In episode 2, I explain why a condition caused by the presence of a third 21st Chromosome is called “Down syndrome”?
This podcast covers subjects that are also written about in this post about Dr. Down and Dr. Lejeune and this post about the use of the word “syndrome.”
If you would like to learn more about Dr. John Langdon Down, please see this website. More about Dr. Jerome Lejeune can be learned by visiting the Lejeune Foundation’s website.
At the end, I explain why I still refer to the condition as “Down syndrome”, even though I believe the condition should be referred to as “Trisomy 21.” Feel free to share in the comments to this post what you think the condition should be referred to as and why.
Dear Mark:
I’m sorry for posting this comment here, but I was unable to figure out how to leave a comment on the NIPT article I wanted to comment on. I’m 45, 1 month until I am 46 and just confirmed I’m 6 weeks pregnant. Needless to say, spouse and I very shocked as this was not planned. Everything I read fills me with fear. My question is regarding NIPT available, due to the risks associated with my age alone, won’t I automatically “fail” those tests. I know they take into account mothers age, and the blood results, but won’t my age alone sway the results to the worst possible outcome and make me fail. Is there one better brand test NIPT than another that I should request?
Also, one chart I saw showed that at age 46 my chance of downs is 1/23 and other chromosomal abnormalities 1/16. On the surface that looks scary but is my math correct that a 1/23 change =.043% or 95% chance of not having and a 1/16 = .0625 or 93% of not having.
I’m so scared of this testing. My other pregnancies 10+ years ago only had ultrasounds and I think a triple screen blood test. This is all new and scary to me based on my age. Can you offer any advice? Thank you in advance.
Your age would not affect the results other than making a screen positive result have a greater chance of being a true positive. The labs do not publish the information so that you can decide which one is better. I would suggest discussing with your health care provider and insurance which one would be covered. Your math is correct; even as women age and the chance for Down syndrome or other conditions increase, because they remain relatively rare conditions, your chances remain much higher that your pregnancy will not have a genetic condition.
Thank you for the quick response. I feel better and think I understand now. My age alone won’t make me fail. However if I do screen positive it’s more likely to be a “true” positive at my age. I wonder if the reverse is just as true. If I screen negative is that more likely to be correct as a “true negative” due to my age? I know it’s a screen not a diagnostic test.
See this post for more about cfDNA screening and resources recommended for expectant moms who receive a result indicative of Down syndrome. Hope it helps.
Mark, my Panorama test result came back High Risk for Trisomy 13 with a risk 1:2. I went to the post you most rescently linked and the PPV calculator for Trisomy 13 at my EDD agebif 46 does not give a result. I used the age of 44 and it gave me a ppv of about 76%. I was thinking that PPV value would increase with age, so at 46 my changes are probably higher it’s a true positive. Do you know of any T13 resources that might help me understand and interpret better? My doctor was truthful and said the result was 1:2 so it’s a 50/50 toss in her opinion, but I thought the PPV calculators were based on high risk category and not the actual ratios.
I’m scheduled for a CVS next week but under so much stress with this.
I would follow up with Natera to explain the discrepancy between the on-line calculator and its labs’ reported PPV. For more information about Trisomy 13, here is a link to their support organization. It is an advocacy organization. I wish you well with your CVS and recovery.
Also, thank you for this website.
Hello Mark, thank you for this very informative website and introducing the calculator.
Like many I have been left confused by the NIPT test. My wife is 36 and NT scan was good bar the hyper plastic nasal bone. Her pappa levels were also low 0.440 and Beta hCG was 1.51 these combined with her age gave us a 1 in 8 chance of the fetus having trisomy 21. It was suggested that we do a non invasive test (serenity). We did the test and the results came back aneuploidy detected (Fetal Fraction 10%). The Genetic Councilor explained everything to us and explained that there is a 0.06% chance of a false positive 6 in 10000 chance. Having gone through the calculator I see there is a 12% chance of a false positive which is ironic because to start we had a 1 in 8 chance now we have the same odds. My question is what is the Fetal Fraction and what role does it play.
