20 Nov 2019
If you or your partner have been pregnant in the last five years, or you have seen news stories about pregnancy screening and Down’s syndrome, you will have probably heard of non-invasive prenatal testing (NIPT), or the ‘Harmony test’ as its often called (which is one of the test’s brand names).
For an update since this blog post, read Non-invasive prenatal testing is starting to get the attention it deserves;
NON-INVASIVE PRENATAL TESTING IS STARTING TO GET THE ATTENTION IT DESERVES
This is a newish kind of screening test in which a blood sample from a pregnant woman is used to test for a range of genetic conditions in the fetus, with varying levels of certainty. NIPT has been shown in multiple studies to be very good at identifying the most common chromosomal conditions – Down’s syndrome, Edwards’ syndrome and Patau’s syndrome – particularly in women who have a higher chance of having a fetus with one of these conditions. You still get some false positive results, but far fewer than with older screening tests. NIPT for these conditions has recently become available to pregnant women in the higher chance category in the NHS in Wales, and it has been promised to women in England and Scotland in the near future.
However, NIPT can already be accessed through numerous private clinics and hospitals across the UK for around £500. It is pretty accurate for Down’s, Edwards’ and Patau’s syndromes even if you are not in the higher chance category, and the test is available from around 9 weeks of pregnancy.
The Nuffield Council on Bioethics’ 2017 report on the ethical issues raised by NIPT discussed the offer of NIPT in the private sector. We highlighted some serious issues with how some (not all) clinics and NIPT test providers are marketing and offering NIPT in the UK. Disappointingly, despite our best efforts to raise these issues, little has changed.
Our main concerns are:
1. Misleading use of statistics
The websites of most private providers state that NIPT is ‘99% accurate’ or has ‘99% sensitivity’. I think most people would assume that this means their result will tell them pretty much for sure whether their fetus has one of the conditions or not. But as the conditions affect less than 1% of all children born, a dummy test that gave everybody a low chance result would be 99% accurate.
A more helpful statistic is the positive predictive value. Sometimes NIPT gives a high chance result when the fetus does not actually have the condition. If you receive a high chance result for Down’s syndrome, there is a 1 in 5 (20%) chance that the result is wrong and your fetus does not have the condition. For Patau’s syndrome, there is a 1 in 2 (50%) chance the result is wrong, and for Edwards’ syndrome, it’s a 3 in 5 (60%) chance. So, if you want to know for sure, you will also need to have a diagnostic test such as amniocentesis. Some companies give people’s results as being ‘positive’ or ‘negative’, which as you can see is highly misleading or, at best, confusing.
2. Poor information about the tested-for conditions
Very fewprivate clinics or test providers include information about Down’s syndrome, Edwards’ syndrome and Patau’s syndrome in their marketing and information materials. In the NHS, the development of balanced and up-to-date information about the conditions has been central to the aim of ensuring women and couples make informed decisions about NIPT. Public Health England has spent a year consulting with support organisations and families of people with the conditions to help them describe, as neutrally as possible, what having a child with one of these conditions might mean. Yet, in the private sector, you’re lucky if they have included the web address of a Down’s syndrome organisation.
At the Nuffield Council, we believe it's only ethical to offer NIPT within an environment that enables women and couples to make informed choices, and the provision of high quality information about the tested-for conditions is crucial to this.
3. Offering NIPT where the accuracy is low or unknown
Many clinics and NIPT test providers offer the option of testing for a range of other, often very rare, genetic conditions. These include those caused by unusual numbers ofthe sex (X and Y) chromosomes, such as Turner syndrome and Triple X syndrome,and those caused by small bits of DNA missing, called microdeletions, such as Prader-Willi syndrome and 5p deletion syndrome.
Information relating to the accuracy of NIPT for these conditions is often missing from websites and public materials. This is probably because the limited research that has taken place has shown that NIPT performs poorly for many of these conditions.
