Advice about Prenatal Testing

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  • Some advice needed re: prenatal screening tests/amnio

    (9 replies)

    I am 37, currently 17 weeks pregnant, and with UCSF. I did IVF with donor sperm (i'm going to be a single mom). I was healthy before getting pregnant and feel really great right now. But I'm reminded often that I'm of advanced maternal age and any pregnancy over 35 is considered high risk, and the chances of abnormalities go up significantly when you're over 35. I had my first and second trimester blood tests and also the NIPT at week 10.  I have an anatomy scan in 1.5 weeks, so hoping to get more info then as well. NIPT (Harmony) results:Trisomy 21: Low Probability,  Less than 1/10,000 (0.01%) Trisomy 18: Low Probability Less than 1/10,000 (0.01%)Trisomy 13: Low Probability Less than 1/10,000 (0.01%) Sex Chromosome Aneuploidy Panel: Low Probability 2nd Trimester blood test results:AFP: 0.72 MoM
    Down syndrome: 1:6,900
    Trisomy 18: 1:80,000
    SCD: less than 1:10,000 I am very happy with these results, but the genetic counselors still haven't said they don't recommend an amnio. They keep saying NIPT isn't 100% and false positive rate is < 0.1%. I just don't know what to do! Since I'm going to be a single mom (well my family is going to be really involved, so I'm not really alone in this), I don't really know how to proceed and who to talk to about this. Has anyone been in a similar situation?

    As you know there is a small risk of miscarriage from an amnio. I had my daughter at 39 and had the other tests done, but the amnio seemed like overkill. Also, I was given an amnio following a fetal demise a few years before (to try to determine the cause) and got an infection from it; that could cause an additional risk if you are pregnant. Nothing in this life is certain; the information you already have is leaps and bounds ahead of what our mothers had and I'm not sure we're better off for it. Love your baby and hope for the best.

    I'm not a doctor, just a scientist, and I had my kids at 37 and 42. The risk you list are very very low. The risk of miscarriage with amino is not trivial so I wouldn't consider an amino with these results. If you are still concerned, ask about a "cell free DNA test" which will take fragments of the baby's DNA which circulate in your blood and test these for many chromosomal abnormalities (Down's plus many more that aren't in the current state of California run screening). The downside is that these tests are expensive and might not be covered by your insurance, but the upside is that they are likely very accurate and entail no risk to your baby. (If these tests show normal results you almost certainly will have a chromosomally normal baby. A positive result means either you or the baby has chromosomal abnormalities - usually this is the baby, but very rarely these tests pick up metastatic cancer in the mom). 

    I went through a similar situation, they told me I might have a baby with Down syndrome. It is not fun to be reminded that all the time, but I talked to other mothers and they told me that's what they do if you are over 35. I kept my baby. My pregnancy went fine and when my son was born he didn't have Down syndrome. However, over the years I discovered he was diferent than other children, when he was 5 he was diagnosed with ADHD. He is a beautiful child, life is a little bit hard but we just keep going. No regrets at all.  Good luck.

    I had my first and only child in my early 40s. It sounds as if you are asking if you should have an amnio or not. In my experience, the question to ask yourself if whether having adverse test results will cause you to act or not. Our genetic counselor told us it's a decision making tool. As I was high risk, I had CVS done (CVS earlier than amnio, i think early testing options have changed since), two times for two pregnancies. The procedure itself is not fun but it is bearable and, in my opinion, it was worthwhile for us to have certainty in a few key areas of what is definitely an uncertain overall journey. My best wishes for you.

    I'm really surprised your genetic counselor is suggesting you need an amnio. I had the same NIPT results as you and I'm a bit older (38 at conception) and was told the risk of miscarriage from an amnio far outweighed the risk of a chromosomal disorder, based on my NIPT results. Both my OB and my genetic counselor agreed on this. Same story with my earlier pregnancy (36 at conception). If you're really considering an amnio I would at least get a second opinion from a genetic counselor in a different practice. But I really don't think you need an amnio. Congrats and good luck!