We had CVS yesterday and are now waiting on the results.
Also the Genetic councilor mentioned that the reason the test may be wrong is if my wife as some form of a tumor, do you have any thoughts or knowledge of this?
I look forward to your response.
Regards
Graham
That is a puzzle, given that using the calculator, based just off of your wife’s age, the PPV would be 88% with a 12% chance of a false positive. If you use the 1-in-8 revised figure based off of the ultrasound findings (which I don’t believe is recognized as able to provide that precise of a PPV), then the PPV is 98% with a 2% chance of a false positive. Either way, statistically significantly higher than the GC’s quote of 0.06% chance of a false positive. Regarding the fetal fraction, I’m mostly aware of cases where the fraction is too low for measurement which can suggest still an increased chance for a tested-for condition. On the final question, cfDNA results have been shown to report on possible cancer tumors. However, from what I am aware of, that possibility arises when the result shows unusual measurements for the presence of extra chromosomal material, but not those tied with known conditions like Down syndrome. As for your CVS, FISH results are still considered just screen results and diagnosis is only provided by the full test results.
Hello Mark, thank you for a very informative website. We were given a risk of 1 in 8 for down syndrome after my wife had her NT. This was due to a hyper plastic nasal bone, my wife’s age (36) and her bloods Pappa 0.44 and hCG 1,54. It was suggested we go and do a NIPT (serenity) and meet with the genetic councillor. We opted to go ahead and the results came back aneuploidy detected (fetal fration 10%) for trisomy 21. After meeting with her the councillor said that there is a 6 in 10000 chance of a false positive working off their specificity of 99.94% (Sensitivity 99.14). She did say that in more academic countries ( we are from South Africa) the councillors would always suggest the couple doing a CVS and so we opted to do so. We are now waiting on the results. I have two questions: 1: What is the fetal fraction? 2: At the bottom of their performance data table they have the follow
• For chromosome 21 PPV = 0.9581 and NPV = 0.9999 (How do I interpret this)
• For combined 13, 18, 21 aneuploidies PPV = 0.835 and NPV = 0.999
• Overall False Positive (FP) % = 0.2 and False Negative (FN) % = 0.026
Thank you in advance.
Regards
Graham
The numbers at the bottom appear to be what the lab is quoting as their general PPV and NPV for those tested conditions as it is averaged over all the reports they have issued that have been “positive” and “negative.” They still would not be specific to your wife’s actual sample.
I just wanted to provide a follow up for anyone who may visit this site. I was scheduled for a CVS Test on 5/2. The evening before I started spotting. When I went for my CVS @ 12 weeks there was no heartbeat and the baby measuresd 9 weeks 5 days. They suggested I schedule a D&C so they could test the remains, but I ended up miscarrying at home the following morning 5/3.
I’m posting this mostly because I am still traumatized by the lack of support I received from my doctor, spouse, and the genetic counselor I saw. Once my NIPT test came back 1:2 for trisomy 13 I was told it was a horrible outcome, and termination was the best choice. I was basically on my own, all of them telling me abortion is a good choice. I prayed so hard for the NIPT to be wrong and I did not want to terminate under any circumstances. I went for the CVS because I was bidding my time with my spouse hoping for a positive outcome. I will forever feel guilty for being relieved to have miscarried instead of being coerced and mentally bullied into abortion (the pressure was unbearable mental torture)I have so much more compassion for women in this situation because I never realized the external pressures that are put on them to choose abortion, it is utterly shameful and as a married mother I would never have imagined my spouse pressing me to abort. For anyone visiting this site, please try to find support for what YOU want to do. I follow many trisomy blogs now and see the joy these children bring to their families. NIPT testing is a nightmare, not a blessing in any way. I’m glad when I had my other children this technology did not exist.
My condolences on the loss of your pregnancy. How awful to hear of the pressure to abort. While this book is titled for Down syndrome, I expect much of the same advice may apply to your situation and wanted to pass it along in case it may be helpful. It is available for free as a .pdf.