Testing for Chromosome Abnormalities
When you are pregnant, you will be offered lots of tests.
There are tests that look at your blood type, your immunity to German measles, your blood count, your antibodies, your blood sugar, and your exposure to syphilis, hepatitis, and HIV. At some point, you will also be offered testing to see if you are at increased risk of having a baby with a chromosome abnormality. This menu of chromosome tests can be confusing. What do we mean by increased risk? Compared to whom? What do these tests tell us exactly? When in the pregnancy should they be done? Why do we focus on Down syndrome, when there are hundreds of possible chromosome abnormalities? Are the tests dangerous or invasive? Can they be wrong? Do I even want this information? What do I do if testing is abnormal?
See what I mean? Confusing. Before you have any screening for chromosome abnormalities, your OB provider will explain testing options. To begin with, these are options. Most people elect to have testing of some kind because they want to be able to prepare for the possibility of having a child with abnormal chromosomes. Or they may choose not to continue the pregnancy. Some families decline all testing, saying that they are not concerned about chromosome abnormalities; they will love their baby regardless, and they don’t need to know about a possible abnormality before birth. Whatever you decide, remember that this is your decision; there is no right or wrong answer here. It’s our job to explain all your options, not to push any particular test.
Although the biggest risk factor for having a baby with abnormal chromosomes is maternal age over 35, the majority of babies with abnormal chromosomes are born to women under age 35. Why? Because women under age 35 have more babies, period. This is why all pregnant women, not just those over 35, are offered to screen. Most of our tests are focused on finding fetuses with Down syndrome (trisomy 21), because this is one of the few chromosome abnormalities that are not miscarried in early pregnancy. And Down syndrome can be difficult to detect without special screening because many babies with Down syndrome don’t have any ultrasound abnormalities. When we are talking with you about which test may be the right one for you, we tailor our recommendations to your particular pregnancy. Here are some of the tests that are offered routinely.
• First-trimester screening: Between about 11 and 14 weeks, we can measure the fluid-filled skinfold on the back of the baby’s neck (the nuchal translucency, or NT). Babies with Down syndrome tend to have a thicker measurement. A thickened measurement may also increase the chance of other chromosome abnormalities, and also increases the risk of various birth defects, including heart defects. The first trimester screen for Down syndrome combines the NT measurement with blood work which measures your levels of PAPP-A and HCG. This test will be abnormal in up to 90% of Down syndrome fetuses.
• Second trimester serum screening: This screen, called the quad screen or Penta screen, is a blood draw which measures levels of 4 or 5 substances in your circulation that are produced by the pregnancy. The combination of values can indicate whether you are at increased risk of having a baby with Down syndrome, trisomy 18, or spina bifida or other abnormal openings in the baby. This test will identify 75-80% of babies with Down syndrome.
• Integrated or sequential screening: These tests use both first trimester indicators (the NT and blood work) and a second trimester blood draw to assess the risk of Down syndrome, trisomy 18, and spina bifida. Combining first and second trimester values increases the sensitivity of the test, and can identify 90-95% of babies with Down syndrome.
• Noninvasive prenatal testing: NIPT is definitely the new popular test right now. About 10% of the DNA circulating in mom’s blood belongs to the baby. Researchers have worked for many years to develop an affordable test to isolate and examine this fetal DNA. NIPT is a blood draw which can be done any time in the pregnancy after 10 weeks and can be a very sensitive test for Down syndrome, trisomy 13, and trisomy 18, as well as X and Y chromosome abnormalities and some other genetic information, like fetal blood type and a few single-gene problems. There is much more for you to know about this test.
• Amniocentesis: This is still the gold standard of genetic testing, because it looks at all chromosomes, not just those associated with Down syndrome. Amnio can also test for hundreds of gene abnormalities, as well as viruses, bacteria, and other substances in amniotic fluid which can tell us about birth defects, infections, and fetal metabolism. The catch? Amnio is an invasive test; it requires placing a needle into the amniotic sac and withdrawing a small amount of fluid. When the amniotic sac is punctured, there is a small risk of leakage of amniotic fluid, bleeding, or infection. Amnio is typically offered to patients who are considered to be at higher risk for chromosome or genetic abnormalities. It is very accurate and will diagnose 99+ percent of chromosome abnormalities.
• Chorionic villus sampling (CVS): CVS is also an invasive test. It is usually done between 10 and 12 weeks of pregnancy. To perform the test, a small plastic catheter is placed up through the vagina and cervix, into the placenta, where a small amount of tissue is collected. Or it can be done through the abdomen, with a needle. Like amniocentesis, CVS looks at all the chromosomes, so it is a diagnostic test, not just a screening test. Also like amniocentesis, there is a small risk of complications which might result in a miscarriage. The complication rate with CVS is a little higher than with amnio, about 1%.
• Ultrasound: Ultrasound is a wonderful screening tool. It can help us to determine when you are due, assess fetal growth, discover twins, and pick up many birth defects. Some birth defects increase the chance of a particular chromosome or genetic problems and can prompt us to offer you additional testing. I can’t imagine practicing Maternal-Fetal Medicine without ultrasound, but it has limitations. You should never assume from a normal ultrasound that everything is okay. An ultrasound can appear normal, but the fetus may have a chromosome abnormality or major birth defect that is undetectable with ultrasound. People sometimes have a false sense of reassurance with a normal ultrasound and decide not to have any genetic testing. Remember, a normal ultrasound does not rule out chromosomal problems. On other occasions, I have seen an abnormality in early pregnancy which goes away later on. If we had not done an early ultrasound, we never would have had to worry.
This is a lot of information about chromosome testing, but we have really only scratched the surface! When you are pregnant, you are usually counseled by your OB provider about screening options for chromosome abnormalities. You will talk about pros and cons of each test, the potential risks, and why we would recommend one test over another, depending on the circumstances.