This means that, if you chose to test for these other conditions (and I can understand why many women opt for this when NIPT is marketed as being 99% accurate) and you get a high chance result, there is a high probability that the result will turnout to be wrong. You’re left with a choice between having an amniocentesis, which carries a small risk of miscarriage, to get a definite result, or living withthe uncertainty. We have heard from women in this position that the anxiety this causes can be huge.
We believe that clinics and test providers should stop offering NIPT for conditions where it does not offer an accurate prediction, and that they should provide full information about the limitations of the tests they do offer.
4. Lack of follow-up support
Some private hospitals and clinics offer a full package of care that includes pre-test counselling, access to a healthcare professional to discuss high chance results, and follow-up diagnostic testing if requested. But many do not offer all this. This is particularly true for those companies offering NIPT on a direct-to-consumer basis, where you order online and the test kit is sent to you in the post.
In many cases, it is NHS staff who have to deal with the fall-out. We have heard that women with high chance NIPT results are going to the NHS for advice, support and diagnostic testing. How the NHS will meet demand for this as private provision escalates is a source of concern.Although maternity care staff are receiving training in preparation for theroll-out of NIPT for Down’s, Edwards’ and Patau’s syndromes, they are less likely to know about the other conditions that private NIPT providers offer to test for.
I’ve highlighted four areas of practice that we are concerned about, but our list ismuch longer (e.g. lack of information about the possibility that NIPT might not produce a clear result either way, or that it might identify secondary findings about the mother’s health, using offensive language when referring to Down’ssyndrome and other conditions, and the offer of ‘baby gender’ tests). We think things could be much better.
We have already produced a guidance leaflet for manufacturers and healthcare providers on the information to include on their websites and leaflets about NIPT.
However, it seems unlikely that self-regulation will be enough. As such, we are delighted that the Care Quality Commission has recently changed its position and now considers NIPT to be within its remit, in line with a recommendation in our report. It has already started carrying out inspections of clinics in England that offer NIPT, so we hope to start seeing improvements in standards of care soon.
In addition, last week we urged the House of Commons Science and Technology Select Committee to investigate the regulation of private NIPT as part of an inquiry on commercial genetic testing. We are also seeking to raise public awareness of the issues (see today's BBC article and segment on BBC Radio 4's Today programme).
We will continue to work with these and other partners in a renewed effort to raise standards among private NIPT providers.
Pregnant women usually find out if they have a higher chance of having a fetus with Down’s syndrome, Edwards’ syndrome or Patau’s syndrome through early pregnancy screening tests, such as the combined test. These tests are offered to all pregnant women in England, Scotland and Wales. The results of an ultrasound scan and blood tests are taken together with the woman’s age to workout a probability score. If the score is at least 1 in 150, the woman is considered to be in a ‘higher chance’ category.
See the Warwick Evidence systematic review of the performance of NIPT across 41studies, which is summarised on p13 of the Nuffield Council on Bioethics’ reporton NIPT. For statistics geeks, in a general population of pregnant women, the positive predictive value of NIPT for Downs’ syndrome is 81.6%, for Edwards’ syndrome is 37%, and for Patau’s syndrome is 49%. The negative predictive value (NPV) tells you how likely it is that a low chance NIPT resultis correct. NIPT has a very high NPV for Down’s, Edwards’ and Patau’s syndromes(99.9%) so you can be pretty certain a low chance result means that you do not have a fetus with one of the conditions.
See the Public Health England screening blog for updates, e.g. https://phescreening.blog.gov.uk/2017/03/24/introducing-non-invasive-prenatal-testing-to-antenatal-screening-progress-so-far/
 Cochrane,an independent research organisation, published a meta-analysisof the evidence on the accuracy of NIPT in 2017. They were unable to perform meta-analyses of NIPT for several sex aneuploidy conditions because there were very few or no studies. Other studies have considered the utility of NIPT for testing for microdeletions, e.g. this study, by some of the leading NIPT experts in the UK, concluded that NIPT for microdeletions is not ready for routine clinical implementation.
