What does your cell free DNA screen result for Down syndrome mean?

PQFThis is a question that gets asked at least once a week in a comment to one of the hundreds of posts on this blog: my blood test just came back for Down syndrome–what does it mean? Fortunately, there’s an on-line tool to help understand these results. 

Usually, the comment continues along these lines:

I’m [this many] years old. I took the [MaterniT21, Harmony, Panorama, etc.] test. Today, my OB called saying the results were positive. I asked what that meant, and she said I had a 99% chance of having a baby with Down syndrome. Is this correct? Please help.

After explaining that cell-free DNA screens like Sequenom’s MaterniT21 or Illumina’s verifi are never positive, and linking to this post on why saying those results are “99% accurate” amounts to malpractice, I then would link to the National Society for Genetic Counselors (NSGC) fact sheet on cfDNA screening.

That fact sheet explains why the critical number is not the claimed “99%” but what the screen result’s positive predictive value (PPV) is. This was a concerned raised in 2013 with the way cfDNA screen results were being reported and leading to much confusion on what a screen-positive meant for the actual probability that the pregnancy was positive for Down syndrome. This is what PPV relays.

Then, I’d link the commenter to this post for the simple chart in the middle that shows the PPV associated with the age of the expectant mother, with the PPV rising with the age, just as the chance for having a child with Down syndrome increases with the age of the mother.

But those figures were based on my own calculations, and, being a lawyer by training, the joke is that lawyers go to law school because there’s no math.

Fortunately, there is now an online tool that provides more precise calculations to determine a cfDNA screen results PPV.

The Perinatal Quality Foundation created a PPV calculator.

The default setting is if you are an expectant mom who had cfDNA screening as an initial screen, then you enter your age and the condition the screen reported detecting. After entering this information, then you can enter the sensitivity and specificity of the cfDNA laboratory (or simply use the default settings for a close approximation). Then, by pressing “Calculate” you will receive your PPV based on a screen-positive cfDNA screen.

The other method is to enter your prevalence, if you had a previous conventional screen, such as nuchal translucency combined or the Quad test. Then, you can enter the lab’s sensitivity and specificity information and press “Calculate” to receive your PPV.

The same calculator also provides the negative predictive value (NPV) for your screen results. The NPV can tell you the probability that you are not having a child with Down syndrome.

Since this tool became available, it is the one I most often use in answering expectant mother’s question of “what does my cfDNA screen result mean?” You can, too, simply by accessing the Perinatal Quality Foundation’s helpful PPV/NPV calculator at this link.

Lastly, professional guidelines recommend that patients receive written informational resources about the tested-for condition when receiving a screen-positive result. The professionally recommended resources for Down syndrome can be found at the Prenatal Resources Tab on this site.

Comments

  1. Olivia says:

    I am 26 years old and pregnant with my first child. My NT scan came back with a 1:13 chance for Down syndrome. They broke those results down to a 7% chance that my baby will be born with down syndrome and a 93% chance that my baby will not have down syndrome. The nuchal fold was normal and the nasal bone was present but my PAPP-A is low and my HCG is high. So they offered the MaterniT21 screening and it came back “positive” for down syndrome. The genetic counselor then went on to tell me she was sorry and that the results are 99% accurate and that I need to find a pediatrician that will take a child with Down Syndrome and get ready for having a baby with down syndrome. After getting off the phone i did some research and a few days later called and questioned her about false positives and it was funny how her story changed to her telling me that a false positive is completely possible and that these tests are not diagnostic and just a screening. She also said that in my blood they did not find Trisomy 21? So i am confused at how they are coming up with the results. I have contemplated my options and decided to get an amnio done which I am having tomorrow just to be sure and not stress for the rest of my pregnancy because ever since I heard those results it has ruined my pregnancy experience with the unknown and uncertainty of knowing if my baby has a genetic disorder or not. Based on my age am I still most likely to have a baby without down syndrome. Also all of my ultra sounds have came back absolutely fine with no markers.

