Prenatal Screening and Genetic Testing: Expert Q&A

All parents-to-be want to have a healthy and happy baby. Prenatal testing can safely determine whether your baby is at risk for genetic abnormalities or specific birth defects. Depending on those results, further testing, called genetic diagnostic testing, may be required to get more information and help you understand next steps. Our board-certified experts Dr. Ryan Longman and Bryanna McCathern will answer your questions coming up right now on At the Forefront Live.

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And as always, we want to remind our viewers that today's program is not designed to take the place of a visit with your physician. Now, let's start off with having each of you introduce yourselves, and tell us what you do here at UChicago Medicine. And Dr. Longman, we're going to start with you.

Hi and good afternoon. My name is Ryan Longman. I'm an associate professor of OBGYN at the University of Chicago. I am an OBGYN that did additional training as a maternal fetal medicine specialist, and then did another residency as a medical geneticist. I function here at the University of Chicago as our director of ultrasound and genetics in the Department of OBGYN. And I'm also our director of Fetal Neonatal Care Center here.

You wear a lot of hats.

Yeah. Busy day.

Yeah, sounds like it. And Bryanna, how about you?

My name is Bryanna McCathern. I am a genetic counselor at the University of Chicago in the Department of Obstetrics and Gynecology. And I see women in consultation regarding any genetic concerns they have.

That's great. And one of the things that I do want to stress to our viewers-- we'll take your questions, obviously, live on the air, so type them in the comments section on either Facebook or YouTube, wherever you're watching this, and we'll get to as many as we can over the past-- or over the next half hour. And Dr. Longman, let's just start kind of with some general, broad questions. And talk a little bit to us about prenatal screening. What is it, and what is prenatal genetic testing?

So prenatal genetic testing-- or I'll kind of can maybe back up a little bit more. And you know, when someone kind of comes into our office, just kind of what you can expect. So when you come in to see us for a prenatal genetics visit, it's kind of like going to your regular doctor. You would kind of come into the office and see us, and we would go through some things like a history, talk about past medical issues, surgeries, medications, allergies.

One of the other special things that we do is we also kind of take a very detailed family history. So we kind of do a family pedigree. We actually draw out the family tree. And then taking into account any kind of lab tests that the patient may have had, we kind of put everything together and see if there is any kind of history of family-inherited diseases that we can pick up on. And we spend a little bit of time talking about genetics and how it works, different type of testing modalities, and any kind of indicated testing based on that kind of history.

Interesting. And part of what I think makes what you do so special, again, we talked about this on another show here earlier this week, UChicago Medicine believes in really a multidisciplinary team approach when they work with patients, when you all work with patients. And that's why you have so many people involved in the process. And I just think that's really-- I think it's really fantastic. It gives the patients the best care possible. And I don't know if you want to talk more about that team approach, but it sure does seem to make a positive difference.

So let's talk a little bit about what are some of the factors that maybe should be considered when a family is thinking about screening or testing. And Dr. Longman, we'll throw that one to you.

So anytime we kind of talk about testing of any sort, I guess with any kind of patient, and whether it's prenatal genetic testing or you're kind of considering getting testing, one of the things that I always kind of talk about with patients is how is this testing going to help them and what are they kind of looking for to kind of get out of the testing. So a lot of what we do is this kind of really education and providing options for patients, and also kind of trying to get them to where they need to be.

So one of the things that we kind of spend a lot of time testing for is something called aneuploidy in the fetus. We try to either do a risk assessment, either diagnose or make a risk assessment as to the fetus's risk for things such as Down syndrome, like trisomy 21 or trisomy 13 or 18. And one of the things we discuss with the patient is what kind of testing, or if testing is even appropriate for them.

And I think some of the things that kind of come up in that kind of counseling is, a lot of times, patients will say, well, I really do want genetic testing. It will kind of really help me make a decision as to whether or not I will continue with the pregnancy. If there is some kind of significant genetic abnormality, they may make a decision that they may not want to continue with the pregnancy, whereas I have other patients who say, well, maybe I'm not very interested in getting testing done because I would continue with the pregnancy regardless of whether or not my fetus has a genetic abnormality.

