Fig. 1 U.S. NIPT Brands
For years, I’ve been presenting at conferences on prenatal testing for Down syndrome, explaining how the new tests are based on cell free fetal DNA or “cffDNA.” Turns out I was wrong. Here’s why.
This past week I gave a poster presentation at the Annual Clinical Meeting for the American College of Medical Genetics (ACMG). There is where I learned I was mistaken about the basis for newest form of prenatal testing.
Poster presentations are where you stand in front of a poster and present on the information it displays. (I’ll have more on my particular poster later). One of the first conference attendees to walk up to talk about my poster was a medical geneticist that, we figured out, was stationed with me when I was in the United States Air Force. In talking about the newest form of prenatal testing, non-invasive prenatal testing (“NIPT”), he off-handedly mentioned, “well everyone knows cffDNA is really placental DNA.” Well, this everyone did not.
NIPT has received a lot of media attention, due in no small part to the private laboratories promoting their various versions of it. Currently, in the United States, there are four laboratories that provide NIPT: Sequenom, Ariosa, Verinata, and Natera. Figure 1 displays these laboratories’ respective NIPT tests in clockwise order, respectively. In the professional medical committee opinions and materials from the testing laboratories, where reference is made, often it is to “cell free fetal DNA.” So, I suppose I should be forgiven for not understanding that the DNA was not, in fact, fetal DNA.
Instead, it is placental DNA. Now, here’s where we time travel back to high school. Some of us may remember cellular biology: the nucleus, mitochondira, etc. When a conceived cell implants into the mother, the cell has divided into further cells that perform certain functions. There are the cells that go on to become the fetus; there are those cells that go on to form the placenta (these cells come from the group of cells called “cytotrophoblasts”); and, there is even other genetic material which performs the function of anchoring the fetal and placental cells to the cell wall of the mother (called “syncytiotrophoblast”). Figure 2 is a rendering of these various forms of cells.
Fig. 2 Implantation of blastocyst
It turns out, that almost all of the cffDNA found in the maternal blood stream actually comes from the DNA of the cells that form the placenta or perform the anchoring function, not the cells that form the fetus. Therefore, it’s not entirely accurate to use “cell free fetal DNA” when discussing MaterniT21, Harmony, Verifi, or Panorama-style non-invasive prenatal testing.
As a fellow conference attendee explained, this is a distinction without much difference; while it is not cffDNA, in his opinion, it was not that big of a deal to refer to it as cffDNA. And, perhaps it’s not. But, I would guess that expectant mothers would think differently on the accuracy of a test if it were explained to them that the test did not actually test fetal DNA, but instead was “cell free placental DNA.” And, based on one of the last presentations I attended, they would have reason for that different perspective on the test’s accuracy.
The last session’s speakers presented cases involving various genetic issues arising in the prenatal stage, including false positives and false negatives they had experienced with NIPT. It is for this reason—that there are false positives and false negatives—that NIPT was revised from NIPD, non-invasive prenatal diagnosis (and will soon undergo another name change).
In one of the presentations, the presenter explained how a patient had received a positive NIPT result that ultimately was found to derive from what’s called “placental mosaicism.” “Mosaicism” occurs in the case of triploidy where there is a triplicate of a chromosome in some, but not all, of the cells. In placental mosaicism, the placenta can have cells with triplicates of chromosomes while the fetus does not have any triplicate chromosomes in its cells. Indeed, the diagnostic test that can be performed in the first trimester, chorionic villus sampling (“CVS”), tests placental cells, and has returned results of Down syndrome even when the fetus does not have Down syndrome, because the particular placental cells tested had a triplicate of the 21st Chromosome.
The presenter on the false positive based on placental mosaicism concluded by saying that because NIPT tests placental DNA, the most it can ever become is as accurate as a CVS. While CVS is considered a diagnostic test, CVS results still have the risk, however slight, of returning results from a mosaic placental cell that is not represented in the fetus itself.
Placental versus fetal DNA may be a distinction without much of a difference when it comes down to the accuracy of the results. In the vast majority of cases, the results will be accurate for the fetus even when the test is of placental DNA. But, this is more than just a semantical difference—or, even if that is all it is—then there is a significant semantical reason why “fetal DNA” was chosen over the more accurate “placental DNA.”
Mothers will expect prenatal tests to be of fetal DNA, not placental DNA. If “placental DNA” were used, perhaps expectant mothers and general society would further appreciate how the newest wave of prenatal testing is, in most cases, not actually testing DNA from the fetus, but from the placenta. Using precise language would further make clear that NIPT results are, at best, highly accurate screening tests, but not certain enough to make any decision without first receiving a diagnostic test result.
Update: For more lessons learned about NIPT (including why it’s NIPS) click here.
Update: The National Society of Genetic Counselors has issued a fact sheet on NIPT, which is linked to and covered at this post.
Update: The largest known clinical study of NIPS discusses the testing of placental DNA.
I am a patient who took the Panorama NIPT. I was high risk for Trisomy 13. An amnio later determined my fetus has 46 chromosomes — normal, no Trisomy 13. Looks like I have confined placental mosaicism (will be diagnosed once I deliver and the placenta is examined). It’s important for women to know that these tests are not 100% accurate and that CPM has cause a ‘false positive’.
Chelsie–your comment was well-timed as it arrived while I was at a conference giving a talk on the accuracy of the newest prenatal testing for Down syndrome and other aneuploidies. Thank you for sharing your experience.–Mark
Here is my story. I am not sure what to make of it but if you can tell me what you think it will help me a lot. I am 31 and my wife 33. We got pregnant after an IUI. Now at week 10 the u/s showed a slight thicking behind the neck. The dr asked us to take Panorama test. We did that (at week 11) and after 3 weeks it came back inclusive for Trisomy 21 (others were negative). The dr says the report said “not enough fetal fraction”. I guess that means they did not have enough cells from fetus to test with. Panorama asked us to resend the sample so we did that (this is week 14 now). After a week it still shows inconclusive ! This time the dr says the report shows sample does not meet some metrics . And mind you we sent two vials of blood (not sure if they used both or not).Now we are going for Amnio at week 16 . My question is what is the precedence of this? What do we make out of it. Have you encountered any such case ? if yes what was the outcome? Thanks in advance !
By coincidence, Natera, the NIPS lab that offers the Panorama test, hosted a webinar on Tuesday entitled “The importance of fetal fractions.” The presentation made the point that low fetal fractions makes NIPS testing less reliable. A questioner asked what they do if an initial test is inconclusive. The response was they ask for another sample and they usually are able to report a result after the second sample. So, by using the term “usually” (or a word like that, I’m paraphrasing the response from memory), that would suggest that, yes, Natera has had second tests come back inconclusive. Because they didn’t speak to it, I do not know what they suggest in such a situation. Hopefully, you at least were not charged for the tests since you never received a result. Another consideration would be to see if another NIPS test could be done, e.g. MaterniT21, Harmony, or Verinata to see if one of those returns a result. Each NIPS lab uses a bit of a different testing method. One of the critiques from the professional organizations is that there is currently no data set by which to compare which of the tests is more accurate than the others because of the way each lab controls what information they release about their tests. Feel free to provide an update either here or privately to me via e-mail at mleach[at]downsyndromeprenataltesting[dot]com.
Natera just posted its webinar on fetal fractions from earlier this week. Here’s the link.
I too, have just received my 2nd “no result” from the nipt harmony test. I’m 35 and got preg via iui, I took the first test at 10.5 weeks and the second at 12.5 weeks. I’m wondering if perhaps the iui had something to do with it or perhaps vanishing twin? I’m scheduled for an amnio in 10 days… Really frustrating!!!
I just took the amnio 2 days ago. My harmony test came back greater than 99% abnormal. I’m upset why my doctor sent me to do the prenatal screening in my second trimester instead of first trimester. Now that I’m about 21 weeks, I can’t imagine myself aborting my baby since I have already felt him move a lot. At the same time, dealing with a child with Down syndrome is very challenging. I’m so angry since I found out the non-invasive prenatal testings can be done as early as 10 weeks. This would make it so much easier for parents to abort if they feel the need to before feeling their babies move. I’m stuck in this dilemma. I’m hoping there’s a miracle that my harmony test was wrong by confirming it with an amniocentesis.
This is relatively new for our OBs in the US. Im 14 weeks and mine didn’t know about it until I asked for it. The important thing to remember is that even if you HAD taken this test at 10 weeks, you would have had to wait until 15 weeks for an amnio anyways. A CVS tests the same placental dna as the cffDNA test you had.
My first child had full (not mosaic) T13 and because two of these three chromosomes were attached to eachother, I have decided to DNA test anytime I am pregnant. I had a CVS with my 2nd child (healthy) and will be having the Harmony done tomorrow for the 3rd. I am 14 weeks.
Felicia, thank you for sharing your experience and reasons for prenatal testing. I hope the NIPS test provides the information you are looking for. I would be curious what Ariosa (and any other NIPS lab) would say about what their detection rates would be for not just T13, but the joined T13 in your specific situation.
I’m confused here. You do understand the baby is moving even before you can feel it right? That your baby is alive even before you feel it move or see it on an ultrasound. Do some research, watching In the Womb by National Geographic, might help. Life begins when sperm meets egg. I had an ultrasound last week at 9 weeks 3 days. The baby was moving. Yes. Shocker. The babywas already alive and moving and a heartbeat was seen and heard. My son is seven and that night he said to me “Mama! It’s so cool! Did you know I am already a big brother? Because that baby is already alive in you.” A 7-year old gets that but adults don’t seem to. It boggles my mind and makes me very angry more people don’t do the research and unnecessarily choose to make themselves God and end lives
It’s a personal choice, and, surely, you are not entitled to judge others. I speak as one who is a lover of Christ.
I don’t think that this is the goal of this blog or comment board- to decide whether its wrong or right when there is no real answer, only a very hard, personal choice. It is no one’s right to judge someone in a heart wrenchingly difficult situation.
Mark, I wonder if you would consider closing comments on this post that is over a year old. It keeps attracting questions that we all get notifications on that are usually expectant parents seeking answers that you keep needing to refer back to their doctors or genetic counselors for real answers on their individual cases. Just a gentle suggestion?
Thank you, Victoria. I apologize if the commenting is an annoyance. However, I am glad that readers still comment and ask questions on a post from a year ago. This post is one of the most often read on a daily basis, so I would like to leave comments open so that readers with questions may post them.
Mark, my concern was the tenor of the comments right above me where I replied and wondering if the “space” left open was in some part attracting drive-by judgements. But let me try not to fix what is not mine to fix.
I always appreciate your input, Victoria. Thank you.
These tests identify also the sex of the fetus. Is it possible to find that only from placental DNA?
My understanding is yes because if there is a “Y” chromosome found, then that would mean the fetus is a male, and the absence of a “Y” chromosome means the fetus is a female. But I welcome any links on this.
Hi- I will be 14 weeks pregnant on 12/28/13. I was just informed that my Panorama drawn at 11w4d resulted in Triploidy X. I was advised to immediately follow-up with a CVS. We are devastated. Are there cases of placental mosaicism of “triploidy x” where the fetus could still be healthy and diploid?
I will see what I can find, but I would recommend consultation with a genetic counselor.
Thank you- we absolutely will. I’ve been sleepless, scouring the internet for hope and information, and found this article. Granted they are case reports, but given this research is so new, with much to be learned, I will not ignore it, and wonder if the author’s deductions about placental/maternal mosaicism are true. See link
http://pregnicare.co.il/Assets/articles/secondary%20findings%20from%20non-invasive%20prenatal%20testing%20for%20common%20fetal%20aneuploidies%20by%20whole%20genome%20sequencing%20as%20a%20clinical%20service.pdf
Thank you for the link to the article. Regarding your test results, did they report triploidy or triple X, also listed as 47 XXX? The impact of the two conditions are on opposite ends of the spectrum, with triploidy being incompatible with life while women with an extra X chromosome may live their lives unaffected. Another thing to keep in mind, a CVS also tests cells from the developing placenta, just as NIPS/Panorama does; therefore, CVS also has a risk of diagnosing a condition in the placenta, not the fetus. An amnio, on the other hand, is of the fetal cells. Having said all of this, I’m glad you will be meeting with a genetic counselor. If you need help finding one, the National Society for Genetic Counselors has an on-line search tool at this link.
Thank you for the info and link of counselors. Two of the four NJ university hospitals that I called, thankfully returned my call immediately. We are on our way to meet with the genetic counselor and have a CVS. Unfortunately, the results indicated Triploidy X (69 chromosomes XXX). I will probably need an amnio as well to test fetal cells, but will discuss this with the counselor. I have realistic expectations but need all the information available. I will definitely discuss the case reports of placental vs fetal chromosomal variation, and if this can even exist in triploidy X.
I hope you receive wonderful care.
Thank you- the genetic counselor was incredibly thorough. Most importantly, she informed us that our OB misread the results. It was indeed Trisomy X that was reported, not Triploidy X! We proceeded with the CVS to better prepare ourselves for whatever is actually going on with our viable, baby girl- thanks for the support!
Thank you so much for sharing and I’m glad you received thorough care. Misreading results is built into a process where humans read the results, but wow–what a misread! The Lettercase pre-test pamphlet refers readers for more information about Trismoy X to this link. I hope that proves helpful and wish you well as you move forward.
I recently decided to have the Panorama test done, due to a slightly elevated risk for Trisomy 21 from our Nuchal Scan (1 in 405). The Panorama came back showing 96% risk for T21, from a fetal fraction of 4.6%. My husband and I were clearly devastated and assumed the worst given that all the research claims that they have 99.9% accuracy and 0% false positives. However, we have now received the results from our amniocentesis which have (miraculously!) confirmed that our baby doesn’t have T21 (or any other chromosomal problems). Natera have provided no explanation as to why this could have happened or asked to see my final amnio results. I’m not sure how they can get away with claiming to have no false positives when clearly I’m not the only person this has happened to.
Found this link in my search for information about false positives. The NIPT companies really need to provide better information about what their statistics truly mean. Im still waiting for my CVS results to compare with the Panorana, and may still need an amnio. However, I really needed more information about the Panorana (all nipt’s) and there is not a lot out there…
http://thednaexchange.com/tag/nipt/
Thank you for sharing Stoll’s post. It is one that I’ve been meaning to comment on further and will likely do so thanks to your reminder. Another of her posts prompted a series analyzing the predictive value of the new prenatal tests, like Panaorama. That series is at this link. In addition to Stoll’s good work on this issue, your point is one that has been expressed by professional medical societies and in medical journals: that the accuracy of the new tests remains questionable because the test manufacturers control how and what information is shared.
In my recent reply to another comment on this post, I shared how you are not alone in your frustration and concern about how the new test’s results are presented. Professional medical societies, journals, and practitioners have all expressed a “serious concern” about the risk of misunderstanding non-invasive prenatal screening results as being more accurate than they really are. However, it is not in the labs’ business interests to suggest their tests are less accurate than they market them to be. 23andme recently had a class action lawsuit filed against it based on consumer fraud for alleged misrepresentations about its test results. Unfortunately, it will likely take a very bad situation before a patient is damaged enough that they will be willing to put themselves through the stress of a lawsuit for misleading information about the tests.
I had an NIPT done last week; not sure of the name but it was through Kaiser Hospital in Oakland, CA. The results returned a 70% high risk result for Trisomy 18 based on a fetal sampling of 4.6%. I then had a level 2 ultrasound where the doctor indicated strong markers for Trisomy 18. I took an amnio today and am praying that the results return a normal chromosome result. My question is, with odds stacked against me with the NIPT and ultrasound, what are the odds that both are wrong? I’m currently 18 weeks pregnant and baby is measuring 18 weeks. Doctor stated baby appears to have brain cysts, clenched hands, abnormal feet, challenges with swallowing ambiotic fluid and small head and chin. This sounds so devastating!
I wish I could tell you precisely, but though I cannot, I hope you will have access to a genetic counselor who should be able to. Of the false positives that I’m aware of for NIPT, they do seem to be represented by more Trisomy 18 findings than others. The Trisomy 18 Foundation is a very good and compassionate organization. I hope you will seek them out should your amnio confirm the screening findings and they can support you now while you wait.
Thanks so very much Mark for your reply.
What was your amino result? Hoping your holding a healthy baby today. I am going through a similar situation.
At our 20 week ultrasound, our doctor saw a couple of markers for Trisomy 18. She recommended that we do the Harmony test first to see if we had a high risk. The results came back negative for Trisomy 18. (0.01% risk) Last week, we buried our baby. He was diagnosed with Trisomy 18. I don’t think these tests are as accurate as they claim to be and I wonder how many other false negatives are out there.
Brenda I am extremely sorry for your loss. I received a t18 diagnosis and awaiting amniocentesis results to confirm. My NIPT test said 70% t18. Do you mine sharing what the markers were? I have markers as well according to the dr – thickening in the right ventricular heart wall, small stomach bubble, small chin, close eyes. He also says both hands of the baby were clenched with overlapping digits. However, the hands weren’t clenched on the 12 week ultrasound. I’m 18 weeks and the baby is also measuring the same.
Hi Michelle, I’m sorry for all the worries you’re experiencing in your pregnancy with this baby. Right now the NIPT are used for screening purposes that then lead to a referral to maternal-fetal medicine specialist for further evaluation. I’m glad to know that amniocentesis is being done as that is the only current true diagnostic test that can give you answers about your baby’s genetics. The advantage of the amnio is also that it can go beyond just Downs, T18 or T13 to more rare chromosomal disorders or deletions or partials. I’m hoping with you that the amnio results are positive showing no problems. If a T18 diagnosis is confirmed, I hope you’ll find support with us at the Trisomy 18 Foundation at http://www.trisomy18.org.
Michelle, do you mind me asking what NIPT test your doctor used with you? Harmony? MaterniT21? others?
It was verifi I believe. The box was purple.
Victoria thank you so much for your response. Can you tell me (if you’re aware) of what other chromosome disorders would yield the type of markers as mine and is the outcome if fetal demise that of trisomy 18
Michelle, the outward features that can be seen on ultrasounds are shared by any number of disorders. I wish I could be more definitive than that, but the amnio will provide some answers to all these questions. Feel free to reach back out to me at vjmiller@trisomy18.org when you learn of the results.
Victoria
Thank you dearly! This is hard because of everything I’ve read and heard of T18, except the clenched hands which wasn’t seen in the 12 week ultrasound (baby was waving) seem on the mild side, unless a hole in the heart can develop from a mild thickening of the right ventricular wall.
Michelle,
At our 20 week ultrasound, the soft markers were plexus cysts (which they weren’t worried about), clenched fists and hypoplastic left heart syndrome. When he was born, there were alot more markers that they didn’t identify on ultrasound.
Brenda thanks for sharing that information with me. My amniocentesis results were given to us yesterday evening and it was positive for t18. Words can’t explain our devastation.
Brenda, my condolences for your loss. Thank you for sharing your experience, since I have not had many share about false negatives. The Trisomy 18 Foundation has featured recently some resources for grieving parents. I hope you will receive support as you feel guided to do so.
Brenda,
I am sorry to learn of the loss of your little one to T18. And of the false negative, I know was especially upsetting and probably left you unprepared. Did you learn some other way of your baby’s diagnosis before birth? I do hope you will connect with us at the Trisomy 18 Foundation where you can share your loss with many other parents who have also lost their precious children to this devastating condition at http://www.trisomy18.org
Victoria,
We had a couple of soft markers, (heart defect, clenched fists) but because of the negative result on the Harmony test, we thought we were in the clear. Obviously, we can never trust the Harmony test or any of the cell-free-dna testing again.
Oh Brenda. I know exactly how you feel as this is very close to my own story where we were “surprised” at birth thinking we were in the clear after having lost 2 previous pregnancies. But what that experience really drilled in my head was the importance of doing prenatal diagnosis and not trusting the screening tests completely.
I know you wanted to be much more prepared to make choices in the best interest of your child and family — and you would have. You can’t help but feel like you put your trust in the wrong things. I came to feel that I couldn’t trust anyone (no thank you to those reassuring pats on the head that everything’s fine), and only HARD DATA could I trust. So yes — tests — and show me the results — that became my “take away.”
So bottom line — only an amniocentesis can provide that HARD DATA today. And like you, I wish I had been able to KNOW in advance after a missed prenatal screening. Please know that you will find peace with all that happen over time. Meanwhile, I’m listening. If you’d like to email me you can reach me at vjmiller@trisomy18.org.
Take care of your heart, dear.
I guess my whole issue is the fact that we didn’t want to do invasive testing which is why we did the Harmony test. I mean what’s the point of doing cell-free DNA testing otherwise. The whole hype around the Harmony test and others like it is that you can avoid doing invasive testing like the amnio and do the Harmony test first (because its 99% accurate)–and then if the Harmony test says you are positive (or high risk) you can then choose whether or not to do the amnio. But hey, if its negative or low risk, then the amnio is not as important. THAT is how it is promoted–THAT is how it is hyped to be.
Hi. I’m 33 years old (my husband is 31 yrs old) based in India and we conceived using an IUI procedure at first attempt. I did my triple test and Nuchal translucency (1.5 mm) at 14 weeks, and I was shown to have 1:124; an increased risk for Trisomy 21. As per my Last Menstrual Period (LMP) I am at 17 weeks and 3 days, but scans at different centres show different weeks.. last scan 7 days back showed 15 weeks at the lab where I have scheduled a cell free DNA test on 10 Feb. It is highly expensive as they claim to send the samples to the US for testing. I am reluctant to do an amnio and wanted your input here. Should I go in for the CFF DNA testing and keep the faith that the result will be accurate (& favorable of course) or go in for an amnio directly? The results take 10 days in CFF and as per LMP I will be at 19 week+. Thanks for your help.
Mothers who intend to continue their pregnancies whether their child has Down syndrome or not, are increasingly relying on the CFDNA test results, & forgoing the risk of miscarriage associated with an amnio. Mothers who are considering termination are having the amnio in order to be certain that their child has Down syndrome or does not.
Mark I really agree with your comments. It was the amino positive results that led my husband and I to decide termination. Do you have any knowledge or resources about the success of IVF with pre-genetic screening testing on first cycle after an D&E? My D&E is scheduled tomorrow and my husband and I want to do this option when we try again in about 3-4 mos to be in a better position since we lost this baby to trisomy 18 at 19 weeks.
Michele, search the blog for PGD & you’ll find a post which has a link to ACOG’s statement on PGD. ACOG does not recognize it as an effective screen for aneuploidy, but I’m aware of it being done. I would recommend talking w/a genetic counselor or medical geneticist.
Thanks Mark – I can tell you that our Genetic Counselor said she felt it was a good idea and would put us in a better position when trying to conceive again.
And parents who want to be prepared for other conditions besides Down Syndrome (Trisomy 18, Trisomy 13, and sex chromosome trisomies, need to consider which screening tests can best give you that information. Other conditions than Down Syndrome also have a “marker” of increased nuchal translucency early in pregnancy. As is always the truth, only the results from an amnio are definitive in terms of diagnosis. Parents have to weigh the risk of how not knowing might impact their birth planning and choice of hospitals (some parents want to be at a hospital with high level NICU), risks of unexpected stillbirths against the risk of miscarriage from an amnio. Performed by MFM specialists who do amnio tests regularly, the risk of miscarriage is very low. But you can always ask your specific doctor how many miscarriages have occurred in their practice after performing an amniocentesis.
Mark, thank you for this article and it’s excellent explanation of what these tests actually look at and where there are still challenges. I had the Panorama test done at 13 weeks. The genetic counselor called and said that I had low risk results for everything but Turner Syndrome. However, she and the other counselors were baffled by the risk result. They usually get a 99/100 on reports. My Monosomy X risk came back at >73/100 or 73%. Also, my ultrasound was excellent. No markers for any signs of monosomy/Turner’s. They suspect possible placental mosaicism but of course I would have to do an amnio for further confirmation.. My question is if any if the false positive/mosaic cases you’ve heard about had similar strange percentage statistical results on these NIPTs?
Laura–I am most familiar w/T18 readings resulting from placental mosaicism. However, from memory, I want to say there was a study by one of the labs that did report strange percentages for the sex based aneuploidies. I hope your GC will be able to counsel you further.
Hi Laura – my test came back at 96% chance of Trisomy 21, and the doctors came back with the same comment that it was normally >99%. Mine turned out to be a false positive. The amnio came back completely clear, so no sign of mosaicism either. My fetal fraction was 4.6%, which I believe is quite low and therefore may have impacted the results. Good luck – I hope the test turns out to be false for you too.
Charis-thank you so much for sharing your experience! Brought tears to my eyes and gives me some hope that the test might be wrong. So glad that everything worked out for you. 🙂
I will start by saying that I have birth to a completely healthy baby girl four weeks ago. The 6 months prior were very stressful after a positive high risk for T18 on the Panorama prenatal test at 17 weeks.
Needless to say we were devastated. We chose to not do an amnio as termination was not an option for us, and I didn’t want to put the small risk on my daughter. Sitting with anxiety was not easy but I took the time to prepare for the worst, educate myself extensively on these tests and T18, and ask friends to pray for us.
We went in for monthly anatomy scans which continued to show her developing normal. We were sent for a fetal echocardiogram which was perfect. The doctor was hopeful. I was hopeful after reading several studies that show the strength of level 2 ultrasounds in diagnosing Trisomy 18. Most of these babies show at least two markers by 21 weeks.