    • Based on just your age, a screen positive MaterniT21 cell free DNA result would mean you only had a a 58% chance that the result was a true positive and a 42% chance that it was a false positive. However, you say you had a NT-combined result that recalculated your odds at 1-in-13–I am surprised that they would be reported that high and would ask your providers to explain how they arrived at that probability assessment. If your NT-combined result did result in a 1-in-13 recalculation, then your MaterniT21 result has a 96% chance of being a true positive and a 4% chance of being a false positive. I do not understand why your GC would say they did not find Trisomy 21 in your MaterniT21 blood sample–if not, then it should be a screen-negative result. I hope you share this post with your GC and that she reads not only the post, but the posts linked within the post, so that she may provide more accurate counseling. I wish you well with your amnio procedure and recovery.

      • They came back with the 1:13 because the Papp-a was low and Hcg was on the higher end. They said that most likely will just indicate I will have a small baby or deliver early. The nuchal fold was normal and there was a present nasal bone. They seemed not to be worried about the NT scan until I got the materniT21 results back.

        • I had a 1:17 risk of DS, which I waited out because my NT was normal and a nasal bone was seen. I had the classic low Pap A and high Hsg blood results too. This was before the NIPT was available. My daughter does have DS.

          • Thank you for sharing your experience. What materials or support resources were you provided when you received your daughter’s diagnosis?

  2. Ahmed Thabet says:

    great post

    i hope if you can help me to find all related information about NIPT and how to help pregnant women to making informed choice about it ???

    i wait your replay

    • This post has the links to the fact sheets and the links to the prenatal resources. This post synthesizes the medical recommendations current at the time of its writing on what and how to offer prenatal testing and then follow up after test results.

  3. Adina Stone says:

    I’m 42 and was told my baby girl tested positive for down syndrome. I have a healthy 6 year old . I’m wondering if this is a true positive or if I should consider more test. I know I’m not ready to take on that much responsibility please help I’m devastated

    • See this post here and the links in it for why your screening test is “never positive,” not “99% accurate” and then click the link for the calculator where you can see that the chances of your daughter having Down syndrome are 96% with a 4% chance that your test is a false positive. Because these tests remain screening, all professional medical organizations and the laboratory themselves recommend confirming the test result with an amniocentesis prior to making any decisions about your pregnancy. In the same post, at the end, is the link to support resources concerning Down syndrome, which I also hope you’ll review and see there is a lot of help out there and options.

  4. Thanks for your very informative website. My wife just got tested at 10 weeks by Progenity. She came up positive for Trisomy 21, and is age 40. So according to the calculator provides, there is a 93% probability that our baby will born with Down Syndrome. Am I interpreting this correctly???

    Understanding that this is considered a screening and not a diagnostic test, we would likely need an amniocentesis to confirm. However, the amnio would likely not change her choice to continue with the pregnancy…. anyhow, thanks for the info, and hopefully we are interpreting this correctly.

    • You’re calculation is correct. And, you’re correct, that amnio would be needed if you sought certainty. As you say, though, you intend to forego the risk associated with amnio, since the result wouldn’t change the pregnancies outcome. Having a prenatal test result for Down syndrome and an intention to continue the pregnancy, the book Diagnosis to Delivery was written specifically for expectant mothers in that situation and is recognized as an approved resource by the NSGC, ACMG, and ACOG for expectant mothers. It’s available for purchase or download as a .pdf. I hope you find it helpful.

  5. To Mark Leach,
    Thank u for all of your info, has been very helpful. I am 36 and 21 was pregnant, didn’t get numbers from nipt was jus told that it was normal although my 19 week ultrasound shows an echogenic focus in my baby’s boys heart, I’ve done lots of research and trying to be positive. The dr didn’t seem concerned he said he just had to mention it because it was there. Offered the amnio but didn’t suggest it. Nuchal screen came back normal also, any thoughts from you would b greatly appreciated. -Teresa

    • It sounds like your getting good care. The doctor was correct in sharing the information from the ultrasound and to offer amnio to confirm. The ultrasound finding is considered a soft marker and the nuchal finding would be better to rely upon.