I also kind of throw out something in the middle in there. And I kind of think that genetic testing is maybe important in anyone's pregnancy, especially for things like aneuploidy, because it can kind of help dictate to us how to take care of that pregnancy, that lady throughout the rest of pregnancy, or are there any kind of services that we're going to need immediately after delivery to help that newborn or fetus. So even if it's not about making a decision whether or not you would continue with a pregnancy and using testing for that, I think it can be very helpful in how to manage pregnancy throughout the rest of gestation, and then also making sure that we have any necessary available services at the time of delivery.

Yeah, that's perfect. That's a great point. And Bryanna, I want to bring you into the conversation and just talk a little bit about role, and tell us what a genetic counselor does and how you interact with your patients.

Sure. So as a genetic counselor, our primary job is to really educate patients on whether or not there is a risk for genetic concerns in the pregnancy. And if so, to educate the patient about what those risks are and what testing might be available to clarify it. Our main goal is to help patients understand what risks and testing is available so they can make the decision that's most appropriate for them.

Perfect. And we do have questions coming in from viewers already. We want to remind our viewers, certainly we're happy to take your questions. And the first one from a viewer, during what trimester do you generally do genetic screening? And either one of you can take that.

So there are different types of screening. Screening for chromosome problems can start at the end of the first trimester. The ideal time would be to perform it in the first or early second trimester. And then carrier screening for what we call single-gene disorders, like sickle cell disease or cystic fibrosis, can be performed prior to pregnancy. And that's optimal, if available. Otherwise, that can be performed at any time during pregnancy.

Great. So Dr. Longman, I know you touched on this a little bit, but if you can talk to us a little bit about exactly what happens at a prenatal genetics visit. Kind of walk us through the steps.

Yeah. So as I was kind of just saying before, a patient would come in and we would kind of take a history, go through all their kind of medical issues, do a family pedigree, if needed, or to kind of find out if there's any kind of inherited diseases in the family. And then we also spend a lot of time kind of counseling and really education as it pertains to kind of genetics, how does genetics work when two individuals are having a child together. Go over kind of what could get inherited from mom, what can get inherited from dad, and how inheritance patterns really function.

And then we also kind of, as I was saying before, we go through whether or not there's any kind of indication for testing. Two things that we really always kind of touch on, I think, on every prenatal genetic testing visit is we always kind of talk about aneuploidy testing, as we were kind of mentioning before, testing the fetus to see if there's an increased risk, or we can find Down syndrome or trisomy 13 or 18. And then the other thing, too, that I think Bryanna had just kind of touched on was carrier screening.

We also offer that to all of our pregnant patients or people who are thinking about becoming pregnant to see if they are silent carriers for a genetic disorder. An example would be something like cystic fibrosis, or maybe Tay-Sachs. If we can identify two individuals that are going to have a child together that are carriers for the same disease, then they can have a one in four risk or a 25% risk to have an offspring or a child affected with that disorder. And that kind of in a nutshell is what we do.

Well, and I'm kind of curious, do you have parents that maybe come in from time to time who don't know family background? Maybe they were adopted or something like that? I would imagine that is an area where people are wondering. And how does that work, and how do you help folks like that? And again, either one of you can take that one.

Sure. So when people are adopted, some of the carrier screening that we offer is based on ethnicity and family history. So when that information may not be available, there are panels, like large panels that look for many different recessive conditions, over 100 recessive conditions. And we can offer patients sort of a wide screen to test for those types of conditions if they want to do that type of testing.

Interesting. So Dr. Longman, we have another question from one of our wonderful viewers. If a cell-free DNA test result comes back as low risk, do you need to have any other genetic testing?

So I would back up and kind of say that all genetic testing during pregnancy is really, in a sense, kind of elective, certainly at the discretion of the patient. But people who have had cell-free DNA testing and are low risk, depending on the exact testing that they had, we'd certainly have to see the exact results, but usually that means that they are low risk for Down syndrome, trisomy 21, trisomy 13 and 18.

That would probably make it very unlikely for their child to be affected. It doesn't make the risk zero. There can still be what we call false positives and false negatives with cell-free DNA testing. So it is still certainly possible to have a negative result in a very unlikely situation, but the fetus still to be affected with one of those chromosome abnormalities.