She was born on 1/30 small at 5lbs 2 oz, but appeared healthy. They took the placenta to biopsy it for potential placental mosaicsm (when the placenta can take on extra chromosomes but the fetus is fine). They also drew blood from the baby to karyotype her testing her chromosomes.
This past Friday we got the call. Her chromosomes are NORMAL! The placenta did come back positive for T18. We are the very rare case of placental Mosaicism. Which also explains her smaller size.
Looking back would I have done the test if it didn’t change the outcome and only gave me anxiety. In this case I was ok with it because I was prepared for the worst vs being blindside. I’m not sure I will do it again for future pregnancies. Likely I would only do it if there was a concern on ultrasound so I could be best prepared.
I am so grateful, and truly see her as my miracle.
I know placental Mosaicism is rare, but it concerns me that CVS sampling is considered diagnostic when triploids could be confined to placenta such as proven by this NIPT. There are likely unnecessary terminations after CVS that were false positives.
I thoroughly looked over Natera clinical research and question why they chose to compare fetal fraction to CVS samples. They are essentially comparing placental tissue to placental tissue which would of course give high accuracies. Why didn’t they compare fetal fraction to amniotic fluid?
Ideally it would be great if they could refine this test to truly test fetal cells. Until then, there will always be inaccuracies.
Thank you for sharing your experience, and your point about comparing fetal fractions to amnio versus CVS is a good one. Companies like Cellscape have been working on identifying whole fetal cells in the bloodstream to provide a more accurate non-invasive prenatal test. I’m glad your daughter and you are both doing well.
I’m “assuming” the FDA is aware of this “glitch” before they approve these tests.
The tests actually aren’t required to be approved by the FDA because they are “Laboratory Developed Tests” or “LDTs.” I’m not sure of the regulatory justification, but LDTs are not required to have FDA approval.
My understanding is this: Fetal cells can remain in the mother for years, even decades. Placental DNA is gone from the mother within weeks after giving birth. Therefore, only by looking for placental DNA can one rule out any influence on test results due to the fetus’s older siblings.
That may be the case, but at the same time, testing placental DNA is not necessarily testing fetal DNA and if expectant mothers appreciated that, they would have a more accurate understanding that NIPS remains a screening test, not diagnostic.
I suspect (hope?) that the education is something that is evolving and improving. Though the first time I heard of these tests I was told it was testing the fetal DNA, once I actually spoke with the genetics counselor it was made clear to me that it was testing the placental DNA. (And, truthfully, I’d already discovered this fact through google anyway, because I had many weeks in between first learning of the test’s existence and having it done, and I was really intrigued). Every thing I’ve read about it or heard about it (except for that initial intro to the test’s existence) has made clear that it is a screening and only CVS and amnio are diagnostics. That was gone over extensively by the genetic counselor.
I’m glad to hear you received the recommended counseling. Hopefully more will, as well.
I just received a positive trisomy 13 result from panorama testing (blood drawn at 9 weeks 3 days). I have a cvs test in four days (will be 11 wks 4 days). Reading this thread, wouldn’t cvs confirm what the panorama test already says since it is from the same placenta? I don’t understand. Do I go ahead and do cvs or do I wait for amnio test? I am really praying for a false positive.
Linda–yes, the National Society of Genetic Counselors has noted that because tests like Panorama and CVS can test DNA from the same source, i.e. the placenta, that an amnio remains the diagnostic test to know for certain. See this post about the NSGC’s fact sheet, which is linked in that post. I would discuss your concerns with your medical team.
I have just received the cvs prelim result as positive and finding trisomy 13 on all the DNA looked at. Genetic counselor said this means the fetus does in fact have it and that amniocentesis would likely be the same. Is there too little or no chance that amnio will be different?
Linda–You refer to a “cvs prelim result.” I presume this is a FISH test and by saying “prelim” you are awaiting the full CVS results. FISH tests test a limited number of cells whereas the full CVS test will have tested more cells. If the FISH-selected cells all came from an area of confined placenta mosaicism, then there remains a chance that the full CVS test will show that, i.e. when more cells are tested, if they come back unaffected then the FISH result could simply be positive for either confined placental mosaicism or fetal mosaicism for T13. I would wait for the full CVS results as there are instances when the FISH results do not match the full CVS results. I know this is hard waiting for these results and I hope you receive support and care during this waiting period.
Thank you, Mark, for your prompt responses and explanations. The FISH also picked up t2, which the genetic counselor said is like the least of our worries compared to T13. Wish I can be hopeful but we saw, not definitive but maybe, a cleft palate as well as prominent bladder, which would indicate that the baby does in fact have t13. I’m devastated to say the least. Was really hoping to prove panorama wrong but I’m defeated. Maybe by miracle the cvs result would come back mosaic and baby’s bladder go back to normal size and cleft palate not seen…then amniocentesis result come back negative. But not counting on it…
I just wanted to give an update that my full cvs report came back full trisomy 13. I’m so devastated but wondering if amniocentesis is now out of question since this is definite. I am trying to hold on to any hope that maybe my baby can survive. I can’t find any info on cvs full report coming back with full trisomy 13 result is 100%.
Linda–I appreciate you sharing your results. I would think most medical providers would take your CVS as a diagnosis. Every diagnostic test, even amnio, has a slight chance for returning an incorrect result, but it is so slight that most rely on these results as diagnostic. I hope you have accessed the relevant support organizations and receive support from your medical team during your pregnancy.
Hi, I took the Harmony test at 14 weeks 5 days and got a very strange result of 15% for chance of T21 (5.1% of dna). Neither Ariosa or the fetal medicine doc could really explain this and they did not suggest retesting. The doc suggested amnio and we have decided to do it around 32 weeks (I am now 29 weeks). We have had no markers for anything this entire time, everything has always been in the normal range. This was confirmed again at the 20 week scan. I am so worried and confused. I haven’t been able to find any other instances of this happening online so I was wondering has anyone ever heard of this?
I will see what I can find out for you Sheri.
Sheri–Ariosa calculates a “risk score,” which in most cases is >99% or <0.01%, but there are these "indeterminates." An assumption can be made that Ariosa saw some increase in chromosome 21 but not at a higher probability level. This may occur due to mosacism (placenta or maternal in origin) or simply be a false positive. It sounds as though you are receiving genetic counseling, but if not, I would encourage you to talk with a genetic counselor further. I hope this is of some help.--Mark
Hi Mark, I am 25 year old. Married since one year and 9 months. I had 2 miscarriages on the first trimester due to chromosomal abnormality. I don’t have a problem with getting pregnant. It’s just each time I get pregnant, it stopped. My husband and I had gone through lots of tests and it all shows normal results. My AMH Level showed 1.9. Until yesterday, my genetic counselor told me my karyotype shows 4% 45 X , 6% 47 XXX, and 90% normal. My gynecologist told me that he is afraid that those 4% of cells are in my ovaries leading to miscarriage.
What are my percentage of having a healthy baby? Is there any other test I can do? Do I give a try for iVF? I’m so depressed and helpless.
Thank you,
Maya–I wish I could help you with your question, but the focus of my work is once a pregnancy occurs. Reproductive assistance/likelihood is one step before where I focus my research on. I would seek the counsel of a maternal fetal medicine specialist or ask your GYN who may be a specialist to talk to you about reproductive assistance. I hope you find the help you need.
Hi Maya,
There is a Facebook group of girls with sex chromosome issues (trisomy X just for us). Maybe you can find someone there in a similar situation. I know there are girls with mosaic trisomy X on the site. There is a woman on both groups (who has a son) with xxx, xo, and XX cells. The other group is called AXYS, a support site for moms of girls with xxx and girls with xxx themselves. I’d also see an RE. Good luck to you
Is the 5.1% referring to fetal fraction? Typically fetal fractions below 10% aren’t as good for analysis.
Thank you Mark. Yes Michelle, if the fetal fraction was too low maybe that is what got me the strange result?
Thank you, I guess we wait and see what happens after the amnio.
Hi Mark, my first baby was born with T21 which was a huge shock for my husband and i as we had a low risk with NT scan and perfectly healthy looking baby with our morphology scan. Turns out she had a duodenal atresia and massive VSD and heart valve deformities and we spent the first 3 months of her life in hospital having heart and bowel surgery. I am pregnant again and had the panorama test recently and received a panorama low risk score of <1/10,000 (<0.1%) for all of the conditions tested. At first I was ecstatic but have become increasingly anxious over the past couple of weeks about the chances of a false negative result. I'm afraid to have an amnio and also feel a bit foolish doing this when i got such good result but i have a mistrust of tests after our first baby. Are you able to clarify exactly what the panorama risk score is telling me? Is it saying that they are more than 99% sure that my baby doesn't have any of those conditions? I have spoken to genetic counsellor but they keep reminding me that it's not a diagnostic test and although it's close to 100% it's not quite there. I'm trying to gather as much information about the panorama test as possible before i make a decision on whether to have further testing.
Regards,
Coreena.
Coreena, I would ask your medical professional to contact Panorama to answer these questions for you. Panorama has genetic counselors on staff to advise medical professionals on what individual Panorama results mean for the patient. I hope you get the answers you are seeking. Mark
Hi Coreena,
Just wondering if you ended up going with amino or not? And if you have delivered already? I am debating the same thing at this moment .. H/o post natal diagnosis of ds with my first kid, and now pregnant with second with nipt harmony showing negative result..
Any input from you would be great, thanks
Jessie
Hi Jessie,
I did end up having an amnio after much discussion with my husband, GP and genetic counsellor. The panorama result wasn’t enough to quell the anxiety i started to experience around the 14 week mark and for my own mental health I decided to have the test. Fortunately the amnio went well and confirmed that the baby was chromosomally typical and he is now 7 weeks old.
Thanks Coreena for your reply. I am also very anxious at this point and I am very worried about amino risk as my genetic counselor kept telling me about she saw people having miscarriage after that etc…. I hope I will have a smooth pregnancy and typical baby as well. congrats to you!
Just to update, I have just received FISH results and the baby is chromosomally typical. My doctor asked to take my blood again to re submit for NIPT on his own dime =) He is very curious as to why I got the result that I did. I don’t know if I will hear anything back about it but these tests are obviously fallible.
Thank you for providing the update. I hope any anxiety caused during the waiting period will subside and you enjoy your pregnancy.
Do you have anybody experience with verifi test?
I am so nervous because my first 12week blood test was positive. I am going to verifi on Monday.
Being a screening test, there is no true positive or negative. Verifi, like other NIPS, will provide a more accurate odds assessment, but still has false positives & negatives. Invasive testing is the only way to receive a true positive or negative. I hope you have access to a genetic counselor who can advise you further.
Hi Mark
Why isn’t NIPT test named NIFTY provided by a leading Biotechnology firm called BGI Health from Hong kong mentioned by you ?
Is the Information provided by you is limited to any specific Country ?
Aditi–while I will reference international news, studies, developments, I try to base my analysis of the NIPS tests on professional guidelines. Those I’m most familiar with are from the United States professional medical organizations, hence the concentration on the domestically-available NIPS tests.
Hi Mark
I read at least two posts of women whose genetic test for Trisomy 21, 18 and 13 (e.g. verifi test) came back negative, while it was later found that the embryo was triploid. Do you know why these trisomy tests would not pick up triploidy of the entire genome? It doesn’t make sense to me.
Thank you
I’m not exactly sure, either. But I do know that Natera was promoting its Panorama test as being the only one to pick up triploidy based on it using SNPs technology while all others are using a form of sequencing. Dr. Skotko explained the distinction between the two types of testing in the webinar we did earlier this year, available at this link.
Hi Mark,
Your research is very insightful. After several miscarriages of babies all with chromosomal issues ‘not compatible with life’, I am 12 weeks pregnant with what appears to be a chromosomal typical male. We did the nuchal test and the Panorama test and both came back fine, however, my fetal fraction for the Panorama was “alarmingly” high according to my Dr. (25% at 9 weeks) and my papp-a was on the low side. They now think I have a serious problem with my placenta, will have pre-eclampsia or BOTH. What other tests can I have or is there anything I can do besides “wait and see”? I’m so scared of losing another baby.
Thank you.
Jamie–my sympathies for the stress associated with your test results. For screening purposes, you’ve had the ones I’m familiar with for suggesting issues with the placenta. I would recommend you discussing your concerns with your OB and possibly ask for a referral to a Maternal-Fetal Medicine specialist. I hope these results are not indicative of any true issue and that you have a healthy pregnancy.
Thank you. 16 and a half weeks and so far so good.
Have you been tested for Antiphospholipid Antibody Syndrome?
I was after my second loss and came back negative. Pretty much chalked it all up to “bad luck and bad eggs”.
Well You confused me for sure .. and surely many others too . If the whole basis of Harmony test for CFF DNA is really testing Placental DNA (DNA from Cyto and Syncytio Tropb cells) and not the fetal cells (from inner cell mass) the why would any one ever do that in first place?? We are not interested in knowing the anomalies in mother or dad? we are curious to know whats going on with the fetus. Are you sure that there is NO FETAL DNA ever analyzed in harmony test ? and all the results we get if for incorrectly estimated maternal/placental DNA ? If you say yes , then I would go ahead right now and file a lawsuit against this scientific fraud /scam of harmony test since then its is misleading..
Pls reply and clarify
Vijay–it’s the same dynamic as chorionic villus sampling (CVS). CVS tests the chorionic villi from the placenta that contain cells with maternal DNA and cells with fetal DNA. The labs try to distinguish one from the other and then report out the results as though they are from fetal DNA, which most often they are. However, they can incorrectly identify fetal DNA when it is actually maternal/placental DNA, hence why CVS has a higher false positive rate than amnio and why NIPS tests have false positives and false negatives. The confusion is that non-invasive prenatal screening is perceived as testing fetal DNA. If more understood it is testing DNA that could be fetal DNA or could be placental DNA, then more would understand why it remains a screening test and however NIPS’ accuracy rates are represented, they are never diagnostic.
Hoping you are still replying. We received results for our harmony test indicating that there is a 36% chance of xxy. Here is the confusing part- we did ivf with ccs to avoid chromosome abnormalities as I have a history of losses. How is this possible? Which is more accurate?!?! We are meeting with a genetic counselor and are on the fence about an amino as we wouldn’t terminate for something like xxy.
I am still replying. From your message, you went through an IVF cycle where there was comprehensive chromosome screening (ccs) to screen out embryos with genetic conditions, but, yet, your Harmony test reports a 36% chance your child has XXY. XXY is an aneuploidy. The American Congress of Obstetricians and Gynecologists (ACOG) have a committee opinion on preimplantation genetic diagnosis (PGD) that emphasizes PGD has not been shown reliable enough to screen for aneuploidies. CCS is not exactly PGD, but this may explain how an aneuploidy like XXY may have not been detected. That said, appreciate that 36% still means more likely than not your child does NOT have XXY. I would encourage you to discuss these concerns with your genetic counselor. I would also review any informed consent form you signed prior to undergoing ccs to see if you were advised of the chance that aneuploidy may not be detected. A link to the ACOG committee opinion is at the end of this post.
I’m no expert by any means, but I’ve read a lot on placental mosaicism after dealing with my own experience… Maybe this is what’s happening here. I would imagine that the direct genetic testing of your blastocyst/embryo would be more accurate than placental cell extraction from your harmony test. Good luck to you! My nips and cvs showed xxx, but we skipped amnio. Getting a karyotype after birth.
Thank you–a very good point.
Hi joeys mom – my daughter due nov ’15 has a 34% chance of triple xxx by panorama testing. Was the probability given to you similar? I still don’t really understand it! Hope the birth of your daughter went well and you are enjoying her.
Hi! When I took my panorama, they didn’t give me a %. My daughter’s XXX was confirmed via CVS and the at birth via venous karyotype. She is now 14.5 months and doing great 🙂 Her XXX is just something we keep in mind to be proactive for development but she is a very typical, happy baby. If not for the prenatal screening and CVS, we never would have known. Good luck to you and your pregnancy!
Hi Mark Leach, me and my husband did a harmony test. I am 33 years old and DS results shows good negative results. However, the x, y analysis shows a 8% chance of xxx baby. We would like to seek your opinion on this result and what does it mean? Is it a high enough risk to go for amniocentesis test? We are so worried and torn apart as amniocentesis test carries a risk of miscarriage as well. Kindly reply soonest possible.
Thank you. Joanne.
Hi Joanne- I closely follow this thread and couldn’t help but respond to your post. “DS” is dear son, no? Baby boy? If so, that XXX cannot be your baby boy. If you are having a boy, I would suggest doing a karyotype on yourself. My friend just had her baby two weeks ago; harmony test at 11 weeks showed XXX. The lab actually overlooked the presence of the Y! She had a gender reveal party for her baby, thinking it was a girl with xxx. Turns out, her baby was a boy! She tested herself- SHE was the XXX. Went 36 years without ever knowing she had an extra chromosome, and only learned by accident. (Fyi- she is married, two children now, has a masters degree, and lots of friends- including me.) Just thought I’d share this- it’s a nice positive outcome of how high-functioning these girls can be!
Joanne–first, I would recommend you be referred to a genetics counselor if you haven’t already. This is what is both recommended by professional guidelines, and is just best practice as they are the ones trained in counseling couples weighing the decision of whether to pursue further testing. That decision is determined by your values and what goals you have for the testing and your pregnancy. Secondly, while still a relatively low chance for XXX, you should have received information about the condition. If you didn’t, visit this link, which the National Center for Prenatal & Postnatal Resources includes in its resources for sex chromosome aneuploidies. Third, if possible, I would ask the genetic counselor for the opportunity to visit with a family raising a daughter with Trisomy X. Again, this is what is recommended and is best practice. Thank you for reaching out. — Mark
Hi Mark
Really thanks for your quick reply despite it being a sunday. I read that there are high chances that harmony test may not be very accurate with xy analysis, even through its almost 99% accurate with determining the gender of the baby. Is that true and so u have any statistics on that base on your experience?
Also we would like to find out what is the typical kind of results for xy analysis harmony test would produce? We have done extensive research but it seems that most people would stop at testing for T21, 18 and 33, and would not go on to opt to test for xy analysis via harmony test.
Would again appreciate your feedback on our 2 questions again.
Thanks
Joanne
Joane–my apologies for the tardy reply. You are correct regarding the accuracy rate for sex chromosome aneuploidy (SCA). Because the published studies have been of small sample sizes, the professional guidelines do not recognize the NIPS tests for testing for SCA. I’m not sure how to answer your second question about what the typical kind of results Harmony has for xy analysis. But, I think, related to my answer to your first, is that there simply isn’t enough data published of a sufficiently large sample size to show what “typical” results would be. I hope that helps.–Mark
Hi Joey
DS we meant down syndrome.
Regards
Joanne
What about reports on False Negatives? Have there been many? I am 39yo and had my Fetal DNA blood test taken at 10.5weeks along with my NT scan at the same time. My NT scan showed normal with a low 1.42mm neck measurement. Tech said everything looked good. My MaterniT21 blood test came back 3-Negative. We were comfortable thinking everything looked good. My only concern comes from doctors letting me know that these tests are only 99% accurate and only an amnio is 100%. I am now 16 weeks pregnant. At 14 weeks I had a fetal echo ultrasound performed (my last son was born with undiagnosed TGA) and doctor said heart looks good “so far as it’s still so small”. He was the first to bring up the fact that the MaterniT21 is only 99% accurate and amnio is the only “proof”. He made me concerned thinking I should go for the amnio. To add to that at my 16 wk OB appt I asked my OB and she also would not allay my concerns and just said there have been false negatives as well as postives and amnio is the only 100%. Instead of reassuring me, they are raising my worry level. Here we thought we are “in the clear” with a 3-negative MartniT21 result and a “normal” NT scan. I worry about doing an amnio due to the risk of miscarriage. I am now more confused than ever. Can anyone allay my fears or have there really been many false negatives MartniT21 along with normal NT scan? I don’t know if I should go for the amnio or not with the miscarriage risk!
There are false negatives, but they are even rarer than false positives with the new blood test like MaterniT21. More and more women are choosing to rely on a MaterniT21 or similar type test result showing the pregnancy is not indicative of having Down syndrome than risking a miscarriage with an amnio or CVS. I would ask your OB for a referral to a genetic counselor to discuss your concerns. Genetic counselors are trained in counseling expectant women on the probabilities with genetic tests and how to make decisions consistent with your values.
Thank you so much Mark for your quick reply! What you mentioned, that false negatives are even rarer than false positives, is what I was hoping to hear but of course none of my OB doctors could directly say that. I am setting an appointment with a genetic counselor just to allay my concerns. Thank you again!
Mark,
I am wondering if you would be willing to weigh in on my situation. I am currently 17+2 weeks pregnant with my 2nd child at 31 years old. I am high risk due to an autoimmune disease and my MFM specialist offered Panorama testing at my 13 week NT ultrasound presumably because he thought it was more accurate than the first trimester screen. He did not indicate any concerns with the NT measurement which were in the 1.7/1.8/1.9mm range. The results came back during my 14th week as “no fetal fraction” and they suggested a retest. I had the blood work (and husband the cheek swab) redone at 16+1 and received word this morning the fetal fraction was 2.2% and yet again too low for results. The nurse proceeded to draw for a third Panorama test today (17+2) but I don’t hold out much hope of a result as I’ve read the fetal fraction increase is only about 0.1% per week at this point. I was under the assumption that low fetal fraction in and of itself does not indicate any concerns for the health of the pregnancy. Where I am now concerned is that my primary OB called and indicated that I need an amniocentesis because the continued low fetal fraction somehow indicates a problem with the pregnancy. I have not had additional screening tests as we have put all our eggs into the Panorama basket as it is. Any thoughts on whether my OB is just proceeding with an abundance of caution or whether low fetal fraction at 17 weeks means there is something more likely wrong with this pregnancy?
You are correct that with that low of fetal fractions NIPS results are unreliable. However, I’m not familiar with low fetal fractions being an indicator of concern about the fetus’ health. You mention that you had an MFM specialist who offered Panorama but that your primary OB is the one recommending an amnio. If those are not the same person, I would suggest speaking with your MFM specialist to see what he or she thinks. I would be curious if your OB has any studies that show a concern about the fetus’ health where there are low fetal fractions in the mother’s blood. Whichever route you choose, I hope your pregnancy progresses well and that this does not cause too much anxiety for you.
I had the same thing happen to me. I had a 10 week Panorama, a repeat at 12 weeks and then a third one at 13 weeks because they ALL came back with inconclusive results – “low fetal fraction”. In fact, between weeks 12 and 13, the fetal fraction went down–it was 2.9% at 12 weeks and 2.1% at 13 weeks. Panorama genetic counselor’s advised me to not re-test and said that since I am not at all overweight (19 BMI), it is likely an abnormality.
I found this website that touches on mosaicism and low fetal fraction:
https://www.genomeweb.com/sequencing/importance-fetal-fraction-dna-noninvasive-prenatal-testing
Mark, have you been able to find any links to abnormalities and low fetal fraction? I just find it so odd to get a 2.1% fetal DNA at 13 weeks gestation and can’t seem to find much help.
I do see a specialist and am planning on the amnio. I’d love your take on these bizarre results!
I want to leave my story here. When “false positive panorama results” are googled this site/post is #2. I am 36 years old. I have had 9 pregnancies, 3 living children, one on the way, and 5 miscarriages. I took the panorama prenatal blood test at 10 weeks. It came back with a fetal fraction of 4.4% and a 66% chance of trisomy 21. Our genetic counselor had only seen one other case that was not 1% or 99%. We opted for a cvs that failed because no villi were seen in sample. So 3 weeks later we did the amnio. Fish results normal male karyotype. Full results the same. Baby has normal amount of chromosomes. When asking everybody from panorama, ob, high risk ob, genetic counselor. Nobody seems to be able to explain the number 66%. This definitely is a screening test and no way near diagnostic. I wonder as time goes on how the stats will change with a bigger sample. Thanks so much for this post. Hopefully somebody will read my comment and feel a little hope.
Thanks you Amanda for sharing your experience. I share your hope that expectant moms will be counseled & understand that these new tests remain screening tests, with false positives & false negatives. Congratulations on your new baby.
I am hoping and praying that I will be a false positive. Had the harmony done at 13 weeks with a positive for T21 result at 14 weeks. I’m now 15 weeks waiting for one more week for my amnio on the 22nd. I am scrounging the internet for hope in the form of false positives. Thank you for making feel a little better.
Your chance of having a child with Down syndrome is informed by your age and the Harmony results. See the post here to find where your age is on the graph showing how a “positive” NIPS result can mean only a 40% chance if you’re in your 20’s or a 50% chance if you’re in your early 30’s.
Thank you so much for replying my age at conception was 39 and I am currently 40.
Then, according to just the number crunching, you may have a 10% chance of having a false positive. However, I hope you have received genetic counseling to discuss your personal background and likelihood. I further hope that your amnio goes well and you receive the care and support from your medical team no matter the result. Feel free to check the Prenatal Resources tab when ready and if applicable.
I had the Harmony test because of my advanced maternal age (42). My test came back with a 20% chance of Turners Syndrome. I had an ultrasound completed and met with genetic counselor, but opted not to have amnio because I did not want to put the baby at risk. Genetic counselor seemed to think that there was a low risk because there were not physical indicators of Turners on the ultrasound. We had blood cord tested at birth and there were 46 XX chromosomes…so no Turners. For anyone reading this who may have the same test results as me, please try not to stress over test results.
