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:
- human chorionic gonadotropin (hCG) – the protein hormone that’s used to confirm pregnancy in both home pregnancy tests and blood pregnancy tests, and
- pregnancy-associated plasma protein A (PAPP-A) an enzyme that chops up other proteins
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:
In two-dimensions (hCG is on the x-axis; PAPP-A is on the y-axis):
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:
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:
- human chorionic gonadotropin (hCG, see above)
- 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.
- unconjugated estriol (UE3) – a steroid hormone produced in pregnancy; low levels of UE3 may indicate chromosomal abnormalities
- 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
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.
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.