defects. Before my 2nd level sonogram, I had 2 sequential blood screenings which placed me at 1 out of 1,400 for DS. I already had a fetal echo scheduled due to my son’s condition. Nothing abnormal was detected at 2nd level sonogram. At the fetal echo 2 weeks later, they discovered AV Canal defect. Doctor comes in and suggested further testing one of them being MaterniT Genome because Down Syndrome was most common with this heart defect. I had questioned then why would the sequential screening come back negative and he said that those are 90% accurate but that I could have an otherwise healthy baby. They are basing the DS on the hear defect. He tried to push for amniocentesis and i said nooe, not now nor later so then he suggested the blood work. It came back positive today. We spoke to the genetics counselor which was of no help. All she did was use the same calculator you are using. She said based on my age, the positive would be 51% accurate but due to the heart condition that it places me at over 99% accurate for DS. I feel as if they just put my results in a computer and just based my results in that. No other abnormalities have been detected in a sonogram. Before i found this post I was already skeptical because many tests for DS have false positives. I am not new to the medical field and testing inaccuracies. My husband and I told her that we would place our faith in God and we believed that the child didn’t have DS. The genetics counselor then said “we haven’t come across any false positives” but has never dealt with anyone my age and i stated I promise you I will be your first false positive (my faith in God is strong). She seemed pretty annoyed by me but I also stated how can you place all your trust in a test that is non diagnostic and came out 4 years ago.

    Mark your opinion would be greatly appreciated as well as feedback form anyone.

    This is my story. Hope it helps.

    • Crystal Cotto says:

      Forgot to mention I am 24 weeks along.

      • Crystal–while the calculator is putting numbers into a computer and producing results, the screen positive from MaterniT21 is from DNA from your pregnancy. I’m not sure what the genetic counselor is basing her “99%” figure on when factoring in the AV Canal defect (I suspect she’s trying to impress upon you that the odds are very likely your child has Down syndrome, but I don’t believe there’s anything published that shows adding AV Canal to a cfDNA screen positive equals “99%”). That said, cell free DNA screens like MaternT trump the results of conventional screening for conditions like Down syndrome. Coupled with the AV Canal defect, I think it is highly likely your child has Down syndrome. But, “highly likely” still means there could be a false positive. In any event, you might find it helpful to review Diagnosis to Delivery, written by moms for moms who have a prenatal test result for Down syndrome and are continuing your pregnancy. Doing so would not inject any doubt into your faith, but may help you understand having a child with Down syndrome more and, in the event the screen result is not a false positive, can make you better prepared at birth. There is a section in the book on heart conditions, as well.

  35. Hello!
    I am 34 years old, 20w 5d! in my first trimester I had the Natera test done and it was negative for everything! But for purposes of my question the Trisomy 21 is my concern! The fetal faction was 7.8% so definitely not low, and it showed <1/10,000 and Low Risk! I just had an anatomy scan and now an being scheduled to see a specialist bc of DS indicators! other u/s showed no indicators so Im not sure where it went a-skew!

    My question how common are False-Negatives?

    • False negatives are very rare and ultrasound findings are just “soft markers.” The Natera test would trump the ultrasound findings for Trisomy 21. If there are other genetic conditions suspected, you should be counseled about those.

      • Thank you so much for your prompt reply! Its much appreciated!

        They are only talking about DS at the moment so hopefully these next appointments they have schedule will clear us its just such a crazy ride!

        I also happened to Pprom so its difficult for them to get a clear u/s but hopefully these next dr’s will get something better

  36. Candice Hood says:

    Hey, I had the cell free blood testing done at 11 weeks and it showed that I have a high risk for T21. Of course in said >99% with a ppv at 91%. My question is about the ppv, it states that this number is not related to the individual tested but based of studies done by 60,000 females. What exactly does that mean? And what do you think the percentage is of having a false positive reading. I will be exactly 30 yrs old on my due date. Thank you so much..

    • According to the calculator linked at this post, based on your age and test result, your PPV is 61%, not 91%, with a 39% chance your test is a false positive. You may want to share the post and the fact sheets linked therein with your provider so they may provide more accurate counseling. I really have no clue what the report means when it represents a 91% PPV based on 60,000 women, none of whom are you. Your PPV is personal to your individual chances.

  37. Hi Mark! I’ve found your website to be incredibly helpful. I am currently 17w4d pregnant with my 3rd child. I will be 33 at time of EDD. I was terrified when my Verifi screen tested positive for T21. The genetic counselor did not provide a PPV and essentially told me to expect a child with DS. However after plugging in my test’s factors and age into your PPV calculator (sensitivity 99%; specificity 99.8%; 33 years) I discovered I have a 47% chance of this being a false positive. I am getting an amnio done Friday but had I known this from day 1 I likely wouldn’t have done the screening in the first place. The amount of worry it has cause is unbelievable. My NT scan was normal but 2nd trimester serum screen gave me a 1/200 chance so additional screening was recommended. Am I correct with my PPV or have I somehow misunderstood it. I will report back the amnio results once they are in.

    • Your calculation is correct based just off of your age. If your 2T serum screen revised results are used (1-in-200), then the calculator reports a 71% PPV and 29% chance of your result being a false positive. I hope your procedure and recovery go well and I’m glad you found this site helpful.

  38. Stacy Finney says:

    This was very informative. Thank you for such a great explanation. I also found the PPV calculator helpful. 10 weeks ago, I had very low amniotic fluid and was referred to a specialist. The specialist saw something wrong with the heart and referred us to a pediatric cardiologist and recommended the Progenity Verifi test. We were NOT led to believe that this test was 99% accurate. We were told that it is a screening and that an amnio would be required to confirm diagnosis. We received a positive Down Syndrome result and our doctor told us that we have an 80% chance of the baby being affected (I’m almost 36). Additionally, the cardiologist found 2 heart conditions that are consistent with Trisomy 21. Since we’ve had low amniotic fluid, an amniocentesis is even more risky than normal, so we are choosing to wait until delivery which will be in mid-late February unless he decides to come earlier! Regardless of his chromosomal condition, he is our son, our 4th child, and we are so excited to meet him. We are learning about Down Syndrome as well as connecting with other families with children who have Down Syndrome! It will be an amazing journey!

