Hi ladies
I wanted to share my story in case anyone finds themselves in a similar position in the future and, like me, ends up frantically searching the corners of the internet for a positive story or a glimmer of hope to hold onto. This is my second pregnancy after a sudden and devastating full term loss earlier this year. It has been a very anxious pregnancy from the start. We opted to have NIPT (the SAFE test) done at 11 weeks and much to our shock and horror, a week later the result came back showing a high risk for trisomy 18. However at the 12 week scan the baby looked entirely normal with no soft markers for T18 at all. My combined blood test results (free hcg and papp-a) were also normal. For these reasons I was advised by the fetal medicine specialist that he suspected confined placental mosaicism. I was given the option to have a CVS right away but was advised that the results might be misleading given the possibility of placental mosaicism (more details on this below), and I was told it would be best to wait a few weeks until it was safe to do an amniocentesis.
After a long and torturous month of waiting I finally had the amniocentesis done earlier this week at 15+5 and the PCR results have thankfully come back showing normal results for chromosome 18 (they also looked at 13, 21 and sex chromosomes). We are awaiting the full karyotype results which take a few weeks, but given a normal scan and normal PCR results we are feeling very confident that this was a false positive and that the nightmare is behind us.
I’m sharing this story to make you ladies aware that although NIPT is generally quite accurate and false positives are rare, they clearly do happen and the only way to know for sure is through a diagnostic test like amniocentesis. I have done A LOT of research during the month we had to wait and wanted to share some of my findings in case anyone finds themselves desperate for any reassurance, because I know I was. NIPT is often marketed as having >99% accuracy, and while that is technically correct it can also be very misleading and disheartening if you get a high risk result. The key thing to keep in mind is that as great as NIPT is, it remains a screening test that can only give you a low vs high risk result, and it should NEVER be interpreted as diagnostic. The only diagnostic tests that can provide definitive answers are CVS or amniocentesis, although in certain circumstances even CVS can be misleading (more on that below).
NIPT looks at fragments of the baby’s DNA in the mother’s blood, so from my research I’ve learned that if you get a low risk result you can be very very confident that your baby does not have T13, 18 or 21. However things are a bit murkier than the test makers make them seem if you get a high risk result. Obviously the most common reason for a high risk result is unfortunately that the baby has the condition, but there ARE other very plausible reasons you could get a high risk result even when the baby is fine. Because the prevalence of conditions like T18 and T13 in the population is very low (> PPV for T18 = 63.6%
www.sciencedirect.com/science/article/pii/S1028455919302177
PPV for T18 = 60.7%
obgyn.onlinelibrary.wiley.com/doi/full/10.1002/uog.14792
PPV for T18 = 76.6% [lower and upper statistical limits 47.4-85.5%]
humgenomics.biomedcentral.com/articles/10.1186/s40246-020-00268-2
PPV for T18 = 62.96% [86.7% in advanced maternal age cases]
I’ve been advised that the most common reason for a false positive is vanishing twin syndrome, which is suspected in my case. Because of my history of loss I’ve been monitored quite closely with frequent scans since 6 weeks to ease my anxiety. At 8 weeks I had a high resolution scan and the sonographer noted a second yolk sac, which suggests there may have been a second embryo that never developed or died quite early in the pregnancy. 50-70% of early miscarriage has been attributed in studies to chromosomal abnormalities, so it’s very plausible that the vanishing twin had T18 and this is what the NIPT result was picking up. Studies have shown that DNA from a demised twin can remain in the mother’s system for up to 8 weeks and if a vanishing twin is suspected, NIPT should be done after 14 weeks gestation for more reliable results. Sharing below some literature I’ve found on this.
Fact sheet about T18 and possible causes of false positives: mydoctor.kaiserpermanente.org/ncal/Images/GEN_NIPT-T18_tcm63-1690053.pdf
www.sciencedirect.com/science/article/pii/S1028455919302700
Impact of vanishing twin syndrome on NIPT results:
www.researchgate.net/publication/322488527_Prolonged_duration_of_persistent_cell-free_fetal_DNA_from_vanishing_twin
obgyn.onlinelibrary.wiley.com/doi/abs/10.1002/pd.5817
pubmed.ncbi.nlm.nih.gov/30950018/
Other reasons for false positives include confined placental mosaicism, which is when there is an abnormal cell line in the placenta only. It is often suspected when NIPT gives a high risk result but the baby looks normal on ultrasound. The NIPT looks at fragments of DNA in the mother’s blood, which are marketed as “fetal” DNA but they actually come from the placenta. In the vast majority of cases the fetal and placental DNA are identical as they originate from the same embryo, but in cases of mosaicism when an abnormal cell line develops in the placenta, placental DNA does not accurately reflect the fetal karyotype. In these cases even CVS can give misleading results because it also samples the placenta. This is why I was advised to wait until it was safe to do an amniocentesis, despite the agonising 4 week wait that entailed, as an amnio samples the amniotic fluid and is therefore the most definitive method of testing fetal cells directly.
Some literature on choice of invasive test:
www.tandfonline.com/doi/full/10.1586/14737159.2016.1152890
obgyn.onlinelibrary.wiley.com/doi/10.1002/pd.4659
In my case, without sampling the placenta it’s impossible to know for sure whether the false positive was due to placental mosaicism or the suspected vanished twin, and all our doctors agree that it’s unnecessary to undergo another invasive procedure to find out, given the baby looks perfectly healthy. In all cases I am a high risk pregnancy after my previous unexplained stillbirth, and I will be monitored very very closely and most likely deliver a few weeks early via induction or c-section. Fingers crossed that this little bean continues to be healthy and we get to bring him or her home in the spring (we have chosen to keep the sex a surprise this time around!)
Finally, I will add that my experience with amniocentesis was much better than I expected. I was quite nervous about how I would feel during and after the procedure and was pleasantly surprised on both fronts. The needle looks huge and scary but the procedure itself was more uncomfortable than painful, there was a sharp scratch similar to getting a blood test as the needle went in, and then a very strange sensation of something moving around inside me, and some pressure when it was removed. My muscles around the incision spasmed a bit afterwards but overall it was much less unpleasant than some horror stories I’ve read online where people reported bruising, tenderness and heavy cramping for days afterwards. I’m very lucky to have had it done by an experienced fetal consultant who performed it flawlessly. It is frequently quoted that invasive tests carry a 1% risk of miscarriage but I’ve read that this is based on old data from the 80s, and technology has come such a long way since then. The procedure is now always guided by high resolution ultrasound so they can see what they are doing at all times and to ensure the safety of the baby. My consultant also made sure to only do it once the membranes had fully fused which apparently dramatically brings the risk down. Obviously so much depends on the skill and experience of the person performing the procedure, and you are entitled to ask the hospital or clinic where you are having it done for their specific track record. And obviously whether or not you have an invasive procedure is an entirely personal decision but I thought it was worth pointing out that from my research the miscarriage risks do appear to be overstated.
If you find yourself in a similar position to me, all I can say is that I wish you the very best of luck and I hope this research can help you navigate the rollercoaster with a bit more information. May you find the strength and courage to make decisions that are right for you in the face of indescribable stress and anxiety. This has been a very very traumatic for us, particularly after a sudden loss at the finish line earlier this year, but I’m so thankful the outcome of the amnio was positive and I hope your outcome is favourable like mine 🙏🏼🙏🏼🙏🏼 please feel free to reach out with any questions and I will try my best to answer based on my personal experience and/ or share more of the extensive research I have done.