Advanced Maternal Age

One week ago I turned 35. In pregnancy terms, this makes me officially old.

Visit with the genetic counselor

On Thursday, to celebrate, I got to meet with a genetic counselor through Kaiser (a meeting recommended for AMA women like me). Here’s what I learned:

At 35, my risk for chromosomal abnormalities is much higher than it was at 25. (Okay, so I already knew that!) The counselor was kind enough to point out that – despite the medical community’s black-and-white labeling method – there is nothing magic about the age 35. My risk increased slightly every year, so that now my risk of conceiving a baby with:

  • Down Syndrome (aka Trisomy 21) is 1 in 296
  • Edwards Syndrome (aka Trisomy 18) is 1 in 1152
  • Any chromosomal disorder is 1 in 134

(When you think about the fact that a few months ago, I was looking at odds of successful IVF with my eggs as about 1 in 4, 133 in 134 odds of having a chromosomally-normal baby really don’t look all that bad…)

I also learned a bit about the different disorders. Down syndrome (a disorder arising from three copies of chromosome 21, hence the name trisomy 21) is the most common, but is actually somewhere in the middle of the spectrum in terms of severity and prognosis.

Trisomies 13 (Patau syndrome) and 18 (Edwards syndrome) are more serious. The vast majority of babies with these disorders don’t survive a year. Those that do have severe disabilities.

Then there are the ‘milder’ sex chromosome disorders, like Klinefelter syndrome (in which baby boy gets an extra X chromosome, to get XXY) and Turner syndrome (in which baby girl gets an extra X, to get XXX). These may lead to slight reductions in cognitive function, health problems (e.g. diabetes in the case of Turner syndrome), abnormal physical characteristics (e.g. webbed neck in the case of Turner syndrome, small testicles and man boobs in the case of Klinefelter syndrome) and infertility. (I have to admit to finding it perversely amusing to think about infertility as the most minor of possible birth defects.)

(In case you’re wondering, XYY is also a possibility, but one that apparently doesn’t lead to any noticeable difference in cognitive or other abilities…)

 

Prenatal Screening Tests

To find out my likelihood of having a baby with one of these disorders, I was offered a variety of screening options.

I. California Prenatal Screening Program (PNS)

The first was the California Prenatal Screening Program. The charge for this test is $160 (fully covered by my insurance), and I found it interesting that that the money from all the women who get screened gets thrown into a communal pot. Uninsured women who get a positive screening test are eligible to use funds from the pot to pay for follow-up tests (like amniocentesis), and further prenatal care. Kind of cool.

Anyway, the California Prenatal Screening includes up to three different elements:

A.  A first-trimester blood test that measures levels of two molecules:

  1. human chorionic gonadotropin (hCG) – the protein hormone that’s used to confirm pregnancy in both home pregnancy tests and blood pregnancy tests, and
  2. pregnancy-associated plasma protein A (PAPP-A) an enzyme that chops up other proteins

Image

First trimester hCG levels tend to be a bit higher in Down syndrome pregnancies than in normal pregnancies, while PAPP-A levels tend to be a bit lower in Down syndrome pregnancies than in normal ones. Here are some figures I found on the interwebs showing the rough trends. In one-dimension:

ImageSource

In two-dimensions (hCG is on the x-axis; PAPP-A is on the y-axis):

ImageSource

Notice that there is a large overlap between Down syndrome and normal pregnancies in each plot. The genetic counselor also assured me that the levels change significantly over the course of the pregnancy, so a correct pregnancy date is crucial for an accurate result. Ultimately, this one blood test alone is insufficient to reliably predict Down syndrome risk, which is why the CA screening folks won’t give a result until they have at least one other piece of data, such as the following:

B.  A high-resolution ultrasound called nuchal translucency (NT) ultrasound is used to measure the thickness of a fluid-filled ‘translucent’ layer in the baby’s neck. More fluid in the neck is correlated with higher risk of congenital heart defects, which in turn is correlated with Down syndrome.

Here’s a figure showing normal (right) and Down syndrome (left) NT scans:

ImageSource

As with the blood test, this is all based on correlations, and just gives probabilities. (We infertiles just love probabilities…) Anyway, it is far from diagnostic.

These first two tests are sometimes referred to as the first trimester screen.