    • Thank you for sharing your experience, and I’m glad you were well counseled by your provider. If you haven’t already, you may want to review Diagnosis to Delivery, a book written by moms for expectant moms with a prenatal result of Down syndrome. There is also online support through babycenters Down syndrome pregnancy board and Down Syndrome Diagnosis Network’s Facebook groups. I wish you the best.

  39. This morning I received a call from the Tdl genetics lab to tell me that we were high risk (specifically 99%) of trisomy 21 – downs syndrome. This was following a harmony test. I am 32, partner 33. First & much wanted pregnancy. We are absolutely in shock. Now having to wait until next week to see local consultant to look at option of amino / CVS for further information. We are 12 weeks today. Do not know how we ate going to get through the next few days until we can get further info via local hospital consultant. This 99% chance our little one has downs just keeps going through my head. Cannot believe it. Any support much appreciated. X

    • According to this calculator, your positive predictive value, i.e. the chance your child has Down syndrome, is 68% with a 32% chance of it being a false positive. If knowledge is power, then reviewing some of these recommended resources to have an accurate picture of what a life with Down syndrome can be like may also provide comfort or at least reduce anxiety.

  40. Hi Mark, just wanted your opinion. I am 31 years old, no family history of chromosomal abnormalities on mine or my husbands side. Went for NT scan at 13 weeks 2 days on Dec 23rd and got a reading of 3.2 mm with a CRL of 77 mm. Doctor immediately went doom and gloom and said that it was high and would highly recommend the Harmony test but did not explain it in any way. Had blood drawn and recieved the results by email last Thursday saying I am high risk for T21. Took 2 days to recieve a call back from my doctor to try to get some explantion of the results and they said it did not look good but they were going to refer me to a high risk doctor. Still waiting for a call for an appt. Any input would be appreciated. Thank yoh.

    • See this post here and the fact sheets and resources linked in it. According to the calculator linked in the post, based just off of your age and Harmony test, you have a 64% chance that the Harmony result is a true positive and a 36% chance that it is a false positive.

  41. Thank you for this excellent information guide. My wife (38 y/o) had a Panorama NIPS testing done at 91/2 weeks. We got a call from OB saying that it is positive for trisomy 21. She also mentioned that the test is valid and we should prepare ourselves for the worst. We opted to get it confirmed via Amnio scheduled for next month. My question is the way our test reported was confusing, we were told that we have 57/100 chance of having a DS baby, PPV is 92% and cell free DNA was 5.2% in the blood. What to make of it? Does this mean our child has 92% risk of having DS or 57%??
    Thanks
    worried DAD

    • I’m not sure what the 57/100 figure represents. According to the calculator towards the end of this post, based on your wife’s age and the Panorama result you have an 88% chance of the Panorama result being a true positive and a 12% chance of it being a false positive. Put another way, you have an 88% chance that the pregnancy is positive for Down syndrome. It’s disturbing to hear the OB counsel patients that receiving a screen result for Down syndrome justifies “preparing for the worst.” There is a fact sheet in the same linked post and resources at the end that sound like your OB could benefit from reviewing to have a more even-handed way of describing a life with Down syndrome. I wish you well with the amnio and the recovery.

      • Hi Mark again thanks for your reply. I have an update to give on our case. We saw our OB again last week after Maternal Fetal doctor already scheduled our amniocentesis. My wife was kind of freaking out about inserting a needle in belly without any numbing medicine, so she was looking for excuses not to get amnio done. Anyhow long story short for some reason my wife convinced her Ob to repeat her NIPT through Harmony (first one was Panorama) because she believe Harmony was better. She offered to pay instead of insurance. It was done last week, we got the results. She is low risk for all trisomies with 1 in 10,000 chance of having an affected baby. Her DNA available to test was 8.5% and baby sex was the same a girl. Now we are even more confused with two tests both claims to be very accurate have different results and now makes our decision even more difficult to go for Amnio or not. Maternal Fetal medicine and Ob both admitted they have never encounter a situation like that. MF pushing for Amnio and my wife refusing it and I am clueless what to do!

        • Conflicting results are rare, but that is due primarily to few people having multiple cfDNA results. Not surprising that your MFM is pushing for amnio–it’s what they do, so I understand why they think it’s what should be done, and to know for sure, amnio is the only way. But, you may consider seeking a consult with a genetic counselor or medical geneticist who may be able to dig deeper into your test results and possibly provide the level of comfort you need to feel comfortable with whatever decision you choose.

          • Ok quick update. Our MFM doc reviewed both reports, looked at US of 10 and 16 weeks. (Normal scans with normal nuchal translucency and normal nasal bone, normal heart and vessels etc etc) he advised to forget about amniocentesis and he even told us that he is very sure we have a normal baby. He even discharged us from his clinic. We are happy but with a fraction of a doubt, what if? But my wife has firmly decided not to go for Amnio specially when MFM doc also didn’t advise it.

          • Thank you for the update. Best wishes for an easy delivery and healthy baby.

  42. My genetic counselor said I have a 90% chance of having a baby with Down syndrome. I asked her twice on how she determined that percentage and just kept telling me that it was based on age but wouldn’t give me the actual results of the test just the calculated results. I did a CVS and I am currently waiting on results.

    • You can calculate your own chances by using this online calculator linked here. Though, having had a CVS, those are the results that are considered definitive. Note, however, that FISH results are still considered screening results–only the full results are considered diagnostic.

    • Stephanie says:

      Hi Monica, just reading your post and wondering what the results were as I am in the same situation. Thank you!

  43. I had a blood test for down and my risk factor are 99/100. I’m 40, what are my chances of getting a false positive. I hope to have an amnio done next week.