Thank you for sharing your experience. The professional medical organizations do not recognize any NIPS test for identifying the sex aneuploidies because all published studies have been of populations that are too small. While your encouragement is appreciated, studies show that prenatal testing increases anxiety and, interestingly, this increase happens no matter the result. This is due to the understanding that there are false positives and false negatives.
Hi I am 41 y/o pregnant with baby no3. Nuchal looked fine with adjusted risks= 1:1201 T21 and 1:2148 for T13/18. I had harmony test offered for raised background age-related risk. Yesterday I was called to let me know that the Harmony test result came back with 14% risk for T13 which is considered high risk and offered CVS which I had last night. I am awaiting the results in the next 24-48 hours for PCR and the rest of the results will follow in 7-10 days. I am not sure what to make of these results? The sonographer and consultant took further measurements which showed all organs, brain, eyes, kidneys, heart, limbs to be totally normal so far. What is the likelyhood of this being a false positive. Harmony state 0.1% false positive? How can everything look normal and there be such a big chromosomal abnormality.
Naila–it’s tough to say what a 14% chance for T13 means from a Harmony test. Harmony has published results showing an ultrasound indication prior to a Harmony test makes its test more accurate (see Poster 603 at this post), but I haven’t seen the converse, i.e. negative ultrasound results suggesting a Harmony test is more likely negative. That said, with the nuchal adjusting your probability upward from your baseline maternal age, it would seem that even a 14% chance means you have a greater chance for a false positive than a true positive. Given that you’ve had CVS to confirm, I hope you’ll report those results. Regardless of the CVS results, I hope you will have the opportunity to meet with a genetic counselor to further counsel you on these test results.
Thank you so much for your reply. This is very much appreciated. I will definitely report back with results. I am at HBR so have received flagship support and fully expect to be guided through the results and consequences. The staff were rooting for me hoping that it would be a false positive. They reviewed all the results and images over and over. Absolutely nothing to point to any major abnormality.
Hi Mark,
Just got a call from the unit today. All clear on CVS for T21, T18 and T13. They also tested for CF and that was -ve also. So I will await the culture results but I can now breathe a sigh of relief.
I am wondering if the results might have been affected by my SLE? I have anti Ro and ds DNA and ANA +ve. Not sure if that can affect things?
I shall just enjoy the rest of my pregnancy now and happy with whatever outcome.
Thank you for your help!
Naila–thank you for sharing your results. I hope you have a healthy pregnancy, delivery, and happy baby.
I’d love some of your expertise help, Mark. I’m 23 weeks along, Harmony test came back 99% positive for Tri 21. In fine print it says the results are based on the fetal DNA (which I know is placental DNA), as well as the mothers age (I’ll be 39 when my baby is born), and the results of the ultrasound (which showed no nasal bone–though we could see it when he moved, he was very active! and, a calcium deposit in his abdomen). It was explained to me that when they gathered the fetal DNA, there was some extra material around the 21st chromosome, then they looked at the results of the ultrasound and automatically said high risk, 99%. I’m having an amnio next week just to be sure (hopefully) and for some peace of mind. We would never consider aborting, but want to be prepared as to how to raise our child and care for him in the best way if he indeed has DS. (Also, this is my 7th pregnancy, and they explained that the blood test collects fragments from not only me and my current baby, but also DNA fragments from all past babies). My baby’s DNA was 14.4% of the DNA collected. I have tried to get answers about the percentages are factored into the total risk percentage (the test itself, mother’s age, and ultrasound). The Ariosa clinic was unhelpful on the phone, refusing to answer any questions, and would only speak to our Doctor’s office. I had our Doctor’s nurse call, which she kindly did and still we did not get a clear answer about general percentages of these 3 factors which make up the final result. I think there should be more clarification as to how exactly the result is determined! Your thoughts? Thank you!
I agree that there should be more clarification on how exactly the result is determined–and it’s not just me and you, but every professional society that has issued a statement on this new testing has called on the labs to be more transparent in how they arrive at their results and what their results actually mean. That said, from your description and my understanding, all screening tests take your baseline chance of having a child with Down syndrome based on your age, and then run the findings of the screening test–an ultrasound, blood sample, etc.–through an algorithm to determine your recalculated probability of having a child with Down syndrome. Based on your age being 39 and the Ariosa test coming back 99% positive, then your probability is actually close to 90% chance for having a child with Down syndrome (see this post here). You still have close to a 1-in-10 chance of not having a child with Down syndrome, so I’ll be interested to hear what your amnio results are. If positive, I hope you will receive a copy of the Lettercase book (which Ariosa has provided to the doctors offering its test), be referred to a genetic counselor, and receive the contact information for your local Down syndrome support organization–all 3 things recommended by professional guidelines.
Just wanted to share that my amnio confirmed tri 21. We were hoping to prove the Harmony test wrong, but oh well! We are preparing the best we can for our sweet little guy to arrive and hope to help him have the best life possible. I actually believe it will be a blessing to our family. We will learn so much, meet people we never would have met, have experiences we never would have had, etc. And, our children will learn to be more compassionate and sensitive to those with special needs.
Since I know you have a daughter with down syndrome Mark, I’d appreciate any advice you have. Things that have really helped your daughter, etc. And, what is your opinion of stem cell treatments for DS? I’ve heard it can help improve memory, cognitive function, movement, etc. Thanks so much! 🙂
Kristy–I appreciate you sharing your test result and your outlook on welcoming your son. I would recommend Diagnosis to Delivery and Your Loved One is Having a Baby with Down syndrome. These resources were written for moms such as yourself who are continuing after a prenatal diagnosis and address the myriad of issues expectant moms experience. In my personal experience, the greatest source of support and information which helped my wife and I was our local Down syndrome parent support organization. We were right before the ubiquity of social media, and I know moms now also find on-line support very helpful. I would recommend connecting with the Down syndrome pregnancy board at babycenter.com–one of the moderators is the co-author for Diagnosis to Delivery–and the Down Syndrome Diagnosis Network. I hope these help.
As for what has directly helped my daughter with her development, we were fortunate to have a very good team of early intervention therapists providing physical therapy and developmental intervention therapy within Juliet’s first weeks, then adding occupational therapy and speech therapy by 6 months. We also had a nutritionist for a focused time when Juliet was having some digestion issues. Through our local group, we received new parent support through new parent monthly meetings. When Juliet turned 1, we began adding Nutrivene’s vitamin compound to her food and did that for about a year. Whether that had an impact on her development is difficult to say, but our nutritionist reviewed the ingredients and said it wouldn’t hurt her. I must plead ignorance on stem cell treatments for DS and invite you to share what you learn about that.
Feel free to check in and provide updates, or contact me directly at mleach@downsyndromeprenataltesting.com if I can be of any help. I wish you the very best.–Mark
Just want to say thank you for all the helpful advice and information. I wish all parents who get the news that they are having a down syndrome child could be given lots of helpful and hopeful tips and info. as soon as possible instead of just being referred to a genetic counselor. I think awareness (in a positive light) and optimism are often missing from the conversation, and instead there is lots of worry, concern, and negativity associated with it. At least that’s been our experience this past month. So, your help was very much appreciated!
Thank you, Kristy–I’m glad I could be helpful, which was the whole reason I started this blog. When you feel comfortable, I hope you’ll share your experience with the study being conducted at Duke by some very compassionate genetic counselors seeking to identify ways to improve the prenatal experience. The study can be accessed at this link.
I would really appreciate some perspective on what to think. My cffDNA came back with no risk for trissomies 18, 13 and 21, but a 2% chance of Turner’s. My genetic counselor thinks it might be a false positive since the ultrasound at 12 weeks looked normal. I’m having a second ultrasound at 16 weeks to check for signs before I decide on whether to do an amniocentesis, but the anxiety is huge, since we decided not to move on with the pregnancy in case we do have a baby with Turner.
What does this 2% chance mean? I see other posts with 50% or more that turned out to be normal, but would the amniocentesis give me 100% chance that there is no Turner, or would the follow up ultrasound increase the certainty of this being a false positive? How are these percentages calculated?
Also, the genetic counselor suggested the missing X cells could have come from my DNA, not the baby’s, so we are checking that, but I’m not sure what kind of certainty this would give me.
Any advice you could offer would be greatly appreciated.
Only through diagnostic testing, e.g. a CVS or amnio, can you receive near 100% certainty for whether your child has a genetic condition or not. I’m not quite sure how an ultrasound would show anything one way or another, since I’m not familiar with Turner’s having such significant physical characteristics to appear at this stage of the pregnancy–I would consult with your MFM/OB on that. The professional organizations do not recognize the new blood test as being accurate enough for sex aneuploidies like Turner syndrome. At the same time, lab representatives have privately expressed qualms about testing for conditions like Turner syndrome since it has such a wide range of manifesting in the child, including to the point of almost being non-perceptible. I hope you will receive further genetic counseling and referral to Turner support resources to help with your decision.
Hi I took the maternity21 plus and now the genetic counselor says I’m positive for trisomy 13. She didnt say the % or odds. I’m of course freaking out and tomorrow is my CVS which I’ve been against and I never did it with my successful healthy triplets pregnancy 2 years ago. This pregnancy is a complete shock, we were told my many drs. we couldn’t conceive on our own. So now I wonder if my triplets could be affecting my current placental DNA testing?? Possibly causing the mosaicism… I’m 13 weeks so yet to see an u/s showing any abnormalties. I’m of course praying for my miracle baby to be 100% healthy like her triplet siblings. Any studies showing a false positive for a pregnancy after a multiples one?
Colleen–from a quick search of PubMed, I did find this article that found an association of high false positives for Down syndrome in pregnancies conceived via assisted reproductive technologies. Not exactly on point with your situation, but possibly informative. I would have your genetic counselor ask Sequenom what their clinical data is telling them. Coming up on 3 years since Sequenom launched its test, a situation like yours may have presented itself previously. If you do ask and Sequenom responds, please share.
Hi, I got all clear for trisomy 21/18/13 with harmony test. I also had the nuchal fold combined screening done and that gave me a 1:2 chance of T21. My Papp a was low and the nuchal fold was 2.7mm. I had an hour long scan done at the fetal medicine centre in London (professor Nicolaides centre ) and the dr couldn’t find any other markers from T21. She checked the cord, placental blood flow, nasal bone etc. I am unable to comprehend how one test could give me 1:10,000 result and the other test 1:2. Professor Nicolaides himself offered to scan me himself to recheck the initial scan but I am out of the country. My OB in Australia and the fetal medicine specialist don’t seem to trust the harmony results and say I need an amnio.. I am 40 by the way and just so disheartened by the varying odds, it’s ridiculous. Care to share any light?
Kavi–Ariosa, the maker of the Harmony test, has published research showing that their test is highly accurate after a first trimester ultrasound indicates Down syndrome. That research however was saying that where an ultrasound suggested Down syndrome, the Harmony test accurately identified each true case of Down syndrome. That does not mean, necessarily, that Harmony is equally accurate in ruling out those false-screen positive from ultrasound. However, NIPS is more accurate in ruling out pregnancies for not having a child with Down syndrome than it is accurate for detecting those pregnancies actually carrying a child with Down syndrome. So, the 1:10,000 result from Harmony would seem very reliable. Of course, though, the only way to know for certain is through an invasive diagnostic test. All of that said, you have a unique opportunity given your care by Dr. Nicolaides. Dr. Nicolaides was both a pioneer of nuchal translucency testing and he has consulted for Ariosa and published research on the Harmony test’s accuracy. I would suggest you ask him this question and I would hope you would share his answer.
Hi Mark, since my post I had another scan at 16 weeks and the baby looked good with no soft markers. Obviously 16 weeks isn’t 20 weeks so things may not still be seen but at the advise of Professor Nicolaides and the Professor here in Australia I saw we decided that was the best next move before an amnio. Had there been any markers on that 16 week scan I wouldn’t have hesitated to have the amnio. Obviously we will have the full anatomy scan at 20 weeks and praying that is all clear too. My obstetrician had just been at a conference for NIPT and explained to me that it is 99% effective in detecting T21, so I would be having the amnio based on being in that 1%, which we were not prepared to do with no markers. I assume if she had T18 & T13 something would have been showing up on the scans by now from what I have read.
Unfortunately being back in Melbourne – my initial testing was done in London under Professor Nicolaides clinic, I no longer have direct access to him, but am lucky to be looked after by one of his students from many years ago who remains in contact with Nicolaides. I will be sure to update with 20 week scan details.
Hope this helps someone.
Thank you for the update. I wish you the best as your pregnancy continues.
Hi. I got a “positive” screen result for Down syndrome based on the blood sample taken, even though the nuchal translucency measurement was 1.1mm. I am 35. We did the Harmony NIPS test about 2 weeks ago and it indicated that we were in the clear for Downs, but instead was high risk for Turner’s Syndrome or Monosomy X.
As you can imagine, it has been a helluva fortnight. Each test we took, brought something new to worry about. We got an amniocentesis done yesterday, and the preliminary Fish test result was that they found the second X chromosome and no Down syndrome. All I can say is, I hope that they don’t come back with something else to worry about with the final results.
Just wanted to share my experience and my understanding of the Harmony NIPS.
1. Harmony NIPS tests placental DNA not fetal DNA, so the sample is not the best sample.
2. Harmony NIPS is a reasonably good test for Down Syndrome, but not necessarily the other chromosomal conditions. They say that there is a risk, (99% even) but they have been known to have been WRONG!
So, dear ladies / future parents, take heart and don’t lose hope.
Thanks for the post, Mark Leach. I found it helpful.
Kind Regards,
Am
Thank you, Am. I appreciate you sharing your experience and I’m glad you found this post helpful.
Hi! I am 26 years old, my husband is 32. And I am at my 12 weeks pregnancy with my second child. Today, I was at the doctor’s office-for the first trimester screening, the ultrasound shows that the baby is perfect, however, by the blood levels: I am the high risk group for Trisomy18. They took my blood for Cff DNa screening, and have to call me next week. I am so nervous. Can somebody tell me please how accurate the regular blood screening is? And my doctor said that CFFDNA is accurate for 99%.
Traditional screening tests have between a 2-5% false positive rate. CfDNA tests are more accurate, but still have false negatives & false positives, particularly with rarer conditions like T18. Other posts on the blog explain further. Feel free to share your results & I hope you receive the counseling & support needed throughout your pregnancy.
Hi, I’m 12 weeks pregnant and took the Panorama test 2 weeks ago. My doctor called me on Thursday and said my baby is at high risk for down syndrome, the percentage is 70%. I am 29 years old and will be 30 at delivery. How accurate is the Panorama test? Are the chances of my baby carrying DS really 70% or can they be lower? How do they calculate such percentage? I found your article to be the only one giving chances of false positives. We have an appointment on Thursday with a specialist. But I’d appreciate your opinion. Thank you in advance.
Susy
Susy–Taking your questions in order: How accurate is the Panorama test? No one knows. And that applies to all of the NIPS tests. This is because their stated accuracy is based on clinical trials of small populations (relatively) that have a higher than natural incidence for Down syndrome. Are your chances lower than 70%? More than likely yes. Even if the accuracy was at the stated 99+%, based on your age, that means you really only have about a 50/50 chance of having a child with Down syndrome–meaning you have just as much of a chance of having a child without Down syndrome as you do with Down syndrome. How do they calculate such percentage? I would ask your doctor, because typically the NIPS labs do not report the positive predictive value, meaning how likely it actually is that you are carrying a child with Down syndrome. To see how you have a 50% chance based on your age with a screen-positive result, see this post here. I would ask to see a genetic counselor if you haven’t already been referred to one. If you would like to learn more about Down syndrome, please see the Resources tab on this blog at this link.
Thank you for replying. I have an appointment on Wednesday with a genetic counselor, but the waiting is terrible. I read a lot about the Panorama test and they state that their results are the most accurate ones in the market and their accurancy was also tested on low risk population with the same results. They even provide you with personalized percentage. Mine is 70%. They really don’t give much hope for false positives.
Either way we are keeping this baby, but just debating wether or not to also have the amnio test done or to just tell my doctor to treat this pregnancy as a down syndrome one.
Thank you again.
Susy–many women are making the decision of relying just on the NIPS result and as a result the number of amnios is plummeting–it’s something that is reported at every medical conference since 2012. If you do plan on continuing, then I would recommend you reviewing “Diagnosis to Delivery.” The book is available for free on-line as a .pdf and was written by moms who have supported those continuing after a prenatal test for Down syndrome. If you do read it, I hope you find it helpful.
Susy, my blood test (in July) came back 99% positive for Tri 21. An amnio confirmed it. We wanted to know for sure so we could prepare. I know of no one like me who is currently carrying and planning for a DS baby. From my research and all the people I’ve talked with, it’s not as bad as we are often led to believe. The parents I’ve met of DS children absolutely love their child, and so many have said it has been a blessing. It’s been a bit of an emotional roller coaster as we’ve let the reality sink in, but we are really excited to meet our little guy and know we will have many positive experiences ahead. Yes it will be hard, but we will have precious experiences often. And, so many resources are available these days to give help and support! Best wishes to you!
On-line support for expectant moms continuing their pregnancies can be found at the babycenter Down syndrome pregnancy board. The Down Syndrome Diagnosis Network supports new and expectant parents. You can access DSDN via its website or its Facebook page.
Just an update. Today we went for the NT scan and at 12 weeks and 3 days the measurement was 2.8 mm. They told me that it is higher than normal so they assume the Panorama test is a true positive. Still struggling accepting the new reality. Still feeling scared.
Anxiety is an effect rarely discussed when counseled about prenatal testing. I hope that if you think it helpful you’ll find the on-line resources mentioned previously helpful in dealing with the stress.
I found that website very helpful. Thank you Mark.
Susy, I’d be happy to email back and forth, but don’t want to leave my email address on such a public site (maybe Mark could share it with you if possible, since we have to leave our email address to comment, but it’s not public…..). I am very aware of all the feelings you are going through, I went through it all myself. It’s all I could think about. It consumed everything. I was very worried and had a roller-coaster of emotions. I think it’s a shame honestly that they test for it so early (in your case). It can cause so much unnecessary anxiety and stress! And, I think testing positive for Tri 21 is viewed as such an awful diagnosis and, yes it’s scary but not the end of the world. I am at peace about it now and just want our little guy to be as healthy as possible and have as happy a life as possible. I’d be so happy to talk with you/email you…! Oh, and my cousin and others I know have been through the same thing, but then it was confirmed that they were NOT carrying a baby with Tri 21. So, it could still all be okay and your baby could turn out normal. For me, I’ve met too many parents who ADORE their child with DS and say it’s been such a blessing, etc……that I can’t get too down about it. We’ve had an outpouring of love from our community which has been helpful as well. Just know that I know what you are going through. It’ll all be okay! 🙂
Hi Kristy,
Thank you for replying. Since the test came back positive I haven’t done anything else but crying. I originally took the test just to find out early about the gender of our baby and the positive result was so unexpected.
I’ve read so many wonderful experiences of parents with down syndrome kids and that gives me hope, but I’m still so scared. Tomorrow We have an appointment with a genetic counselor. I still don’t know if I should do the amnio or not. I’m only 12 weeks pregnant so I will have to wait 3 more weeks for it. Nobody better than you can understand our feelings. Either way I do believe that once the baby is born everything will look different and for the better. I wish all the best to you and your baby. Every baby is a blessing from God! We just have to be strong!
Best wishes
Hi Suzy,
I just had the first trimester screening by Verfi and got the dreaded phone call today that the baby most likely has DS! I am terrified and confused! We have an appointment for CVS testing on Thursday, but can’t stop crying! Feeling alone and scared! Praying for a false positive, but also expecting the worst! 🙁 reding these blogs have helped me and I just wanted to reach out to you!
Juliette–thank you for your compliment; I’m glad the posts have helped. Given your name, if you search on the blog for “Juliet,” you’ll find photos of my daughter, who happens to have Down syndrome. I would also point you to this post where you can find out what a “positive” Verifi test really means for you chances of having a child based on your age (e.g. if you’re under 30, you have less than a 50/50 chance). If confirmed or if you choose not to have diagnostic testing and still would like to learn more about Down syndrome, please check out the prenatal resources tab.
Hello Juliette,
I perfectly know how you are feeling right now. When I received the call it really felt like the end of the world for me. A month later things look a little different. I am finally starting getting excited about this pregnancy again. I am still so scared about our baby’s health. We still don’t know if she’ll have health problems. We have our next ultrasound in two weeks and they’ll probably be able to check her heart and let us know what to expect. We opted out for the CVS or amnio. At our last ultrasound they said that the NT scan was higher than normal 2.7 mm so that pretty much confirmed the positive Panorama result. Right now I am 16 weeks pregnant so I still have a long way to go. How far along are you? What helped me the most was reading the wonderful experiences of families with down syndrome kids have to share. Mark suggested us to check the Down Syndrome pregnancy board. I read it everyday and left a message when needed help… Or Hope! Those moms are so supportive and they understand what we are going through. If you want to keep in touch we can ask Mark to share our emails in private so we can support each other during our pregnancies. Hugs to you.
Hello Juliette,
I just wanted to check on you. How are you doing? Have you received the CVS results? I just wish you the best!
Hi Suzy,
Thanks for checking in. It’s been a rough rough couple of weeks and I feel like i am living a nightmare that I don’t ever wake up. Our results from the CVS results were 100% positive 🙁 and then we had a miscarriage. I am absolutely heartbroken and feel like I could never go through this again. I would of been 16 wks this week. It’s still really fresh and I am processing all the emotions on a daily basis . It’s hard to focus and be a put together mama for my two little ones, but they need a happy mama so I am trying my best.
How are your doing and how was your 20 wk ultra sound?
I am so sorry for your loss. Stay strong and your little ones will help you go through this. Time will heal. I will keep you in my prayers. We have our 18 weeks ultrasound on Monday and they will let us know more about her health. Very scared! I really hope she is healthy.
Big hugs on your way!
Thank you!! Just counting my blessings everyday and pray for another miracle some day. Sending you strong prayers as well and let me know how your appt goes on Monday!! Keep positive!!!
I’d love to e-mail you too. Hopefully Mark will be able to provide you with my e-mail or vice versa. You described exactly how we are feeling now. It’s been such a shock for us and I do regret taking that test. It’s been 8 days and I still feel so miserable, but I need to find the strenght to face it and react! Well I hope to hear from you soon! Thank you for your message… It helps knowing there are so many people in the same situation. Hugs
Hi Mark,
Recently, I just received feedback from my insurance underwriter that request me to do amnio test although i already submitted my Harmony Test that shown low risk of Ds 0.01%.
What I confuse which test is more accurate. Per my understanding from my gynae, the harmony test is more accurate than amnio test, and risky to fetus.
Pls help to advise.
Thanks.
YS
I’m concerned that your medical professional believes Harmony is more accurate than an amnio. It is not. Amnio (or CVS in the first trimester) are the only diagnostic tests, but they are invasive and therefore do have a risk of miscarriage. Harmony and others like it (MaterniT21, Panorama, verifi) all have false positives and false negatives. That said, the accuracy for ruling out pregnancies carrying a child with Down syndrome is very high for Harmony and others like it. Many women are relying on the Harmony result if it is a screen-negative rather than risk miscarrying from an amnio.
Hi Mark, I have read this article and the plethora of comments below with a lot of interest. It is the first place I have found that takes a frank and honest view at the various NIPT tests and doesn’t have any bias. I am currently 11+6 weeks, have my NT scan this Friday (NHS) and have also got a Panorama booked for two weeks time and an Amnio for 6 weeks time (both arranged privately). Some have shown surprise at us booking the Amnio so soon without any indicators of anything to worry about and it is not due to the fact we suspect we have issues (no family history and ages 31 & 34) but more due to wanting to be sure as we would take action if we discovered our baby had any chromosomal anomalies. The thing is we decided before we even tried for a baby that we wanted an Amnio but have since been researching the screening accuracies of the NT and the Panorama.Having read your comments on here it seems there are still a lot of issues with the accuracy of the Panorama in particular the fact that it checks placental not fetal DNA – which i didn’t realise until reading your article. As our screening results will be back a week or so before our Amnio we have the ability to make an informed decision but I would dearly love to avoid the Amnio due to the risks and discomfort. I wanted to find out if anyone else on here has had the same dilemma and what they decided to do?
I hope others will respond. As I have mentioned in other replies, more and more women are opting to rely on a screen-negative result from tests like Panorama as their false negatives are very low. So, if they receive a screen-negative, they are choosing to accept the slight risk of a false negative versus the higher risk of a miscarriage from an invasive test, like an amnio.
I commented here back in February after a Panorama test came back 73% positive for Turner Syndrome (Monosomy X). We opted not to have the more invasive yet definitive tests like an amnio since we decided termination would not be an option, but we did have monthly ultrasounds with specialists at a renowned children’s hospital. Every ultrasound was deemed “textbook” and even “A+” by doctors. Our daughter had no physical signs of TS. We were then hopeful that the NIPT was a false positive or that I had placental mosaicism. In August our daughter was born and again she was examined and found to be in excellent physical condition. However, when cord blood tests were conducted it was determined that she has Mosaic Turner Syndrome-some of her cells are missing an X and some are not. I did go through some grief because it’s probable that she will be infertile and may face a few other issues. However, I’m glad that that I know now. We have already met with some TS endocrinologists and together with our pediatrician we are able to monitor my daughter’s progress. I’m so thankful that I read your articles, Mark, because it really helped me to understand what an NIPT is looking at. I truly feel like there needs to be better and more resources to be able to help people know what these tests are and how to handle results. I’m not going to weigh in on parents deciding to terminate except to say this, an NIPT should not be the sole basis on which parents decide to terminate since it’s not the same as tests like an Amnio. Secondly, in the case of TS and especially mosaic TS, these girls have very normal lives. It makes me sad when I read online how many people opt to terminate after a test knowing little to nothing about what TS is or being misinformed. I feel like NIPT’s are a little like opening Pandora’s Box. More needs to be done to help parents with the results they receive. Thank you, again, for your help Mark in helping me to be properly educated about these tests after I initially received my results. I hope others will continue to find this site and read up. 🙂
Laura–Congratulations on the birth of your daughter! And you’re right about parents not making a decision to terminate based just on a NIPS result–even the test laboratories agree that confirmation should be had by diagnostic testing. Thank you for your kind words–makes it all worth it.
