Dr. Fox: Welcome to today’s episode of “Healthful Woman,” a podcast designed to explore topics in women’s health at all stages of life. I’m your host, Dr. Nathan Fox, an OBGYN and maternal-fetal medicine specialist practicing in New York City. At “Healthful Woman,” I speak with leaders in the field to help you learn more about women’s health, pregnancy, and wellness.
Dr. Gelber, welcome back to the podcast. I’m really happy that you agreed to do this. I asked listeners to send in questions for “Mailbag” podcast. And we get a lot of CMV questions, and it’s really hard to answer them briefly. And someone sent a really good suggestion saying, dude, just do a full episode on CMV and pregnancy. I was like, you know, great idea. So, I’m really happy we’re doing this. I’m happy that you’re coming on because I really do appreciate your wisdom on this topic. And it is a very important topic. So, thank you for taking the time for me and for our listeners.
Dr. Gelber: Not a problem. Happy to be here.
Dr. Fox: Excellent. So, I guess, let’s start from the beginning. How would you explain to somebody who maybe doesn’t know what we’re talking about? Like, what is CMV, and why should people care?
Dr. Gelber: So, CMV stands for cytomegalovirus, which is really not helpful to anyone, the name. But it is in a family of viruses called herpesviruses. And, you know, the thing everyone knows that’s a herpesvirus is herpes, like HSV-1, the thing that gives us cold sores, HSV-2, which, you know, typically we talk about giving genital lesions. But, like, chickenpox is a herpesvirus. There are a lot of viruses in that category.
And one of the things about herpesviruses is that they can give you an acute infection where you get sick. So, like, people get chickenpox, they get sick, and then they can get shingles later in life. Like, their latent virus can reactivate, and that can make them miserable, but, like, usually not sick the way the original infection made you sick. And, you know, people, typically, if they get cold sores, the first time they get them, they get pretty sick. And then they get things later, and they’re probably not going to be systemically ill. But with all of these things, you can have virus in your blood when you get infected, when the virus reactivates later.
CMV is something that, typically, we get from other people’s bodily fluids, urine, saliva, blood, in theory, although that’s not a typical way it would get transmitted. And usually in adults, it doesn’t make you sick. It can make some people sick, but typically, it doesn’t make people sick. But it can get into your cells and reactivate later in life. But the reason we care about it in pregnancy is because CMV is the most common non-genetic cause of hearing loss. So, for children who have hearing issues, if there’s not some genetic reason, it’s usually because of CMV. And CMV is very, very common. Between 0.5% and 1% of children are born with congenital CMV.
Dr. Fox: Just to clarify, between half a percent and 1%?
Dr. Gelber: Yes.
Dr. Fox: Right. Okay. Between zero… Yeah.
Dr. Gelber: So, like, 99% to 99.5% children are not born with congenital CMV. So, it’s uncommon. There are, like, 40,000 children a year in the U.S. with symptomatic congenital CMV. And so, people get it because they get exposed to it in pregnancy, but also it’s complicated because fetuses can also get it because their mom had had it in the past, and it reactivates. And so, there’s not a good test to do for people before they get pregnant to say, well, you can’t get CMV in this pregnancy, that your baby is 100% protected. And that is stressful for people because it is in the world around us.
And I think, recently, it’s been on people’s radar more for two reasons. For our patients, New York State made CMV screening part of the newborn screen for…I think, between 2023 and 2024, I think there was a little over a year where when they did the heel stick on newborns, they were sending that for CMV unless people opted out. And it was sort of hard to opt out. So, people generally didn’t. So, a lot of people heard about it because they knew someone who was contacted because…or they were contacted because their baby was CMV positive.
And then, also, we’re still dealing with the repercussions of all of the lockdowns during COVID. I think there’s been a big uptick in a lot of infectious diseases that we didn’t get when people weren’t touching other people. And now, they’re sort of coming…you would have had a steady…however many people a year were getting these diseases and instead nobody got them. And then, suddenly, there were all of these susceptible people getting sick all at once. That’s been a bigger thing with parvovirus than CMV, but I think it’s probably true of CMV, too.