    Thanks

  44. I a have a situation that I haven’t seen yet discussed or asked about here and I would greatly appreciate your input, Mark… I am currently 35 years old and will be 36 at time of delivery. I have 4 healthy boys and I am now about 14 and a half weeks pregnant with di/di twins. I had the Harmony NIPT done at 13 weeks and received the call from my genetics counselor last night that it tested positive for T21. She gave me the whole “99% likelihood” spiel that so many others were given and gave me little to no reason for hope of it being a false positive. She didn’t give me any other percentages or ratios or anything. All testing before has been normal. Their NTs were normal too. I am absolutely devastated right now and have been scouring the internet trying to find situations like mine to see how they turned out but am not coming up with much. I am scheduled for an amnio in 2 weeks, which feels like an eternity away, especially considering I’ll have to wait two more weeks after that to get the results. Is there any info you can give me considering I’m having fraternal twins?? Does this increase the likelihood of a false positive or do my chances stay the same? Thank you so much for taking the time to read this.

    • There is little research regarding twins due to the rarity of twins (I happen to be a fraternal twin, myself). Based on the calculator at this link, according to your age, your chance that the test is a true positive is 79% with a 21% chance of it being a false positive. But that is for a singleton pregnancy. In your case, you may have two placentas, doubling the chances that the cell free DNA tested may have come from the placenta and not from cells that developed into either fetus. Further, the chance of both fraternal twins having Down syndrome are extremely long, so more than likely, even if your test is a true positive, it is for only one of the twins. I wish you the best with the upcoming amnio and recovery from that.

      • Thank you so much for your reply! I HAVE been told they each have their own placenta actually. Would there be any symptoms or potential problems down the line if the T21 DNA did come from the placenta? Ugh… I’m really regretting having this test done. The stress it has caused is just not worth it, even if it does end up being a true positive, I would’ve much rather found out further down the road… Maybe that’s just me, but it has really just sucked all the excitement out of me and replaced it with anxiety and doubt. I really and truly appreciate what you’re doing here by taking the time to answer everyone’s questions, and doing it so thoroughly and kindly. God bless you!

        • Sometimes the placenta can have cells that are trisomy, a phenomena called “confined placental mosaicism.” It only affects the placenta which passes after birth and does not affect the child or the mother. And you’re feelings of regret for having the testing is one shared by many others. The labs marketing would be more accurate if they didn’t just hype the reassurance a negative screen result can provide.

  45. Stephanie says:

    Hi I am 12 weeks pregnant today, I got the call from the midwife yesterday that I was positive for trisomy 21. I asked her how accurate it was she said 99 percent. I go tomorrow for the cvs testing. I am 28 years old. The genetic counselor told me it was 95 percent chance. Although 99 and 95 are not much different. After reading all of this thread I’m confused that maybe my percentage is lower then they are saying? Any feed back would be great. I’m so sad over this.

    • I regret replying after what it sounds like your scheduled CVS. According to this calculator, at your age, the actual chance that your test result is a true positive is 56% with a 44% chance it is a false positive. Your GCs should receive the fact sheets so they stop counseling patients incorrectly.

  46. Hi Mark, I’m extremely grateful to have stumbled upon your site. I had the panorama test done at 9 weeks and 5 days and am 12 weeks and 2 days today. I was called by an OB from my group and told that my test was positive for trisomy 21 and that it is a “good indicator” that my baby has down syndrome. I was called the next day by my own doctor at the same practice who told me that it is just a screening, not a definite result and encouraged me to get further testing. We spoke with a genetic counselor this week who told us our baby has a 99% chance of having DS, which was incredibly discouraging since myself and my husband have been trying to stay positive until we get our diagnostic results. We have a CVS scheduled for Tuesday, the counselor urged us to go ahead and get this done ASAP. We had our NT scan set for the same day, but she told us to cancel it as it would only come back positive for DS as well. She also encouraged us to opt for FISH testing, but from my own research seeing that it is only another screening I think we may opt to skip it. From reading what other people on this thread have posted it doesn’t seem like I was given accurate information at all? I’m 30yrs old, and will be 31 on our due date.

    • Well, the accurate information you received was from your doctor who emphasized Panorama remains a screening test and the recommendation not to have an NT, but not for the reason given. Conventional screening is not recommended following a cell free DNA test result if the patient is seeking information about the condition reported by the cfDNA screen result–conventional screening can lead to confusing mixed results and cfDNA remains more accurate. Your genetic counselor is incorrect on the chances that your child has Down syndrome; at your age, the actual chance based on the Panorama result is around 61% and the chance the test result being a false positive is 39%. You are correct that FISH is still just screening, so the full results are what will provide the diagnosis. All of this is covered at greater detail with links to helpful resources at this post; feel free to consider sharing it with your providers so they counsel future patients more accurately.

  47. Stephanie says:

    Mark, I have been obsessively reading your articles since receiving news 3 weeks ago that my baby tested 99% positive for Trisomy 21. I judged asked for the actual results today. I’m happy to raise a baby with Down syndrome but just became curious after reading other people’s comments. I was given the ClariTest by Genpath. I cannot find anyone online with experience with this test. Do you know anything about this test? Also my fetal fraction is listed as <1%. From my reading, is that not really low? I have a 16 week ultrasound next week where I suppose I can get a better look, although all 3 of my other children had soft markers for DS in the womb and all were born without. Can I ask for another cell free DNA test due to low fetal fraction? Why would they make a conclusive report if it were so low? I am not interested in an amnio.

    • As this post explains, your results are likely not “99% positive.” I agree that less than 1% fetal fraction does sound low. You can always ask for another cell free DNA screen and that screening becomes more accurate the later in the pregnancy is performed. The only factor would be whether it would be covered by insurance of if you would have to pay out of pocket.

  48. Hi there I am 32 with my 2nd baby and I just got Counsyl results back that my baby boy will be XXY (klinefelters). The fetal fraction was 5.1% and the PPV was not predicted on my labs bc of “insufficient prevalence data” which was inscribes in the clinical notes. Can you help me understand what that means? I was 10 weeks when I got the blood work done. Does this mean it was just done too early? What are the chances of this being a false positive? This has been very overwhelming. Thanks in advance.