Hi. Combined screening gave me 1:2 for Downs and 1:17 for Patau. I have read so much about screening tests. I am anxiously awaiting NIPT results but I fear they will be high chance. But reading the false positives I’m more worried.
Hi! I just got an amnio yesterday and they told me results should be up by Thursday. I had the NIPT (harmony) twice last month and both times they came out "inconclusive". According to the genetist that I met yesterday, this is a result they encounter in pregnancies with trisomny 21, but this is the first time I hear about it. I had talked to my doctor and she had just said it happens. I am already 24 weeks because they took all the time in the world to get me tested and delayed. Now, in the case of a positive result for down syndrome, I might not even be able to find a doctor willing to terminate the pregnancy because of moral issues.
I feel all this NIPT hoist is just getting in the way of things. They can only show statistics, I can't even give you that some times. I feel is useless and just time consuming and nerve wrecking.
So my fiance had the genetics test at 12 weeks i think and it came back 94% Trisomy 21. So it was overwhelmingly heartbreaking of course.
she's is 37 weeks and 1 day today and all 4 ultrasounds have showed a perfectly normal baby. No extra fluid in the back of the neck, she has a prominent nasal bone and humerus and femur measure perfect everytime. The only marker on the ultrasound as the little calcium deposits on the heart which i was told are more common in normal babies rather than Downs. All they told me was that it could be a marker for downs, but after extensive research they are more common in normal babies (4 close friends babies had these and were perfectly normal). The only other things now is that her humerus and Femur measure at the 60th percentile for her gestation age but they aren't growing as fast as her head, not a large degree but slightly. This was something that didn't make much sense to me and they didn't really explain it any further. I know big heads run in my family and they told my mom the same thing when she was pregnant with my brother and I.
My fiance is 18 and its our first child but it seems like everytime we get downs out of our head and stop worrying, something pops right back up to remind us that its still a possibility. We met with a specialist and she said that Ava (my daughter) looks perfect, nothing screamed downs.
I'm just kind of curious if this has happened to anyone else? should i be leaning towards a false positive because the ultrasounds came back perfect everytime? Is the prominent nasal bone and normal femur and humerus measurements more accurate than the NIPT?
a speedy response would be awesome as she has already dilated and my daughter should be making her arrival in the next 3 days.
Either way, the best thing is that shes been healthy everytime we've checked in on her. no matter what she is my daughter and I'll love her the same, I'm just trying to be as prepared as possible.
Crossing our fingers that your daughter will arrive healthy, Ryan!
We are in the same situation except we are in week 12 and have just got NIPT results (positive for Trisomy 21) and ultrasound (prominent nose, no signs of Downs whatsoever).
We would also really appreciate an answer to Ryans question.
I have had the same NIPT results. High Risk for T21. NIPT are only considered a screening. I am 34 weeks and every ultrasound has been absolutely perfect with zero signs of T21. I have accepted that our daughter could be born with T21 and I have learned so much with research. Regardless of a diagnosis WE will be her voice. I would love to talk to others who have had similar situations and I would love to know the outcome.
Hi for my wife we recently undergone double marker test. The screening result is negative. But HCG level is little high. Our doctor suggest me to go for NIPT Even though double marker result is negative for confirmation. Could anyone tell me this NIPT is necessary.
Last year when we found out I was pregnant, I had a gut feeling from the start that something was wrong with this pregnancy. We had the NIPT done and it was high positive for Trisomy 13. Because there is a chance of placental mosaisicm, we opted for Amnio. The Amnio confirmed Trisomy 13, which correlated with features found in the ultrasound. Although I understand some people have had negative experiences with NIPT I am very glad I did it, as well as the Amnio as it prepared us for the loss of our baby girl. I can’t imagine what that would have been like if we had no idea what was to come.
Now I’m 11 weeks pregnant again and just had NIPT done. Fingers and toes are crossed!
I know there are many false positive results of NIPT but are there any false negative?