Dr. Fox: Yeah. I mean, I think that there’s a couple of things…and that was a really good overview of CMV. There’s a couple of things to unpack that I think are really key points in that. The first is that, you know, for people listening, like, you know, most viruses that people get and where they would get, you know, whatever it is, a cold, a flu, you know, ranging from mild to severe, whatever it is, if they get it when they’re pregnant, most of those viruses will not infect the baby, will not hurt the baby, will not cause any problems in the baby. You know, no birth defects, no issues, this or this. Like, if someone gets the flu, like, are concerned with the flu with the mother, that the mother is going to be sick. It’s not that the baby is going to be born with, like, congenital flu and have birth defects.
And that’s true with most viruses around, but there are a few that can infect and cause harm to the baby. And CMV is one of them. So, that’s, like, sort of problem number one about CMV related to pregnancy. And problem number two, as what you’re saying, is that it is a…some of the viruses where this can happen, like, for example, like you’re saying earlier, parvovirus, it’s the kind of virus where you could…you get it once and you don’t get it again. Right? So, if you get parvovirus, you’re not getting it again. And so, if we check and someone has antibodies to parvovirus, they’re immune to it, they’re not going to get it again. But CMV is not like that. Meaning, you can have had it in the past, and it can reactivate in your body. And so, finding the antibodies doesn’t give you that sort of guarantee, so to speak, that you’re not going to get it in pregnancy. And I think that’s really sort of what makes it unique, compared to many of the other viruses that we talk about in general.
Dr. Gelber: Yeah. That’s exactly right.
Dr. Fox: So, taking both of those. Right? So, let’s say…let’s take the first part, the part where it can infect the fetus. So, what happens? What could happen during a pregnancy if the mother got CMV during pregnancy is sort of question 1A. And question 1B is if it got reactivated. Right? Because I will…spoiler alert. It’s different. Right? It’s worse if you get it the first time than if you get it reactivated. But sort of what are the things we’re worried about other than hearing loss in a newborn?
Dr. Gelber: So, the reality is that the vast majority of women who get CMV in pregnancy are not going to have children with congenital CMV. Like, the mom will get it, she’ll clear it, the baby won’t be infected, everyone will be fine. But sometimes, like when there is primary CMV, so, you’re getting CMV for the first time, either preconception or periconception, like around the time of conception, or, you know, at some point in pregnancy, about one to…so, about 1% to 4% of women get a primary infection in pregnancy. And then about a little less than half of the fetuses will be infected, 10% to 15% will be symptomatic at birth. And then 25% of them will have something, like, be it hearing loss or neurodevelopmental issues by age two.
So, most people will be fine. The most common thing is hearing loss. But then sometimes babies can be born, and they can be very, very sick. They can have what are called petechiae, which come from having low platelets, or the head can be very, very small. And I hate to say that because lots of fetuses on ultrasound have small heads. And, you know, we think about it, but that is probably one of the things that worries parents the most is they’ll see the number on an ultrasound, and they’ll be worried even though we are not worried. And we’re not missing a lot of symptomatic CMV by not having a bigger cut-off for head circumference. But, like, the head can be really small, and that can be associated with developmental delay. The spleen and the liver can be really big and not functioning appropriately. Especially babies that are born prematurely with CMV can be very, very sick. It is rare for babies to be very, very sick, but it happens.
Dr. Fox: Is there a way for someone to know? Let’s say we did know that they got CMV during pregnancy. Now, that’s a whole other conversation that we’ll have. But let’s say you knew you got CMV in pregnancy. Is there a way to know what are the chances my baby’s going to be symptomatic or not, or sick or not, while you’re pregnant?
Dr. Gelber: Well, if you have CMV in pregnancy, we recommend that you have an amniocentesis, and then we can look and see, did the baby get an infection. And if your amniocentesis does not have CMV in it, it would be very, very surprising if the baby was affected. And then it’s more complicated if there is CMV in the amniotic fluid, because, again, most people will be okay, but sometimes babies will be very sick. And I think it depends on what we’re looking for.
So, if you’re just doing…if you tested someone’s blood every month and there are no signs of CMV, it’s…like, so, you have a positive blood test at some point, but there are no ultrasound findings, that’s going to be a baby that’s more likely to be okay. Whereas sometimes we do an amniocentesis because we see signs of CMV on ultrasound. Either we see something in the brain, it can cause calcifications in the brain, or we see something in the liver or the bowel, or the baby is very, very small, or the head is very, very small. And those babies that are showing signs on ultrasound are much more likely to be sick when they’re born.