    • The chances are more likely than not that you have a false positive. The meaning of “insufficient prevalence data” is that XXY is so rarely occurring, the lab doesn’t have a figure for how often it actually occurs. As a result, it is not possible for them to tell you if you have a 1 – in – whatever chance because they don’t know how often XXY occurs to begin with. From the studies I have seen, results from screening for sex chromosome aneuploidies like XXY are more often false positives than true positives.

      • Thanks Mark so much for your response. This is very enlightening. I know this is a fairly new test but didn’t realize they had such little information on it. Sounds like they should be a warning label on it 🙂 Hoping for a flase positive. Thank you so much again. I really appreciate it.

  49. Hi Mark, I’m 38 and just had CVS done this morning after a positive T21 Panorama result with feral fraction of 12% and a risk score post test of 99/100. The nuchal fold was at 3.3mm also which apparently at 12 weeks 6 days and with the size of the baby should be more like 1.8mm. I was told though by the Portland Hospital that there was a 9% chance the results could be incorrect via research but the paperwork reads like I’ve a 1 in 100 chance of not being T21? I’m not getting my hopes up, it seems pretty conclusive but still confusing?
    Thanks, Clare

    • Based just on your age, this PPV calculator computes your chances that the Panorama result is a true positive as 88% with a 12% chance that it is a false positive. The nuchal fold alone is not recognized as a valid screen, so that should not have affected your baseline chance from which the PPV was calculated. I suspect that like this article reports, the risk score of 99/100 is simply an inaccurate repeating of Panorama’s claimed sensitivity/specificity and not actually your PPV.

      • Thanks for your reply, I appreciate you getting back to me. Clearly not the best odds but I guess it’s something and we just keep out fingers crossed on the CVS results. Kind Regards, Clare

  50. Hello,

    my family doctor offered me either the traditional test or the Harmony test. I chose the Harmony test as it has higher sensitivity and specificity. She told me there’s no need to do the traditional one as long as I will do the Harmony test. However, from the replies I noticed that most of you had gone through both tests. Do you think I should go back to my doctor and ask her to do the traditional test at the same time.

    Thank you for the valuable information you offered in your replies

    Dina

    • It depends on what information you value, but Harmony only tests for T21, 18, and 13. If you want more information, conventional screening reports much more than just those three conditions, albeit with possibly a higher false positive rate for certain of the conditions. More at this post.

  51. Hi,
    I had the Maternt21 test at 12 weeks and the results came back “POSITIVE” for Trisomy 21 and Monosomy X. This is the way it was written on the results handed to me on paper. I didn’t have any percentages just the word “POSITIVE” in all caps. It would definitely lead one to think that the diagnosis was definitive. I’m 38 years old so I was counseled by my obgyn and genetic counselor into thinking that this was it and the results were unlikely to be wrong. I had an amnio and microarray following these results and they both came back completely normal. No extra or missing chromosomes or pieces. I am still puzzled by my NIPT results and don’t understand what happened.

    • The reason for the false positives is due to tests like MaterniT21 testing DNA that comes from the placenta and not necessarily from the fetus; for conditions like T21 and Monosomy X, there is a phenomena called “confined placental mosaicism” where certain cells in the placenta may have a condition like T21 or Monosomy X, but the fetus does not. Particular to Monosomy X, and I’m not saying this to concern you, but there’s a possibility that that result came from your DNA and not the fetus. Just as there is confined placental mosaicism, we all can have some mosaic cells at such a low percentage that it doesn’t really manifest the condition in us. This is something I would discuss further with a Genetic Counselor or Medical Geneticist.

      • Hello Mark, I am thankful to have come across this site. I am a 40 year old mom of 2 and currently 11 weeks pregnant. My OBGYN called yesterday to tell me my test results were 96% accuracy for screening trisomy 21. She recommended I get the CVS test, but there is a very low chance of it being a false positive. I was so sad, but if there is a low chance of it being a false positive why even bother with further testing? I am tempted to get the CVS, but it’s giving me so much anxiety as to why doctors give you these results as if they are true. I asked her if my baby did have trisomy 21 was it because i used norco in the beginning due to back pain and she said no. I was also on adderall and stopped using it when I found out I was pregnant. I’m just hoping once I get CVS screening that I will get accurate results.

        • According to this calculator, based on your age, a cell free DNA screen result would have a 93% chance of being a true positive and a 7% chance of being a false positive. CVS is considered a diagnostic test, but because it tests placental cells, which is the source of cell free DNA, it has a chance of delivering false positives and false negatives, though that chance is very small. For this reason, amnio remains the diagnostic test for confirming cell free DNA results. Professional guidelines recommend having a diagnostic test prior to making any irrevocable decisions about your pregnancy, i.e. termination. On the other hand, many women who decide to continue their pregnancy after a cell free DNA result do so without having a diagnostic test, understanding it is more likely than not that their child has the tested for condition, but that it could be a false positive. There are resources at the Prenatal Resources tab to find out more about Down syndrome; the resources are recommended by professional organizations for expectant mothers. Lastly, the cause for Down syndrome remains unknown; it is a naturally occurring phenomena, not linked to any pharmaceutical use.

          • Thank you for responding. I have read many comments where the mother gets an amnio test and it’s a false result. I guess I will wait and see what the CVS results show being that it’s a free cell DNA test and will post later. My husband and I are ready and we love our baby no matter what. This will be baby #3.

  52. Hi. I had my positive test results from harmony for DS after one week. I have done cvs staight after and it was confirmed that baby has DS. That site gave me hope that harmony test maybe is not acurate , my dc said it is 99.1 but he couldn’t see any abnormalities on scan.
    First blood test and nt scan gave me 1:46, so i thought not so bad.
    However bad news come and decide to terminate it.

    • With your NT-combined recalculated probability, the Harmony result still had a 14% chance of being a false positive. Your doctor is incorrectly counseling patients by telling them its 99.1. Similarly, it sounds like the remaining recommended information to be provided with a screen positive result was not given to you.