So I would say that they are very low risk. I would say if someone absolutely has to know 100%, then what they should do is they should also kind of think about doing a diagnostic genetic test. There are two different types of diagnostic genetic tests that we think about during pregnancy. One is called an amniocentesis. The other is called CVS, or chorionic villus sampling. The amniocentesis we can do from about 15 weeks of pregnancy and on, and the CVS we usually do from about 11 to 13 weeks.

And what are some of the differences between those two testing types? Is one better than the other, or?

So the amniocentesis, just to maybe give a little bit more detail on both of those, so the amniocentesis, as I was saying before, is something we can do from 15 weeks of pregnancy and on. It's an ultrasound-guided procedure. So we look with the ultrasound probe, the ultrasound machine, and we take a very long, thin needle.

We pass it through the skin, through the uterus, into the amniotic cavity. And we take off about 20 to 30 CC's of amniotic fluid. So a very small amount. That sample actually goes to the lab, and they grow up the cells in the amniotic fluid called the amniocytes.

And what they do is they kind of take a picture and they look at the actual chromosomes of the fetus. So you will kind of get a yes or no answer as to whether or not that fetus has Down syndrome, trisomy 21, trisomy 13 or 18. It won't be a risk assessment like in some of the screening tests like in cell-free fetal DNA.

The other test that I mentioned, CVS, chorionic villus sampling, again, we do that a little bit earlier, about 11 to 13 weeks. There's two different methods for doing CVS. One is a transabdominal approach. And that's very similar to the amniocentesis, where we look with the ultrasound probe. Again, we take a very long, thin needle.

We pass it through the skin, through the uterus. But this time, not into the fluid around the fetus. We actually pass it into the placenta. And we take a small piece off, like a little placental biopsy. Again, the tissue goes to the lab, where they grow up the cells and examine the chromosomes the same way. That's with a karyotype.

The other type of CVS that we do is something called a transcervical. There, it is-- for women who have gone for a pap smear before, it's very similar. We put in a speculum. We identify where the cervix is. Under ultrasound guidance, again, we take a long, thin catheter. We pass it through the cervix around the sac to the placenta, take a small piece of that placenta off, and we send it to the lab, where they grow up those cells and again do a karyotype.

All three of those methods, or two different types of tests, CVS and amnio, will both give you the same diagnostic results, a yes or no answer for chromosome abnormalities. The downside is that they do have a risk of pregnancy loss. It's small. It's about 1 in 500 for the amniocentesis and about 1 in 400 for the CVS. So not a huge risk, and what we would kind of think of as an acceptable risk in certain situations. But it is present.

Sure. So another question from a viewer. And this is a good one. Bryanna, maybe you can take this one. Does insurance typically cover carrier screening for couples who are trying to become pregnant but are not at obvious risk for passing on a genetic disease?

For the most common carrier screenings that we do, like things for cystic fibrosis and spinomuscular atrophy and sickle cell disease, most insurance companies do provide coverage for those carrier screens. In terms of doing more expanded panels, it is very different between different insurance providers. And during a genetics consultation, the counselor can help you track your benefits and let you know about whether or not out-of-pocket costs would be expected.

Great. We're getting some great questions from viewers. Here's another one. Is genetic testing typically recommended for older moms? And either one of you can take that one.

I think so we offer genetic testing and put it out there and kind of recommend it to anyone who's thinking about being pregnant. Certainly it may change a little bit of our counseling, depending on patient's age. So as a woman's age goes up, there is an increasing risk for aneuploidy in the pregnancy, for Down syndrome. So classically, it's kind of been as the benchmark as to when to offer diagnostic testing has been at that age of 35 years old.

Now, it's kind of more of we offer diagnostic and screening testing to everybody now. But certainly as a woman's age does go up, there is an increased risk to have a child with Down syndrome. And that would certainly be part of kind of counseling and assessing that risk and seeing which test would be right for that patient.

And Dr. Longman, you mentioned earlier that obviously knowledge is always power, and if parents kind of what to expect. It's also great for the doctors and the caregivers to know what to expect going into birth. What kind of things do you look for and do you need to know, specifically in a high-risk pregnancy?

In relation to genetic testing, or for?

Well, in genetic testing. I mean, what information-- you mentioned earlier that it's good to know going into the birth if there are any particular issues.

