Prenatal Genetic Testing: Everything You Need to Know

Prenatal Genetic Testing: Everything You Need to Know

This article guide will cover everything you need to know about prenatal genetic screening for aneuploidy. 

Prenatal genetic screening is a really important topic because it's the first opportunity to do a test that is going to help you specifically understand risk for you and your pregnancy. This also provides the opportunity to make some decisions that can help your health and then also the potential health of your baby based specifically on you and baby's needs.

Your first trimester genetic screening will be looking for chromosomal abnormalities that your baby might have which are abnormalities with the baby's genetic code. It can be a complicated confusing process so we want to dive a bit deeper into that prenatal genetic testing.

week 9 prenatal genetic testing

Let's talk about what is happening with baby's development in week 9. It's week 9 and baby is already the size of a grape or about one inch long. Every day they're getting more and more details that make them all their own. They have all their essential organs now that are continuing to grow. Their fingers and toes are continuing to get more defined and they can even bend at their elbows.

A screening test is a very sensitive test that looks to detect disease in people or babies who do not have symptoms of that disease yet.

The goal is early detection so that you can either prevent or treat that disease effectively or make decisions ahead of time.

The important thing to remember here is that a screening test is not diagnostic. A positive result on a screening test simply means that you're at a higher risk of having that disease, not that you necessarily have that disease.

Diagnostic tests are a bit more specific and say that a positive result is confirmation of that disease.

Prenatal genetic tests are looking for changes or abnormalities in your baby's DNA or genetic code. We think of that DNA as kind of a blueprint for how your baby's body should form and develop. So we're looking for changes in that DNA with these screening tests .

You may or may not remember from high school biology that every normal human has 46 chromosomes in 23 pairs. So when egg and sperm meet, you get 23 chromosomes from mom and 23 from dad. But sometimes, when that genetic material is coming together there can be mistakes meaning that you get an extra chromosome or you are missing a chromosome. That is called aneuploidy.

Aneuploidy: extra or missing chromosome

The most well-known aneuploidy is called trisomy 21 or Down syndrome. That means there's an extra chromosome 21. Instead of having two, you have three. There is a wide range of possible outcomes that depends on the specific chromosomal abnormality that the baby has. That can be severe intellectual disability or even a shorter life span.

Chromosomal abnormalities occur in 1 in every 150 live births and occur even more commonly in early pregnancy, as chromosomal abnormalities account for nearly 50% of early pregnancy loss. These abnormalities occur with increasing frequency with advancing maternal age but can occur in mothers of any age, notably they are not related to race or ethnicity.

The most common aneuploidy is trisomy 21 or Down syndrome and occurs in 1 in every 700 live births. Other common trisomies include trisomy 18 or Edwards syndrome which occurs in 1 in every 3,000 live births or Patau syndrome, trisomy 13 which occurs in one in every 6,000 live births.

fetus down syndrome

There can also be chromosomal abnormalities with the sex chromosome. Klinefelter syndrome, which is having an additional X chromosome while still having a Y chromosome, occurs in 1 in every 500 males.

Turner syndrome, which is an X chromosome without an additional sex chromosome occurs in one in every 2,500 live births.

As a pediatrician I've cared for children with all of these various aneuploidies and chromosomal abnormalities and it's important to know that they can have a wide variety of symptoms, structural abnormalities and other conditions that need to be thought of. If this is something that comes up on your prenatal genetic screening, it's really important you talk more with your OB/GYN provider and also potentially geneticists to understand what risks and what outcomes are likely after birth.

In addition to aneuploidy, there can also be a smaller loss or gain of the chromosome and that is called a micro deletion or a duplication. While these are called micro, they can actually have huge clinical effects from a non-viable pregnancy to a life-limiting condition in a newborn. 

What are the factors of chromosomal abnormalities?

Risk factors associated with increased risk of chromosomal abnormalities include things like advancing maternal age, a prior chromosomal abnormality in a previous pregnancy, abnormality seen on an early ultrasound in pregnancy or positive prenatal genetic screening.

As we talked about a little bit earlier trisomy 21, 18, 13 as well as those sex chromosomal abnormalities, your risks all increase with advancing maternal age. But those micro deletions and duplications actually don't change very much with maternal age and the risk is about 1 in 270 no matter how old you are.