Dr. Fox: Yeah. And I don’t think…I mean, there’s no way in a podcast we could tell anyone who’s listening, you know, who’s worried about this for their own pregnancy, here’s your chance. Right? It just doesn’t work like that. It has to be individualized. So, on our end, I guess, you know, the amniotic fluid that we test for an amniocentesis is baby pee. And just like in a newborn or an adult, you can do a urine test and check if there’s CMV in your body. What we do is we do an amnio. It’s basically a urine test on the fetus. And if there’s no CMV in the amniotic fluid, basically, the conclusion is not 100%, but as you said, it’s very close to 100% that the baby does not have CMV. And so, you’re probably in the clear, which is great.
Now, if it does come out that there’s CMV, you know, sort of it’s hard to quantify, but logic dictates if we’re seeing abnormalities on ultrasound, that’s more likely to be a baby who’s sick than if we see nothing on ultrasound. And none of these are guarantees in either direction. It just sort of moves the needle a little bit.
Now, what about if we were confident that the CMV that the mother has is not a primary infection, but it’s a reactivation of an old CMV, right? So, we know definitively that she had CMV five years ago. And now, she’s pregnant again, and we suspect that she got reactivation of CMV from a blood test or whatever it is. Is that a situation which is…and I gave the spoiler alert before that is less concerning. And if so, to what degree?
Dr. Gelber: It’s much less concerning. So, for people who reactivate their CMV in pregnancy, like, between half and 2% of newborns are going to develop a fetal infection. And that was compared to primary CMV where 40% of fetuses are going to develop a primary infection. So, it’s like the difference between practically half and 1%.
Dr. Fox: Yeah. It’s so much different.
Dr. Gelber: And then of that, you know, 1% that develops an infection, less than 1% are going to be symptomatic at birth compared to in the other situation where with the 40% of fetuses that were infected, 10% were going to be symptomatic at birth. So, you’re less likely to get the infection. And if you get the infection, you’re less likely to be symptomatic, and then you’re less likely to have problems later. So, it’s not a guarantee. It’s reassuring to have had CMV in the past.
Dr. Fox: So, knowing all of this, right, that CMV is out there and it’s…it is very prevalent. I mean, if you look at…if you just sort of randomly blood test people, you know, about 50% of people will show evidence that they had CMV sometime in their life. It’s very, very common to get this at some point. So, knowing that, what should we be doing about it? Right? Because there’s a lot of debate, and different people do it differently. Like, should we just wait to see if someone gets sick, and if they get sick, test for CMV? Should we be testing blood for antibodies routinely before pregnancy, during pregnancy, serially in pregnancy? And if it’s not determined what the best thing is, what are sort of the reasons why you do one or the other or why there’s disagreement about this?
Dr. Gelber: So, they have looked at this. There have been a few studies looking at checking people’s blood repeatedly. And there’s generally a feeling that we should not be doing that because there tends to be more harm than benefit. Like, in the studies where they looked for people seroconverting, a very high percentage of patients ended up terminating their pregnancies sometimes before doing an amnio. So, they didn’t even know if their baby was infected. They’re like, I’m not taking any chances. And the frequency of that was so high that it was viewed as an intervention that was causing more harm than benefit.
Dr. Fox: Right. And just to…seroconverting means you find someone, they first have no antibodies and then they have antibodies. So, the assumption is between point A and point B, they must have gotten CMV.
Dr. Gelber: Yes.
Dr. Fox: Okay.
Dr. Gelber: So, I’m going to take a step back. What I write in my consults when I see a patient for preconception counseling is that I don’t recommend routine CMV testing in pregnancy. But I qualify it that if you’re going to do this, because a lot of doctors do this, you should do the testing before pregnancy so that if the patient you know is already IgG positive, that’s helpful. And if they’re negative and then later they’re positive, you can presume it’s a primary infection and counsel the patient that way. But just going into it in the first trimester, sending tests for antibodies is frequently very, very confusing. And it can be very, very hard to ascertain how long ago the patient acquired CMV and if the pregnancy is at high risk or low risk.