Yeah. So one of the things that we kind of talked about was doing carrier screening. And there are instances where you can pick up parents that are carriers for specific-- silent carriers for specific genetic disorders. And if the parents are carriers for the same disorder, again, they have a one in four chance or 25% chance to have an affected child.

Some of those conditions, those autosomal recessive conditions that we're talking about can require immediate care for the newborn after delivery. So you know, prenatally, everything may seem normal. The ultrasound will be normal. The prenatal care will be normal.

But a child that is born with one of those conditions can sometimes need immediate care. And I don't necessarily mean 24 or 48 hours after delivery. I can mean immediately afterwards. Sometimes, there can be metabolic conditions that really need therapy or treatment immediately at the time of delivery that will put kids on certain metabolic cocktails or restrictive diets.

And it can be the difference between taking home a child that we think of as intact versus a child that has kind of had a metabolic cerebral insult. So I think that it's very important to kind of get that testing done. And if need be, then make arrangements to deliver at a tertiary care institution that can really have the things that your child will need to take care of them immediately after delivery.

Great. And Dr. Longman, you mentioned a little bit earlier in the program, a couple of times you were talking about aneuploidy. And can you talk about testing? How does the actual prenatal testing for aneuploidy work?

Yeah, so it can be, again, kind of two groups. We kind of spent some time talking about diagnostic genetic testing. It can certainly be the amniocentesis and the CVS that we talked about. And we kind of talked about those time ranges for those, 15 weeks and on for the amnio, 11 to 13 weeks for the CVS.

Again, great thing about the diagnostic testing is that it's a yes or no answer, the fetus is either affected or they're not. It's considered basically as close to 100% as you can get. Again, that downside is there's a very small risk of having a miscarriage, 1 in 500 with the amnio, 1 in 400 with the CVS.

On the other side, there's something we call screening tests. And these can be anything from a blood test to an ultrasound test to a combination of blood and ultrasound. We have ones you can do in the first trimester, ones you can do in the second trimester. I think someone mentioned already on the program cell-free DNA testing.

And that is kind of the hot new screening test that's out. It's very good, and you can perform it as-- it's a blood test that you can perform from 10 weeks of pregnancy on. It's very sensitive and specific for things like Down syndrome, trisomy 13 and 18. But again, it is technically a screening test. So even though very unlikely if you have a negative test, it is still possible to have a false negative.

So Bryanna, how accurate are the results from testing like this?

So with screening tests, it's important to keep in mind do not tell somebody for sure whether or not their baby will have an abnormality. It just determines if their risk is increased or decreased. A decreased risk does give a very low risk. An increased risk does mean that the risk is elevated, but if they wanted to be for sure, they would have to proceed with tests like amniocentesis or chorionic villus sampling. We call amniocentesis and chorionic villus sampling like the diagnostic tests. In terms of chromosomes, that's really going to give us a definitive answer about whether or not the baby has the condition.

Great. Another viewer question. Dr. Longman, what new genetic screenings are on the horizon or currently being studied?

So that's a great question, and something that we have a big interest in. So you know, genetics is a changing field. It doesn't change every year, it changes, I feel like, every month or every week. And when I had started doing genetics, we were doing carrier screening, and we were only doing a few conditions.

It was kind of really-- and what we were doing testing for was what we call single-gene ethnicity-based testing. So we were kind of really testing people for single disorders based on ethnicity. So for example, if you were of Ashkenazi Jewish ethnicity, you may get Tay-Sachs testing.

But now we've kind of really changed. It's really changed for a few reasons. One, the technology has changed. It's gotten quicker, faster, cheaper. And also, we're finding that we're a multiethnic population. If you look at our census data, things have really changed a lot. I think in 2010-- hopefully, we get some new census data soon, but in 2010, about a third of people really kind of saw themselves as multiethnic.

So we've kind of really changed, and now from doing just single disorders based on ethnicities, we've kind of changed and we really like to recommend pan-ethnic expanded carrier screening, where we test everybody for as many disorders as we can. And that has really kind of accelerated over time with our ability to do genetic testing. So it's kind of gone from even 50 to 250, now there are panels with 500.