Hi Mark
Having read through your very helpful info I am a little unsure what to expect in terms of my results as it seems that I will have a higher false pos rate before the blood result is added in. I’m 44, have done IVF, had Harmony at 11+1 and the scan that went with it showed a nuchal of 2.2 (ie very high end of normal). Half of me is thinking I should have gone for CVS/amnio as I’m more likely to get a positive (false or true) with Harmony.
Am I correct?
Thanks
Not with the incidence rate for your age, Clara. At your age, a screen-positive result from Harmony would mean you had around a 90% chance of having a child with Down syndrome and a 10% chance of it being a false-positive. Still, a 1-in-10 false positive chance is not insignificant and I hope you’ll receive genetic counseling to discuss whether you should confirm with amnio. If you were to receive a screen-negative, while there are false negatives, they are much lower and many women are relying on tests like Harmony to avoid the risk of miscarriage associated with an amnio.
Thanks Mark. 2 weeks to go for result. Feels like it’s going to be a long wait.
Hi Mark
We decided to have a CVS (before the harmony came back) at 11+6 after another scan showed that the nuchal had increased to 3.6. Our gut feeling must have been right as the FISH results came in yesterday showing T21. We had a detailed scan before the CVS which showed no other abnormalities- heart function normal, nasal bones present, 3 vessel cord etc. After we got the
FISH results I asked the doctor about the possibility of placental mosacism and she said they had never seen it in a T21 CVS result (I went to a world renound Fetal Medicine centre so I feel they have to be right but I’m still concerned).
I was wondering if you could give me any idea of the answer to a few question I have-
Where the CVS FISH results come back what is the rate of a false positive due to placental mosaicism? With placental mosaicism is there always a mix of abnormal cells and normal cell picked up that leads them to consider a mosaicism? If all the cells have come back as T21 does that preclude placental mosaicism? Are the final results more accurate for T21 than the FISH results or is there no difference?
I am a bit lost as the consultant in charge who was also present said he felt that there was a 90% chance that everything would be ok as there were no markers after a 45 min detailed scan that was rechecked several times so the FISH came as a bit of a shock.
Many thanks
Clara
Clara–you’re reaching the boundaries of my knowledge. My understanding is that CVS has higher false positives than amnio because of the increased chance that the CVS tests the mother’s cells versus the fetus’s. Also, while FISH is often relied upon, again, my understanding is that it is not as definitive as other genetic diagnostic testing. All that said, I would rely on a CVS FISH result positive for T21 as a true positive. I appreciate your sharing your experience and concerns as it illustrates how non-definitive prenatal testing is, even when it is named a diagnostic test. I hope you will access the prenatal resources linked on this site as they may answer further questions you may have about having a child with Down syndrome.
Hi Mark,
Does Harmony test put in age as a probability factor when calculating the risk? I am 31 y/o, and just received a 1/10000 low risk result. But I did have a baby with DS that was completely not diagnosed till after birth. I am contemplating if I should go forward with amino, because I am scared of the 1/10,000! As my last pregnancy was given some very low risk after the two trimester blood tests! My genetic counselor kept saying amino carries more risk than my current Harmony stat, in your opinion, you think the test is better at detecting negative?
My understanding is that all screening tests factor in your age and, in your case, your increased baseline chance for having a child with Down syndrome since you already had a child with Down syndrome. Your GC is correct that the chance that you have a false negative is far slimmer than the chance you will have a miscarriage due to the amnio. The incidence of false negatives is rarer than false positives with non-invasive prenatal screening. More and more women are relying on a negative NIPS result to avoid the risk of miscarriage with an amniocentesis.
Hi Mark,
I am a 42-year old and had the panorama. It came back low risk for all but I am worried about false negatives. But after reading the above explanations about how a false negative can happen, would it be correct to think that if it also came back with the sex being male, then I wouldn’t be at risk for a false negative? (Assuming they examine the same cells for both trisomy determination and gender determination). In other words, they couldn’t possibly have erroneouslybtested my cells rather than the fetal contribution to the placenta. Please let me know if my thinking is correct or not.
Thanks.
Tricia
Tricia–what you say makes a lot of sense. I would recommend talking to a medical geneticist about your rationale if you want medical expertise. False negatives are very rare and more and more women are relying on a screen-negative NIPS result and avoiding the risk of miscarriage with a diagnostic test. I hope you enjoy your pregnancy.
Tricia did you follow up with any medical experts on this?
Thx
Mark,
Would you please clarify the nature of the maternal blood sample? Reason being that I had a genetic counseling, in which I was told that while the maternal blood sample is used for Harmony, there are fetal cells circulating in the mother’s blood. As a clinical laboratory professional, my question would be as follows:-
1) How exactly does the Harmony test isolate cffDNA? It would make sense to me that if maternal blood is obtained as the testing sample, there had to be a threshold of the number of fetal cells detected in the sample in order to deem the sample a ‘qualified’ sample. Do you know this threshold percentage (meaning the isolation method to identify and separate fetal cells vs. maternal cells in the blood sample? Let’s say it’s 10%. Is a 25% fetal cells sample considered a better sample that a 13% fetal cells sample? Or is it simply a matter of the presence of fetal cells above the 10% threshold? Do you know if the cffDNA fragments are being amplified and/or optimized before identifying the target sequence of Trisomy 13, 18, 21?
2) The genetic counselor mentions “mosaicism’ factors in the Harmony test, meaning that cells obtained in the maternal blood sample is actually placental cells. But the perinatologist said there is no doubt that ‘fetal cells’ are being tested, but not placental cells. Thus, this is contradictory and confusing. If indeed there is exchange of fetal and maternal blood in the umbilical cord, wouldn’t that explain that it’s actually fetal cells that is mixed in the maternal blood? Or does maternal blood contain placental cells DNA & fetal cells DNA, as well as maternal DNA?
3) I’m not so much concerned false positive rate, as that would be confirmed by amnio. But I’m curious what causes false positives? On the other hand, what is the false negative rate of the Harmony test? And if there are incidences of false negatives, can you suggest me links for research and perhaps elaborate on the factors that resulted in the false negatives?
4) What is the distinctive factors in defining tests as ‘screening’ vs ‘diagnostic’? While Harmony claims 99% detection rate, what is the efficacy and accuracy rates? Do you happen to know the specificity and sensitivity percentages of the Harmony test?
I understand my questions go beyond what some patients may ask, but I hope you can give me a bit of guidance in terms of making a decision of Harmony Test vs Amnio?
Regards,
Wendy
Wendy–I’ll try to answer your questions in order as best I can:
1. Key distinction is what is being tested with Harmony and other NIPS tests are not fetal cells, but DNA passed through the placenta. This means it can be free floating DNA from the fetus, from the placenta, or from the mom. Each laboratory sets what is called a “z-score,” which is a threshold for how much cell-free DNA is identified in a sample. If it’s below that threshold then the testing does not have the state accuracy rates. I do not know what Ariosa is setting as its z-score now that the test is in commercial usage. I do not believe the fragments are being amplified/optimized, but that is something also that is lab-to-lab specific.
2. Responding to the perinatologists, no lab says they are testing fetal cells. There are labs trying to develop tests as there are full fetal cells found in the maternal blood stream (Cellscape is one I’m aware of), but none of the current tests test fetal cells. They test cell-free DNA passed from the pregnancy through the placenta.
3. False positives can be attributed to a number of factors: the DNA is from the placenta and there is placenta mosaicism for a trisomy is a common reason but can also be because the mother’s body mass index has been shown to correlate with higher false positives. There are incidences of false negatives but these are much fewer than false positives.
4. The distinction between screening versus diagnostic is how accurate the tests are. Amnio and CVS are considered diagnostic because they have a high level of accuracy, even though even those tests have false negatives and positives (but they are very rare). I do not know what the specificity and sensitivity percentages of the Harmony tests are now that it has gone into commercial usage–no one does about any of the labs as the stated rates for all tests are based on clinical studies that had abnormally high incidence pregnancies with aneuploidy not representative of the natural population incidence for aneuploidy.
With all this said, NIPS tests remain the most accurate screening test on the market. Prior to undergoing a diagnostic test and risking miscarriage of your pregnancy, NIPS should be considered as a screen. More and more women are opting to rely on the NIPS result and avoid the risk of miscarriage, particularly if they plan on continuing regardless of the result.
I hope this helps.
Mark
Hi Mark,
I have read and re-read the post and comments here many times now. I had the Harmony test done and everything looked okay, but showed 99% chance that my daughter has xxx. I realize this isn’t a huge deal, but hearing anything but perfection about your baby is kind of scary. I just turned 35, I’m 15 weeks along (12 when I had the Harmony test 10th 9.6% fetal DNA – I had one drawn at 10 weeks and didn’t get a result) and I’m on the heavier side, but not huge.
The genetic counselor made it sound like there was pretty much a 50/50 chance of this xxx being true. She also mentioned that it could be me with xxx, which we found interesting because I do display several of the traits.
Then I met with a geneticist and he pretty much told me that the test is very accurate. He explained how they do these tests and said that because of this it would have thrown the ratios all off if I were the one with xxx and the lab would have known it was me, not the baby. Basically he said my baby probably has xxx and I do not.
So, who do you think I should believe here? Have you heard anything more about these tests for sex related issues?
Thank you!
Megan
I’d listen to your genetic counselor. As this post covers, what is tested is not fetal DNA, but DNA passed through the placenta, meaning it can be DNA from the child, from the mother, or from the placenta. From a very cursory on-line search, the reported incidence rate for Trisomy X is around 1 in a 1,000. This means the odds are about the same as a 30-year old mom has for having a child with Down syndrome. As covered in this post, even if Harmony has an accuracy rate of 99.5%, a screen positive really only means a 50/50 chance–just as your GC counseled you. It would seem they could rule you out as possibly the one with Trisomy X if they did a karyotype of you. Also, the professional medical organizations do not recognize the NIPS tests, like Harmony, as accurate for sex conditions simply because the sample size of their published studies have been too small. I hope this helps.
Thanks so much, Mark. I really appreciate your input here.
Hi Megan,
I would also recommend a karyotype to rule yourself out. I did the same, and the xxx was indeed my daughter, not me. This was not the case for my friend who did the harmony. The results showed xxx. She got tested and the xxx was her- the harmony somehow overlooked the Y of her son. If you are interested in connecting with other moms and expectant moms of girls with 47x as well as girls with xxx, there is a facebook group as well as a yahoo group. Good luck to you!
Hi,
I’d love to know the name of this facebook group! How is your daughter doing?
Thank you!
Do a search for AXYS/trisomy X. Keep in mind that it is a support group. Many posts are about moms voicing concerns. Every xxx girl is different. Just because one girl may have a given issue, doesn’t mean your girl will have that issue. However, it was nice to “meet” other pregnant moms going through the same thing. I dealt with intense anxiety and depression during my pregnancy, but eventually I began to bond with her. When she was born, I fell madly in love with her- and it deepens each day. She is such a good baby. I worry every day, but we will deal with any issue as it comes. She is a beautiful, smily, happy, baby and sleeps like a champ. She does have some low tone in her upper body, so I will remain vigilant and get her PT if need be. Knowing the dx helps so that I can stay on top of things and act right away should she need intervention. Anecdotally, my friend that was dx with xxx at 36, is happily married with two children, lots of friends, and is a masters-level trained educator. If you’d like to email, I consent to Mark that he give you my email address.
Hi again –
I had my amnio this week and was supposed to get the FISH results today. The counselor called and says my results are inconclusive due to there being blood in the fluid, so they cannot determine whose cells belong to whom. They did report that all the cells they examined were xx, though, which I am going to take as a good sign. I was wondering what your take on this info is? Do you think I am silly to think this is a good sign?
Megan
Megan–I’m sorry to hear this. While even amnio and CVS have a very small chance of a false positive or negative, having an inconclusive also can be very frustrating. To be honest, I’m not sure what to make of the report, so I would ask your GC or MFM if they think it is a good sign. Wish I could provide more reassurance. Mark
Hi Megan! I have a 5 month old daughter. I had the harmony test done at 14 weeks and the test came back with increased risk for trisomy x. It was only 20% chance but after reading the accuracy of the test I was really upset because they obviously found something on the test. I decided not to do amnio because I did not want to put her at risk. We had a kariotype of her cord blood at birth and all was OK with her, so it was either the plascenta or my cells. The test caused me a lot of anxiety in my pregnancy and once I found some of these sites I was able to let go of my worries. The genetic counselor did not see any other indications on ultrasound and for me she already had several false positives for trisomy. I knew that no matter what we would be ok and would deal with whatever challengers came or way….so I let go of those worries. Good thoughts to you and I hope you have a safe rest of your pregnancy. Just think …..in a few months you will have your little girl in your arms….. They are so precious.
Thank you DIanne!!!
Yes, I have an amnio scheduled for next week basically just so I can know conclusively, but I am also worried about the risks, of course. I am keeping this baby as long as she will let me and I was really sad to hear that some people do still terminate for XXX. Really interesting that you got 20% for it. Mine was 99%. I’m glad your baby doesn’t have it even though xxx really doesn’t seem to be a big deal. I hope I get similar results!
I meant to say monosomy x. For my test it came back that either there was a missing or partially missing x chromosone. The genetic counselor felt quite certain that the risk was low so we decided not to do the amnio. I would have had the amnio if it came back as a higher rate. I am sure all will go well with the amnio. I will keep you in my prayers and thoughts. Please keep us posted if you are willing to share.
Hi again,
Well I got my full amnio results after 10 days and it came back negative for triple x. I really couldn’t believe it. I just wanted to post the conclusion to my tests for the next Mom who gets a positive for Triple x on the Harmony test. False positives definitely really do happen.
I think I am going to ask my OB to test me just to see if I possible have 47xxx. I’ll post again if I get any more answers. Thanks everyone!
Megan–thank you for sharing “rest of your story.” I hope you enjoy your pregnancy and welcome further updates as you find them appropriate to share.
Hi Mark,
I have read majority of the comments and testimonies. They have given me hope but I’m still uneasy. I just wanted to post my situation, current test results and follow up with my amino results within the next two weeks. Let me know what you think of my results. I am already in consultation with a Genetic Counselor. She has been awesome through this situation.
Perhaps my information can help someone who can relate as I have related to some of the older women who posted above.
43 yr old, 7th pregnancy, 4 healthy boys, 2 mc (6 weeks and earlier)
———————————————————————————-
First Trimester Scan – 11/07/2014 at 12wks 5days
My Test Results:
PAPPA-A = 1988ng/ml (1.60 MoM) | Usual range <0.4
hCG = 94.9 IU/mL (1.03 MoM) | Usual range 2.5
Nuchal Transluncency = 2.5mm
My Patient Risk:
Age Risk for DS = 1 in 25
Down Syndrome Risk = 1 in 114 | Reference Range 1 in 270
Trisomy 18 Risk = 1 in 2099 | Reference Range 1 in 100
Expanded Test Information:
Calculated Gestational Age = 12.6 weeks
NT MoM = 1.56
——————————————————————–
Harmony Test – 11/14/2014 at 13wks 4days
Fetal cfDNA Results = 5.6% (what does this % mean Mark, I forgot to ask the Gen Couns)
T21 = High Risk greater than 99/100
X,Y = XXY Kleinfelter Syndrome
T18 = Low Risk
T13 = Low Risk
So, from my numbers, not only is there a possible chance for Downs Syndrome but it also has an extra X which brings on additional health issues.
I am now 16 weeks and will schedule for an amino. I am holding out that I am a false positive.
I will post back with my results.
Site where I found the MoM ranges: http://geneticsmadeeasy.com/preguntas/pregunta46.html
The hCG Usual range did not post correctly. It should be 2.5
Tasha–thank you for sharing your results–interesting to see them listed. I believe the 5.6% for cfDNA means the amount of cfDNA found in the sample, what some labs call a “z-score” with I believe most accepting anything 5 or higher in the testable range. I am curious as to what Ariosa/Harmony specifically means by stating that T21 is high risk at greater than 99/100–is that it’s sensitivity/detection rate or is that what Ariosa is computing as your positive predictive value. I would seek clarification on that. I wish the best for your amniocentesis.
That’s the Probability score (column). For the Result column it says High Risk. I do not see anything on the paperwork indicating a Positive Predictive Value. Should it? The paperwork is very basic without any “real” data..unlike the First Trimester Scan which gave all those details I listed above. What are some questions I can ask my Gen Counselor about the PPV? Is the PPV critical for making an analysis?
I just scheduled the Amino for 12/17/2014. I will let you know how that goes and any test results.
The PPV is what your NT results reported in the numbers “1 in 114 | Reference Range 1 in 270.” Meaning, based on your NT, your adjusted chance of having a child with Down syndrome was 1-in-114–actually lower than your baseline chance based on your age. I expect the 99/100 from Ariosa’s report is simply repeating its claimed accuracy rate for detecting a pregnancy with Down syndrome. However, even at that high of a detection rate, there are still false positives. Based on your age, at that accuracy rate, it means that you have around a 95% chance of having a child with Down syndrome and a 5% chance of the test being a false positive (see this post for further explanation). I would ask your GC to confirm this analysis. As for the XXY, I’d ask for clarification from Ariosa on what its sensitivity/detection rate is for XXY, since it’s not shared in your report like the 99/100 is for DS. Then, your GC can also do the same PPV analysis for XXY. PPV can at least inform you on what your true odds are for having a child with Down syndrome whereas 99/100 is not your actual probability.
Hi Mark,
I just wanted to report back that I received my aminocentesis results back on Monday, December 29th. It came back positive for Down Syndrome and negative for Klinefelter Syndrome.
Tasha–thank you for sharing your results. Reading back through this thread, I was glad to see you are receiving support from a genetic counselor you describe as being awesome through this. At the Prenatal Resources tab are resources recommended by professional guidelines. I hope you’ll find those helpful as well. I wish you the best.
Hello Mark,
I had a very high risk positive result in my 13 weeks NIPT for Turner’s syndrome. Right now I’m 16 weeks pregnant and in the ultrasound everything looks good. I had an amnio last friday and I’m waiting for the results. Do you know if in the case of having only parcially missing x chromosome that would be shown in the amnio results?, I want to be completly sure that the baby has no Turner’s syndrome at all.
Thank you very much, I find your website really helpful
Blanca–I wish I could help you more, but I’m not for certain about the ability of amnio to determine whether there may be partially missing x chromosome, i.e mosaic Turner syndrome. I would refer you to a genetic counselor and the Turner Syndrome Society. I hope they may provide you the answer you’re looking for, and feel free to share it if you do find out. I wish you the best. Mark
Tasha,
Hoping all is well and anxious to hear your results from the 17th.
Thank you for sharing your results as they looked very similar to someone near and dear to me. I’m hoping for the best for all of you, even if that means peace of mind from a definitive test result.
SKay
Hi Kay,
Thanks for checking in on me. I posted my results earlier today. Here is what I wrote above:
I just wanted to report back that I received my aminocentesis results back on Monday, December 29th. It came back positive for Down Syndrome and negative for Klinefelter Syndrome.
I just want to thank you for being so helpful and responsive to people’s comments. Our sweet baby boy is 5 1/2 weeks old and he does have Down Syndrome, though you wouldn’t really know it from being around him. He is just as strong as our other children were at this age (we were told he’d have low muscle tone, that was not the case). He is so very sweet and precious and has been such a blessing. I’m sure as he grows it’ll become more apparent but we won’t love him any less. In fact, he seems to be a favorite already among family and extended relatives! We had been worried from the prenatal diagnosis but all of that worry and anxiety were for nothing! We tried to prepare as best as possible and were grateful to learn of many resources available. We met other parents with children with Down Syndrome and heard such sweet, positive, happy things about raising a child with DS. I think there is too much worry and negative connotations out there about having a child with DS. Honestly, of all the different kinds of special needs conditions that exist out there, I think DS is pretty awesome because people with DS are extra loving, easy-going, and happy (from all we’ve met and talked with). It has already blessed our older children who have become much more sensitive and aware towards others with special needs. It has enriched our lives for the better. I look forward to the future with more hope and joyful anticipation than every before.
Kristy–thank you for sharing your experience. I’m glad to hear your son is doing so well and you have received such good support. Feel free to check back or e-mail (mleach@downsyndromeprenataltesting.com) should questions arise or you have news to share.
Hello Mark, we got our results from the harmony test this week: >99% positive for BOTH T21 and monosomy x. Our genetic counselor says she has never seen both together in all her years in the job and I can’t seem to find any references whatsoever online to any statistical data or personal experiences like mine.
We were offered the test based solely on maternal age (I’m 42) and we are at 16 weeks. We are scheduled for the detailed ultrasound and amnio next week.
Any info or links you can give me on double positives?
Thank you!
Jeri–Scroll through the comments here to see about Tasha’s experience. Not a dual diagnosis of Down & Turner (Monosomy X) syndrome, but a dual NIPS result for Down & Klinefelter (XXY) syndrome. Amnio confirmed Down syndrome, but was negative for Klinefelter. In my reply to Tasha, I explain how the “99% positive” likely is Ariosa quoting its claimed sensitivity, i.e. ability to detect those pregnancies actually carrying a child with the tested-for condition. However, it is not Ariosa’s positive predictive value. Based on your age, with a screen-positive Ariosa test you have approximately a 95% chance that your child actually has Down syndrome, but that means a 5% chance of a false-positive. Your probability for Turner syndrome is about half as likely as it is for Down syndrome, making the positive predictive value less than the 95% chance you have for Down syndrome. Your GC should be able to do what is called a “Bayesian” analysis to give you more precise positive predictive value numbers. I would consider contacting the Turner Syndrome Society to see if they have any information on the incidence rate of a dual diagnosis with Down syndrome. Hope this is somewhat helpful.
Thank you so much for the immediate response, Mark!
I will indeed look through the comments again for Tasha and I deeply appreciate the information you’ve shared. I will check in after the amnio.
Jeri
Hi Mark,
Just checking in to post that our amnio confirmed Downs but the Turners was indeed a false positive. I had such a hard time finding anything about double positive nipt results online that I just wanted to make sure this fact was here for people in the future who get this rare result. Being told there was >99% chance of our baby having both was so overwhelming…I hope in future they will start giving families the real risk percentages for each condition. It would have given us comfort to know (before we got the info from you) that the risk of Turner’s on top of Downs was much lower than they presented.
Deep thanks for your efforts in shining a light for us all.
Be well,
Jeri
Jeri–Thank you for sharing your results and I appreciate your kind words. I’m glad the information here was of some help. I further hope the information at the prenatal resources tab is helpful for you. I hope you get the support and information you need going forward.
Hi, I had my CVS result and it says my baby has Edwards Syndrome. I am devastated. Please can CVS ever be wrong?.
CVS tests cells from the placenta called chorionic villi. Sometimes, the tested cell can be of the placenta, not the fetus and there can be placental cells with Trisomy 18, called placental mosaicism. However, for CVS, this is very rare. The instances of a false positive are so low that that is why the medical community considers a CVS diagnostic, i.e. definitive. However, I would talk with your Maternal-Fetal Medicine specialist, OB, or genetic counselor to find out if they have had false positives in their practice, as that is most relevant for your situation. Professional guidelines also recognize that contacting parent support organizations can be very helpful. The Trisomy 18 Foundation can be contacted via its website at this link. I hope you get the support you need and accurate information you deserve.
Hi, thanks for this blog. I have received a positive CVS result for T18. I am devastated. Please can a positive CVS result ever be wrong?.
Please see my immediate reply above to Ogom.
Dear Mark,
Thank you so much for providing advise here, your comments are so useful.
I have received my results for the Harmony Test two days ago and I feel that my doctor was not in a position to adequately explain them to me (over the phone). My risk for T21 reported by Ariosa is 37% (should be 99%. Is this correct? We have been almost certain of having a DS child for the past days as we were not able to figure out what 37% means and I could not find anything on the Internet, but now I have some more hope. A CVS is scheduled for tomorrow (I am 12/13 weeks pregnant) and I will report back here to add more information for other parents. What do you think our risk actually is?
Sorry, some of my text went missing somehow….This part is missing: I understand from the comments above that in rare cases, Ariosa estimates risk calculations below the normal results of either 99% (for high risk). Is this correct? My doctor (who does not have experience with positive test results so far…) said on the phone that the chances of a false-positive are >0.01% and that in all likelihood, the child will have DS.