Dr. Fox: Yeah. And in practice, this happens all the time where people, they get a blood test in the first trimester. There are some antibodies to CMV and then either there’s an assumption, oh, I must have gotten CMV in pregnancy, or a question, did I get CMV in pregnancy and it’s hard to sort it out. And that’s because the antibodies is not that straightforward. I mean, for those listening who care, there’s two kinds of antibodies we look at. There’s the IgG and the IgM. And the thought is that when you get…and this is true for many viruses, but when you get CMV, the first thing that comes out positive is IgM. They sort of happen rapidly. And then eventually your body develops IgG. And then eventually after that, your IgM goes away.
And so, the thought is, if you find someone who has IgM alone, the thought is they just got CMV. If you find someone who has IgG alone, it means they had CMV a while ago. And if they have both IgM and IgG, the thought is they’re sort of in between those two. But the problem is the time frames on these are very imprecise. Is that days? Is that weeks? Is that months? Right? Is it years? It’s not well mapped out. So, frequently, someone gets…you know, you check them in the first semester and they check them. They have no antibodies. Fine. You have not gotten CMV in your life. You’re at risk for getting it in theory. Fine. Or if they have IgG alone, you’re like, probably you had it a while ago. You’re not immune because you can get it again, but you’re fine.
But if they have IgM and IgG, which frequently happens, you don’t know. Right? Did they get CMV a week ago? A month ago? Did they get it three years ago, and now, it’s reactivating? Or is it like it’s in…or is it just your IgM lasted longer than most people do? And so, it’s very, very confusing. There is a secondary test called avidity testing, which helps to sort that out, but it’s not perfect.
And so, I agree, there’s always a lot of confusion when that happens. Yet there are doctors here who send them routinely, even though sort of the U.S. sort of base organizations recommend against it. And then in certain countries like in Israel, they do recommend testing it routinely, and they do. And so, it’s not like, yeah, it’s different in different places, but these same issues arise no matter what…what the policy is or what the practices is, there is still confusion if you test in the first trimester. And sometimes you can sort that out, and often you can’t.
Dr. Gelber: So, the argument for testing in the first trimester is there is…there have been a few papers. It is not, like, the standard of care. There isn’t enough data to say this is 100% the right thing to do. But there have been several papers that have shown a benefit of high-dose valacyclovir, Valtrex, to decrease fetal infection in patients with first trimester CMV.
And so, if you test someone and they’re at risk, they’re IgM positive, they’re either IgG negative or IgG positive with low avidity, you can give them a high dose of valacyclovir. It’s 8 grams a day. It’s a lot. And it’s enough where 2% of people who are taking that dose have reversible damage to their kidneys. And so, it’s not nothing. Like, people who are taking this medication have to be monitored because it can be toxic.
But they’ve shown that for people who take this and tolerate it, when you do an amnio later, their fetus is less likely to be affected, and then they can stop it. And so, the argument for screening is that if you screen, you’ll find something that you can treat and decrease the likelihood of something bad happening.
Dr. Fox: So, what’s the argument against screening then?
Dr. Gelber: That we don’t have enough information, and that we can do that in the first trimester, but we don’t really have the data for the second and third trimester. And, you know, with more…we may find out about more toxicities for Valtrex or, you know, harm or something. You know, you want more studies before you say all 4 million pregnant women in the U.S. should be screened for this.
Dr. Fox: Right. And again, like you said, sometimes when you roll something out in a population, there are consequences that are unintended and may make it worse. So, for example, like you said, if not everybody who does the screening really understands this very well, and the message that patients get is from the blood testing, your baby has CMV, they may choose to terminate the pregnancy or, you know, whatever. Bad things can happen. They certainly can get a lot of anxiety. They can get a lot of harm to their well-being in that sense. And so, it’s not the simplest thing in the world in current state. We’re 2025 or if this podcast gets dropped in early 2026, the current state amongst U.S. sort of OB and MFM societies is not to do this testing routinely, but it is done elsewhere in other countries, and some people in the U.S. do it anyways. But it’s a really interesting question about which way is actually better. And maybe this will change with time. I don’t know. I’m not sure how it’s going to play out.