Where you were screened as low risk but it was not true
I read a case where the ultrasound showed some indications but the harmony test said low- baby was born with trisomy 18.
So they say the NPV negative predictive value is more accurate but still not fool proof
I received my NIPT results over the phone by my family doctor who said my results were great and I have nothing to worry about. 2 weeks later I received a phone call from a different doctor who asked me to come in and discuss my results. For Trisomy 18 my results came back as 1 in 432 and Trisomy 13 came back as 1 in 153 - I just missed the cutoff. Is there a chance my baby can have Trisomy 18 or 13?
Hi all, just wanted to write to try and ease everyone’s worries about their test results. Here is my story , making it short of course. I’m going all the way back to 2004. When I was pregnant and I took this test. The results came back positive for trisomy 18, a fatal syndrome, I don’t remember the exact percentage but it was in the 80%’s. So it was pretty high. As you can imagine I was devastated. Yet I declined any invasive tests and only went for some level II ultrasounds, which kept coming back normal. Yet my doctor kept saying the percentage was very high and to be prepared. At 32 weeks my water broke. I went to the hospital and ended up having a c-section 3 days later. My baby was born at 32 weeks. And he was born a healthy baby. He is now a stubborn, fortnite addicted 😒, yet very smart, 15 year old. Please do not loose faith. Faith is everything!
My NIPT test has come back as 'high probability' for three copies of trisomy 20. Have there been cases where this has come as false positive?
Hi I aborted a baby at 18 weeks in 2014 because the hospital spent so much time messing about as first they delayed cvv then it was to early and not fused (placenta) that I got to 17 weeks pretty quick when they in desperation suggested I go private for NIPT . I Did results were positive for downs . I was 32 had a 11 year old and 5 year old (healthy) . Going through the same now . 5 years later and I can't help wondering if the same happened to me? The heart was fine bones ect ... Not sure about nasal . It does worry me as they attach all current findings scan image My ect to blood sample . Surely this isn't needed if the test is so good? I am now 12 weeks and the hospital seem to have already put me down as a lost cause . They said they have never come across a lady too have two DS pregnancies. I am awaiting Nipt results . But this time WILL FOR SURE. Have a diagnostic test hopefully Cvv.
Lisa what was your outcome
Thank you so much for this. I just got a test back saying the baby had markers for Turner syndrome. And I was completely a wreck. I've spent the last day balling my eyes. Until finding all of these articles about how uncommon this really is. So many articles on the NIPT inaccuracy specifically for sex chromosome disorders. Giving me the strength to think positive. My doctor says there's a 33% chance that it's true, 67% it's not. Praying it was another false positive .
But as you mentioned, if it is, it stinks that they told me gender, we were planning something special to find out, and instead we got this hurricane way... Really all a heartbreaking experience. Praying for all moms who have to go through this anxiety .
Read your story and was wondering how every thing went !
My 25 yo daughter is going through the exact scenario you just described! Had a lackluster gender reveal on Thanksgiving and she is having another ultrasound 12/6 with possible amniocentesis. This article has helped calm me a great deal. Prayers for your daughter's health!
Madison I am going through the exact scenario right now and my anxiety is through the roof. I’m 12 weeks at 37 and drs say to get an amnio to be certain but I don’t want to. How did everything turn out for you and your baby.
Last year I was pregnant with my first pregnancy and I went in for my NT scan at around 12 weeks and it came back abnormal at 4.6 I believe. The perinatologist told me the US revealed signs of tuners syndrome. He then offered me the NIPT and that told us it was coming for accurate with Turners. He then did another US and the baby started collecting fluid in her abdomen and other organs. He then offered a CVS and those results came back with a diagnosis with Turners. We were told due to all the findings in the US the baby would eventually pass or I could have a stillborn. We were already devastated from week 12, we opted for have an abortion and the doctor who took care of me told me we had made the right decision and that my baby was really sick. It’s a tough situation to be in, but if you want definitive answers have a CVS or amnio to make sure. If the results won’t change the outcome of your baby, then don’t do the testing.