Christine–from what you have shared, I would understand Ariosa to be saying that based on its testing, you had a 37% chance for having a child with Down syndrome, meaning Ariosa is reporting the positive predictive value. Put another way, Ariosa is saying you have 63% chance of not having a child with Down syndrome, meaning more likely than not you are not carrying a child with Down syndrome. The 99% number is Ariosa’s claimed accuracy for detecting pregnancies that are actually carrying a child with Down syndrome, but that still leaves a certain percentage receiving a false negative. Similarly, Ariosa claims a greater than 99% ability to identify those pregnancies not actually carrying a child with Down syndrome, but, again, that leaves a certain percentage that would incorrectly receive a screen-positive, i.e. a false positive. For your OB to be correct that the false positive chance is 0.01%, you would have to be 50 years old or so–I doubt that is your age. If you are younger than 50, than Ariosa has a chance of false-positive between 5% (45 years old or so) to 60% (under 25). I would have your OB contact Ariosa to ask them what their report of 37% means; Ariosa and all other NIPS labs have genetic counselors on staff to interpret the results. If you are proceeding with a CVS out of a belief that you have a 99% chance of having a child with Down syndrome, that is not correct information. If, however, you’re proceeding with a CVS because you want to know for certain, a CVS or amnio were always the only tests to know that from the beginning of your pregnancy. If, however, you chose a screening test because if the result came back “low risk” you would avoid the risk of miscarriage associated with a CVS/amnio, then, again, I’d have your OB call Ariosa to explain their results and do that before you undergo the CVS. Hope this helps and if you proceed with the CVS that the procedure goes well.
Dear Mark,
The ultrasound scan was normal (giving us a bit of hope on Monday) and the CVS on Tuesday turned out to be normal as well. I am sooo relieved as it turned out that my husband and I moved into completely different directions regarding our feelings towards this child. I think it would have been extremely difficult for either one of us to accept the other one’s feelings and opinion. I was actually more scared of this conflict than of the Down Syndrome in the past days.
I now hope that the CVS (which was done two days ago) will not lead in a miscarriage or harm the child in any way…
Thanks a lot for your advice and I wish you and your family the best for the future!
Best from Germany!
Christine
Christine–thank you for sharing your results and I’m glad the procedure went without incident. I hope things resolve with your husband and that you enjoy the rest of your pregnancy.
Hello,
I received a call yesterday from my Genetic Counselor saying that I tested positive for Down Syndrome and that they are 99% sure that my baby boy has Down Syndrome and to prepare ourselves for this result. I had the Verifi Free Cell DNA test. She kept saying that it was 99% accurate and really gave us little or no hope. I am scheduled for an Amnio on 1/21/15 and I’m scared to death. My husband and our parents are devastated. I just don’t understand. I am looking for any glimpse of hope that I can find and I’m not reading a whole lot about the Verifi test and I’m starting to worry that this test was wrong to get in the first place. I had a sequestial ultrasound last week and everything from the ultrasounds down to the blood work have all been perfect I just don’t get it. If anyone can give me any information I would greatly appreciate it. These next few days are going to be the longest days of our lives. Thank you in advance!
Kristi
Kristi–I’m very sorry to read of your genetic counselor telling you they are 99% sure your child has Down syndrome based on verifi having a claimed accuracy of 99%. He or she should know better. I say that declaratively because the National Society of Genetic Counselors put out a fact sheet seeking to address this misunderstanding about non-invasive prenatal testing. See this post which has links to the fact sheet. None of the tests like verifi have that accuracy rate. Depending on your age, receiving a screen-positive verifi test would still mean it is more likely than not that your child does NOT have Down syndrome. See the graph at this post to find your positive predictive value. In fact in a major study done by verifi’s laboratory last year, they found that their tests only correctly predicted if a pregnancy was actually carrying a child with Down syndrome 45% of the time. I’m sorry to hear you’ve been given bad advice and I hope you’ll share the fact sheet with your genetic counselor and ask him or her to ask Illumina (the maker of verifi) what your positive predictive value is.
Hi Mark,
Thank you so much for your response. Reading that and the posts you pointed us to gave us some hope. Although we are preparing ourselves for the worst but who wouldn’t. I forgot to mention in my original post that I am 34 years old and my OB suggested I see a genetic counselor because I would be 35 when I delivered. I’m still devastated, confused and so scared and wonder if I should have ever gone to see the GC in the first place. We go from sadness or anger to crying I just can’t wait until we have the amniocentesis so we can take the next step. Thank you again Mark and for everyone’s posts. They really helped me feel like we’re not going through this alone.
Kristi
Kristi–I’m glad you found this site helpful–really the whole point I started it. I hope your amnio goes well.
Hi: We just received a “positive”, 99% risk for Trisomey 21based on the Panorama Test. My wife is 40, and we do understand that she is in the higher risk category, but something still troubles me with the test. According to the Genetic Counselor, this test analyses cells that come from both the mother and the fetus, and according to her, past DNA from other births, etc.. About a year and a half ago we had a miscarriage. My question is, do past births/miscarriages play a role in this Panorama test? Are there any studies that have looked into how past birth/miscarriage cells affect the results of the test?
Thank you for any information you can provide.
BTW – I have researched the 99% risk factor and understand that Genetic Counselors do not understand the statistics behind these tests.
Steve–thank you for noting that there is no such thing as 99% risk based on tests like Panorama. Regarding your question on previous pregnancies/miscarriages: yes, from my understanding and discussions with genetic counselors and geneticists, cell free DNA from every pregnancy remains in the mother’s blood stream. Therefore, there is a chance that the cell free DNA tested by Panorama was from a previous pregnancy, just as there is a chance that it was DNA from the placenta of this pregnancy and not from the fetus. That said, given your wife’s age, a screen-positive Panorama makes a false positive unlikely, but there remains a chance of a false positive, still. I am not aware of studies that have found false positives based on previous pregnancies, but perhaps your genetic counselor would search to see if there are any if you asked her.
Mark – thank you for your reply, and thank you for all your efforts in maintaining this website and for the wonderful job that you do in informing people of all the relevant subject matter.
In our case, after the “positive” Panorama results, we were offered an amnio to confirm. We declined the amnio because, basically, a confirmation for us would not change any course of action. Although we understand the risk of the amnio to be small, we felt that it was still too great of a risk for us. Off course, this was a personal decision. We have decided to do just all the proper sonograms going forward, to ensure that all internal organs (i.e heart) are ok. So far everything is great and we are letting nature take it’s course. I can honestly say that now is the only time that we are enjoying this pregnancy.
I do appreciate what these NIPS are attempting to accomplish. I do think, however, that the companies offering these tests are obligated to educate the public properly; in a way that any parent can understand (not a PhD in statistics). Additionally, they should be forced to disclose all appropriate false positive/ false negative data on an ongoing basis, while at the same time stipulate clearly that these tests are NOT FDA APPROVED and are SCREENING TESTS ONLY – NOT DIAGNOSTIC. As you will notice, specifically for Panorama, such disclosures are not clearly stated, and the FDA disclosure is in very fine print, buried at the bottom of their web pages. You will only see this if you are lucky enough to scroll all the way to the bottom. This, to me, borders on the unethical. With that said, I am also skeptical about their reliability.
Thanks again for all your hard work!
Thank you, Steve. The concerns you voice have also been voiced by the International Society for Prenatal Diagnosis and researchers at Harvard in the New England Journal of Medicine. Many parents are making the same choice you are to rely on the NIPS result and avoid the risk of miscarriage with diagnostic testing. While you still may have a false positive, I hope you find the materials at the Prenatal Resources tab helpful for preparing for your child.
I live in Europe and had the Ariosa / Harmony test done twice, based on samples taken at about 13 and 17 weeks pregnant. The results were inconclusive both times, reportedly due to low foetal DNA levels. I did not receive the original US lab results, but only a memo from the partner lab in Europe. The paragraph describing the method used did refer to “foetal DNA” and not “placental” DNA, which I now understand is a misrepresentation.
When the results of the first test came back inconclusive, I was told that this can happen in 3% of cases, but if re-taken that percentage drops to 0.6%. I was also explained that it can be linked to the mother’s (excessive) weight. I weighed 46 kg. I wonder whether these percentages are in fact understated and whether the rate of unsuccessful tests is actually significantly higher. Any views on that?
Anyway, the lab proposed to either have a third attempt (but recommend I would rather go for alternative testing/screening methods) or get reimbursed. Is reimbursement a common practice in such cases? I would have thought that for an established procedure the lab would consider their work done anyway. It makes me wonder whether they are well aware of significant limitations of their testing and would rather pay customers back to reduce the risk of complaints.
I then started looking into Panorama and was initially very enthusiastic about their claims of being able to work with low foetal DNA levels better than their competitors. Then I “researched” a few opinions and am now skeptical. i will either go for amnio or cross my fingers.
Rox–I’m sorry to hear of your experience. It’s frustrating the lack of information shared. It is unknown how the labs are performing with their tests now that they are being offered commercially and globally. All of the quoted rates are from clinical studies that have been criticized for being incomplete, not sharing the raw data, and involving populations with artificially high incidence rates for Down syndrome and the other tested-for conditions. Reimbursement is common if the lab still gets a no-call on a re-draw. Why that is the case is left to us to speculate.
I am 43 and pregnant with my 2nd child – due to my age I had the Panorama test at 9 weeks and the results were negative with no reported problems.
I then had the nuchal at 12 weeks and and the measurement was 2.6mm. My blood was also taken to be tested for the pregnancy hormones. This was done with the maternal and fetal medicine doctor. The measurement was higher than I’d like but was told it was within normal range. But a week later then doctor called to let me know the results came back with a risk for down syndrome. A 1 in 4 risk.
I made an appointment with the maternal fetal medicine doctor for an amniocentesis. I was told they prefer to do the test at 17 weeks so I am now waiting for that test to be done on Feb 9th. I am concerned now and waiting is tough! I am know the nuchal can also have false positives but I have to know for sure and cannot wait till my due date in July.
Thanks again for this info! The article combined with the comments have been a big help!
Melanie–thank you for sharing your experience, as anxious as it is. While there are false positives and negatives with any screening test, there are much more false positives for a nuchal than false negatives for Panorama. I’ll be interested to hear if that is the case. Regarding the amnio, the earliest it is to be performed per medical guidelines is after 15 weeks, so your doctor performing it at 17 weeks is consistent with the guidelines. I hope the procedure goes well.
Thank for the quick reply Mark! I forgot mention in my previous post that I was 40 for my first pregnancy I had the MaterniT21 test and the nuchal in the first trimester – both came back negative. I guess due to my lack of knowledge on all things pregnancy at that time I assumed everything was ok since my doctors assured me those tests are reliable.
I guess we were lucky my son was born healthy with no issues! The pregnancy journey is quite the experience….so much to learn and understand.
I’ll report back after we receive the amnio results in a couple weeks.
Hi! I just got my Panorama results. I took them at 10w3d. Doc’s tech called and said: everything is low risk and it is a boy. I called Natera because I wanted the actual results, so yeah they are low risk, All the trisonomies are <1/10,000. However, the fetal fraction was 7.8%, which seems sort of on the low side. Does this make it more likely for a "false negative"?
My doc has recommended amnio since day 1 when i met him, at 4 weeks. His take is: amnio is gold standard, just do that and don't worry about anything else. He says he has done 2,000 and never lost a child. Well, I can't help but feel apprehensive about it anyway.
A little about me, I am 34. Both my husband (36) and I had genetic testing (through Counsyl) prior to conceiving. He came back at 0 and i came back with 2 defective genes, but since he wasn't a carrier, the genetic counselor was not concerned. We have no history of down syndrome in my family or his.
We went to a boutique sonogram place where the tech – not doc – mentioned that the nuchal size was on the thin side (at 11w1d), my doc doesn't do NT testing.
Anyway, does the low fetal fraction make it more likely that i could have gotten false negative? Any research on any false negatives with panorama? I'm trying to decide whether to do amnio or not.
Thanks!
Ali–your fetal fraction is not on the low side. Anything above 5% is considered a reliable amount for the claimed accuracy rates of each test. False negatives remain a possibility, but are very rare. Given your age and the screen negative with more than enough fetal fraction to test, I would say it very unlikely that you have a false negative. Your doctor is correct, though–from the beginning, the only way to know for certain was with an amnio. I would say your chance of a false-negative is as much or lower than the chance of miscarriage with an amnio.
I am 43 years old and found out I was pregnant going through the scheduling process for a hysterectomy. So I was very surprised at the least to find out I was pregnant. I am now 17 weeks along in the pregnancy and found out a few weeks ago that my verify test came back as positive for trisomy 21. And we are devastated. Although we will love this child regardless if the diagnosis is true. My concern is the following:
Upon receiving the results my doctor urged me to get an amnio to confirm the diagnosis. I had asked the doctor how accurate the result was and she stated 99% sure the results are accurate. She also urged me several times during the visit to consider aborting the pregnancy.
With her stating the results as being a 99% diagnostic result. I have decided not to get the amnio. but now I am unsure based on your article.
My other concern is this. All of the research I have done states that these tests are diagnostic and not screening tests. so based on these reports I am concerned how many pregnancies have been aborted because of this misrepresentation.
thank you.
Thank you for sharing your experience. Tests like verifi, Harmony, MaterniT21, and Panorama are no diagnostic. To make this point, the American College of Medical Genetics and Genomics refers to these tests as “non-invasive prenatal screening” or “NIPS,” to emphasize that they are screening, not diagnostic. The Society for Maternal-Fetal Medicine issued a statement to make the point that cell free DNA testing/NIPS is not diagnostic after an expose reported women were terminating based just on a NIPS result. The National Society for Genetic Counselors has issued a fact sheet in an attempt to clear up the confusion over the accuracy, or lack thereof, of NIPS. Feel free to share these posts and the actual statements with your medical professional so future patients are accurately counseled.
Thank you for your quick reply. What questions would I need to ask my doctor to find out what the actual percentage rate would be? For example in an earlier post you mentioned that a women of 35 years with a 97% positive based on NIPS was actually 62%. Also I did find another site helpful in this topic as well that you may be interested in sharing with people as well. that site is http://necir.org/prenatal.testing/
Thank you.
Positive predictive value is explained at this post with two other posts further explaining it linked at the bottom. Based on your age, with the quoted rate from verifi, your positive predictive value is somewhere around 95%, i.e. your screen positive has a 95% chance of being a true positive. But, I would discuss this with your genetic counselor and ask your provider to specifically ask Illumina (the maker of verifi) what your positive predictive value is based on their tests performance.
Thank you also for the link to the NECIR webpage. I wrote about its expose at this post.
Hi Mark,
I’m 32. Today received Panorama results of 36/100 risk for T18. I’m 13w5d today. Ultrasound came back normal with no markers for Edwards but i know it’s very early so the ultrasound doesn’t help much. Fetal fraction 4.4%. We are doing a CVS on Friday.. ill be 14w1day then. (Are CVS tests okay at that gestational age?)
We’re wondering if the risk is truly 36% or worse? Very confused with how to reconcile a 99% accuracy with a 36/100 risk. Does the low fetal fraction mean they maybe found some bad indicators but there could easily be more that weren’t detected because of lack of fetal dna? So basically, does the low fetal fraction mean i’m MORE likely to have Edwards?
We’re trying to figure out how much hope we should have.
Laura–I’m not sure what “36/100” means. Check this fact sheet offered by the National Society for Genetic Counselors and you’ll see it emphasizes the need for labs to report what is known as “positive predictive value” or “PPV.” PPV is how likely it is that a screen positive is a true positive. For instance, if you received a screen positive for Trisomy 21, Down syndrome, from a Panorama test with a 99% rate, it would really mean you had just slightly more than a 50% chance of actually having a child with Down syndrome. There are several factors to suggest your screen positive from Panorama is a false positive: [1] your age, 32 is not considered “advanced maternal age” and the incidence for trisomy conditions doesn’t begin to rise markedly until after 35; [2] it’s Trisomy 18, which has a very low incidence rate, i.e. it is a rare condition, and therefore your baseline chance for having a child with Trisomy 18 is very low; and [3] the low fetal fraction, which correlates to less precise results. See this link for one clinic’s experience which showed a screen positive for Trisomy 18 or 13 actually meant the odds were it was a false positive. Regarding your CVS, typically the timeframe quoted for performing that test is 10-12 weeks; I have not heard of it being performed at 14 weeks. Referring back to the fact sheet, you’ll also see how a CVS may not share any more accurate information than your Panorama, since it could test the same DNA material, which is not necessarily from your baby. Finally, an amnio can be performed after 15 weeks and does not have the limitations of a CVS. I would ask your genetic counselor or maternal-fetal medicine specialist to ask Panorama for clarification on what 36/100 means and then discuss with them the relative pros and cons of having a CVS at 14 weeks versus waiting to have an amnio. I hope this helps and that whatever procedure you choose goes well.
Mark:
First of all, you provide an amazing service to service by answering questions and I am so grateful. I was completely lost yesterday with the results and your patient, logical answers in your article and the comments were grounding and comforting. To me, nothing eases the “shock” of bad news better than education—even if the information is disheartening it still provides a sense of control. My husband and I read every word you have written on this site yesterday. And now, you responded to my post within 14 hours. Thank you so much.
I wish Panorama did provide the PPV but they did not. I set up a phone call with a Panorama genetic counselor for this morning. A seemingly knowledgeable woman called me to tell me the appointment was set up in error by a new employee, because they do not offer that service. (Frustrating because my OB advised me they couldn’t explain the results so I should contact Panorama, and Panorama advised me they couldn’t offer clarity so contact my OB.) I did manage to frantically squeeze in a few questions before she hung up. She said my score means a 36% risk of Trisomy 18 and so it does not entirely fall in line with their 99% or .01% normal rates. She said they more often receive the 99s or .01s but they get these middle-of-the-road answers from time to time. I asked if they had a percentage of how many times those with 99% wind up actually having the disease and she said she did not have that information. She did believe the low fetal fraction had something to do with my odd 36/100 but said the low fetal fraction was probably already factored into my risk assessment. Ultimately, she was not very helpful but I believe I was mostly looking for reassurance, which obviously no one can give me.
I read Katie Stoll’s articles as well. I am confused with other studies that report the extremely low false positive rates and that probably is due to my confusion in how these numbers are calculated. Sorry to be a dunce, but if PPV is true positives/overall reported positives… is the false positive rate =false positives/the entire number of people tested that had conclusive results?
So for an example, let’s say 5000 people test. 200 get positive results. 150 are true positives. 4798 are true negatives. 2 are false negatives.
Would PPV be 150/200=75% with a false positive rate 50/5000= of 1%? So each of those 200 positives really only have a 75% chance of the disease rather than a 99% chance? Or wait, is the false positive rate the false positives/population who tested who are truly negative for disease? 150/4798=3% Either way, “false positive rate” sure can be misleading, or maybe I’m just foolishly giving myself false hope.
Thank you for the information regarding the CVS vs. the amnio. I do think we would prefer an amnio to eliminate the possibility of the placental mosaicism. My impatience wants me to do the CVS immediately but the amnio sounds like the wiser, more trustworthy option.
I have had no live births. I did have a miscarriage in June. (fetus only developed until 4w5d) but of course it runs through my head that perhaps that baby’s DNA was somehow in my blood. (I know this was discussed in a few comments above.) i also hope we don’t have the rare condition that makes you repeatedly wind up with chromosomal abnormalities.
I wish I understood better what went into the NIPS calculations. We can’t ignore that there must have been concrete abnormalities in my blood/fetal DNA that point to Edwards Syndrome. I also wish I knew of more people that received the middle reports like we did, instead of .01 vs 99. I’m struggling to know how to apply other studies to our numbers. If we wind up negative, are we a “false positive”? or are we in a different category because we were assigned a 36% chance? And I wish I knew if I should take any reassurance in the lack of Edwards Syndrome markers in our 13w5d ultrasound yesterday. Where is that crystal ball when you need one?
Sorry for my long-windedness. Thank you for listening.
amazing service to people*
Laura–thank you for the kind compliments. I’m glad what is shared here was of some help. Certainly more than the circular finger-pointing you received from Panorama and your OB. I’m actually surprised by that. All of the labs, including Natera (maker of Panorama) tout that they have genetic counselors on staff–I know many of them and they are knowledgable professionals. Typically, they do not speak directly to patients, but they are there on staff to advise providers what test results mean. So, I would ask your OB to call Natera and talk to a genetic counselor about your results–if for no other reason than that is what both your OB should do and what Natera should provide.
Hopefully, my explanation of PPV and FPV can shed some light on this.
I’ve written about this at this post with links at the bottom to two other posts. So, please read those as well if what I write here doesn’t make sense.
As in those posts, I’ll use a 30-year old mom, simply because it’s easier working in round numbers. A 30-year old mom has about a 1-in-1,000 chance for having a baby with Down syndrome (I have to use Down syndrome because it’s the incidence rate I’m familiar with; the rate for Trisomy 18 is much lower, I believe 1-in-5,000 population-wide, which means likely even rare in a mom of your age, i.e. below 35).
Okay, so let’s take the 30 year old mom’s incidence rate and say there are 100,000 pregnant 30 year old women (as there are in any given year in America). Remember the incidence rate for Down syndrome is 1-in-1,000. So, out of those 100,000 moms, 100 of them are actually carrying a child with Down syndrome (100,000 X 1/1000 = 100). Therefore, 99,900 of those 30 year old moms are not carrying a child with Down syndrome (100,000 – the 100 carrying a child with DS = 99,900).
So here are our two populations: 100 30 year old moms actually carrying a child with Down syndrome and 99,900 not carrying a child with Down syndrome. Now, let’s test all of them with Panorama/verifi/MaterniT21/Harmony, you pick. In your case Panorama.
Those tests, NIPS tests, say they can detect a pregnancy carrying a child with Down syndrome with 99.5% accuracy. This is called the test’s “sensitivity.” This means that of those 100 moms actually carrying a child with Down syndrome, the Panorama test will correctly detect 99.5 of them. Let’s round up and just say Panorama would report a “positive” for every 30 year old mom actually carrying a child with DS.
That sounds very accurate. But, wait.
NIPS labs also say they can detect those pregnancies NOT carrying a child with 99.9% accuracy. That sounds almost near perfect. But, let’s see what happens when that percentage is applied to a big number like 99,900. Those are the 30 year old moms who are definitely not carrying a child with Down syndrome. Well, 99,800 will receive a screen negative result (99,900 X 99.9% = 99,800). But, that means 100 of those moms definitely not carrying a child with Down syndrome will be told their Panorama test is “positive.” Those are the “false positives.”
This is why when a NIPS test result is reported to a 30 year old woman, she could be in the 99% population, and be a true positive, but she could just as equally be in the 0.1% population who received a false positive. Hence, her positive predictive value is 50%, because she has an equal chance of her NIPS test being a true positive or a false positive.
As for false negatives, go back to the population of 100 30 year old moms actually carrying a child with Down syndrome. Instead of rounding that 99.5 up, round it down so that 1 of them received a “negative” from Panorama. That’s a false negative, since she is actually carrying a child with Down syndrome.
I would ask for clarification on whether the 36% Natera reported is your positive predictive value. If it is, then that means you have a 74% chance of a false-positive, i.e. a 74% chance that you’re not carrying a child with Trisomy 18.
Again, I hope this helps.
hi Mark,
just updating you. FISH results came back normal. Still anxious about a partial that will be revealed in the full results but already greatly relieved… you were such a comfort to talk to in this time.
Even though we received good results today, i’m still in this mode to be worried about something! i keep wondering if the results were wrong or if i misunderstood the Genetic Counselor (phone call broke up so she left me a voicemail saying “good news in FISH results”) but we didnt have a conversation.
We’ll see in the end but i think so far, we can sleep a little easier.
Laura–thank you for the update. Your persistent anxiety is one shared by many who go through prenatal testing. Knowing there are false positives means there can also be false negatives. But, it sounds like you’re getting the reassurance from the diagnostic tests that you likely sought with the screening tests. I hope you will enjoy your pregnancy!
hi Mark,
we received “normal” amnio results yesterday. (25 hours to get FISH results, 13 days to get full amnio results.) Obviously we are extremely happy and feeling more relaxed. Thank you so much for the information and communication during this time. We appreciated it SO much. I am still frustrated that no one was able to really explain to us what caused them to believe we were at high risk for Edwards or the PPV, but it’s over now. We are very fortunate that we lucked out here.
Thank you!
Laura
Laura–I’m glad you finally got some clear results. I wish you well with your pregnancy.
Dear Mark,
I have just received devastating harmony results which state that there is a 99 percent chance of my baby having Down syndrome. I am 38 years old and the scans all looked very promising. I am starting week 14. Please can you tell me what is the likelyhood of it being a false positive?
Thank you for your help as the waiting game is so difficult.
Lauren
Lauren–If you’ve read through the comments on this post, then you’ve already seen how there’s no such thing as a 99% chance from any of the tests like Harmony–you only get that level of certainty with an amniocentesis. Based on your age, and without knowing anything further (i.e. whether you had another screen result or a prior pregnancy positive for an aneuploidy), roughly you have a 1-in-5 chance that your test result is a false positive. Put another way, you have a 4-in-5 chance that your child has Down syndrome. But, I would encourage you to have your health care provider specifically ask Ariosa, the maker of Harmony, what your positive predictive value. Further, if it was your health care provider that told you had a 99% chance, then they should get the facts about non-invasive prenatal screening (NIPS), as provided by the statement at this link from the National Society of Genetic Counselors. Finally, Ariosa is one of two labs who have agreed to distribute the recommended resource about Down syndrome with a positive NIPS result to their provider network. If you were not provided a copy of the Lettercase booklet, Understanding a Down syndrome Diagnosis, you can access an on-line version at this link and ask your provider to order copies for his or her patients. I hope the information helps and frames the information provided by the Harmony test with the rest of the information about having a child with Down syndrome.