C.  The final data point that can be used as part of the California screen is a blood test in the second trimester. This test is sometimes called the quadruple test or quad screen, as it measures the levels of four molecules:

  1. human chorionic gonadotropin (hCG, see above)
  2. α-fetoprotein (AFP) – the most abundant plasma protein in human fetuses; its function in humans is unknown; AFP levels are elevated in pregnancies of babies with certain birth defects, including Down syndrome and neural tube defects like spina bifida.
  3. unconjugated estriol (UE3) – a  steroid hormone produced in pregnancy; low levels of UE3 may indicate chromosomal abnormalities
  4. inhibin A – a protein that inhibits follicle-stimulating hormone (FSH) production; inhibin levels are especially high in cases of Down syndrome, and especially low in cases of Edwards syndrome

 

Image

Like with the first trimester screen, the specific levels of these molecules can either more closely resemble a ‘normal’ or a ‘Down syndrome’ (or other chromosomal abnormality) pregnancy.

Even with all three data points, the best the CA screen can do is give probabilities of an abnormality. A probability of 0.5% (1 in 200) or greater is considered a positive test. In other words, the vast majority of women who get a ‘positive’ screening result will go on to have normal babies.

 

II. Non-Invasive Prenatal Test (NIPT)

The genetic counselor informed me that I’m also eligible for a very new blood test called the Non-Invasive Prenatal Test (or NIPT). This test is so new that Kaiser just began routinely offering it to women over 35 in June (which may explain why my OB failed to mention it in our first prenatal visit…even after C and I had made it clear that we wanted every non-invasive test available…)

This test is also a blood test, but instead of measuring the levels of proteins and small molecules in my blood, the NIPT looks at fragments of DNA in my blood. This post is getting rather long, but I’ll try to give the basic gist.

Apparently if you looked at all the DNA in my blood right now, about 10% of it would actually be pieces of DNA from my baby’s blood. Unfortunately, there’s no easy way to recognize which DNA is from me and which is from baby.

It is, however, possible to extract the DNA soup (including mine and baby’s) from my blood, and then make copies of certain portions of DNA from certain chromosomes. (For any biology types, they use quantitative PCR for this.) To detect Down syndrome, they make copies of a piece of DNA that only appears on chromosome 21, along with copies specific to several other chromosomes. Then they compare the amount of chromosome 21-specific copied DNA to the amount of other chromosome-specific copied DNA.

  • If the amounts are the same, it suggests that there weren’t ‘extra’ copies of chromosome 21 floating around to begin with, and that my baby probably does not have Down syndrome.
  • If there is an excess of chromosome 21-specific DNA, it suggests there were extra copies of chromosome 21 in our combined blood. Since we are pretty sure I don’t have Down syndrome, the most likely explanation is that my baby does.

This test catches a higher percentage of Down syndrome cases than the California screen (99% versus 90-95% for the combined CA screen), and has a much lower false-positive rate. (The detection rate is a bit lower for some of the other chromosomal disorders, for reasons that I haven’t taken the time to investigate.) It doesn’t, however, give any information about neural tube defects (which the California screen does), and it still does not give a definitive yes or no answer. For that, one would have to do chorionic villus sampling (CVS) or amniocentesis, both of which actually look at the full set of chromosomes in baby’s cells.

 

What I did

So, if you’ve been reading this blog for long, you know that I’m a sucker for data, so perhaps it comes as little surprise that I requested both tests. I gave blood for part A of the California Prenatal Screening right after my first OB visit three weeks ago. No doubt my results are sitting on a computer somewhere, but they won’t release them until I’ve completed my nuchal translucency ultrasound (part B)…which I’ll do bright and early tomorrow morning.

Last Thursday, after my meeting with the genetic counselor, I gave a blood sample for the NIPT. I’m told the results of that test should come back to me within a week. (Oh, and did I mention, the NIPT will also tell us baby’s gender?!)

Given that the NIPT is so much more accurate than the California screen, one might argue (as the genetic counselor sort of did) that the NT ultrasound is a waste of time. For one thing, there’s a decent chance that the CA screen may indicate an abnormality, while the NIPT may come back normal. If that happens, it may indicate that baby has a chromosomal disorder but is in the very small percentage of cases that are missed by the NIPT. Or, it may mean that baby has no chromosomal disorder, but has an unrelated congenital heart defect (giving rise to the thicker-than-usual nuchal translucency). Or (most likely) it may mean that baby is fine and the CA screen gave a false positive.

The uncertainty could easily cause a lot of stress, which is why the genetic counselor was careful to make sure I didn’t choose it blindly. I’m probably being a bit naïve (or arrogant?), but I’d like to believe that I could think logically about the likelihood of each possibility and handle any ambiguity that might arise.

Also, I really want to see my baby in high resolution.