And one of the things that we're kind of exploring in our clinic is doing something called exome sequencing as a carrier screening method. And this is where you will sequence out all the coding regions for genes in the genome to see if people are carriers. And that is really, I think, the next step, and something we're starting to explore doing in our clinic.

Interesting. So Bryanna, here's another question from a viewer. Do the genetic screenings indicate that one of the parents could have one of these disorders and maybe not be aware?

Most of the disorders that are on carrier screens are severe disorders that have an onset in childhood, which is why they were selected for carrier screening. There can be rare circumstances where somebody might have a more mild form of the disease and might not know it and be detected through carrier screening. It's not very common, but if we have that type of result, we would certainly see the patient and refer them to the appropriate specialist to determine if they need special medical care. But that's certainly not common.

Great. So Dr. Longman, we've heard a lot about-- heard about a lot of different tests, and some of the new tests, even, possibly that are coming out soon. So how do you decide which type of testing is appropriate for which person?

So you know, again, I'd like to think that we try to, when it comes to aneuploidy testing and also carrier screening, we're, again, really more about kind of presenting all the options about educating people about genetics, how genetics and inheritance works, and then kind of explaining and educating on all the different testing options out there, and helping the patient come to the resolution of what testing, if any, is the appropriate testing for them to get.

That's great. And one of the things, I can't stress this enough, when we talk about the team approach that happens here at UChicago Medicine, it's just such an important part of, I think, the whole care plan. And Dr. Longman, I don't know if you can talk to us a little bit about how important that is from your standpoint to have multiple people involved in a process like this, people like Bryanna, because it does make a difference.

Yeah. So it definitely does in genetics, and it also does-- I know the other hat that I wear is as our director of Fetal Neonatal Care Center. And that's kind of a place where we take care of fetuses with special issues. If someone has a fetus that has maybe a heart defect or a brain abnormality or a limb abnormality or some kind of structural abnormality or something special going on, we have really a wonderful team approach.

So the patient can come in, certainly get an ultrasound, meet with us on the genetic side. If they need any kind of fetal echo from peds cardiology, fetal MRIs we really specialize in. We also have all the subspecialties, too, on the peds side.

So we have a high-level NICU. We have peds urology, peds neurology, peds cardiology, again. And then we will all kind of get a chance to see the pregnant individual, evaluate the situation, and then we also have meetings where we all kind of come together and come up with a group plan so we can all kind of discuss and make sure that we're all on board and we can do the best we can to help optimize the best outcome we can for that newborn.

You know, Dr. Longman, I know we spoke just briefly before the show about this next subject, and I think, again, it comes back to making things safe and also convenient for the patient, telehealth and video visits. I know that's an area that you're interested in. Can you fill us in a little bit on some of the future plans there?

Yes, so one of the special and I think really cool things about genetics is that we can do a lot of it through the internet, through video visits, what we would like to call telegenetics. So not only can we view you over the internet, like what we're doing right now, we can certainly do the history, we can take the pedigree that way, too, we can do educational things, find out what testing is best. We can also work with a lot of labs, too. Even if you don't want to come into the hospital, maybe you want to get carrier screening done.

So for certain things like carrier screening, you may not even need a blood draw. Sometimes, kits can be sent to your house, and it can just be an issue of doing a buccal swab or we call it swish and spit, and get some DNA that way to do the testing. Sometimes, for some tests, like cell-free DNA testing, it does require a blood draw. But we can also certainly work with mobile phlebotomists from different laboratories, and have them come to your house to draw a blood sample that way. So again, a very exciting time in genetics. And I think that telehealth really lends itself to a telegenetic approach.

Great. And Bryanna, you get the final question. If someone is interested in having one of these prenatal genetics consultations, how do they go about making this happen?

The easiest way would be to talk to their provider and just request that they be referred for a genetic counseling appointment. And if patients want to self-refer, they can always call the main line and set themselves up for a genetic counseling appointment.

Perfect. Well, we are out of time. Thank you for taking time out of your busy days to share this information with our viewers, and also thank you to those of you who watched and participated in our program today. Some really great questions.

Please remember to check out our Facebook page for our schedule of programs that are coming up in the future. And to make an appointment, go online to UChicagoMedicine.org. Or you can call 888-824-0200. Thanks again for being with us today, and I hope everyone has a great weekend.

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