Hi Madison T! Praying for you and your baby. Can you please update us on how things are going?
Not only should it be more clear about the false positives but also about the false negatives. We are part of that o.o1% who was given a negative but went on to have a little girl with DS. It should be made clearer.
And for the record she is perfect, wouldn't change her for the world and she had taught us more in her 3 little years than we could ever imagine. She is happy, beautiful and our world.
We are going through the same thing. All tests were negative. NIPT & ultrasound were negative/no risk and just had a baby with indications for Down’s. Very hard to process when all tests indicated no risk for your baby. Zero resources online discussing these findings.
What was your result ? Was the NiPt test results correct ie did the amnio confirm what you already know ??
Hi wouldn't get an amnio based on those results. You're at risk of putting a healthy baby through a miscarriage
it normally means out of 20 babies 1 baby will have whatever you've been tested for
What you have to remember are that the NIPT is a screening test not ???? accurate. I had my NHS test and it came back high for downs pateau and Edwards. I've just had the NIPT and it's come back as clear for Down syndrome and pateau syndrome but a HIGH result for Edwards. The NiPT results combined with the NHS results I believe mine to be accurate
I would like to know this one too! I live in The netherlands and we had a positive on a duplication on Chromosome 2. We did a amniocentesis and are awaiting results. Hopefully the result will come in in the next week....
How accurate would the NIPT be on these findings?
What does it mean to high risk (1/20) in case of NIPT.?
I'd like to know too. Got a 'low risk' NIPT last wk, so I'd like to rest on my laurels and not get amnio.
What is the accuracy of NIPT for more rare syndromes such as partial chromosome deletions?
Hi, I just got my results from the NIPT test, I'm 23 years old, I was 10 weeks pregnant at the time of the test. The test said “Positive” for Down Syndrome, with a 53.3% PPV. I have a sister who has DS so I wonder if that increases my chances of this “positive,” being accurate. Can you help me make sense of this? Does it seem likely this result is accurate?
Alterntively speak to Antenatal Results and Choices (https://www.arc-uk.org/)
Hi. Interesting to learn about the false positive results.
Is it possible to get a false negative result?
I thought the amino test was diagnostic.... so that superceeds the NIPT. Sounds like you had a false positive?
It is really very informative for peoples like us, My wife was reported NIPT highly positive(1/20), then we go for amniocentesis that comes negative for down syndrome. I want to know that if amniocentesis is negative, than I have to be worry about NIPT or not.
Hello last week we had positive trisomiy 21. But we dont have any symptomps without a litte bit stomach bigger (18mm). Not double bouble. My wife is 30 years old (newly) and pregnancy is 24 weeks. And also this nipt test show that foetal fraction is only %6 is it enough? Yesterday we did FISH amniosyenthesz
Hi, I was just searching the result regarding my first combined test in Scotland. I could not find any result about Edwards' syndrome (Trisomy 18) and Patau's syndrome (Trisomy 13) on my report paper but only Down's syndrome. Are you sure that in Scotland all pregnant women are offered those three primary test during first trimester?
We had a positive test for trisomy 13 with the NIPT test showing 99.9% accurate when I was 18 weeks pregnant in November 2018 and the consultant on that day offered nothing but abortion because the test is 'so accurate' was his words, we booked the abortion and went home with broken hearts, cried for hours , I later contacted the hospital and requested an amniocentesis to make sure before I done the worst thing in the world and abort my baby, I had to have ? not 99.9%, after 2 weeks of hell waiting for our results they came back AND THEY WERE CLEAR! Our son is now 4 months and perfect! That doctor nearly took his life and god knows how many healthy babies due to the NIPT test results only, lucky I had the knowledge and guts to wait a little longer for second opinion or he not be here now!