    First, keep in mind that the vast majority of babies born to older mothers are healthy. But I had my now 10 month old at 45 and can relate to your worries. My first trimester screening with NT scan resulted in a positive screen (1:88) for Downs. We decided to do a CVS to rule it out, since the risk of miscarriage from CVS was lower than the Downs risk. That's the calculus that I was comfortable with, and it may or may not make sense for you. Fortunately, the doctor and nurses who did the procedure were very experienced and clearly knew what they were doing. And as we expected, CVS came back negative. That gave me some peace of mind. But it was scary for a few days because of pinching sensations at the needle insertion site.

    I think there are clear risk levels at which they offer additional diagnostic procedures, but I don't think they specifically recommend for or against them because it's such a personal decision how you weigh those relative risks.

    Ultimately, you want to be clear on why you want to know, and what you think you would do if there is a serious birth defect.

    I am 36 and  34 weeks pregnant (also via sperm donor and also ivf). My insurance is through Kaiser so they may have different standards of care than UCSF but when my NIPT came back low probability that was the end of it-  no one recommended an amnio and I was never referred to a genetics counselor. I guess if you're really worried you could request an amnio, the risk of miscarriage is real but quite small.  I took a lot of comfort from the 20 week anatomy scan. They probably also measured your baby's nucal fold at 12 weeks via ultrasound (a marker of downs). I had some non-related complications early on in pregnancy that kept me preoccupied so it didn't even occur to me to still be worried about the genetics! Hopefully you can ask your Dr. what they recommend? My guess is the genetics people have to be slightly vague for liability reasons. Congrats on your pregnancy and best of luck!

    Yes! Congrats!!! You will be over the moon when your little one comes:)

    Similar circumstances and results for me. Kaiser said my results were great and I didn't need the amnio, but my friend who was the same age did because she is diabetic and was a higher risk.

    They did however send me in for a 3D ultrasound around week 32-33 to see how big the baby was in case they had to deliver early. And they started non-stress tests plus weekly ultrasounds around week 36-37 to monitor my fluid levels. And I was induced at week 39 after they told me the risk of birth complications increases dramatically after 39 weeks for women over 40.

    BTW, I saw a fertility acupuncturist to help get pregnant and she also helped me get ready to be induced. Kaiser said induced births could be 2-3 days of labor, but with her help mine was less than 24hrs after my water broke. And I swear by the epidural:)

    With my first kid, I was scared to do any testing because I was REALLY advanced maternal age (41) and was so terrified of miscarriage. I don't think that was a rational decision, but I was just like -- that was what I did. My mom actually screamed at me because of this and I had to not speak to her at all for the last few months of my pregnancy because anytime I spoke to her she harangued me. That was fun. My baby was born prematurely, but had no genetic problems -- healthy as a horse, just small. I did do CVS with my second baby, which is the one that you do at like 10-11 weeks. Oh dang - but you missed that window, did the doctor not suggest it?? Sheez. Anyway, so now you are wondering about amnio. I don't feel comfortable telling you it'll be okay, but my thinking was, my numbers are great, we are peeking at that baby very often via ultrasound, she looks normal, it's all bound to be okay. That being said, I am sort of a golden retriever, emotionally, and I generally think EVERYTHING Is going to be okay. Hope this helps. I suspect it doesn't. Ugh sorry. Congratulations on your pregnancy tho, you're going to do fine! 

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Questions about Prenatal Testing More Advice & Reviews Advice about Specific Tests

Scary 1st Trimester Screen - Amnio? CVS? Neither?

Aug 2011

I am 35 and in the 12th week of my second pregnancy. I had a first-trimester screen today, and had normal results for the nuchal fold scan and one of the blood tests. The kicker was the PAPP-A blood test, which was .13 MoM. This is very low, apparently. The overall Down Syndrome risk calculation the genticists run came up with a risk of having a Down Syndrome baby of 1/39, which seems incredibly high to me, given the nuchal test was normal. The perinatologist recommended an amniocentisis or a CVS. We have no family history of any genetic disorders, and the twins from my first pregnancy are healthy and happy.

I have been reading a ton about the PAPP-A results, their reliability, how different factors can affect them (including IVF, which we did and which has been found to be a factor in low PAPP-A levels). Also, the doctor never even mentioned the host of other issues I read about that could come along with low PAPP-A, including low birth weight, interuterine growth restriction, and other things. So even if the amnio/CVS come back negative, we still could have problems with this pregnancy.