  53. Hi Mark I am 37 and pregnant with my 2nd baby and I just got Panorama results back that my baby boy will be XXY (klinefelters). The fetal fraction was 13% and no PPV was given. The Panorama test claimed 89% sensitivity. We opted for an amnio next week but the genetic counselor state Parnorama is a reliable test and they are rarely wrong. Is this accurate?

    • According to this online PPV calculator, given your age and Panorama’s stated 89% sensitivity, the likelihood that your result for XXY is a true positive is 36% and the chance that it is a false positive is 64%. Given that the odds are that the test is a false positive, you may want to share the online calculator with your genetic counselor so he or she counsels future patients more accurately.

  54. As a follow up to my earlier post which for some reason I can’t find.

    Briefly, we had abnormal NIPT (panorama) for T21 at 9 weeks of gestation. We were asked to get amniocentesis but as we don’t believe in termination of pregnancy we opted against it. On follow up visit, on my request OB agreed to repeat the test via Harmony, and it came back normal. This caused further confusion and we were again asked to get Amnio which we again refused. On 8/3/17, my wife delivered a healthy 9lb baby girl. Bottom line is that these tests are good but not perfect and statistically it makes sense to repeat the test with a different company and if it gives the same result then there is a high likelihood that it’s truly positive. Most of the time these tests are > 90% sensitive and test repetition and getting the same result can bring that percentage close to 98-99%. Considering Amnio has a risk of loosing pregnancy 1-2% of the time, I consider repeating the test is less risky than going for Amnio. Doctors usually do not recommend that but for those who do not want Amnio because of risk of loosing the baby or in our case fear of needles, I don’t think test repetition is a bad option. What are your thoughts about it?

    • Thank you for sharing your experience. I agree that a second NIPT screen is not typically performed, usually due to lack of coverage reasons. But the reasons you give could be helpful to a patient. It’s an option that is not recognized by guidelines, but doesn’t mean a patient wouldn’t determine that the out-of-pocket costs for a second NIPT could be justified personally if they wish to avoid the risk of miscarriage from amnio or value confirmation of the previous result for planning purposes. Frankly, I hadn’t considered a second NIPT as something to include in a prenatal testing protocol, but you make a good case for one if it is what the patient wants based on what they value. Thank you.

  55. Hello. I am 34. Will be 35 when I deliver. The NIPT came back and told me I am high risk for Downs. They did a nuchal translucency and told me it was increased and now my chances are about 85 %. I don’t believe this. I will keep this baby no matter what, but feel they are wrong and basing on probability/

    • According to this online calculator, based on your age, your NIPT result has a 75% chance of being a true positive and a 25% chance of being a false positive. Just a nuchal translucency measurement, alone, is not recognized as a screen for Down syndrome. With a prenatal test result for Down syndrome and an intention to continue the pregnancy, this book is the recommended resource for learning more about Down syndrome and continuing a pregnancy. I hope it is helpful, if you choose to consult it.

  56. Hi there,

    Is this thread still active?

  57. By the way, the entire British healthcare system called NHS, officially states and their nurses and doctors state that the test is more that 99% accurate, and false positives are more than 99.7% accurate, we proved them wrong recently. The test is only available privately. Malpractice at country level.

    http://www.rapid.nhs.uk/

    • Thank you for sharing. I thought though that the NHS recently chose to cover NIPT for “high risk” pregnancies.

      • Not yet, they do not offer it in the NHS. I have heard in Scotland they might, in general the Scottish system is more generous. In UK it is all about money, and the budgets are too small, but you can have it done at private clinics for 500 gbp or 650 Usd. We are Americans in the UK we had the NIPS done in America on a visit, Then went back to NHS Doctor we were told it’s more than 99% accurate. Using your info I corrected them. Many people in UK get this test at private clinics and it’s scary that the NHS is saying this and the consequences it might have. Below is the link.

        http://www.rapid.nhs.uk/guides-to-nipd-nipt/nipt-for-down-syndrome/

  58. Hi Mark, I’ll be 35 at EDD. My NIPT result came back last week as “Aneuploidy Suspected- Borderline result suggestive of trisomy 21”. I asked GC what borderline really mean but she didn’t give much helpful info that I need. All she said this test is highly reliable especially for Down syndrome detection. I was terrified and lost sleep since hearing this devastating news. If the result falls on the borderline, does that mean the chance of false positive is slightly greater than that in Aneuploidy Detection category? You have any inputs? Everything looked normal at 12 week NT ultrasound. I’m having amnio in 2 weeks. Waiting w/ uncertainty and anxiety is really a torture.

    • If your result had simply been a screen positive, at your age, the online calculator computes a 21% chance that it is a false positive. I expect that the reason they described the result as “boardline result suggestive” is because your sample did not come back as a simple screen positive, so, yes, I would expect that means a greater chance of it being a false positive. Medical guidelines instruct to treat those borderline results as still a “high risk” result, but the chance for false positive remains. The amnio will provide definitive results.

  59. Hi Mark, I got 2 in 3 chance of Down Syndrome for my baby at 12 weeks. Was told 33% chance of baby being okay in prenatal screening – ultrasound and blood test results, had NT of 3.4 and short nasal bone.

    I got Panorama done and it is Negative, am given 1 in 10,000 chance.

    I have a healthy 4 year old daughter and am 36 years old.

    Wondering if Panorama could be False Negative and if I should go for amnio. Thank you.

    • It sounds as though you had a conventional screen, likely the Nuchal-combined, which reported a 66% positive predictive value for Down syndrome and then had a Panorama screen negative result. Tests like Panorama take precedence over conventional screens for the limited conditions they are recognized to test for. So, the Panorama result trumps the conventional screen result for Down syndrome. Still, as screening tests, there remains the possibility of a false negative or that the conventional screen may have detected a condition that Panorama does not test for. From the beginning, an amnio was the only way to know for certain. That said, many women rely on the Panorama screen negative to avoid the risk of miscarriage with amnio.