Thank you very much. The doctors in the hospital have confirmed to me today what you said. I now have to wait 10 days for amnio and results. Such a long time to have an answer.
Dear Mark, i did the amnio today and I was told that in 3 days they will tell me whether or not my baby has Down syndrome, then if it is negative for DS I will have to wait 2 more weeks to find out whether the child is healthy or if it is mosaicism. What are the odds then for these final results between healthy or mosaicism please?
Thank you again for your time
Lauren
Lauren–this question may exceed my ability to answer, so I would follow up with your genetic counselor or practitioner to ask your question. But, based on my previous response, you have about a 20% chance of a false positive Harmony result. I would think this applies for both typical Trisomy 21 and mosaicism, i.e. if your initial report is negative for Down syndrome, then you would have a 80% chance that what was tested was mosaic Down syndrome. However, the breakdown between whether that is mosaic with your child or from your placenta is something I haven’t seen broken down. I would encourage you to wait to get the full results in two weeks as those will be the more complete report. More waiting, more anxiety, I know. Such is this process.
If i understand correctly, partial trisomies/mosaicisms CAN be detected in the prelim FISH results if affected cells are present in the sample they spot check? With my amnio, the FISH looked at 50 cells. So there is still a chance of partial/mosaicism, but it could have been identified if any of the first 50 cells had the abnormality?
oh and i forgot something-i thought amnios eliminated the possibility of placental mosaicism? I thought this was one of the advantages over CVS? (sorry, nervously awaiting my own results so i’m also curious..)
Laura–you are correct with both comments: that FISH results can be mosaicism and an amnio avoids placental mosaicism since fetal cells are what are tested. So, a revision: if the FISH results are negative for Down syndrome, because FISH only looks at a certain number of cells, there remains a chance that the fetus could still have mosaic Down syndrome, but I would think that is exceedingly rare; if the FISH results are positive for Down syndrome, the chance remains it could be mosaic Down syndrome, confined to that section of cell lines tested by FISH. Hence why patients should wait for the full test results if possible.
Thank you so much for this article Mr Leach. I have received my “Harmony” results this week and it showed high risk for trisomy 13. When I asked Kaiser if I could redo the exam they said no. I don’t understand why. They’ve offered me a CVS, which I declined. I want to proceed with my 2nd trimester blood work and ultrasound before I decide on doing an invasive test, which in that case will be an amnio by week 18. This is making me very upset and I find they’re taking advantage of so many family’s fears. If I ever get pregnant again, I will decline this test.
Rosana—I’m glad to hear the information here was helpful to you. Redoing the test is typically only done if the first test provide a “no result.” Since you got a result, I expect that’s why they won’t redo it. That said, I would ask your provider to ask Ariosa, the maker of Harmony, what your positive predictive value is based on the Harmony result. Trisomy 13 is the rarest of the major trisomies. As a result, odds are you could have a false positive. Further, with Trisomy 13, often physical markers can be identified via ultrasound, so waiting for your 2nd trimester blood work and ultrasound should provide you more information before deciding on diagnostic testing. I hope you get the information and support you deserve.
Thank you so much for your response, Mr Leach. It means a lot to me and I am sure it’s being extremely helpful and comforting to many other families. I’ll keep you updated about the upcoming procedures.
Hi, again, Mr Leach,
I just got an email from Kaiser’s genetics department. This is what they say: “Unfortunately, Ariosa cannot report a positive predictive value for NIPT because the sample size for T13 cases is too small. We have been keeping track of cases at Kaiser (across California). We have seen 8 cases of +NIPT for trisomy 13, 4 of which were confirmed by diagnostic testing, and 4 that had normal chromosome pattern on diagnostic testing.”
At this point I don’t think I can trust them. No one ever mentioned a possibility of CPM and all they want to do is a cvs, which from what I hear can also be inaccurate. Their main point seems to be about whether or not I would keep my baby if I knew she had Trisomy 13. Thanks for bring a source of information for me and all the other families.
Rosana–Thank you for providing this update. Interesting to hear it reported that the sample size was so low, Ariosa can’t provide a PPV for Trisomy 13 and in Kaiser’s experience, PPV would be 50%, or, put another way, a 50% chance of a false positive. You care correct that a CVS can test the same cells that Harmony and other NIPS tests, which can have confined placental mosaicism of the trisomy. The National Society of Genetic Counselors make this point in its recent fact sheet (covered here at this link). I hope your medical team supports your decision to get more information.
Hi, Mr Leach,
I am here to report the results of my ultrasound and amnio performed on March 18th. Both are normal. Another unfortunate flaw of the NIPT test. My family is relieved and thankful that we found you and your research team at the University of Kentucky. You offered us a great deal of information and comfort. Thank you, thank you, thank you!!!
Rosana–glad to hear your family is relieved and that the information here helped in some way. I hope you enjoy your pregnancy and all goes well.
Hi Mark
Have you heard of the Harmony test getting gender wrong at all? My Harmony test results indicate that I am having a boy. As an older mother (40, 41 when when the baby is delivered) this is potentially my one and only chance to have a child and I was really hoping for a girl. I already have 2 stepsons.
I appreciate that ultimately gender doesn’t matter and I am lucky to be having a child at all
Thanks
Rose
Rose–I thought that NIPS tests like Harmony were diagnostic when it came to sex, particularly for detecting male (since how else does the mom have a Y-chromosome in her blood stream absent a rare genetic condition herself or a previous pregnancy with a male child). However, it was explained to me by a genetic counselor that NIPS tests, like Harmony, remain screening tests for sex, meaning there can be false positives and false negatives. Provided your child cooperates in the second trimester ultrasound, you should have visual evidence to suggest what sex is your child.
Hello,
I am now 20 weeks in my (2nd) pregnancy, and in January I had a NIPT test in Belgium were I live. The results of NIPT were positive, so no problems detected. Also, they said it would be a girl.
Today I have had a 20-week screening ultra-sound at the hospital, where they could clearly see that it will be a boy.
Because of the discrepancy between the NIPT and the ultra-sound, I have a new appointment at the hospital on Monday at the Genetics department to discuss what to do. Probably we may have to decide or decide against an amnio.
Since the NIPT test in Belgium is only done since a short while, do you know the percentage of accuracy of a NIPT test when it comes to gender/sex determination?
And are there numbers available on discrepancies between NIPT and amnio for gender determination?
What would be the general ‘medical advice’ a mother in the US would get in my situation? (I am a bit uncertain about the advice I will get on Monday, as I am the hospital’s first patient with these results…)
Of course we are hoping that the NIPT gave a wrong result about the gender, but when it turns out to be correct, than it is probably so that we will have a boy with female hormones (or how do you subscibe it, I don’t know yet… I don’t know much about these ‘cases’)
I would be grateful for any information you could give me on the subject.
Kind regards,
Ann
Ann–this is a bit out of my area of knowledge. However, in a sting operation some companies reported normal female results for a fetus from blood samples taken from non-pregnant women. Your results may be explained by a low fetal fraction issue or a sample mix-up, or some other unknown reason. I would not jump to the conclusion that the most likely explanation is that there is a hormone related concern in the baby. Gender prediction is not 100% with any NIPT.
Hi, went to the hospital today. We are doing a second nips to check with the first one.
Apparently, they aren’t thinking straight away to hormone related issues, as the anatomy scan clearly showed a healthy boy… They are clueless at the moment, but like in the story of joeysmam’s friend, they suggested it might be so that the Y chromosome was not detected for some reason…
Thx for your reaction on this subject!
Feel free to share what the second one reports, if you wish to. Definitely curious.
Hi- not sure if situation is the same, but my friend’s NIPS resulted in a female fetus. Upon anatomy scan, the fetus was male. In her sample, the Y chromosome was not detected, or noticed. Unrelated to hormone levels. Baby boy is healthy and thriving.
Hi Mark,
I had a 10 week Panorama, a repeat at 12 weeks and then a third one at 13 weeks because they ALL came back with inconclusive results – “low fetal fraction”. In fact, between weeks 12 and 13, the fetal fraction went down–it was 2.9% at 12 weeks and 2.1% at 13 weeks. Panorama genetic counselor’s advised me to not re-test and said that since I am not at all overweight (19 BMI), it is likely an abnormality.
I found this website that touches on mosaicism and low fetal fraction:
https://www.genomeweb.com/sequencing/importance-fetal-fraction-dna-noninvasive-prenatal-testing
Do you think the lab is implying I may have placental mosaicism or a fetal mosaic trisomy? The lab will only speak to my Dr so it’s hard to get a lot of questions answered. I am awaiting CVS results, but if I have some sort of mosaicism, wouldn’t that not be revealed by the CVS either?
Have you been able to find any links to abnormalities and low fetal fraction? I just find it so odd to get a 2.1% fetal DNA at 13 weeks gestation and can’t seem to find much help.
Thank you for any help!
Thank you for sharing your experience. From what I do understand, some genetic conditions can be seen with a low fetal fraction, but there isn’t a lot of data since many labs aren’t publishing fetal fraction/result studies. The low fetal fraction could be fetal indication or could be normal fetal level with an increase in maternal fraction that can show as low fetal fraction. A detailed level II ultrasound at 16-18 weeks should identify any major trisomy and periodic growth scans after that to monitor the child’s growth, but overall most people with fetal fractions lower than 3.5% have unaffected babies.
Hi Mark
I’m 19 weeks and just got the results of a Harmony test back. Everything was low risk apart from a result of a 51% chance the baby will have a XYY chromosome arrangement. Does this mean what it says? A half half risk of having XYY? Or does the fact a higher risk was detected at all mean that there must be something wrong and therefore it’s most likely it has it.
Kate–I have no clue what the “51%” means: does it mean that you have a 51% chance of having a child with XYY? Does it mean that Ariosa’s test detects 51% of all pregnancies carrying a child with XYY? I would have your OB ask Ariosa what the 51% means and then specifically ask for what your positive predictive value is for XYY based on your Harmony result. Scroll up and you’ll find other comments from moms who received false positives for sex chromosomal aneuploidies (SCA). Professional guidelines do not recognize NIPS tests like Harmony for detecting SCA’s because all published studies have been of such small sample sizes.
Thanks Mark. Great site.
Hi Mark,
I am 38 years old and currently 34 weeks along. I had a NIPT (Verinata) test done at 10 weeks with normal results. The test revealed baby to be a boy. My pregnancy has gone so smoothly. I had an ultrasound at 32 weeks and was contacted by an OB specialist to inform me that my son has “mild pyelectasis” (renal pelvic inflammation). The nurse mentioned this to be a “soft marker” for down syndrome but in the same sentence said the “good thing” was my NIPT test was normal. At this point I do not want to have an amnio because of the risk involved and regardless of the outcome our son will be loved and welcomed by our family. I’m very confused and want to be prepared. What are the chances of the NIPT test giving me a false negative? I can’t help but feel worried.
Thank you…
Andrea–using a rough estimate for your chance based on your age of 1-in-100 for having a child with Down syndrome, receiving a “normal” Verinata result would mean your chance for having a false negative is approximately 1-in-12,500, or a 0.008% chance. Put another way, you had a baseline chance of NOT having a child with Down syndrome of around 99.0%; with the Verinata result, your chances of NOT having a child with Down syndrome increased to 99.992%. This chance of NOT having a child with a condition is called the Negative Predictive Value (NPV). More can be read about that here. All this said, though, I’m a lawyer and we’re not known for our math skills. I would recommend you have your results interpreted by a genetic counselor or medical geneticist to confirm my calculations. I hope this is helpful and you get the reassurance you need to enjoy your pregnancy.
Thank you very much Mark. I will see the genetic specialist late this month. This helps me understand and feel much better.
Mark, I have been reading this feed and it has helped me understand so much. I wanted to say that you are a kind and compassionate man and it is reflected in your writing and has been much appreciated. Thank you for your time and responses. It has brought me a lot of comfort in this last week. I had my first daughter right after I turned 38. It was at a birthing center and she was completely healthy and beautiful. We declined all testing other than our ultrasounds. I turned 41 in January and we are expecting in July. At our 20 week ultrasound (To get clearance for our planned home water birth) the specialists said there was a problem with the heart. Only a person who has experienced this could understand the complete shock and devastation. Our original diagnosis was TOF and in the next several days we had read everything and were accepting the diagnosis. We had another appointment at Children’s Hospital with a cardiologist specialist where we were told the original diagnosis was incorrect. At that moment, I knew that a different heart diagnosis could mean DS. The specialists told us that with complete atrial ventricular canal defect she took one look at my age and said our baby would have T21. We left traumatized and after reading everything I could get my hands on I discovered that there was still a chance of no DS. I read many statistics regarding the heart defect = T21. It was mostly 1 in 3 will have DS but a few said 1 of 2. Still there was hope. Amnio is not an option because termination is not an option but then we were told that there was a 99.9% accurate test with a blood draw so I took the test so we could be certain and prepare. I thought this was a sure thing. When our doctor called she said she got the results and our girl would have T21. I went on message boards to find support and instead discovered how many moms were claiming they had false positives with the same test (Baby Center). While it was slightly hopeful to hear how wrong these tests can be, I am not convinced at all it would apply to our case with the heart defect. There were no other markers on the ultrasound so our hope is that we have only the heart surgery to focus on. I was hoping you could explain our results. It ready T21 Prior risk 2/100 Panorama risk score >99/100 Result High Risk Fetal Fraction: 15.8%. I am still unclear what fetal fraction is. Any thoughts? It is greatly appreciated and I also want to thank everyone for sharing their stories. We are hoping to get a new g. counselor as ours was extremely offensive. It has been a rough journey but we feel like we were chosen.
Autumn–thank you for sharing your experience, though I wish it were less of an emotional and stressful roller coaster for you and your pregnancy. Here’s how I would interpret the Natera Panorama test results: based on your age, you had a baseline chance of 2-in-100 of having a child with Down syndrome (1-in-50 or a 2% chance); the Panorama test results adjusted that chance to 99-in-100, or 99% chance that you would have a child with Down syndrome; the Fetal Fraction of 15.8% means the blood sample consisted of 15.8% cell free DNA from the pregnancy (versus the remainder being cell free DNA from you). However, this is my interpretation and I’m not a geneticist or genetic counselor. I would have your provider call Natera and ask them specifically what your test results mean. Because, even though you had a 2% baseline chance for having a child with Down syndrome, a “screen-positive” Panorama result, which is what you received, still means you would only have somewhere around a 95% chance of having a child with Down syndrome (more on that here). Put another way, you have a 5% chance of a false positive. That said, with the accompanying heart defect, I would say it is very likely your child has Down syndrome. Since you intend to continue your pregnancy, I hope you will find the resources at the prenatal resources tab helpful. I would direct you specifically to Diagnosis to Delivery, a free downloadable book written by moms for moms continuing a pregnancy and its companion booklet “Your Loved One is Having a Baby with Down syndrome.” The booklet is for your loved ones to help them know how to support you through your pregnancy and at birth. I hope you find these resources helpful.
Fast forward seven months after our 20 week ultrasound detected a heart defect followed by NIPT a few weeks later resulting in 99.9% risk for T21, we have a beautiful little girl with AVCD and T21. My pregnancy was horrible because I was so scared, sad, and uncertain of both. The heart defect was more definite but I was so uncertain of DS due to so many false positives but continued to prepare. I continued to find more false positives. I knew that the possibilities were slim with the NIPT, heart defect, and age 40 but I never gave up hoping. The minute she was born, I knew and I moved on to just loving her. She will have surgery in about two months and we are looking forward to alleviating that worry. I was banking on other parent’s experience that it will all be wonderful and they were right. I can’t express the love we have for our girl. She is magical. We spend our days adoring her, enjoying her progress and infectious smiles. I will be forever changed and continue to reach out to other parents to share information and experiences. American society has come so far but have a long way to go. I would not wish my prenatal experience on my worst enemy. I would wish that every parent could know the love and joy our babies with DS bring. I just wanted to share my results and experience.
Autumn–very thoughtful of you to come back and share your birth story. I, too, hope many expectant mothers appreciate the insights you gained from your experience. If you accessed the resources I previously shared, then this may be repetitive, but a new resource was published since you left your first comment. Available at this link is the new book, “Welcoming a Newborn with Down syndrome,” which focuses on the the very first weeks of having a newborn. I wanted to share it in case it may be of some help. Congratulations on the birth of your daughter and I hope her surgery goes well with a complete recovery.
Hi Mark,
I am constantly worry about false negatives.
I am 34 and will be 34 at the time of birth of my child. I am 18w5d. Tomorrow is my anatomy scan which has me anxious.
Pre-conception Counsyl genetic testing with my husband/father of child was negative. I tested positive for 2 genes, but he was negative for all 102 genes tested. Panorama at 10w3d = low risk. AFP screening (California), today doc’s office called and she said it was normal/negative.
Doc recommends amnio to everyone, regardless of age or history, I have declined so far.
What should I ask tomorrow at my anatomy scan? Call me paranoid, but I feel like my doctor may miss something and later blame it on the fact that i didn’t have an amnio, despite his recommendation. So I want to make sure I ask the right questions.
Thank you,
Ali
Ali–I would explain your concerns and ask that he look for any “soft markers” associated with a genetic condition. These can consist of clearer indications like a heart defect or issues with the GI tract, and then softer markers like short long bones, e.g. shorter than expected humerus or femur. There have been studies showing an association between the absence of a nasal bone and Down syndrome, and anecdotally doctors say they can tell from a shorter than proportionate pinky finger, but these are not definitive for any condition, hence why they are called “soft markers.” I would be prepared, though, that by asking for these reviews, your provider may practice defensively and suggest there are some when objectively he would not. Currently you have only received indications that you are not expecting a child affected by a genetic condition. Your provider is correct that the only way to rule out for certain any condition is through an amnio. I hope you get the reassurance you are seeking.
The information you provide about these screening tests has been very educational. I am 44 and pregnant for the first time. Received results from the Panorama test yesterday that shows high risk for Trisomy 18. My husband and I were very upset. I am scheduled for a level II ultrasound and an amnio next week. It seems due to the rarity of trisomy 18, it is possible that the screening test is a false positive. There seems to be a lot of data out there on Downs Syndrome and age in relation to these screening tests, but not much on trisomy 18.
You are correct that there is not as much research out there on Trisomy 18 as there is for Down syndrome. There are studies mentioned at the posts here and here which found that a screen-positive for Trisomy 18 meant the mother likely was not carrying a child with Trisomy 18. I hope your ultrasound and amnio go well.
I had the amnio done this last Tuesday (March 17th) evening. I elected to do the FISH test too but now I see this also uses cell free DNA. I expect the FISH results today. The doctor wasn’t able to see much on the ultrasound since I have a lot of extra “tissue” in the middle (did say the head measured normal). So he wants to try again in 4 weeks when I will be 22 wks along. My husband and I are on pins and needles to get the amnio results! It truly is agonizing not knowing.
It is cell free DNA, but from amniotic fluid, not blood. Well, I held out high hopes that my screening tests were false positives, but unfortunately they were not. I got a call from the genetic counselor this morning and she said the FISH test confirmed the trisomy 18. So now we are waiting for the full karyotype to see what we are dealing with.
Renee–I appreciate you sharing your experience, as painful as it is. Coincidentally, Wednesday, the day after your amnio, was Trisomy 18 Awareness Day, chosen for 3/18 representing the triplicate of the 18th chromosome. Here’s a post of mine which shares more information on Trisomy 18 and links to helpful resources. I hope you get the support and care you deserve.
If you have been helped by the information shared here or elsewhere on the blog, then in honor of World Down Syndrome Day (March 21), I hope you will support the National Center either through taking advantage of Lettercase’s sale or with a donation. More here at this post.
Hi! I am 35 (will be 36 at delivery). I am currently 14 weeks, 5 days into my 5th pregnancy (4 live births). I had the Harmony blood test drawn at 10 weeks, 4 days. While I have not seen the results with my own eyes, what my OB explained was this…
The lab was unable to separate maternal DNA and fetal (placental) DNA. There was “too much variance” and a second attempt would yield the same results. I asked for clarification, and it was explained that they just couldn’t separate the blood.
The OB did say that I was the first patient in their practice to have this happen and to the best of her understanding, it doesn’t indicate a health concern and could possibly mean that the baby’s DNA is nearly identical to mine. It does warrant a 16 week ultrasound (also had one at 10 weeks), so that is scheduled for April 9th.
Have you seen or heard of this type of result before?
Thank you for your time.
Jo–I have not. “Unable to separate maternal DNA and placental DNA” is something I have not seen reported or shared by anyone else here or elsewhere. There are some other on-line forums where other moms may have had this experience. babycenter.com has a Down syndrome board as well as a prenatal testing board which might be helpful. You may also consider asking your OB whether you can have a sample sent to one of the other labs that perform cfDNA/NIPS testing. I hope all goes well with your pregnancy.
Mark, I am 35 years old and had 2 miscarriages in the past 9 months. The first one was genetically tested by Natera and was a genetically normal boy. With the second I had Panorama done which came back positive for T13. Follow up with perinatologist a day after revealed fetal demise. After i passed the baby it was also genetically tested by Natera which confirmed the T13. I am still devastated from my losses but very much want to give my 2 year old son a sibling. I have been considering IVF with PGS (preimplantation genetic screening) so that I avoid this situation again. Can this test for more conditions than NIPS? Is there a certain company that you feel is superior at PGS? I understand that ultimately an amnio is the best however I feel I may end up going crazy because you have to wait so long to have that done.
Marsha–with pre-implantation genetic diagnosis (PGD), a cell from the embryo developed outside the womb is tested–conceivably, PGD can test for every genetic condition since it is testing the genetic make-up of the embryo. I do not know of a certain company that is better than any other for PGD.
Hi mark,
I have been avidly reading your blogs and comments over the last week as I sadly had a high risk result for T18 from a harmony test.
To add I am 41 and will be 41 at due date.
My journey started with my 1st NT scan. Baby wasn’t measuring the required length to do the test, but the sonographer mentioned she thought she saw a raIsed NT.
On this basis I decided to go and take the harmony. I was scanned on the day of the harmony test and a NT of 3.5 was recorded and entered on the paperwork to be sent to Ariosa.
I then went back to the hospital 4 days later for the repeat of my regular NT scan and the NT had gone down to 2.5mm and they were very happy it was a normal looking scan.
I got a call after 2.5 weeks to say my harmony results were inconclusive so I had to have a redraw and then waited a further week for the final result to come back.
Now, my questions are this?
Will my NT of 3.5mm have adversely affected my harmony result? Due to the fact that it had decreased a fair bit?
And can lower fetal fractions contribute to false positives?
Thank you in advance.
Claire–I hope what you’ve found here has been helpful. I am not aware of how the thinning of the NT could effect the NIPS results. I am aware that when there are low fetal fractions they often result in inconclusive results or “no calls.” I am not aware of low fetal fractions being associated with false positives. Given you have done online research, I expect you have found the Trisomy 18 Foundation, but I link to it in this post which discussed Trisomy 18 further. Trisomy 18 often has markers that appear at a second trimester ultrasound. I hope your team is supporting you and getting you the information you are seeking.
Hello Mark, first I found your article VERY helpful in realizing the Fetal DNA test I had is actually a placental DNA test! It is a much more informative article on this topic than others I have read. I am 36 and pregnant with my second set of twins. The test for Trisomy 21 came back positive-high risk. But it could not indicate with fetus. I am wondering how accurate this test result is in the case of twins ( they are fraternal twins ).
Thank you.
Oh, I took the test at 20 weeks, and decided against the amnio. I am now 25 weeks.
Due to the relative rarity of twins, and even greater rarity of twins with one having Down syndrome, I am not familiar with a study of a sufficient size to provide reliable data on how accurate the detection rates are. That said, as shown in the graph at this post, if it were a singleton pregnancy, a screen-positive NIPS at 36 means you have about a 75% chance that the test is a true positive and a 25% chance that it is a false positive. Diagnosis to Delivery is a resource written by moms for moms who have decided to continue a pregnancy with the expectation that their child has Down syndrome. A companion book, is also available for loved ones so they can know how to support the mom. Both resources are available at this link. I hope this is helpful and being a fraternal twin myself, I will say I enjoyed always having a playmate in my brother (and continue to do so into adulthood).
Thank you Mark, your articles are great! I understand the age factor %, but it almost sounds as if the test will always show some kind of “false positive” result no matter what age? So what does that mean is going on with the cell development and if the child doesn’t have DS, why does the test even give an indication of a false positive- whether .05% or 99.5%?
Anyway, it sounds like with twins in utero- the NIPS test may be less accurate, even at my age of 36? ( at least that’s what I understood you to say). The ultrasound came back fine with both babies growing at a normal rate and no signs of DS. Just the “positive” from the fetal DNA test.
Also, is DS hertitary?
1. Regarding why there are false positives: because what is being tested is not fetal DNA, but placental DNA and the placenta is a unique organ, having sometimes confined placental mosaicism with cells having a trisomy while both the mom and baby do not. Yes, there is always the chance of false positives no matter the age of the mom.
2. Yes, having twins means the quoted accuracy rate of NIPS tests do not apply, because those rates are based on singleton pregnancies.
3. The only heritable form of Down syndrome is called translocation, where one of the parents’ actually only has 45 chromosomes because one of his or her 21st chromosomes instead migrated and attached itself to another chromosome. Therefore, when the child is conceived, the child can receive that extra 21st Chromosomes. This form of Down syndrome, however, is very rare, I believe it accounts for something like 2-3% of all cases of Down syndrome.