Has anyone ever experienced a normal nuchal result, but bad blood test results? Had a low PAPP-A? Should we do a CVS or the amnio? Should I get a second opinion? I'm so confused, we have only a short window to decide, and there are so many factors to consider...I personally don't think I'd want to terminate this pregnancy if there is anything wrong, but my husband emphatically disagrees with me (I recognize this is a whole advice topic on its own). Anon


I was pregnant at age 39 and was over 40 when my son was born. I had a CVS done around 10 weeks. I would recommend it; it was a great relief to get happy results. I feel that I could not have waited for the amnio. Email me if you'd like me to discuss the CVS further. It was a breeze!
I was 43 when I was pregnant with our first and only daughter (a natural pregnancy after I'd completely given up on IVF, IUI, etc.). I had a normal nuchal fold test but based on results from one of the blood tests, the geneticists calculated that we had a 1 in 7 chance of a Down's pregnancy--much higher than the standard calculated risk even for my age. We did an amnio and that was normal (although as you have pointed out that does not necessarily mean all is OK; amnio only tests for a very limited range of chromosomal defects). So we proceeded, still with tremendous anxiety. We now have a lovely, healthy, normal daughter about to enter 3rd grade. Likely you will be fine also. Remember that based on the odds you were given (1 in 39), you can look at the flip side: you have a 38/39 chance of everything being OK. Understanding the Anxiety
Hi -- Sorry you're in this position. We were in the exact same boat with our first child over 3 years ago. Normal nuchal measurements, really low Papp-A, with the calculations showing us with a much higher risk of Trisomy 13 and 18. Unlike your situation, neither of us were conflicted about what we would so if the baby turned out to have Trisomy 13 or 18, as these are lethal genetic defects, so it may not be exactly the same. However, we decided to get a CVS (which has a cut-off of 13 weeks, so if you want one, you have to do it FAST!) and I'm so glad we did because it was so reassuring and allowed us to relax and enjoy the pregnancy rather than living under this anxious cloud. In the right hands (we went to SF Perinatology -- they are beyond expert!), CVS has a very low pregnancy loss rate. Newer research shows it to be equivalent to amnio in terms of risk of loss. The risk of loss was much lower than the risk of having a baby with a trisomy, so it made a lot of sense to us to have it done.

The other stuff you read online, about potential pre-term labor, etc, you should know has very little evidence to back it up. Our midwife told us there was really no evidence about what a low Papp-A means in light of normal CVS results, but because Papp-A was a placental hormone, some people thought it might signal some kind of inadequacy with the placenta, and cause the placenta to crap out early. So the standard procedure is to put women on a regimen of weekly NSTs (non-invasive testing) after 32 weeks. But there's really no evidence that this helps. I found the weekly testing incredibly annoying (because it was time-consuming) and ended up having a healthy baby boy at 41 weeks with a very large placenta if I remember correctly. So in our case, the whole fear about placental insufficiency seemed unfounded and just another thing to worry about.

This time we skipped the first trimester screen altogether and just got the CVS. I didn't want to mess around with all of that other stuff. Sympathetic


First, you are right to have some doubts about the test results since the blood test (quad marker test) can be influenced by many things (i.e. incorrect conception date etc...but you should be sure about that with IVF); also I'm a scientist and labtests can give you a false result at times - maybe ask to repeat the blood test (not sure if the time window has passed for that but maybe they still have the blood and can do the Papp determination again?);

But in any case, all those tests give you are probabilities, diagnosis is only possible with Amnio/CVS. CVS is riskier but can be done earlier. Both carry a significant risk of you losing the baby just due to the procedure. So you have to weigh that risk (which seems to me exacerbated here bc of difficulty conceiving) with how much you want to make sure that you don't give birth to a child with Down syndrome.

You mentioned you would like to have the child even if it's handicapped - then I wouldn't do neither CVS or Amnio and just try to forget about the results. It's 98% likely that your baby is perfectly fine according to the nrs. you quoted.