      • Thanks. What could be the other conditions that conventional screening may have detected? I am in dilemma to go for amnio because of miscarriage risk but still want to ensure the outcome. What is the ratio of miscarriage?

        • There are a variety of other conditions that conventional screening detects that cell free DNA screening does not, but conventional screening, particularly for these rarer conditions, has even more false positives. The relevant risk for miscarriage is the experience of your practitioner and the facility where it is performed: the more experience they have, the lower the risk and the less experience they have, the higher the risk.

  60. Hi Mark, I just wanted to report back. I spent hours on your site when we first received test results that our daughter tested positive for T21 with the NIPT test. Thank you for all you do. I was given a test by GenPath called ClariTest. They won a lawsuit this past March to use the technology from Illumini’s Verifi (research was my therapy) anyway I’m 35, this was my fourth pregnancy. My fetal fraction was reported <1%, still reported as positive and my dr fully backed the test as infallible with a 99% accuracy. My daughter was born last Friday and she does not have Down Syndrome, we received the kareotype results back Monday. Just thought I would share. I think these tests are flawed and no one is taking the time to explain that, minus you. Thank you !!!

    • Congratulations on the birth of your daughter. Feel free to share the fact sheets linked within this post with your doctor so that future patients are counseled correctly. Or, file a complaint with the hospital where he/she has privileges or your state’s board of medical licensure. Or, simply enjoy raising your little girl!

  61. Hi Mark,

    I’m 36yo. After the initial NT scan with combined bloods, I was given a high risk of Downs at 1/43 chance, although the NT scan was reportedly normal, with 3.36mm NT.
    I then was recommended to do the Harmony, in which it came back at 99% positive for Down’s Syndrome with 6.2% fetal fraction.
    I am now referred for an amniocentesis and am waiting to be contacted for an appointment as I am just 15weeks along today.
    I would love your insight to this. I have been reading the above comments, but not really making much sense of it all.
    Many thanks in advance.
    C

    • Based on just your age, your Harmony result means you have about an 18% chance that it is a false positive. You can view those results at this calculator. Actually, even with your screen-positive NT-combined test, the false positive rate remains the same. So, you have roughly a 1-in-5 chance that your child does not have Down syndrome. You should have been provided resources with your test result. Here is the recommended resource about Down syndrome.

      • Thanks Mark for your prompt reply. I’ll just have to wait for my Amnio test and results.

        Thanks again,
        C

      • In the future, would you recommend after the initial NT scan with combined bloods, if it came back high risk, just to go on and have a CVS or Amnio straight away and skip say, the Harmony test altogether?

        Unfortunately no, they didn’t provide any resources. I’m in Australia, so I’m not sure what there code of practise is, this is my first pregnancy, so completely unsure of protocol or the way things are done and what to expect with the medical care.

        Thanks again.

        • Specific recommendations are patient-specific, determined based on the patient’s preferences and values. If you value information over any risk to your pregnancy, then it would be recommended to have an amnio, as that provides the most definitive information. If you are generally risk-averse, then it could be recommended to have the Harmony test, since you may rely on the relatively low chance of a false negative should you get a negative Harmony result, thereby avoiding the risk of miscarriage with amnio.

  62. I had the informaseq done and got a positive result for Down syndrome I am 39 and will still be at delivery. What are my percentages? Please since my ob gave me none and acted as she’s ever heard of such numbers. Thank you

    • Based on your age and test result, according to this online calculator, you have a 9% chance of your test result being a false positive and a 91% chance that it is a true positive. An amnio can provide a diagnosis. Feel free to share with your provider this fact sheet about tests like Informaseq so that she may better counsel other patients. You should have also received information about Down syndrome with your test result; this online resource is recommended by the professional guidelines.

  63. I am 37 and am now 12 weeks pregnant. I had the harmony test at 10 w 1 d and it came back with a 49/100 for Tri 18. My genetic counselor and dr both said this was an unusual result as harmony usually comes back as a lea ss than 1% or greater then 99%. Have you seen a result like this or something similar? My ultrasound at 11 and 5 appeared to be normal but dr said still too early to tell much at that point on ultrasound. Baby is measuring corred or big even.

    • As this post reports, your providers greatly misunderstand what a Harmony result of 99% or less than 1% mean–those numbers only refer to the test’s relative accuracy for detecting those pregnancies actually positive for the tested for condition; that accuracy must then be compared with the incident rate for the given condition. To Harmony’s credit, they reported back your PPV based on the test result and your age: according to this calculator, a screen positive result for T18 at age 37 means you have a 51% chance of it being a true positive and a 49% chance of it being a false positive. Feel free to share this fact sheet on testing like Harmony with your providers so they may better counsel future patients. You should have also been provided information about T18; the Trisomy 18 Foundation is a recognized resource for patients to learn more about the condition and available support.

      • The genetic counselor made it sound like when the test comes back on a gradient scale like mine rather than the greater than 99% it meant that there was not enough evidence for them to say greater than the 99% that they generally report. Does that make any sense? I’m really just trying to come to terms with all this and understand it best I can until I can find out for sure with an amnio at 15 weeks. Thx!

        • I’m curious what she’s basing her advice on–if it’s one she inferred or was told by a rep. Either way, it’s incorrect. As this post covers, it is only in the extremely rare instance that any of these cell free DNA screens would have a 99% PPV, e.g. the expectant mother already has a child with the tested condition and is over 40. Instead, I expect that she (incorrectly) relied on Harmony initially reporting out 99% as meaning a 99% chance of being a true positive and that Harmony has since changed how they report their test results due to pressure applied by professional organizations and criticism.

  64. Worried_Dad says:

    Hi Mark, Thank you for the wealth of information you have posted on here. I’ve found it incredibly helpful. My wife had the Panorama by Natera done on Oct. 16th because she is 35 yrs old and this is our 3rd pregnancy and she is considered advanced maternal age. She was 10W 1D then. Yesterday, Oct. 24th, her Dr. called with the results to tell her the results returned a “High Risk” designation and a Risk Score Before Test of 1/181 and a Risk Score After Test of 9/10 chance / probability that our baby would have Trisomy 21. That score was described to us as the chance or probability. The PPV on the 2nd sheet of the report for Trisomy 21 with the Panorama is 91%.