Inam thankful to find this post. I read through all the comments but only saw one that is similar to mine. I took the Panorama test at 10 weeks. The test came back low risk for all tests except there was “no result” for the gender and monosomy x. They said they could not tell the maternal Dan from the baby or Turner syndrome. I am confused as to why the other tests had results but not gender and monosomy x. I am also not sure if this is something to worry about or not. The 15 week US was normal and the doctor is not concerned, but I still continue to find examples online of others that have experienced a similar result (there are none). Mark do you have any insight at all? I appreciate you open answers!
Thanks
Stefa
Stefa–I can’t provide any definitive answer. I will say that the latest guidelines have emphasized how these new tests are not valid for identifying sex-based conditions and other research has shown that a “screen-positive” result for a sex-based condition means, more often than not, that it is a false positive. You don’t even have a “screen-positive” but rather a “no result” meaning your chances are even less likely for a sex-based condition. That said, I would have your provider ask Panorama’s laboratory Natera specifically about your test results and see what Natera’s explanation is.
Thanks Mark for your answer, much appreciated!
Mark, one question, do you have that research link you mentioned?
Stefa: I believe there are other studies, but this was the one I saw most recently at the 2015 ACMG conference finding that a “screen-positive” result for a sex chromosome condition turned out to be a false positive 60+% of the time.
Great – thanks very much!
Hello Mark, hello Stefa,
Great thanks Mark for such a good post, very glad to find it.
This morning I have received the results from Harmony tests. The same as Stefa’s results: it came back with low risk result except “no result’ for Gender and all X, Y analysis.
The comments received from Harmony are the following: In less than 0.5% of cases, Harmony test is not able to report a result for Y or X,Y analysis. There are many possible reasons for this. Technical reasons include variance in the assay data. Biological reasons may include a maternal chromosome condition (such as mosaic monosomy X or XXX), mosaicism (maternal, fetal, or placental), demised co-twin, or copy number variant. In the case of a biological cause, repeat analysis would not be expected to yield a result.
No Result for X,Y analysis does not necessarily indicate an increased risk for X or Y aneuploidy in the fetus. It means that we were not able to provide a risk assessment.”
It is also clear that Harmony test would not go for re-testing, which is quite disspointing, as this option should have been included in case of such result.
Would appreciate lots if you could keep posted in case something new found on this subject.
Many thanks
Will do, Olga, and thank you for sharing your experience. You likely have already done so, but rather than assume they wouldn’t do a retest, you could ask your provider to request a re-test (or ask for discount or full refund of any cost for the original test, since you did not get what you paid for).
Hello Mark,
Many thanks for your reply.
Unfortunately my provider (who had been very supportive and helpful) would not able to retest or refund any money. Just because based Ariosa Lab declined the retest even after several discussions, they can not do anything and to take my case any further. My provider refered me to other center, who have had such experience. After several discussions yes that is correct, there will be 50% of chance to get the results on the tests, however this a different Center provider and this means that I have to pay additional 500 Pounds to carry on testing. Sounds very discriminating from the side of Harmony Test Ariosa Lab ,as for example in the second Center, where I had been referred to, the second chance for retesting is given free of charge and all depends on patient’s choice to do it or not, so might be a reason that this Center provider has a slightly different contract agreement with Ariosa Lab, to conduct ‘No Result’ tests in any case.
Thank you,
Kindest regards,
Olga
You may want to contact Ariosa directly to ask them. Some have been successful in at least challenging having to pay for a test.
Thank you lots Mark,
I have contacted fetal foundation and had been advised that X,Y analysis are not repeatable in any cases, only 3 main tests of Harmony one are repeatable.
Thank you for your support,
Kind regards,
Olga
Hello Olga – I have no new information to share. Other than to say I am now at 26 weeks and still no issues seen on the Ultra sounds. The doctor is of course checking for any markers, but the baby is developing on schedule and is showing no ultra sound signs of any problems so far. It is a girl which we now know from the ultrasounds.
I had the Panorama test and not the Harmony, and I am happy to see you received a bit more feedback on what the potential causes could be. I didn’t get much except to say they couldn’t separate my DNA from the baby’s, they were too similar, or it could be Turner’s, or other “unknown” reasons.
I will share any updates as time goes on.
Thanks for sharing your experience, it is good to know there are others “out there” 🙂
Stefa
Hello Stefa,
Thank you so much for your reply. I am very happy that your baby is developing well. As I have just stepped in to the second trimester,I still have to wait for a while for the main scans that are starting normally from 20th week of pregnancy.
I have also talked to NHS and they have offered a Quadraple test for me, well as I have already some results from Harmony one, they would not go for it, but Harmony or Panorama ones do not include AFP test, therefore NHS decided to carry a Quadraple test in this case.
Will be glad to hear your news and how all goes!
All the best and take care,
Olga
Hi I am 34 years old, from Germany and 16 weeks pregnant. The Harmony Test result shows that T13,18,21 is good with the negative result that there is a 1% chance the baby got xxy.
The combination of nuchal translucency and the results of serum screening and the maternal age, which I did some weeks before the Harmony Test, did show a very high risk for all trisomies (1:8, 1:10, 1:12), which, according to my doctor in Germany was most probably a false positive test result.
After having a lot of confusion the last weeks, I am now thinking about doing an amniocentesis to get more clarity on these results (as Harmony Test does not to be super safe for T 13/18 and even less reliable for xy anomalies).
I know that an amniocentesis also represents a risk, but if you start reading, also about Klineflelte, you get unsecure. Is there anyone, who got a similar result? Bests from Frankfurt
Angela–not the same exact situation, but scroll up to see Tasha’s comments and my replies. I hope that helps.
Hi Mark, thanks for your quick response. I read Tasha’s and your comments. Will most probably do the amniocentesis to crosscheck. Would be interesting, how high the detective range is for xy anomalies (Harmony Test)? Any idea? I was just wondering how they can evaluate the probability of 1 percent for xxy? Bests, Angela
Angela–scroll up to my response to Stefa, which links to a study presented at the recent ACMG conference finding in that health system’s experience that a “screen-positive” for sex chromosome aneuploidy actually had a 60+% chance of being a false positive.
Angela–coincidentally, this same day a relevant comment to your situation was shared at this post of mine. Scroll to the end for Catherine’s comment.
Hi Mark, thanks a for letting me know-just read her comment. This is so encouraging! I will most probably do the amniocentesis, too. Hopefully, with a similar good result! Keep you posted… Thanks and best regards, Angela
Hi Mark
I came across this website in a Google search and very relieved I did. There is so much confusing information out there. I have read some similar stories to mine but hoping for some clarity.
I’m 35 years old. I had the harmony at 10 w 4 d and tested positive for trisomy 13. I had a full scan at 12w 3d and there were no markers. Scan was completely normal and I was advised that if I had just had a scan and no harmony test I would be in the low risk category. However, given abnormal harmony we opted for a CVS. The initial test (3 days later) tested negative for trisomy 13 with absolutely no signs. However, 10 days later, they have now fully tested and I received a call that a small number of cells have tested postive for trisomy 13. Ie mosaicism. I now have to wait to 15 weeks for an amnio. The specialist is optimistic that is it likely confined to the placenta. But also advises that mosaicism can be hard to see in scan as physical signs not obvious. My question is. How likely is this to be confined to placenta and not the baby. I’m incredibly anxious now at almost 14 weeks I have to wait for the amnio results.
Tali–thank you for sharing your experience, though I’m sorry to hear it–two diagnostic tests is one too many. If you scroll up and see my reply to Linda, there’s a link to a fact sheet from the NSGC which explains how a CVS has limited diagnostic capability since it tests the same DNA materials as tests like Harmony. From just an online search, I found this website which summarizes studies of prenatal results for mosaic Trisomy 13 with links to the actual articles. An article from two years ago appeared in Genetics in Medicine describing a case of confined placental mosaicism for Trisomy 13 which had caused a test like Harmony to report “positive” for Trisomy 13. I don’t know if there is any definitive statement on the odds of confined placental mosaicism versus fetal mosaicism for Trisomy 13. That said, Trisomy 13 is a rare condition, around 1-in-10,000 babies born will have it. Mosaicism is even rarer. And confined placental mosaicism is a known phenomena. The amnio should provide the certainty you are looking for and I hope that procedure goes well. If you were not referred to a genetic counselor or medical geneticist to discuss your particular case, I would consider asking for that referral to see what they can tell you.
Thank you so much for your quick and detailed reply. Knowing how rare it is helps put the odds in my favour and allows me to cope better until I have the amnio and get the results.
I was wondering though. My initial FISH came up completely clear on the CVS and only picked up once detailed test run 7 days later. Does this mean anything?
Also- I was advised that the second harmony test they ran came in just below the high risk line (the first was just below). This means, I would have got a negative on the second test. Assume this indicates that there are low levels of mosaic trismony 13.
It’s a bit of a guessing game as to whether it is confined or not to the placenta. Hoping the odds remain in my favour given the low levels found?
Tali–all of that suggests that whatever the amount of mosaicism, it is low and based on my previous response, more likely confined to the placenta. But, again, I would discuss this with your medical team and be interested in hearing what they say. I’m glad this site has been of some help to you.
Hi Mark
I got final test results from my amnio today. Although it’s been a very anxious few weeks, the results have come back clear and we are thrilled and relieved. The mosaicism is confined to the placenta. I had a low level mosaic below 15 percent in the placenta so unlikely to cause issues for the pregnancy.
I wanted to share my story and happy ending for others who may be going through the same thing. I also wanted to thank you for your website and providing some comfort while I was looking for information.
Tali–thank you for sharing your final results. You are not the only one receiving these conflicting results and having an example of how it worked out in your case will be helpful for others. I hope you enjoy your pregnancy.
I took the test at 11 or 12 weeks they called me today and said I will have to re take my blood something ab to much maternal dna? ?? What do that mean!!?
Denisha–I would suggest you have your provider ask that very question. I can only infer that the sample provided did not have a high enough percentage of cell free DNA to be tested.
I tested 99.9 for T21 Risk with Panorama and just ran across this article: http://www.seattletimes.com/seattle-news/health/uw-experts-shed-light-on-false-positives-in-prenatal-tests/ Could you explain? *Representatives for Natera, which makes the Panorama NIPT, said their screen doesn’t count chromosomes at all, but instead uses single-nucleotide polymorphisms, or SNPs, to analyze the ratio of fetal to maternal DNA in the blood. It effectively accounts for the extra copies, said Dr. Susan Gross, Natera’s chief medical officer.*
Thanks for sharing the article. As it reports, extra DNA on a mother’s chromosomes is just one of the reasons for a false positive. As this post (and others on this site) detail, false positives can also occur due to the material being tested not necessarily being from the fetus but instead the placenta. Also, if you were told you had a 99.9% risk for T21, then you were given bad advice. Scroll up and you’ll find links to other articles discussing positive predictive value and negative predictive value. Regardless of what your readjusted chances are for having a child with Down syndrome, Panorama and tests like it remain “screening” tests–meaning they have false positives and false negatives. To know for sure, you will need to have diagnostic testing and an amnio is the test with the greatest accuracy since a CVS can test the same placental DNA as a test like Panorama can. I hope you get more accurate information and support going forward.
Thought I’d give my experience with harmony testing .. had bloods taken at 11weeks3 days ..results were low risk and greater than 99 /100 female fetus ..couple of weeks later we announced gender. Well at ob appointment at 16 weeks ..my obstetrician thought boy ..said to wait till 19 week scan ..it’s most likely correct . Well 19 week scan said boy. We did the harmony bloods again ..nearly 20 weeks now . Same result ..so I was told most likely girl with cah diagnosis. Many appointments later and stress .. we planned for a daughter .. fast forward to a scan at 29 weeks .. 100% boy by another experienced sonographer . So now we have to start again ..plan for boy and pray all is ok with this baby. Fetal DNA was nearly 8% and nearly 12% respectively. I feel like a fool trusting these tests and results on gender.. it’s caused so much anxiety and stress not to mention money and time too 🙁
Thank you for sharing your experience. I hope all goes well with your pregnancy and whether there is a condition or not, you receive the support and care for yourself and your child.
Hi, at 12+2, the NC measure was 2.5mm, and combined with blood work, I was told there was a 1/230 chance of chromosomal abnormality. I had a version of the Panorama test (from France, and found out after the fact that it was abbreviated, only T13,18 and 21), came back low risk for all three, which felt very reassuring. However some soft markers, eg short femur bone, have shown up on u/s since, and the experience of the above posters with NIPT errors has me worried again. My doctor has refused to discuss; can you give me your thoughts, please?
False negatives are very rare with NIPT, but, as you note, NIPT only screens for a finite set of conditions (covered in these posts here and here). Perhaps your provider is under the misunderstanding that screen negative NIPT is either a true negative (which it never is) or negative for more conditions than just the major aneuploidies. I’m a bit surprised that your doctor has refused to discuss this with you–that seems to risk a medical malpractice claim should there be a complication with your pregnancy. If he or she won’t speak with you, I would ask to consult with a different provider.
Thank you so much for your reply, it’s very helpful. The doctor’s attitude has basically been ‘either get an amnio or stop worrying’. For many reasons, I have since changed doctors -and countries, now in the UK. The latter told me that as long as the femur is within the normal range, I shouldn’t worry, but I did since read somewhere that a measure in the smaller 5 percent is a strong marker for DS… All very confusing!
My understanding is that the placenta can show chromosomal irregularities but the foetus still be healthy. Is the reverse also possible?
Thanks again, all the best!
Vanessa–any ultrasound finding is considered a “soft marker” since it is not close to diagnostic or reliable on its own as a screening test. I share that in the hopes of putting an UT reading in perspective. You are correct that the placenta DNA tested may not have aneuploidy but the fetus may have aneuploidy.
Thanks again for taking the time to answer me, really very much appreciated. All the best, Vanessa
Hi Mark. I have read through most of the posts on tis thread. I see this new cell free dna testing is definitely not an exact science, but very helpful and useful in most cases. My particular situation is as follows….I had my 1st ultrasound at 8 weeks, there were twins, but only one fetus had a heartbeat. I went back for my 12 week ultrasound and everything looked great, the living baby was moving and healthy with a great heartrate. The demised baby was still there in the other sac, just much smaller. I was highly recommended to do the genetic blood draw for chromosonal disorders because I am 35, and had heart issues as a baby. I took the dr’s advice. The reults came back positive for trisomy 21. A lab company called counsyl did my screen. They gave me 66.6% chance for DS. I started researching this looking for any reasons for false negatives and found very few articles related to the subject. The ones I did though were very scholarly and indicated that a vanishing twin has a definite affect on the results because it is reading both babies cells/dna. The main reasonn you lose a twin is for chromosomal disorders, so I couldn’t help but think these results were skewed and maybe it was getting cells from the demised twin? I did go on to have a level 2 ultrasound followed by an amnio. I should get my FISH results tomorrow, but I am praying and hoping my baby boy is OK. The ultrasound shows NO indicators, so that made me feel better but the only definitive thing is the amnio as we all know. I have since found out…getting the positive trisomy 21 results, I shouldn’t have taken the bloodraw, because the results are NOT accurate and I was irritated that my dr didn’t know or mention this. What if I would have gone and aborted based on the screening results and my baby was fine? I wanted to post in this discussion thread because I hope for any peopl in my same boat or similiar will understand that a “vanishing twin” can have a result on your blood results. I don’t know until tomorrow if this was the case for me, but I sure wish it would have been explained better. I wish I found more people to talk to about my situation and wish there was more research done! All we have is hope and the info our dr gives us. I will post my results of the amnio once I receive them.
Heidi–thank you for sharing your experience. I have a fraternal twin brother so I’m interested in twins as well. You are correct that under previous guidelines, cell-free DNA was not recognized for twins or multiple gestations. And you are correct that the demised twin could be the source of the cell free DNA (or any prior pregnancy you may have had, actually). All that said, there remains very little on what the accuracy is with twin pregnancies. If you search the site, you will find the recommendations for the ISPD, which I believe address twins, and if not ISPD, then ACOG’s new guidelines may (which can be found at prenatalinformation.org, where I blogged about those guidelines). I am interested in your amnio results and hope you will share those.
Hi Mark. Thanks for your response. I received my FISH test results from the amnio back Friday afternoon….Negative for Trisomy 21!! I understand that I still need to wait for the full lab results to come in in 10 days or so while they do the full karotyping. I believe the fish results are almost a guarantee though from what I’ve read. From what the perinatal dr who did the amnio told me, this means that the demised twin definitely had trisomoy 21. I really wish that my other OB dr. would have educated me on the possibility of this happening and the definite chance of the demised or vanishing twin causing a false positive on the cell free dna genetic screening. I had to go out and do research and call the genetic counselor from Counsyl labs to find out all of this on my own and I’m thankful I did……. I wasn’t told by my dr any of it. I didn’t even know what a “vanishing twin” was?! There needs to be MUCH MORE research on this gray area. Lots of worrying and scare the last couple weeks. I am so thankful and relieved to find out that the twin baby that made it is healthy with no chromosomal disorders and after all of this research I’ve done- I have so much empathy and compassion for the moms out there that are going through the same thing.
Heidi–medical practice will improve if their errors are pointed out. I would consider sending a note to your OBs office sharing how you wish they had provided you more information and the emotional turmoil you endured for having to find out on your own. I’d write it in the vein of a patient sharing their story, rather than a complaint and pointing blame. Or, feel free to simply email a link to this blog post and ask that they read your comments and consider it the next time they counsel an expectant parent. Thank you for sharing your experience.
Heidi, i am so happy for you! i thought of you all night long after i read your post to Mark yesterday–anxious for your results.
I was told our baby was positive for Edwards syndrome in February. He is currently staring up at me from his bouncer –12 days old with completely normal chromosomes. I also was extremely disappointed with the lack of knowledge from my OB, the testing company (Panorma) and even the genetic counselor we met with who advised us to go ahead and set up a termination. The GC did suggest waiting for the results before going through with the termination but said our amnio would most likely come back positive as the Panorma test was rarely wrong..No one seemed to know anything about positive predictive value or any other factors. No one had understanding of a positive result that wasnt ‘99.9%’ or what would cause a false positive.. ugh, terrible memories! I brought this up to everyone throughout my pregnancy–doctors, nurses, other pregnant girls, etc in an attempt to spread the word that the test is somewhat flawed and poorly understood. I found more information and comfort from Mark than anyone else.
The silver lining is that for the rest of the pregnancy, we had our negative amnio results to reassure us that our baby was most likely healthy.
I hope you are able to enjoy your pregnancy now! let us know how the full amnio results turn out!
Hi Laura,
Thank you for thinking of me! I am so happy for you as well! This new genetic testing is scary!!! You are left feeling that all of your hopes are left up to faith, prayers and science that is not clearly understood by even your dr? It is definitely frustrating that we are not given more information or hope for that matter. Once I insisted on getting a copy of my lab results and requested a call from the GC, was the 1st time I was given the actual 66% value for my test- which wasn’t accurate anyhow. The GC made me feel much better than the dr and obviously knew more about the test. Did you ever find out what caused your false positive? In my case, it was definitely the demised twin carrying the extra chromosome. I want to find the correct boards to post/blog on this topic so I can share this with moms that are in the same similar situations as well. So much of the research I found was old and I couldn’t rely on the validity of it for that reason. I will definitely post the full results when I get them! I’m happy I can enjoy my pregnancy now and will likely be switching dr’s to a specialty, high risk office. Let me know if you have any websites you found to share your results on too if you don’t mind.
I’m 39 14 weeks pregnant. Panorama came back showing 99%risk for T21 Down Syndrome from a fetal fraction of 18%.
can this be false positive? Doing amnio in 7 days, very nervous?
I also had NT scan last week, but because of my uterus they could take exact measurments. However, The technician said that the nasal bone was present and the amount of fluid didn’t look abnormal.
please advise if you had such high risk factors and amnio came back clear.
A review of the comments on several of the posts on this blog are from moms who received false positives, but the majority are those concern the sex chromosomes. That said, as discussed further here, that quoted “99% risk” is their sensitivity rate, not your actual chances for having a child with Down syndrome–given your age, your chances with a screen-positive Panorama result is actually around 90%, not 99%, or, i.e. a 10% chance of it being false positive.
thank u for your comment!!! but I was told the “over 99%” is the percentage of my risk of having a child with DS not the sensitivity rate and is very high since people could have 20, 50, 60%, etc. risk factor. I know that Natera claims that their tests are 99% accurate but I didn’t think that the doc meant that.
I now that at my age I have 1 in 100 chance of having a child with DS.
whst’s the likelyhood of amnio being clear?
our genetic counselor didn’t give us much hope, especially that my fetal fraction was 18%
Unless you had a screening test prior to your Panorama that reported an increased chance, then your baseline chance at the time of taking the Panorama test was the 1-in-100 based on your age. Therefore, with Panorama claiming 99+% sensitivity and specificity, even at those percentages, you would still have a 10% chance of a false positive, and that’s your chance of the amnio being clear, 10%. Your genetic counselor is correct that the higher the fetal fraction the more accurate the screening results.
Mark, we want to try to get pregnant again.
would you recommend doing an IVF with frozen cycle and PGS/PGD or other testing to lower the chance for another DS pregnancy.
what are the other options that we have?
It would be very hard to go through another termination at week 16.
Best,
justyna
Unfortunately, ART (assisted reproductive technology) is a field I have little experience with. For what it’s worth, an ACOG opinion, reaffirmed in 2014, does not recognize preimplantation genetic screening (PGS) for screening for Down syndrome outside of research studies. In the end, ART is expensive (at least it is here in the USA) and your odds of having another pregnancy with Down syndrome, while elevated for having had a pregnancy with Down syndrome, still remain relatively low. I would discuss this with your genetic counselor or MFM and I hope they can provide fuller advice.
Unfortunately the hopes for false positive Panorama results didn’t come true. Amnio at week 15 confirmed Complete T21. I terminated T weekend 16:(((((
Based on the NSGC guidelines (see Table 1 here) and your chance based on your age (see Chart in middle of this post), I calculate your chance of having a child with Down syndrome in a subsequent pregnancy as 2% or 2-in-100 or 1-in-50. This is based on your age based chance being 1:85 multiplied by 1.7 per the NSGC guidelines.
Hi Mark, I’m not sure if I’m commenting in the right place! We are 13.5 weeks gone, I am 32 and have had the Harmony results stating 99/100 high risk for T21 (in the results table on lab document not the accuracy percentage). The table says 1/10000 for T18 & T13. We are hoping to wait for an Amnio to confirm at 15 weeks though still waiting to speak with consultant. Anyway I notice the Fetal (or placental) cfDNA was 20% – this seems very high? I am guessing the higher the percentage of cfDNA in the sample then the more accurate? We also had a very early natural miscarriage (4-5 weeks) approx 2-3 months before falling pregnant with this pregnancy – could DNA from this baby be interfering with these results? (We also have a healthy 2.5 year old girl)
Many thanks
I would ask whether your Harmony result is the “positive predictive value” or simply Harmony’s claimed sensitivity rate. Absent any other recalculation prior to taking Harmony, based on your age the PPV would be closer to around 60% not 99%, meaning a 40% chance of a false positive. Your fetal fraction is high, but cfDNA from all pregnancies remain in your bloodstream.
Hi Mark, thanks for your reply. I have read the results document and it states ‘ The probability result reported is not equivalent to the PPV’. The probability result they gave us is 99/100. I have emailed them for a more detailed breakdown of my results as there is limited information on the results document – it is more like a summary document to be honest.
If it’s not the PPV, then what does the “probability” stand for? I’ll be interested in what they tell you.
We have had a confirmed Down Syndrome result from the Amnio test we had performed last week. Thanks ever so much for your information you have shared though, it has really helped us learn a lot more about the blood test. xx
Thank you for sharing your results and I’m glad some of what I’ve written here was helpful. Per the professional guidelines, I hope you were provided educational materials with your amnio result, but if not, please consult those at the Prenatal Resources tab. I hope those are equally helpful.
I have spoken to the consultant and booked an Amnio for 2 weeks time. He agrees about my concerns regarding these results and says we need an Amnio for certain. Will report back afterwards whether good or bad news!
Mark, if cfDNA remains in our bloodstream how accurate would a NIPT test be after giving birth to a beautiful T21 baby? We would like to have another baby and want to be prepared in case we are blessed again with Down Syndrome. We are also meeting with a genetic counselor as well. To be honest my main concern is avoiding a hospital birth. After having experienced a birthing center birth and a hospital birth I don’t know if I can go through another hospital birth experience. Thank you.
One of the early criteria for cfDNA screening’s accuracy was being considered “high risk,” which included having already had a pregnancy with a child with Down syndrome. That said, the cfDNA from the prior pregnancy would remain in your bloodstream and could be the basis for a false positive for a subsequent, unaffected, pregnancy. However, if your true concern is avoiding a hospital birth, a study out of the Netherlands or Denmark found nor significant impact between home births and hospital births for babies with Down syndrome. Moreover, any physical conditions that would suggest the need for higher-level care would not be reported by cfDNA but instead picked up by a higher level ultrasound, which you should already have since you’re already considered “high risk.”
I’m 39 and was 14 weeks pregnant when Panorama came back showing 99%risk for T21 Down Syndrome from a fetal fraction of 18%. We did Amnio at week 15 and it confirmed that it was Down Syndrome. We terminated at week 16. This is very heartbreaking as it was my first pregnancy. My doctor said we need to wait at least 3 months to try again. My biggest fear is to have that happened again. I know that my risk is still my age risk 1 in 100, but I wonder what’s the propability of having 2 T21 pregnancies in a row…
would you recomend to do PGS and IVF with frozen cycle to minimize the chances of having another T21 pregnancy? what do u think about PGS?