  6. Karen Costa says:

    Hi Mark
    I’ve been perusing your site and reading through comments for hours now. Leaving a comment/question is so out of character for me, but I’m trying to get used to the unexpected.
    I’m 35; 22 weeks pregnant. I have a 16mo old son. We are so excited to welcome our daughter in April.
    During her anatomy scan, performed at a special facility, (since I’m an old mom), pyelectasis was found. The physician stated everything else looked good and to not worry about the kidney finding. The condition is found 1/100 pregnancies and usually corrects prior to delivery. However, This prompted me to do a NIPS. I didn’t do any with my first pregnancy.
    My OB uses Natera’s Panorama.
    The screening came back positive 79% for trisomy21 with 18% fetal fraction- seems like a solid number in comparison to others who have commented.
    I did use the calculator and it came back 75% positive 25% false positive.
    I’m surprised that the genetic counselor and medical staff don’t use the anatomy scan collectively with the screening data. When I mentioned that point, the counselor stated that the anatomy scans often miss things and are really only 50% accurate. We have opted out of the amniocentesis and are going to start preparing. I have bookmarked Diagnosis to Delivery.
    So really, I’m posting for:
    1. Other parents who have a difficult time finding information online, regarding these screenings, that isn’t coming from the companies themselves.
    I hope to come back in April and report my outcome
    2. Did I use the calculator correctly? So Natera is saying there’s a 79% chance that my Baby has Down’s and there’s a 25% chance they’re wrong?
    Thank you more than you know for diligently getting this conversation going and shining a light on this subject
    Karen

    • Karen–thank you for doing something unexpected for you by leaving your helpful comment. When I enter your age into the calculator, it returns a positive predictive value of 79% with a 21% chance that the result is a false positive. It would seem Natera is using the same calculation and a credit to them for presenting the PPV. I hope Diagnosis to Delivery is helpful and you can find more online support through the babycenter board listed in that book. The Down Syndrome Diagnosis Network also provides resources and support for new and expectant moms, which you might want to check out.

  7. Please share your thoughts…

    After four losses, including a ruptured ectopic, two surgeries, and three IVF cycles, I am in my 16th week with what seemed to be a typically developing pregnancy until today.

    Today, I received news that I am very high risk for Downs Syndrome based on my Sequential 1 & 2 screen. I am 33 years old. My results taken at 16 weeks, 1 day are as follows:

    Down Syndrome 1 in 6

    NT: MoM 0.86; Value1.3 mm
    PAPP-A: MoM 0.51; Value 672.6 ng/mL
    AFP: MoM 1.06; Value 35.3 ng/mL
    UE3: MoM 0.47; Value 0.40 ng/mL
    HCG: MoM 3.88; Value 142.1 IU/mL
    DIA: MoM 2.94; Value 546.9 pg/mL

    Prior to this testing, I attempted NIPT testing three times (twice with Natera, once with LabCorp). The results came back inconclusive each time. I read that repeat inconclusive results can be a sign of abnormality. However, I am on blood thinners (Lovenox, Fish Oil, Baby Aspirn) and at the time, other immune medications (prednisone and Neupogen), which my doctors believed contributed to the results. The genetics counselor at Natera also agreed. Now I am inclined to believe the inconclusive results were a sign of abnormality.

    The genetics counselor is suggesting I try NIPT again. She recommended that if the results are again inconclusive or high-risk, do amnio. My husband and I are very uncertain of amnio given my history and need to be on blood thinners. We also would not terminate this pregnancy. The only reason that I can see at this time for amnio is preparation for a baby with a disability or peace of mind to learn that the result is negative. I am concerned about the risks of amnio given my history. The idea of risking miscarriage just for peace of mind is overwhelming.

    What are your thoughts about these results? Trying the NIPT again? And amnio?

    • You are correct that inconclusive results are to be considered a sign of being high risk per the most current practice guidelines. That, however, does not mean your pregnancy is positive for Down syndrome. The sequential screen, while one of the more accurate conventional screening methods, is not as accurate as NIPT and I’m not sure what the basis is for a positive predictive value of 1-in-6–but even at that ratio, you still have an 83% chance of it being a false positive. If peace of mind is worth it, then I would recommend having NIPT one more time prior to an amnio. NIPT becomes more accurate the later in the pregnancy it is conducted as more cell free DNA will have accumulated in your bloodstream. I wish you well.

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