    We have two healthy boys (2 and 4) and had never gotten results suggesting any risk and as you can imagine they were very shocking and we are a wreck now. Similar to others, we actually got a Panorama in March 2015 when my wife was 10 weeks pregnant with our now 2 year old son and Natera offered to cover the cost of it. We initially got charged $2,000 for it and our insurance wouldn’t cover it but we received a call from Natera saying that they would “work” with us and that it was new technology and they didn’t want the cost to discourage people. We got a new new statement where it was all somehow covered and we didn’t endup paying for it.

    The OB didn’t offer much other information or counseling besides that we were being referred to MFM and that they would take it from here. My wife called MFM after not hearing from them and the scheduler said they would contact us in 3-4 days. My wife called back today and got a really nice nurse who confirmed we would get scheduled today and now have an appointment for Friday. Oct. 27th, at which point my wife will be 11W 5D. The OB said these tests are 99% accurate. I’ve been reading previous posts on your site and am just really lost. I see some consistencies in our experience as with others related to the lack of information or explanation provided, but in general I am just really confused / worried / sad. We had a consult with a Natera employee today to talk through the results at 2 PM. I had read several of the articles/posts on your blog today so I was a little prepared. She explained that the High Risk Score After Test of 9/10 and the 91% PPV are basically the same thing but that they just rounded down from 9.1/10 to 9/10. This doesn’t really seem right to me. She never said that this was a test of the placenta or the fetus, I asked her and she confirmed that it was from the placenta but that it’s very accurate because they essentially found cells in my wifes blood that contain 3 chromosomes in chromosome 21. The fetal fraction rate is 10%. I’m expecting that MFM will suggest a NT at our appointment Friday, and I know that in our area the CVS is not offered, only the amnio. I’m praying/hopeful that we have a false positive but I am really struggling to stay positive and my wife is a wreck.

    • According to this online PPV calculator, based just on your wife’s age and the Panorama result, the PPV would be 79%, meaning you would have a 21% chance of the result being a false positive. If you enter the prevalence rate that you report, 1/181, the PPV is even lower, 61% with a 39% chance of it being a false positive. So, I’m not sure where either your physician or Panorama are getting the 91% PPV chance. According to current professional guidelines, conventional screening like an NT-combined test should not be conducted independent of other screening results as it increases the odds of differing results and increased confusion; cfDNA screens like Panorama trump conventional screening for the conditions cfDNA screens for (T21, 18, 13 and male or female). Feel free to share this fact sheet with your OB so that future patients are more accurately counseled about what the 99% marketing message means. You should also have received information about Down syndrome. This link is to the resource recommended by professional guidelines. If interested, there is a DAD specific support group for fathers of children with Down syndrome, which can be accessed at this link.

      • Worried_Dad says:

        Thanks for your reply. What sensitivity and specificity rates are you using for the calculator?

        The 91% PPV they referenced is from the 2nd page of the report. This sample High Risk report that is on Natera’s website contains the same 2nd page as the result that was provided to us. If you look at the table for conditions, Trisomy is listed 1st and the 4th column is the Positive Predictive Value and for Trisomy 21 its 91%. That’s where the Natera employee got the 91% that she referenced to us. Here is the sample report:

        http://www.panoramatest.com/panorama-test/clinical-information/sample-reports

        Can you explain a little more on when you said this “According to current professional guidelines, conventional screening like an NT-combined test should not be conducted independent of other screening results as it increases the odds of differing results and increased confusion”. Are you saying that they shouldn’t do the NT separately from the cfDNA we already did?

        • I am using the sensitivity and specificity rates that autopopulate on the online calculator, which I would still use since the Panorama report does not give specific percentage rates for sensitivity or specificity, both are just listed as greater than 99%. It also seems concerning that Panorama would be reporting the PPV for your wife at the same level as that of a 37 year old, since your wife is 35. Regarding the NT-combined: NT-combined can test for far more conditions than what Panorama does, but for the conditions that both test for, the Panorama result is the more reliable. Therefore, doing the NT-combined test for the purpose of evaluating your pregnancy’s chance for Down syndrome is not indicated as NT-combined has far more false positives and false negatives than Panorama for that condition. If, on the other hand, the NT-combined is being performed for other conditions not tested for by Panorama, then fine, but you should either ask for the results for Down syndrome not to be returned or understand that whatever their result, they would not be considered as confirming or negating the Panorama result.

          • Worried_Dad says:

            Thanks Mark. Just to keep you updated. We met with the MFM this past Friday. We met with a Nurse Practitioner first who was really nice and tried to provide as much education as she could even though both my wife and I have done a lot of research by scouring the internet, joining facebook groups, talking to parents of children with down syndrome, etc. We then had the sono where they were checking for the fluid behind the neck (NT scan). It took the sono tech quite a bit of time to be able to take the measurement and then she left and came back with a nurse, the nurse practitioner and the MFM doctor. The MFM doctor opened the conversation with asking us if we had discussed how we were planning to proceed with the pregnancy, and we simply stated that we are still trying to learn more about the results. She proceeded to tell us that if it were her, she would terminate because she works a lot and wouldn’t be able to do it. I said that since the Natera blood test was only a screen, and especially of placental DNA that we wouldn’t be making a decision like that from a screening test. She corrected me and told me that it’s not placental DNA, that it’s fetal DNA and she told me that I “need to get that out of my head”. I didn’t want to debate her, but I really didn’t like her attitude. We asked her about the NT and she told us that it was 2 CMs and the nasal bridge was present, and its considered normal, but that the results from the Natera test would trump that. The next steps they offered are the amniocentesis but we’ll have to wait till 15-16 weeks gestation or the CVS that can be done now. They don’t do the CVS where we live so we will be driving 2.5 hrs tomorrow to Chicago to get the CVS done there.