Also, I wouldn't be pushed by the husband on this - you are the mom and we moms have the right to protect our babies. anon


I also had a normal nuchal fold measurement but a very low PAPP-A test, which made my risk of DS very high. We chose to have an early amnio at 16 weeks and everything was normal chromosomally. However, my pregnancy became very complicated around 20 weeks with hypertension, pre- eclampsia and ultimately HELLP syndrome. My previous pregnancies were healthy and uncomplicated, with a normal PAPP-A each time. I have since seen women with abnormal PAPP-A numbers and complications, some with IUGR, some with hypertension and pre-eclampsia, others with minor fetal abnormalities. I have also seen plenty of cases without any complications of having a low PAPP-A. Many OBs like to monitor women with more frequent ultrasounds if you have a low PAPP-A to check fetal growth, along with regular visits with blood pressure and urine protein monitoring. Whether you choose CVS or amnio is a personal decision, but just be aware that you may be at higher risk of other complications because of your numbers. In my case, I was induced only a couple weeks early, and fortunately my baby was okay. Good luck, and I hope that you are able to get some clarity around this issue. Been there
I had a similar experience during my first pregnancy: PAPP-A was extremely low, while beta hCG and the NT measurement were both normal. As a result, the combined first trimester screen put me at a 1/74 risk for Down's syndrome (I was 37). Actual values were as follows (in case it is helpful): PAPP-A: 0.21 MoM (0.5th percentile); beta hCG: 0.89 MoM (50th percentile); NT: 1.1 mm (an excellent measurement). Your PAPP-A result is obviously a little lower than mine was, but at 0.5th percentile, mine was clearly in the extreme low range. In light of those results I scheduled an immediate CVS. However, due to a structural problem with the uterus I ended up having an amniocentesis instead at 16 weeks. During the 4 week wait period I did a lot of research on the topic - as well as a lot of worrying. I was nervous about the 1/74 risk of Down's, as well as the host of other problems that, according to the literature, can be associated with low PAPP-A levels even in the absence of a chromosomal abnormality, i.e., IUGR, low birth weight, problems with placental function, etc.. The amniocentesis came back normal. Later in the pregnancy it was discovered that I had placenta previa (most likely the reason for the low PAPP-A). Despite this, I had a perfectly healthy baby - and no major problems due to the previa, though I did end up requiring a c-section.

I am not sure how exactly you could benefit from a second opinion. It sounds like what you need is to be matched with a good genetic counselor who will be able to go over the results and options with you (I take it you didn't get much help from the perinatologist). That said, the blood tests are nothing more than a screen, based on which you were advised to consider further testing. I don't think you will get a different opinion anywhere. These physicians are pressed for time, and honestly, when it comes to the various details and statistics, a good genetic counselor may actually know more, or at lest be able to deliver more to you. However, I don't think anyone out there will advise you not to pursue additional testing - simply because you screened positive (based on your ''numbers''). Keep in mind though, that these numbers are derived from a computer-generated algorithm that incorporates your age, along with other factors (I believe in most clinics ''positive'' means anything greater than 1/100). Of course, whether you choose to follow that recommendation or not is a personal decision that is entirely up to you.

If you do decide to pursue further testing, I highly recommend DR. James Goldberg of SF Perinatal. He is the absolute best - exceptionally skilled, experienced, considerate, and makes you feel very comfortable. I cannot say enough wonderful things about him. I have had two amniocenteses with him and had an excellent experience both times. CVS v. amnio - both provide the same information. The main advantage of CVS is that it's done earlier in the pregnancy, so you get information about a month sooner. Previously it was reported to carry a slightly greater risk than amnio, but I believe that estimate has changed and now both are considered equally safe. Rarely, a CVS either cannot be performed or results are inconclusive, in which case an amniocentesis really is the only option. I personally think that both are very safe procedures, especially if performed by a skilled physician, and I wouldn't think twice if faced with the decision again. Incidentally, my second pregnancy screening test put me at a very low risk, and I still decided to have an amniocentesis because for me, knowledge is key. But everyone is different, and you need to decide what is right for you. If I were in your position though, I would probably go for CVS.

That other issue you alluded to is a really tough one - I'm sure many couples don't discuss these things in advance because they are so unpleasant to think about. Unfortunately, I don't have any advise on that one, but I will say that some women may chose to have amniocentesis strictly because they want to ''know'', period. Both amniocentesis and CVS can be used to detect a multitude of conditions other than the major chromosomal abnormalities that are routinely screened for via bloodwork in the first trimester. Some need to be specified, but others (chromosomal) can be detected as part of the standard karyotype. Reduced PAPP-A levels are relevant only in the risk assessment for Down's and Trisomies 13 &18 (though the last two are typically associated with abnormal hCG levels in addition).