 

What if?

In all this talk about the science behind these screening tests, I’ve conveniently avoided the most important question that all this brings up.

Namely, what will we do if the screening tests (particularly the NIPT) show a chromosomal abnormality?

The short answer is, I don’t know.

After all that we’ve been through, it’s hard to imagine choosing to terminate this pregnancy under any circumstances. In particular, I don’t think I’d terminate if faced with any of the ‘mild’ abnormalities (Turner or Klinefelter Syndrome). I don’t even think I’d terminate in the case of Down syndrome. (The way I see it, this may be my only chance at genetic parenthood, and I’d rather be mom to a child with Down syndrome than to no child at all…)

The decision gets harder for the ‘severe’ chromosomal abnormalities – trisomy 13 or 18. Could I continue with all the emotional and physical pains of pregnancy and childbirth, knowing that my baby would in all likelihood not survive infancy?

On the other hand, could I choose to end a life – my baby’s life – even knowing that it wouldn’t live long anyway?

I just don’t know.

And then there’s the fact that this isn’t just my decision. This decision would affect C too, and we’d need to somehow arrive at a plan together.

It’s enough to make me think that the people who refuse to test are on to something. Perhaps mothers like me – who aren’t prepared to terminate yet do decide to test – are just betting on a negative test result so that we can enjoy rest of our pregnancies with one less thing to worry about…

Well, I’ve already placed my bet, so all I can do now is wait and hope that my big gamble pays off.

I’ll keep you posted.

Advertisements
Previous Post
Next Post
Leave a comment

29 Comments

  1. I disagree about the NT being a waste of time. With the traditional CA screening, if the NT is abnormal, then a woman is considered to screen positive (her blood work isn’t even factored in) in particular, the greater the NT measurement, the higher the likelihood of an abnormality. Additionally, even in the case when a CVS or Amnio reveals a normal karyotype after an abnl NT, there is still a 5% chance of another structural abnormality, so it is prudent to do a fetal echo and other detailed follow up scans. Putting a positive spin on the situation; if you have a normal NT, then that’s very reassuring!

    Reply
  2. Excellent post and I am so grateful that you have such a logical mind to present everything clearly. I have always been very confused about all these tests. Now I have a better idea. I am glad that your pregnancy is going so well and you’re ready for these tests. I used to think that I wouldn’t test at all. Now I may want to know. And oh, happy birthday!

    Reply
    • Thank you Isabelle! It’s funny, because I sort of think I might not test if I had it to do over… Aw, who am I kidding! I could never turn down free information! 😉

      Reply
  3. As always, very informative and especially useful for me right now, as I’m meeting with the genetics counselor this week and have to make the same decisions. You always lay everything out so logically and I appreciate all the data points. For what it’s worth, I think you made the right choices.

    Reply
  4. Yes, Happy Belated Birthday! Thanks Isabelle! I meant to include that in my comment too 🙂

    Reply
  5. Love your posts in all their informative goodness. I am like you. I’d want all the (non-invasive) data, but I don’t know what my approach would be if it brought me positive results. I think that this is normal, though. In my opinion, it is impossible to know how you would handle that sort of situation unless you are IN it. Why prepare your answer when you can’t fathom the complexity of your emotional and physical and logical response.

    Goodluck with the screen. Odds are that all will be well, and you will love every minute of staring at your sweet, healthy baby while he or she kicks and stretches and waves in high definition. The profile shot will be your best friend. Look forward to the update!

    Reply
    • Thanks Lentil! The ultrasound was definitely cool. We could see baby flailing around and gulping down amniotic fluid like a fish! Unfortunately, I was too frazzled to enjoy it. First there was traffic that made me late, then my bladder wasn’t full…even though I followed their directions. And then, C and I got confused about the cm to mm conversion and convinced ourself that baby had a NT of 20…TEN TIMES the normal size.

      I want a do-over!

      Reply
  6. The whole pot thing for underinsured women is awesome! Once again, you rocked this information and made it easy to understand. You are definitely in the right profession. I’ll be thinking about you and baby. Can’t wait to hear that everything is fine. 🙂

    Reply
  7. Very informative post!

    I don’t think you need to make decisons about all of the ‘what if’ scenarios yet. I think this is one of those situations where, until you are actually faced with it, there’s no way to know what you would choose to do. Let’s hope you don’t have to make any difficult decisions. I had my daughter at age 36, and all of her screening tests came back with good strong odds that everything was fine. I have a feeing yours will, too. Keep us posted!