          • I’m shocked if that is how your MFM acted–essentially saying abort based off of a screen result because it doesn’t fit her schedule to perform an amnio. She is the one who needs to get it out of her head that cfDNA screening is fetal DNA versus DNA from the placenta. Regarding a CVS: the NSGC recognizes that because a CVS is also a biopsy of cells from the placenta, it could report false results, and further recognizes amnio as the more accurate diagnostic test. Regardless, safe travels and I hope the procedure and recovery goes well. FISH results are considered screen results, not diagnostic; only the full report is diagnostic.

  65. My husband and I just received a possible diagnosis of T21 for our first pregnancy. I had just turned 36 when I got pregnant and in NYC they term that as a high risk pregnancy and require you to meet with a GC. All of our ultrasounds so far have been good and our first trimester scan at 11w3d showed a healthy, typical baby. Our NT was much lower than the number at which they get concerned. My hormonal levels were very slightly elevated and lower than perfect 1s, but did not raise red flags. A week later, our GC called to say we had tested positive for Trisomy 21. I wish I had found this site first so that I would have known to ask what percentage of placental cells were tested and the actual results, not just “positive.” I had a CVS a few days ago. FISH results from CVS show the same but we won’t have a full work up for several more days. Either way I will have an amnio since CVS also tests placental cells. I know that in very rare cases placental and fetal DNA differ. In some ways our GC has been great, offering to have us meet with families with children with DS and offering support. However, I think the results were presented very badly. They didn’t even tell us which test they used and we definitely got that 99% line. I pushed back on this a bit b/c I had heard some questioning of these tests and was then told that there was a 15-20% chance it was wrong. No idea where this number came from, potentially predictive value? Can you offer any insight on how often FISH differs from final CVS? Or how often CVS and amnio differ? We’re grieving, doing a lot of research and trying to figure out next steps. It’s really throwing me for a loop that they have seen no soft markers. Even the day of the CVS, our NT levels were still healthy and the baby has shown a nasal bone since the 11 week scan, heart and brain both look good.

    • I should add that my research suggests it was the Verifi test b/c we had work done at Mt. Sinai in NYC. Also, they started me with a DS risk of 1:130 ( I guess b/c of age?) and lowered that to 1:252 after my first trimester scan. That was before blood test results.

      • Based on just your age, this online calculator computes the PPV to be 82% with an 18% chance that the cfDNA screen was a false positive. That’s considering the cfDNA screen by itself. Coupled with the FISH results, it would be very unlikely the cfDNA screen was a false positive–however, you should have the full results in a few days. I would talk with your GC and consider whether to undergo an amnio. While CVS tests DNA from cells from the placenta like cfDNA screening does, the chance of a confirmatory CVS of your cfDNA screen being a false confirmation and the cfDNA being a false positive would be very low, i.e. unlikely. One thing to consider, though it would likely cost out-of-pocket, is another cfDNA screen. That screening increases with accuracy as the pregnancy progresses. If you received another screen-positive, again that would make the chances of the results being false positives very low. On the other hand, if the second cfDNA screen was a negative, then that may justify an amnio to confirm. I’m glad to hear your GC has been supportive. If your GC didn’t provide you already, this is the link for the resource on Down syndrome for couples receiving a prenatal test result. If you choose to continue, this link is to the recommended resource for mom’s continuing after a prenatal test result.

        • Thank you for the quick response. Does it make sense to have another cfDNA even if the full CVS confirms? Thanks for the resources as well. Trying to gather as much info as possible. I spoke to my doctor and it actually was the MaterniT21 with 11% of cells.

          • If the CVS confirms, that can be treated as diagnostic. I suggested a second cfDNA screen if you were considering doing an amnio after you receive the CVS results.

  66. Maria Clinton says:

    Hi Mark
    This post has given me enormous amount of information thank you. At my 12 week scan I did the combined test which gave me 1:30 of baby T21. As I have had 3 mc recently I elected for the harmony test which I was told came back positive with 99% accuracy. I am 39 and understand my age is a factor. I had the CVS done on Friday and hoping for FISH results today. We have decided if baby is ds we will not continue with the pregnancy. My concern is should i of waited and done amino for more accurate result. The hospital will want to arrange tx on FISH results or do I wait for full result. I realise at my age I am grasping straws but that’s all I have.

    • Whether calculated based on your age or on the combined result score, the Harmony result means you have a 91% chance of it being a true positive and a 9% chance of it being a false positive. FISH results are considered screening results, not diagnostic. You should wait for the full CVS results. If they confirm the Harmony result, then the CVS can be considered diagnostic.

  67. Just got a positive result for my 4th baby, I’m 36 and 11 weeks. 75% chance is what was told to me. I️ read somewhere that being on Lovenox can affect the accuracy of these results. What is your knowledge of that. I’ve got Factor 5 Leiden & take lovenox everyday of my pregnancies.

    • Based on your age, this online calculator reports a PPV of 86% with a 14% chance that it is a false positive (presuming the condition reported was Down syndrome). I had not heard of Lovenox affecting cfDNA screening–but I also was unfamiliar with Lovenox in general. From a quick internet search, I did see where Lovenox may result in low cfDNA for screening purposes, but I do not know how that would affect your odds. I would reason that since you received a screen result, then the Lovenox did not affect the amount of cfDNA to be tested. You should have also received information about Down syndrome with your screen result. If you did not, this link is to the recommended resource for those receiving a screen result or diagnosis.

  68. Hi Mark. I’m so terrified now, I have 29 years old, my harmony test doing at 12 weeks was positive >99/100 for t21. It is my third child. At echographie baby have nasal bone and normal clarté nucale. Sorry for my bad English, can you tell my what is my chance my baby not have trisomie 21. Doctor said <1% chance I have a normal baby…. my amio is in 2 days and I will have a FISH test… thanks

    • Based on your age, your chances of your Harmony result being a true positive are 58% and the chances that it is a false positive is 42%. Your doctor is incredibly ignorant on the relative accuracy/inaccuracy of these tests. FISH results are only screening results–they are not diagnostic. Only the full amnio report is a diagnostic report.

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