So that was a lot of setup to get to the point where we can actually talk about what your options are for screening and help you be prepared for that conversation with your ob/gyn provider.

Options for prenatal genetic screening

The American College of Obstetrics and Gynecology or ACOG recommends that genetic screening as well as diagnostic options be discussed and offered to all patients regardless of your age or risk factors. Then after you talk about it, it's up to you to decide if you want to pursue that testing or decline.

It's really important to sit down and think about what your specific risk factors are for carrying a fetus with a chromosomal abnormality. This is where we encourage you to sit down with your ob provider, review your personal history, your family history and then think about what the options are for testing, what the outcomes of that testing is and how it would affect your choices about what to do with your pregnancy.

When thinking about prenatal testing the question was: does it help us at all? The two big reasons to get tested would be:

  • If it was positive, would it change your decision about carrying the pregnancy to term?
  • Does it help plan at all?

When it comes time for screening in your first trimester or a little bit later, if you show up tardy for your first prenatal visit, there are two big options when it comes to screening:

  • The first is the classic first trimester screen and this consists of a blood test and a very specialized ultrasound.
  • The other option is a newer test called cell-free DNA.

First trimester screen

The first trimester screen can be done between 10 weeks and 13 weeks and 6 days. The blood test portion of that looks at three specific markers and then combines that with a very specialized ultrasound where they measure the fluid filled portion of the baby's neck called it nuchal translucency. That gives you a risk of chromosomal abnormalities. The detection rate for down syndrome with the first trimester screen is between 82% and 87%.

Now say you were a little bit late for your first visit and showed up in the second trimester. You could consider what's called a quad screen, where they add a fourth additional marker to this traditional first trimester screening. Unfortunately this fourth marker doesn't really increase the sensitivity of this test, but it does mean that there is still an option for this classic screening, even if you show up late to prenatal care.

Cell-free DNA

The other option for genetic screening in the first trimester or at any point in pregnancy after 10 weeks is called cell-free DNA. Believe it or not, throughout pregnancy there are small fragments of babies DNA actually circulating in mom's blood. What this means is that this test can look directly for chromosomal abnormalities in baby by doing a simple blood test on mom. Cell-free DNA is an excellent screening test it has a 99% sensitivity for detecting trisomy 21 and 13 and a 98% sensitivity for detecting trisomy 18.

Cell-free Fetal DNA

It also has a really low false positive rate, which means that there's a very small chance that it falsely tells you there is an abnormality when there isn't one. The other fun thing about cell-free DNA is they can tell you the sex of baby well before you could see it with an ultrasound. So if this isn't something you want to know at this stage of the game, be sure to let your specialist know. 

Combined screening

Other potential screening that your provider may discuss with you are what we call combined screening. That means it uses blood tests that is drawn in the first trimester and combines that result with a blood test that is drawn in the second trimester. These are things like the integrated screen the serum integrated screen the stepwise sequential screen and the contingent screening, all of which your provider can talk with you about.

prenatal fetus trisomy test

As we mentioned earlier, all these tests are technically just screening tests, meaning they let you know your risk of having a baby with a chromosomal abnormality. So with that your question is probably well what happens next if one of these tests comes back positive?

The next step after a positive screening test would be just a discussion about pursuing a confirmatory diagnostic test like a CVS (chorionic villus sampling) or amniocentesis. These tests aren't done first right off the bat because they do require a procedure. What that means is both CVS and amniocentesis require an invasive procedure to actually take a sample from within the uterus.

For a chorionic villus sampling, what that means is actually using a long needle to take a small piece of the placenta. This is standardly done between weeks 10 and 13. For an amniocentesis, it uses a similar long needle to sample the amniotic fluid or the fluid within the uterus itself and this is generally between weeks 15 and 18. 

Because of the invasive nature of these confirmatory tests, after a positive screening result, your provider is going to sit and talk with you about what your revised risk of a chromosomal abnormality is that you had this positive test. They're going to talk to you about what that genetic condition might mean or look like in a baby and they are probably going to recommend that you see a genetic counselor to get more detailed information. At that time a more comprehensive OB ultrasound is also done to help aid with your decision making about the next best step.