ACOG does not recognize PGS as being effective for screening for aneuploidy, however I would defer to a medical expert on ART for discussions regarding IVF as my experience is limited in that area.
Mark, you said “cfDNA from the prior pregnancy would remain in your bloodstream and could be the basis for a false positive for a subsequent, unaffected, pregnancy”
Could that mean that after terminating the first pregnancy due to T21, getting pregnant again within a couple of months, and doing Panorama Test on week 11-12 could possibly give us incorrect results?
For how long does the cfDNA from the prior pregnancy could be present in the bloodstream and could be the basis for a false positive for a subsequent, unaffected, pregnancy?
My understanding is that cfDNA from all previous pregnancies remain to a certain amount in the mother’s bloodstream. For how long and how much, that is unknown. My understanding is that while the amount of cfDNA from prior pregnancies will diminish with time, there remains the chance that the cfDNA tested could be from a previous pregnancy and not the current one. But you are testing for reassurance that your next pregnancy will not have a child with Down syndrome. cfDNA screening’s ability to identify pregnancies NOT carrying a child with Down syndrome is more accurate than its ability to identify pregnancies carrying a child with Down syndrome. Therefore, if you were to get pregnant and under cfDNA screening and the result came back “screen-negative,” then odds are both [1] that the test tested the cfDNA from your current pregnancy and [2] very likely that you are not carrying a child with Down syndrome.
Mark, thank u so much for answering all my questions. Very much appreciated!
I am also waiting for my amnio results. I have learned a lot from this whole process and would like to share my experience. Hope this helps.
Our pregnancy was progressing well- our NT test and first ultrasound all were normal, but our first screen came back with a 1:57 chance of Downs (trisomy 21). We were quite surprised with this news, since my husband and I are both 31 and have no relative risk factors for downs. We immediately took a Panorama NIPT test, hoping that the odds were in our favor. The test, however, came back inconclusive and had a note stating “do not retest with this NIPT test”. Apparently, the Panorama test was not able to separate the baby’s blood from momma’s blood and overall has a higher inconclusive rate than the other NIPT tests.
We then met with a genetic counselor and after much discussion, decided to take the Maternity21 NIPT test (which has a less chance of inconclusives) and also had a level 2 ultrasound at 15 weeks. The ultrasound came back completely normal with no soft markers, but the MFM doctor told us that 50% of babies with downs do not exhibit soft markers when examined with ultrasound technology.
1 week ago, we received devastating call stating that our materniT21 test results showed that we had a 80-95% chance of having a child with Downs. We were heartbroken, to say the least. That same day, we rushed into our MFM dr’s office and had our amniocentesis. We needed to know our results for sure, even though we were highly certain our child had downs, especially with the MaterniT21 NIPT accuracy of 99%.
My husband and I received a call from our genetic counselor 24 hours later stating that our FISH tests came back negative! We were….confused, relieved certainly, but mostly confused. So, we have an abnormal first screen, inconclusive panorama, highly abnormal maternity 21 test, and ….a normal FISH? Something just didn’t add up. How could an NIPT test that is touted to be so highly accurate give a completely different result than the FISH test? That is when I came across this post.
Our genetic counselor did a little digging for us. She called Sequenom/MaterniT21 lab, which told her that out of the 16% fetal fraction (which is supposedly good), only 4% came back showing trisomy 21. According to our genetic counselor, there may be a chance that I have trisomy 21 mosacism confined to the placenta, therefore causing a false positive on the NIPT, but normal FISH results. Since the only way to differentiate whether the trisomy 21 is in the placenta vs baby is with an amniocentesis, we will have to wait and see. So, here we are, 5 days out from our amnio, with these two thoughts:
1. We have confined placental mosaicism. (wanting to know the odds of this? see below)
2. Our child has mosaic downs syndrome. The probability of having a child with downs in our age group is 1/600, and only 2-3% of downs cases are actually mosaic. So, our chance is quite rare.
My question to you is this: How often does confined placental mosaicism occur? Is this rare?
Thank you for recounting your experience. Unfortunately, the best answer to your question on how often does confined placental mosaicism (CPM) occur is “I don’t know.” Prior to cfDNA, instances of CPM that I’m familiar with were limited to chorionic villus sampling (CVS), which was the rarer of diagnostic tests performed. Since cfDNA, with the number of false positives being reported, CPM is now becoming more of a known and experienced phenomena. I hope things go well with your amnio and that you receive good support.
Hey Steph,
I don’t know the answer to your question, but I kind of had the same situation with Triple X. Because of the possibility of it being the placenta my drs watched it very carefully, which I thought was kind of cool. Anyway, I ended up with a very healthy 10 lb baby, so I hope you do too! (though maybe not 10lbs)
MegaN – what probability of triple x were you given? And can you remember the fetal fraction?
My report said 99%. I can’t quite remember the fetal fraction – above I said it was 9.6. My memory says it was a 6 something, so I’d have to look to be sure. I posted everything right around this time last year.
Thanks Megan we were given 34% probability of triple x with harmony test 6.4% fetal fraction. No error margin given as this is unknown for sex aneuplodies. Cannot understand how the probability of 34% is worked out. Baby due in 1.5 weeks and then 2 week wait for karyotyping so I’ll update then!
Hi Mark, I’m in the UK and have just had NIPT through Genesis Serenity (who I believe use Verify) following being classed as high risk of T21 based on NT measurement, HCG & PAPP A levels. T21, T18 & T13 have come back clear which is a great relief but my results say suspected XXY. However the lab also say my results were borderline and have requested a re-draw (which I have done.) They couldn’t explain why my results were borderline (apparently they ran 2 tests with he same sample which both came back borderline) and said this has only happened twice before. I’ve spoken to a GC who wasn’t particularly helpful as couldn’t explain further and just explained how the test works and said that a ‘borderline’ ‘suspected’ result is classed as a positive result and that placental mosaicism is very rare and probably unlikely. She advised the only thing I can do is have an amino to confirm their results, which I wouldn’t do as wouldn’t risk miscarriage. The lab couldn’t give me any idea of rates of false positives as they said they don’t have this data, only that XXY is ‘likely’. I’m now having a stressful wait over Xmas and the new year for my re-draw results but wonder if you can shed any light on this or give any indication of general rates of false positives for XXY. Many thanks, Tracy
Tracy–none of the professional guidelines for cell free DNA (cfDNA) screening like Genesis Serenity’s recognize those screens for detecting sex chromosome aneuploidies (SCA) like XXY because none of the published studies have been of a sufficient number of cases to demonstrate reliability. At the American College of Medical Genetics & Genomics annual conference in March, I recall research being presented where cfDNA screening for SCA had more false positives than true positives. As for the reason why the test came back borderline, there are any number and only the lab would know the one real reason. I regret that the lab has not provided the promised serenity its name markets itself as providing.
Hi Mark, Thanks so much for your reply. I’ve literally just had the result from my re-draw emailed through and they have no identified no SCA, with my results consistent with normal XY! Am hugely relieved and happy, but with with the information you have provided, I would urge anybody else considering NIPT screening for gender / SCA to think really carefully about it and the potential for unnecessary stress that it can have. The last two weeks have not been good for me, my relationship or the baby as myself and my partner have been non-stop worrying and I really wish we had left the ‘gender’ box unticked when we went for the initial T21,13 &18 screening. Heartfelt thoughts to anyone else out there in a similar position and Thank you again Mark for your blog and keeping the thread / comments going as it provided me with much needed grounding over this last week. Tracy
Thank you for both sharing your results and for your kind words. I hope you enjoy the remainder of your pregnancy.
Hi Mark, i hope that you are still responding to this thread. You’re clearly offering a much needed sounding board that should be offered by the testing labs for patients with unclear results.
Today i received my harmony results: low risk for T21, T18 & T13, male baby, but sex chromosome aneuploidy is listed as ‘inconclusive’. Fetal fraction was 7.5%. There was no explanation for the inconclusive result. I am strugglimg to find any explanation as to the reason for the inconclusive result when there was adequate ‘fetal’ DNA to test for the other trisomies and gender. Do they require a higher proportion of fetal dna to test for sex chromosome aneuploidy?
The only lab instruction is that either a re-test or ultrasound examination should be considered, which seems odd since i don’t believe sex aneuploidy would be visible on ultrasound.
I would be very grateful for any suggestions you could offer in relation to why this inconclusive result may have arisen. My GP has not seen this result before and was not able to help.
Thank you
Bronwen
I wish I could provide more information, but unfortunately the result of “inconclusive” is a mystery, including often for the lab itself. Harmony has marketed itself as being targeted for the major aneuploidies, ie T21, 18 & 13, whereas other laboratories have aggressively marketed the expansion of their panel to include sex chromosome aneuploidies, eg Illumina’s verifi and Sequenom’s MaterniT21. Nonetheless, the American College of Obstetricians & Gynecologists do not recognize cell free DNA screening as valid for detecting sex chromosome aneuploidies simply because a sufficient sample size has not been tested to establish accurate detection rates. All this said, I would recommend asking your GP to press Ariosa (the lab for Harmony) on what your results mean and for a re-draw at no cost to you.
I should have mentioned in my comment above that i chose to screen for sex chromosome aneuploidy because my only previous pregnancy miscarried due to a very odd chromosomal abnormality: 1 fetus detected with single gestational sac and yolk sac, but chromosomal analysis of 30 cells showed 45x (13 cells), 46xx (14 cells – possibly my cells), 47xy +16. The specialist mentioned she had never seen weird results like these before.
My partner and i both had blood tests to look for chromosomal abnormalities in ourselves. We tested normal 46xx and 46xy, but i noted the lab only examined 5 cells in each of us which i suspect might not have detected a subtle mosaicism, if present. The specialist agreed the analysis was inadequate but the re-test has not yet been re-done….
I agree that it seems unlikely that an SCA (sex chromosome aneuploidy) would show up via ultrasound.
Thank you Mark. I really appreciate your help.
Hi everyone.
Our second child had 4.4mm NT and we decided to tests NIFTY (Harmony – the blood was send in Hong Kong Labs). The result come back with 1:20 T21 for 5,4% DNA fraction. So this literally tell us that the new child (boy) will be born with down syndrome.
I have 38 years old and RH positive and my wife has 38 years old and RH negative and the baby has RH positive like mine.
We decided to keep the child. We will love the child no matter what …
My wife is now in the 18 weeks of pregnancy.
PS:
The first child was the same … with RH positive and my wife was vaccinated to protect the baby at that time.
The first child is a boy at 2,7 years old, was borne in July 2013 – without any syndrome.
Thank you for sharing your experience. You may want to seek clarification from NIFTY on the meaning of your report. I read a result of “1:20” to mean that your new baby boy has a 1-in-20 chance of having Down syndrome and a 19-in-20 chance of not having Down syndrome.
Yesterday the child was born. He has down syndrome. We are happy that he is alive … we have worries, but we love the boy from the start.
Thank you for sharing and I wish your son and your family well.
Hi mark. Back in November 2015 I commented above that we received a positive T21 result and decided to terminate at 17 weeks. Fast forward to now and we are now 9 weeks pregnant with twins! We are anxious to get abnormality testing underway and have booked in for the harmony test for 10.5 weeks. I am nervous about testing so soon after an abnormality pregnancy – could it really skew the results? Last time i had a massive % of Fetal fraction (20%), is there a higher chance of that DNA still being present?
Somewhere in a reply to another comment on this blog, I linked to a study that explained that while fetal cells can remain, cell free DNA from the pregnancy leaves the mother’s bloodstream relatively soon after the end of the pregnancy. I would discuss with your provider how the results should be interpreted since you have twins. Being a twin myself (fraternal), I wish you well with your pregnancy.
Hi Mark, just to update. We have had the results back from the Harmony test today for this twin pregnancy. The results show Low Risk for T21, T13 and T18. I suspect from the result that the previous pregnancy DNA didn’t interfere with this pregnancy.
Thank you for providing the update. I hope this pregnancy goes well and you have a good delivery.
Hello Mark,
Thank you kindly in advance for sharing all this wonderful data regarding what they are referring to “Cell Free DNA” testing.
I got pregnant with my first child the same month I turned 35, after an IUI in February. We’ve had an ultrasound at 7w, 9w, and 12w. None of the ultrasounds reflect any signs of T21.
I did the cell free dna testing at a strong recommendation from my OBGYN (The Women’s Group – North in the state of Florida) at 12w 4d. Ten days later I received a call while at work that the results came back abnormal and told that the results are 99% accurate. I was devastated to say the least. My husband and I a couple hours later went and spoke with my OBGYN. She only said that the she was sorry but that the results are 99% accurate and that most people after hearing this news rush to terminate the pregnancy.
I received nothing from my OBGYN other than an apology for the bad news and strong recommendation to terminate my pregnancy.
I scheduled an appointment with a specialist for June 3rd. They will do an ultrasound, and if here are any abnormalities they will do a FISH test and then do an amnio if I elect to all the same day.
Based on your age, you have a 21% chance that it is a false positive–far from the 99% accurate that your OB is confused about. Please see this post for a link to the calculator where you can see your false positive chance. And, click the other links on fact sheets for yourself and provider, who would greatly benefit from educating herself so she can accurately counsel her patients. Plus, see the Prenatal Resources Tab for the Lettercase book and other helpful links so you get the accurate information about Down syndrome.
Hi there
Firstly – thank you so much Mark for this site. It was so reassuring and really helped me as I went through this emotional rollercoaster.
I promised myself I would post my story to provide those of you going through this with some positive outcome. If you scroll up to around March 2015 you will see my original post. I too had the harmony test at 10 weeks and tested positive for trisomy 13. At 12 weeks I had a scan with no signs of any issues and a healthy looking baby. However – given the test results and the ‘99.9 percent’ outcome I opted to have a CVS. What I hadn’t appreciated as the test was so new was that the harmony test picks up placental cells and that the placenta can have an abnormality while the foetus can be completely normal. The cvs tests the placenta as well. To cut a long and emotional story short. The FISH result was all clear, but 10 days later I got another call that some of the cells tested positive. There was a possibly for mosaicism where some cells could be impacted. Again my scan looked completely normal. I ended up with an amnio at 15 weeks and at 16 weeks I received news that the foetus was normal and that I had confined placental mosaicism.
It wasn’t that the harmony test was inaccurate – my placenta did have a small strip of cells (10 percent) of trisomy 13. It probably is 99.9 percent accurate. However – this is NOT 99.9 percent accurate with regards to the foetus. My baby was absolutely normal. Thankfully the specialists I had were aware of the shortcomings of the test and a termination was never raised. Rather – it was taken as a potential risk and i needed to have an amnio to rule out any issues. I only wish I hadn’t bothered with the CVS or places so much reliance on the way the test is marketed. The stress alone can impact a pregnancy.
For those of you wondering how it has turned out, perhaps you still have that little niggling concern I wanted to let you know that my little girl is now 7 months. She’s completely gorgeous and according to my paediatrician at her 7 month check up – advancing ahead of her age. Sitting , crawling and babbling happily.
Thank you for sharing this follow up post and I’m glad to hear your daughter is doing well. At this post, there is more written on why tests like Harmony are almost never 99.9% accurate for Down syndrome. With your specific case involving Trisomy 13, even the labs do not report their tests as 99.9% accurate for a condition as rare as Trisomy 13 and the newest guidelines do not recognize cell free DNA screening as anywhere close to that level of accuracy.
I’m just curious, but I have had 2 boys and my last boy was born just over 3yrs ago. I am 15wks 6d and my panorama blood test says I am havin another boy. Is there a possibility it is wrong?
I have not delved into the relative accuracy for sex identification through cfDNA screening, but, cfDNA leaves the mother’s bloodstream within hours of the pregnancy. Therefore, if your Panorama test picked up DNA from a “Y” chromosome, it seems almost certain that that is because you are pregnant with a boy. I would ask your doctor or genetic counselor.
Hi Mark,
I had the Panorama at 9 weeks 2 days. Per the GC at Panorama my fetal fraction was ‘great’ for that point in my pregnancy. I received negative/low risk results on all factors being tested and the T21 was 1:10000 risk. I am 39 and will be delivering the week of my 40th bday. I had the NT test as part of the first trimester screen in California. My NT was normal but my PAPP-A was elevated at 1.37 and my HCG was slightly low (I forget what it was but slightly below normal). This test alone gave me 1:44 risk of DS. I have been very confused because I was so confident in the Panorama result of 1in 10,000 for DS and now this much higher risk result leaves me wondering which to trust and considering an amnio. My perinatologist and GC said it is the NIPT that is more accurate and that the ‘adjusted’ risk considering age and the first trimester screening would give me a 1:3100 risk (they said multiply the first trimester screen risk by 70?). They said my age and the serum levels could have set off the high risk with the first trimester screen and they re assured me the NT was normal. Our plan is to have the 2nd trimester screen and fetal anatomy scan (at 18 weeks) and then make a decision about amnio. Any insight on this scenario? It seems sometimes the NIPT is used after a positive first trimester screen but I did the tests in the reverse order and am left wondering. Also, what is the ‘multiply it by 70’ referring to? I was told they would do the same with my adjusted 2nd trimester screen result and that would be my final risk assessment. Any insight is appreciated.
According to the most recent professional guidelines, conventional screening like NT and second trimester screening are not recommended if the mother has had cell free DNA screening, as you did, for the very reason that you relay: increased anxiety from competing results. Conventional screening has far, far, far, far more false positives than true positives when it reports its results. The opposite is true with cell free DNA screening for a mother at your age and, particularly, with a negative result. The only way to know for certain is with an amnio, but, per the guidelines, additional screening is not recommended and you should base your decision on your cell free DNA result.
Thank you for your reply Mark! This site has been very helpful. My concern is could there be a false negative with the NIPT due to mosaicism? I know false negatives are even more rare than false positives but again the variance in risk of 1:10,000 with NIPT to 1:44 with the first trimester combined screen is confusing and raises doubt, hopefully very unnecessarily though.
NIPT is a screening test, so there are false negatives and false positives, but far fewer as compared to conventional screening like NT. I would discuss the differing results with your genetic counselor or medical geneticist as they may be able to explain the differing methods by which each test arrives at its result.
Hi Mark, thank you so much for all the information you provide through your site – I have found it very useful. I am 33, and my baby is high risk for T21 (Illumina and quoted greater than 9/10, although when I questioned whether that was my own personal risk or the test’s sensitivity the doctor and midwife didn’t seem very sure and certainly couldn’t answer any questions about PPV). However, I had the NIPS after high NT readings of 5.9mm and 4.7mm, and the consultant can’t see the crux of the heart clearly yet so there is possibly a heart defect. I have been clinging to stories of false positives, but with my added risk factors (NT and heart), I think T21 is looking very likely. I am currently awaiting the results of an amnio. My hospital say they have never had a NIPS false positive. Can you offer any words of comfort? Thank you.
This post here collects the links to helpful resources like fact sheets about cfDNA, Down syndrome, and a PPV calculator. Based solely on your age, your Illumina results would mean your PPV is around 71%, meaning you have a 29% chance of a false positive. However, given your other soft markers, the NT (NT alone is not considered a reliable screen for Down syndrome) and the possible heart defect, those would suggest the chance of a false positive is less than 29%. At the end of the post are links to Down syndrome resources–I would recommend reviewing those as many other moms have found them comforting while awaiting the birth of their babies.
Hello Mark, I got a call from my doctor that my materni21 came back positive for T21, that I have 85% chance of having a baby with downs. She called me today to explain the results as I couldn’t stay on the phone before because I was at work and was so upset with the news. She said they found normal and abnormal cells which is a better sign that my baby might not have downs. She said the abnormal cells may have come from the placenta alone. Have you ever heard of normal amd abnormal cells at the same time and do you think it’s possible my baby doesn’t have Down’s syndrome?
I have not heard of the lab affirmatively reporting a finding of normal and abnormal cells, but, yes, there is a chance your baby doesn’t have Down syndrome because MaterniT21 is a screening test and has false positives. As this post explains, the abnormal cells could be from the placenta, not your baby.
Thank you so much for replying back. I appreciate it. She also said that the T21 cells they did find were less then usual. She mentioned possibly Mosiacism.
Hi Mark,
I just turned 36 years old a few weeks ago and this is my first pregnancy. Today I’m at 20 weeks 4 days with a baby boy. At 13 weeks exactly I had my first trimester screen (NT + blood test), which gave me an adjusted risk of less than < 1/10,000 for Trisomy 21, 18, and 13. I also had a cell-free DNA screening at 13 weeks exactly (I'm not sure which brand), which came back negative for Trisomy 21, 18, 13, and the sex chromosome conditions.
I also had my maternal serum AFP taken at 17 weeks, and everything looked good (negative for spina bifida).
I had my 20 anatomy scan at 20 weeks and 3 days. Everything checked out normal except the nuchal fold measured at 6.4 mm, which they said can be considered a soft marker for Trisomy 21. I immediately met with a genetic counselor, who told me that my cell-free DNA test results are still very strong but that if I wanted to know for sure if there was an abnormality that I would need to have an amnio. The genetic counselor said that she wouldn't be able to adjust my risk with a number based on this soft marker and that she couldn't advise me whether or not to take the amnio – that it was a personal decision.
The baby was in breech position during the anatomy scan. I learned from a few articles that nuchal fold measurements can be significantly greater when taken in breech position. Also, they estimated during the anatomy scan that my baby weighed 14 oz. I've read that babies at 20 weeks weigh 10 oz, on average. Do you think it's possible that everything is fine and that my baby is measuring an increased NF because he was in breech position and because he's big for his gestational age?
I'm wondering if I should ask for a repeat ultra sound before moving on to an amnio? How do you think I should weight the NF measurement at 20 weeks against the first trimester screen and cell-free DNA screen? Do you think an amnio is necessary?
Many thanks in advance,
Daniella
Your cell free DNA results trump the soft markers, particularly given your recalculation from your 1T combined test. As the genetic counselor said, only you can decide whether you think you need the definite result of an amnio–but that was the case from the beginning. If though you would consider terminating based on a genetic condition, then you should have the amnio before making that decision. Right now, your screen results do not suggest any condition.
You explained in your article that a false positive may occur in case of placental mosaicism, i.e. the placenta can have cells with triplicates of chromosomes while the fetus does not have any triplicate chromosomes in its cells. Can you explain how false negatives occur?
Why CVS is more accurate than NIPT since it also tests placental cells?
Is it possible that the fetal DNA also to have mosaicism and the amniocentesis gives a false result? This is very important because since there is a significant risk of miscarriage (1 %), i think a woman should do it only if it has an extremely high level of accuracy.
What is the accuracy of the combined nuchal tranlucency/PAPP-A/hcg/NIPT screening?
I understand that you are not an expert but these points are not at all clear in the media nor in the prenatal diagnostic centers and should be clarified to help a woman decide what to do.
False negatives can occur due to the situation you suggest: the fetus is mosaic but the area of the placenta tested is not, or the fetus is Trisomy 21, but the area of the placenta tested was not. False negatives can also occur just through lab error. CVS is more accurate than NIPT because actual cells, not cell free DNA is tested, and, from my understanding, the cells tested are closer to the region that grows into the fetus than the area of cells from which cell free DNA derive. While the chance that the fetus is mosaic and an amnio would result a negative result, this is considered so rare an occurrence due to the rarity of mosaicism and the amount of fetal cells tested in an amnio, that amnio remains considered diagnostic. There is no reported accuracy for the combo you suggest of combining the combined nuchal screen with NIPT; rather NIPT is considered to trump all other conventional screening for the conditions NIPT is recognized as accurate for testing for (T21, 18, 13, and sex).
I had a healthy boy in July 2014. Then went on to my second pregnancy and in March 2016, our baby girl was born – unexpectedly with Down Syndromw (the gynae missed that fact during the ultrasound screenings). She passed away when she was 38 days old. Since then, I have had five miscarriages: October 2016 at five weeks, February 2017 at 12 weeks (Turner Syndrome diagnosed on fetus via CVS and missed miscarriage a few days after CVS), May 2017 at 7 weeks, July 2017 at 6 weeks, and October 2018 at 5 weeks. Hormone tests were done on me and my husband’s sperm was examined after the third miscarriage, and the results showed no abnormalities. I am now almost twelve weeks pregnant again, and currently 36 years old. I have had one ultrasound at nine weeks, which showed a baby that was measuring one day ahead with a heart rate of 130 bpm. A genetic counsellor recommended the TriScreen NIPT test to me, which we proceeded to do for Trisomies 21, 18, 13, and sex chromosome abnormalities. Blood was taken at ten weeks six days gestation. I received the results yesterday, which indicate “negative” for all tested abnormalities, but report a fetal fraction of only 2%. The lab says they feel confident in the result from a FF of 1% onwards, but many sources seem to indicate that such a very low FF at almost 11 weeks gestation can indicate (possibly other) abnormalities (e.g. triploidies) in the fetus. (I currently weight 66 kg at a height of 1,72 m, and obesity can hence not explain the low FF.)
What would be a reasonable way to proceed?
If you must know, then have an amnio, while accepting that there is a risk of miscarriage. Otherwise, you could rely on NIPT result and see if there are any signs in a second trimester ultrasound or have NIPT again in the second trimester (though that would likely have to be paid out of pocket); a second negative NIPT might give you the assurance you seek.