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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).
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
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.
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
Also, I wouldn't be pushed by the husband on this - you
are the mom and we moms have the right to protect our
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.
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
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).
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.
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
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
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...).
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.
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
And the company:
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
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.
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.
These technologies are coming, but not likely for a year or
- Biotech dad
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