NIPT should always be made to have follow test with amniocentesis for full results ? of the babies DNA not 10%. False positive's can happen due human error but what's not Right and Certainly not Acceptable is the poor advice after the NIPT test like we had, it's is not good enough in NHS in this day and age. I feel sick to the stomach how many babies not made it due to NIPT Test.
We hoped our NIPT was false positive.
But turned out to be true for Down syndrome.
Also, early 12 weeks scan could show some signs of Down (like a heart problem, nuchal translucency), so you could skip NIPT and get cvs or amnio.
Same question we went to NIPT test and reports came as baby girl is the gender report is right or wrong
Recently we had taken NIPT blood test and based on result Dr confirmed that we have blessed with two girls. when we google there are more discussions that NIPT gender goes wrong, hence, though of getting some info whether we can believe on the NIPT blood test on gender or not?
This article, I believe, contributes to the confusion many women are experiencing regarding these 'noninvasive' tests. First, they have some doctors treating these tests like they are diagnostic and recommending abortions based on the results. Then, we have articles like this; which, before getting to more clearly worded pro and cons, spends 4 paragraphs containing sentences such as, "NIPT has been shown in multiple studies to be very good at identifying the most common chromosomal conditions - Down's syndrome, Edwards' syndrome, and Patau syndrome - particularly in women who have a higher chance of having a fetus with one of these conditions." I ran a business for 15 years, during which time I learned that people are receiving more written information than ever before but are fully and carefully reading less of it than ever before. Even sadder than the fact that people have, no doubt, aborted perfectly healthy babies based on their misunderstanding of the true accuracy level of this test, is the fact that so many people will jump at any new test which purports to 'protect' them from having an, in their estimation, 'less than perfect child.' I have a daughter with a Trisomy 13q/15q translocation. She has been one of my life's greatest teachers and one of my greatest joys! She is 32-years-old.
Hi brilliant article, I have read similar concerns everywhere about NIPT.
Could you recommend best private clinics to have NIPT testing??
It's still better than combined nhs test & not invasive as amnio & cvs..
I won't be alarmed if my results are elevated because of everything I have been reading but it's experience & way forward if there is some accuracy sometimes..
I'm afraid we're not the right people to give you medical advice. Your doctor or midwife should be able to offer you some information.
Thanks for your advices. The NIPT result said 99% positive, I do worry... Could you please advise me what test I should take next?
NIPT offers a good prediction of whether a fetus has Down's syndrome – better than the 'combined test' alone, which is currently offered to women in the NHS. But it is important to be clear that NIPT is not a diagnostic test for Down's syndrome. There is still the chance of a false positive result.
So, finally we should not believe NIPT result for Down Syndrome predictions?
Thank you for raising this point - you're quite right. We'll try to get this across if the opportunity arises in future.
I do wish that someone would explain properly to women why seemingly accurate tests can produce so many false positives.
It is, of course, because we not only need to consider accuracy but prevalence.
It is possible to have two tests for different diseases that have exactly the same accuracy (sensitivity/specificity), but the test for the rarer disease will produce many more false positives. So, for instance, the rarer Turner's Syndrome could be tested for using NIPT but would either produce too many false positives to be useful of it would need to have much higher accuracy than the NIPT for the more frequent Down's syndrome.
Equally, the rarer the disease in a particular age group, the greater the proportion of false positives. So although the accuracy of NIPD may be the same across different age groups of mothers, the number of false positives will be greater in younger women.
I very much wish that you had been clearer about this with the BBC, both in the interview with the Today Programme and any input you may have had in their recent article about NIPT and Turner's Syndrome.
Thanks for the positive feedback Alison
This is a really helpful article for those of us involved in counselling women for these tests. I have shared it with my screening and fetal medicine colleagues and we will take particular note of the PPV for high chance results - this mirrors our experience especially for Edward's and Patau's syndromes where we are always mindful about scan findings alongside these results as an apparently normal scan with a high chance NIPT result for trisomy 13,18 raises the suspicion that the result is not correct and/or may be a result of placental mosaicism