    Reply
  8. Sheesh! That’s a lot of information to take in!

    Reply
  9. Lauren

     /  November 19, 2013

    Love all the science! When I had my son, my triple screen showed a 1:130 chsnce for Downs. It probably wouldn’t have freaked me out (I didn’t know that this was relatively high for my age) except that my on-gym prefaced this all by saying “you tested positive for the Down syndrome test.” (Note to all ob-gyns out there…) Anyway, I got a CVS (the most advanced test out there only a few years back), and I was so happy to have the peace of mind that we were negative for downs, along with all the other chromosomal disorders. It was also pretty cool yo know the gender so early on!

    Reply
    • Yikes! That would be a terrifying way to present the information. I’m glad the CVS cleared everything up.

      Reply
  10. Lauren

     /  November 19, 2013

    While I’m on here, can I trouble you with one more dhea question (which I’ve started taking as we’re having trouble ttc #2):

    Did dhea affect your cycle at all? For the first time ever, I’m getting no peak day on my cbfm. I’m doubting that this is a coincidence. Any input (from you or anyone!) would be appreciated, because the Internet seems to have little to say about this!

    TIA and thinking of you…

    Reply
    • Interesting! I would’ve said that I noticed no side effects from the DHEA…but my CBFM also mysteriously stopped working for my last two cycles (including the one I conceived on). After the first CBFM fail, I started using OPKs again, which seemed to work fine still. I also still got EWCM, which is why I was inclined to blame the CBFM rather than my cycle. Maybe the DHEA interferes with the CBFM detection?

      Very interesting!

      Reply
      • Lauren

         /  November 19, 2013

        So your cbfm just konked out or broke one month? That’s a pain.

        I’m kicking myself for not charting this month, obviously. Also not sure about ewcm this month because we’ve done lots of bd-ing this month so it’s been difficult to tell (sorry tmi!).

        My re also told me not to take dhea (I’m at cornell, where I think they tend to be pretty conservative with anything considered alternative) so in thinking ill stop taking it. Which will be hard, because the studies that are out there look so enticing!

      • CBFM didn’t conk out; it just never gave me a peak, even when OPK did, so I thought it was broken.

        Most of the pro-DHEA studies come out of the same (dubious, in my opinion) clinic in New York…I wrote a post about it awhile back… I only tried it as a last-ditch effort with my eggs.

        I think it’s great that you’re at Cornell. I would totally take my RE’s advice too if I were in your shoes! Best of luck!

      • Lauren

         /  November 20, 2013

        Hi, sorry to keep hounding you about this because I’m sure you don’t feel like being dragged back into the IF trenches, but I’m just wondering: did your cbfm start showing just Highs all of a sudden? And if so, was this happening after you had begun the dhea? I know I’m grasping at straws here, but I’m trying to glean any and all clues about what might be going on. But yes, you’re right I should listen to my re on this. I’m guessing he’s much more informed about this than dr. google is.

        Enjoy enjoy enjoy your pregnancy!

  11. This is so tough. One of my greatest fears is getting pregnant and then discovering the fetus has a serious defect. I think I might be more afraid of that than of never getting pregnant at all. Like you I don’t know what I would do if faced with a test result that showed a serious problem. But I am sure I would get all the tests because I would want to know. I hope that all your test results are what you hope for and you get to enjoy an uneventful pregnancy!

    Reply
  12. very informative.. we had first pregnancy in my wife age of 45.. everything goes normal and today we have twin girls, now in age of 14 months )))
    keep this blog alive

    Reply
  13. Nicole

     /  August 16, 2015

    I have Turner syndrome and for you to say “I have to admit to finding it perversely amusing to think about infertility as the most minor of possible birth defects.)” is really offensive to me you have no idea how sad it is to hear you can’t kids… So offensive.

    Reply
    • I’m sorry that my words hurt you. My intent – as a person who struggled with infertility myself – was to point out that I consider infertility to be a serious concern. (Hence the quotes around the word ‘milder’.)

      Reply
  1. Halfway there | the infertile chemist
  2. 11 weeks, NIPT, and Outlander spoilers | the infertile chemist

Leave a Reply

Fill in your details below or click an icon to log in:

WordPress.com Logo

You are commenting using your WordPress.com account. Log Out / Change )

Twitter picture

You are commenting using your Twitter account. Log Out / Change )

Facebook photo

You are commenting using your Facebook account. Log Out / Change )

Google+ photo

You are commenting using your Google+ account. Log Out / Change )

Connecting to %s

%d bloggers like this: