Natera’s Panorama booth
Or based on Harmony, verifi, Panorama, or any of the new prenatal blood-based tests for Down syndrome.
The new blood-based tests highlight their accuracy. Natera’s Panorama, Sequenom’s MaterniT21, Ariosa’s Harmony, and Illumina’s verifi all promise the most accurate prenatal screening results for Down syndrome. But, the emphasis should be on the fact that these are screening results.
Screening vs. diagnostic
When the American College of Obstetricians & Gynecologists (ACOG) changed the standard of care such that all women were to be offered prenatal testing for Down syndrome in 2007, it did so based on the advances at the time made in screening tests. When those guidelines were issued, the new screening test was the first trimester nuchal translucency-combined test, which had a false-positive rate of around 3-5%. For this reason, ACOG issued two guidelines in the same year recommending women be offered prenatal diagnostic testing as well as screening testing, and emphasizing that screening testing should be confirmed by diagnostic testing for a patient to be certain of the result.
Diagnostic testing is needed because screening testing is not diagnostic testing. Screening testing, like the nuchal test and the new blood-based test, simply recalculates a woman’s chance for having a child with Down syndrome. But it is still just a chance. Screening results are never diagnostic. For patients to have the level of accuracy to be considered diagnostic, only a CVS or amniocentesis–the most common prenatal diagnostic tests–reach that level of accuracy.
Irreversible decision
For this reason, when the professional guidelines were issued for non-invasive prenatal screening (NIPS) every medical organization emphasized that NIPS still had a chance for false positives and false negatives necessitating diagnostic testing to confirm results if a patient wanted to know to a diagnostic accuracy.
A NIPS result cannot be relied upon as a diagnosis.
Most women choose to terminate following a diagnosis. A study of NIPS (cfDNA screening) accuracy in the general population whose lead author was also the lead researcher for verifi stated that:
The positive predictive values of cfDNA testing (45.5% for trisomy 21 and 40.0% for trisomy 18) underscore the need for follow-up diagnostic testing to confirm true positive results before decisions are made about irrevocable clinical intervention and to resolve discordant results.
Yet, we know women are terminating based only on a NIPS result and not a diagnosis.
17%
At the 2013 conference for the American College of Medical Genetics and Genomics, two presentations shared how women were terminating based on a maybe. In one case, a woman terminated her pregnancy based on a NIPS result only to learn that her fetus was not positive for the NIPS-result condition. In another instance, a NIPS lab representative presented to an invite-only lunch that the lab had followed up with providers and learned that 17% of patients receiving a screen-positive NIPS result had chosen to terminate without having a diagnostic test.
Don’t abort based on a maybe
Sequenom’s MaterniT21, Natera’s Panorama, Ariosa’s Harmony, Illumina’s verifi, LabCorp’s InformaSeq, and any other blood-based prenatal screening test does not report diagnostic results. False positives and false negatives remain. Before any irrevocable decision is made, the professional guidelines and medical professionals recommend that patients receive confirmation from diagnostic testing.
But, women right now are terminating based just on a “maybe.”
It’s tragic that women choose to abort their child only because of Down syndrome. If only they knew what they were missing. I am an idealist–I wish we lived in a world where all people could be valued as is, where children are given the ability to exist just because they are created.
And as this post discusses, some are aborting simply because their child might have Down syndrome.
Yes, that’s a terrible thing for sure. But I’m also torn–it is easy to think, “oh, how awful for them that they aborted for nothing,” but the bigger picture is that aborting for Down syndrome is aborting for “nothing” too.
Why would aborting based on a screening result that their child might have Down syndrome present a concern whilst aborting because the child does have Down syndrome not present a concern? It’s a screening result, and the mothers make an informed choice based on the chance profile. That’s the whole point of it.
I’ve written before about how this underlying assumption is unethical:
“On the other hand she adds confusion by bringing in the 5% false positive results. These are pregnancies with a positive screening for Down syndrome when the child doesn’t have Down syndrome. Most of these unborn children are killed through a selective termination or from an invasive test. But, this is all smoke and mirrors. The underlying assumption here is that harming those without Down syndrome is wrong and that harming those with Down syndrome is acceptable, or even desirable. Two class of human beings, one worthy of life, the other unworthy of life. This attitude by medical professionals is offensive and devalues the lives of those living with Down syndrome and other disabilities. Anything that devalues the lives of people with Down syndrome is unacceptable. The ethical focus would be to reduce harm to all of those pregnancies.”
http://www.savingdowns.com/genetic-expert-diana-bianchi-misrepresents-new-eugenic-test-for-down-syndrome/
Couldn’t have said it better Mike. If a couple would consider abortion, I’d dare say they’re willing to take the risk of a false positive.
Had a positive result reported to me, nothing more on copy on requested, from Maternit21. Had level 2 ultrasound, only showed echogenic foci, and fetal echo nothing presented. I’m 37. Not sure what to do since they say 99% accurate yet I keep reading articles stating they are not representing the truth. Also the original study was with 200+ women in 2011. Where is the current statistics? Any insight? Thinking amnio.
None of the NIPS labs, like Sequenom, have reported how their test is actually performing in the commercial setting, but experience is showing that none are as accurate as how they performed in a clinical study. Even if the accuracy was 99.5%, though, based on your age, it means you have a 20% chance of a false-positive (see this post for explanation). As this post covered, the only way to receive a diagnosis remains through a CVS (first trimester) or amnio (second trimester). You may want to consult with a genetic counselor as you consider your decisions. I hope you receive the support and information you deserve.
I hope you have the opportunity to link in with some families living and loving with Down syndrome, who are best placed to shared the lived experience. Genetic counsellors have pretty limited experience at best, and many have a bias that may not be helpful for you. Congratulations on the pregnancy.
Hello, I am so glad to have came across this info. Downs does not run on either of our sides of family. I am thirty nine and pregnant w my second child that is due in May 2015. My first child is almost 8 and does not have any genetic probs. I will not be 40 till August. I just got my results the day before Thanksgiving, what a downer!!! So with my age they recommended me having extra screenings and my first trimester screen came back as a 1 in 43 chance of downs.I also had the cell free DNA test that came back at 99.6%. I really am scared and do not want a amnio due to risks!! Can you recommend anything for me about my situation that I can ask the doctors about my test or any thoughts for me? PLEASE help!! I don’t know what to think or do. Angie
As covered in this post, given your age, you have likely a 10% chance for a false positive. If you are inclined to continue your pregnancy regardless of whether your child has Down syndrome, many women are opting to rely on the cell free test and avoid the risk of miscarriage. A resource for mothers who have chosen to continue is downsyndromepregnancy, which has a free .pdf book that has been recently updated. If you don’t know what you may do with your pregnancy if your child has Down syndrome, as this post covers, you can only know for certain through a diagnostic test, like an amnio. If curious about what a life with Down syndrome can be like, professional guidelines recognize that local parent support organizations can be very helpful. It’s where I found the best information when we learned our daughter had Down syndrome. You can find your local group at this link. I wish you well and hope this has been helpful.
Great website – thanks. I have a ” positive ” Harmony Test and CVS as a result tomorrow. What concerned me about the test provider was that they couldn’t provide me with a positive predictive value and kept quoting figures that were actually Sensitivity/Specificity. Actually I don’t think they knew what a PPV was , let alone the difference. I also enquired about the effect of earlier (10+ weeks gestation) rather than 12+ weeks gestation would have on the amount of cell free fetal DNA available available for genomic sequencing. Again- no answer available.
Annie–thank you for sharing your experience. Interesting that you couldn’t receive a PPV, since I recall Ariosa being one of the few that initially reported results in that format. From the studies I’ve seen, the later in gestation, the more accurate the test because of increased amounts of cell free DNA (see this post for explanation as to why it is not “fetal” DNA, necessarily). I hope your CVS goes well.
Hi just as a bit of follow- up I had a CVS that confirmed T21. Interestingly the nuchal was very narrow and given that the harmony test only was 75% chance rather than the expected greater than 99% I was told that first trimester screening would probably not have given me high risk. In which case I would have waited to have an amino ( given age related risk) and have been many more weeks along -changing possible management options and probably increasing emotional anguish. Regards.
Annie–thank you for sharing your experience. I hope you also received the recommended information and referral to support services per the professional guidelines of ACOG, ACMG, NSGC, and AAP, namely referral to a genetic counselor, a copy of Understanding a Down Syndrome Diagnosis, and the contact information for your local parent support organization. The last two are included in a list of other recommended resources at the Prenatal Resources tab. I hope you receive the accurate information and support you deserve.
Thanks Mark. I received genetic counselling about findings and diagnosis and relevant organisations for support – for every option/choice that was available. No expectation was given to me regarding what I “should “
While this blog attracts comments about poor care, I know that there are many, many good doctors who deliver care as they should when offering and counseling about prenatal testing. I’m very glad to hear you received the care all women should.
Hi Mark, My Nuchal test results were a 1:23. I’m 41, pregnant 13 weeks with my second child. I did the MatirniT21 and the genetic counselor said it was positive for Downs. You keep mentioning to meet with a genetic counselor but at least this one says the genetic tests are 99.9% correct and that there aren’t false positives with Downs. I don’t think they are necessary the right people to meet with. I am going to do an amnio at 16 weeks to confirm the diagnosis to prepare our family. Have you ever heard of someone having two false positives with the nuchal and the genetic testing? Thank you, Katie
Katie–I recommend seeing a genetic counselor for at least a couple of reasons: [1] it’s what the professional guidelines recommend for interpreting genetic test results, and [2] I am an attorney with a master’s in bioethics, but zero medical training. That said, just like there are some ill-informed attorneys, obstetricians, engineers, and any other profession, so, too, are there ill-informed genetic counselors. I would e-mail your genetic counselor the fact sheet by the National Society of Genetic Counselors so that he or she does not make this same mistake again when counseling another patient, as there are most assuredly false positives. I am not aware of someone having a false positive with a nuchal and NIPS, but that does not mean these do not occur, and statistically they remain a possibility. I hope you get better and more accurate advice with your amnio results.
Even CVS isn’t necessarily representing the whole picture, as it only tests for the placental cells, not the fetal cells…( placental mosaicism exists, which rarely affects the fetus) it looks like the last line diagnostic test should be the amniocentesis corroborated with follow up scans and echocardiogram.
The NSGC fact sheet on cell free DNA recognizes this limitation of CVS.
Hi,
I am 25 yrs old and pregnant with my second child, my first miscarried very early on only a few weeks before I became pregnant again. I took the InformaSeq blood test screening in my 24th week of pregnancy and was told that it came back positive for Trisomy 21. There is no history of IDD on either side of the family, and my husband has 4 other healthy children. I am worried sick about this baby but don’t want to do the amnio because of the associated risk factors. I just wish there was a way to know for sure without risking harming him. What are the odds this test gave me a false positive?
Based just on your age, the estimated false positive rate is almost 60% (see chart in middle of this post). Meaning: if you did not have any other screen result to adjust your odds of having a child with Down syndrome, then your baseline chance based on your age was about 1-in-1,300. Applying the claimed accuracy rates of testing like InformaSeq means a screen positive result really only has a 42% chance of being a true positive and a 58% chance of being a false positive. Another factor that may contribute to the analysis is your previous miscarriage. Most pregnancies with a child with Down syndrome naturally miscarry, but the cell free DNA from all of your previous pregnancies can remain in your blood stream. Therefore, perhaps the InformaSeq result is correct, but it is correct for cfDNA from the pregnancy you miscarried and not the one you are currently carrying.
I’m 36 years old and did the cell free DNA test with Labcorp at 11 weeks. Results came back high risk for trisomy 21. NT scan shows no markers and baby measuring 4 days ahead. Genetic counselor told me its 99% accurate and OB dr. said I need to make a decision. I went to a high risk Dr. And he suggested doing an amnio at 15 weeks if we want to know for sure so we scheduled that for next week.
This is such a stressful time I don’t know who to believe.
It is not “99% accurate” and your Genetic Counselor and OB should know better! (See this link here). Based on your age and your NT scan showing no markers, your cell free DNA screen result means you have an 82% chance that the screen result is a true positive, ie that your child will have Down syndrome, and an 18% chance that the screen result is a false positive, ie that your child does not have Down syndrome. Your high risk Dr is correct: the only way to know for sure is with an amnio, which should not be performed before 15 weeks. Also, per professional guidelines, you should have received written and support resources with your test result. You can find these at the prenatal resources tab.
Thank you for your response. I did call the genetic counselor today and asked her if the fact that I didn’t have any markers made a difference. She didn’t really have an exact answer but said that 20% of women carrying trisomy 21 do not show markers. When my husband and I went for our “counseling” session we were given no support resources nor were we given our test results. I am not sure if that is because we did not want to know the sex of the baby. Our high risk Dr. seems to be the most supportive and positive. Thanks again for your help!!
I’ve had 5 pregnancies , 3 of which I had the Harmony for. One turned out to be marginally higher risk than wanted. First trimester regular screening very low risk ,no soft signs ,really small nuchal. CVS confirmed full trisomy 21. Try not to read anything much into numbers after a non invasive pregnancy test. It’s either really really low risk of something else. It’s only a screening test ,not diagnostic. Think of it as something that gives you peace of mind with the really low risk (and therefore no need for CVS or amnio) or something that means you need to think about a diagnostic test.
Thanks Annie! I could have done a cvs but the high risk Dr suggested an amnio because the cfdna test I had takes from the placenta and so does a cvs. The waiting is agonizing. I’ll be 15 weeks next Tues and have amnio scheduled for wed. We should get FISH results on Fri after.
Kudos to your high risk DR for noting what is being tested.
All the best with the wait x
I am 36 years old. My first child had a genetic disease that was terminal. I have 3 healthy children now. My youngest is only 1 1/2. I took the unformasque. It came back positive for downs. I go in for a stage 2 this week. I don’t understand how the results work. What are my odds???
See this post here and the links within it to better understand what your cell free DNA screen results mean. Using the calculator linked in the post, you’ll see where you have about an 82% chance of having a child with Down syndrome based on your InformaSeq results and an 18% chance that the result is a false positive. I hope you’ll also review the resources linked at the end of the post to also learn more about Down syndrome.