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.

  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.

Trackbacks

  1. […] the University of Washington Medical Center further demonstrate how “99% accuracy,” the oft-made claim by NIPGS laboratory marketing literature, should be understood as not suggesting a 99% chance that […]

  2. […] their tests are “99% accurate,” the study found that in a high risk population, the positive predictive value (PPV), i.e. the actual chance that a “screen-positive” was a “true […]

  3. […] predictive value (PPV) means how likely a “positive” test result actually means the tested-for condition is present. […]

  4. […] time on Google and we stumbled upon a man names Mark Leach, who had articles and boards filled with stories of people like us, people who had received scary […]

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