Bottom line - only you can decide. But it sounds like you could benefit from some counseling to help with the decision. Finally, you are hearing from someone who had an exceptionally low PAPP-A and perfectly normal outcome (my son will be 3 next month and is absolutely healthy). Best of luck to you. I am happy to discuss this with you further if you would like (just ask the moderator for my email). -Monica


Alternative to Amnio/CVS: Blood Based Screening

April 2011

I am 38 years old, 12 weeks pregnant, and a family member just told me they read about some ''brand new'' (not sure what exactly that means) alternative to amniocentesis/ CVS: it is a non-invasive genetic test that scans the fetus' DNA through the mother's blood--it's called Blood Based Genetic Screening. So it is a simple blood draw and then computer technology somehow separates the baby's genetic material from the mother, just like amnio but without any associated risks. This is different, I believe, from the blood drawn in the 1st/2nd trimester that's part of the Triple Screen. Has anyone else heard of this/done this yet?? I would love an alternative to amnio with just the same diagnostic accuracy. Hopeful


Dear Hopeful - Although there have been some major advances in blood-based prenatal testing, and this approach may eventually replace amnio/CVS, it hasn't yet become cost-effective or robust enough to use in the clinic. There are companies that will do blood-based paternity testing, but for more comprehensive prenatal analysis, I believe that CVS or amnio are still the only options. I've had both (amnio first pregnancy, CVS with a second, twin pregnancy) and although they involve some short-term pain, for us it was well worth it to know that everything was okay (I was 43 during my second pregnancy). The risk of infection or miscarriage is very small with experienced doctors. 3 healthy boys
Hi! I really, really understand your interest in this! It is true that tests like the one you described have been under development for a few years by a few different groups (see e.g. http://fcmb.dk/ for one of them). I heard from someone at UCB that these tests are about one year away from being on the market. You should ask your ob/gyn though, it is possible that there is a test on the market already (but keep in mind that even if it, it will be very new, possibly still needing some fine tuning...). Anon
I am a nurse-midwife and have never heard of this. The best non-invasive test that I know of is the combined nuchal translucency (via ultrasound) and maternal blood test. The nuchal translucency has to be done before 14 wks 2 days, and the blood draw before 13 wks 6 days. CNM
I saw an article about that too, but I am not sure the test is in use yet, and I am not sure if it can detect anything other than Down Syndrome... See NYT article link below: http://www.nytimes.com/2008/10/07/health/research/07down.html?pagewanted=2 And the company: http://www.sequenom.com/home/products---services/diagnostics/prenatal- diagnostics/fetal-nucleic-acid-technology/ Andrea
I believe you are referring to Fully Integrated Screening. This is a three part test involving two blood draws for you and an ultrasound of the baby's nuchal translucency (back of the neck). The first blood draw occurs now (approx 12 weeks), as does the ultrasound. You are then given a preliminary result. The second blood draw occurs between 15-20 weeks, and provides you with your final result. This testing is similar to the ''triple screen'' you mention, but about 10% more sensitive. In other words, it is non invasive and provides quite good information, but not as much accuracy as the CVS or Amnio. (Quick summary of the choices: the ''triple screen'' -- now actually called ''quad screen'' -- is 80% sensitive, the fully integrated screen is 90% sensitive, and the cvs/Amnio is 99% sensitive. Sensitivity refers to true positives. This means, for example that Fully Integrated Screening picks up 90% of the babies who have a chromosomal abnormality.)

By State law, all women in California are offered Fully integrated Screening. Of course, you can decline in favor of no testing or cvs/Amnio. Your Ob-Gyn should be able to discuss all of this with you in depth, or refer you to a Genetic counselor, if you have more involved questions. In the end, the decision is not only technical, but emotional. Usually, one choice just ''feels better'' than the others. Good Luck Local Ob-Gyn Nurse Practitioner


I know of several technologies that have been developed for testing fetal DNA in maternal blood, including one developed by Stanford Professor Stephen Quake. That technology is being developed by a company called Artemis Health. The company has not yet received FDA approval for the test, so it is not yet available. http://news.sciencemag.org/sciencenow/2008/10/06-03.html These technologies are coming, but not likely for a year or two more. - Biotech dad