Dr. Gelber: Yeah. I mean, I think it would be surprising to me if at some point it didn’t become routine, but I think we need more data. We might need different medications. I mean, because, you know, this thing with renal failure is not nothing. And so, you don’t want…and this thing with people terminating pregnancies isn’t nothing. And so, you don’t want people terminating pregnancies that would have been just fine, and you don’t want people getting sick.
Dr. Fox: Yeah. Yeah. There was some hope, I remember years ago, for a different treatment of IVIG, intravenous immunoglobulin, but most of the big studies that were done looking at this were unfortunately not successful. So, again, sometimes when there’s early promise to a medication and then you do a larger follow-up study, you find, you know, this didn’t actually help at all. And so, now, we’re just causing anxiety and all these treatments and all this stuff when it didn’t actually help. So, I agree. It would be nice to have a bigger study showing that an intervention is beneficial before you roll it out to everybody. I mean, 4 million people is a lot of people.
Dr. Gelber: And then the other thing is that there are a lot of people working on CMV vaccines, but there is nothing currently available. [crosstalk 00:24:11].
Dr. Fox: Why is that? You’re a vaccine expert.
Dr. Gelber: I have no idea. Apparently, it’s hard.
Dr. Fox: CMV is a hard one. Yeah. I mean, every virus sort of [crosstalk 00:24:20]…
Dr. Gelber: I don’t know if it’s because there are different serotypes. So, you know, we talked about how CMV can reactivate, but the other thing is that there are different strains of CMV. So, you could get infected with one strain and not another strain. That’s another way you can get non-primary CMV.
Dr. Fox: Yeah. No. I think one of the really important takeaways for our listeners is this is a complicated topic. And if you are thinking about blood testing or you had blood testing and the results are a certain way, make sure that the person who’s discussing it with you is an expert. And that might be an MFM, it might be OBGYN who knows about this. It might be an infectious disease doctor. It sort of depends, you know, sort of where you are on this, but you have to make sure they really…they have a sense or you get a sense that they really understand what they’re talking about here. Because if someone…if you get a blood test and someone says you maybe have CMV, then probably they’re overstating it because there’s…we don’t know that from a blood test. You really need to do more investigation to find that out. And that’s because, I mean, we get…I get consults all the time, you know, baby has CMV, and then you figure out, well, no, like, the mom might not even have CMV. Like, there’s so many steps that have to happen before we can make that diagnosis. And that’s just an important point for this, I would say.
Dr. Gelber: Yeah. I mean, the vast majority of people I see who are IgG positive, IgM positive in the first trimester, because that…you know, it was just a test that was done routinely. They go on and have an amnio. The vast majority of them are negative. Like, their baby is fine. Their baby is not infected with CMV.
Dr. Fox: That’s good. That’s reassuring.
Dr. Gelber: But I think people are almost always very, very upset with that result.
Dr. Fox: With which result?
Dr. Gelber: The result that their baby is at risk, that they might’ve had CMV in the first trimester.
Dr. Fox: Yeah. I know that’s a very scary diagnosis to get. Good. Awesome. Shari, thank you for coming on to clear the air about CMV. I think this is really helpful, and definitely more than we could just…I could just answer in, like, a three-minute “Mailbag.”
Dr. Gelber: I’m going to mention one other thing.
Dr. Fox: Oh, good. Hit me. Hit us.
Dr. Gelber: Because, you know, I always have another thing. The data we have is, like, data…it’s the same data about, you know, the number of affected babies, you know, is… I have the same numbers I had when I learned about this 30 years ago, but the pediatricians are doing amazing things. And they now have therapies for the newborns, which have decreased the likelihood of hearing loss, decrease…and increased just the wellbeing of these babies. So, I don’t have updated numbers, but you know, one of the things about a child being diagnosed with CMV is the pediatric landscape is, you know, the obstetricians, we’ve done nothing in 30 years, but the pediatricians have really moved the field.
Dr. Fox: That’s amazing. No. And that is important because it’s…it would also…it would definitely give a lot of support to screening newborns routinely. If you could screen and do something and improve outcomes, that makes a tremendous amount of sense for screening. And that’s sort of the paradigm.
Dr. Gelber: Yeah. And I mean, they have the same problem, which is that the…some of them screen newborns and, like, when they screen the babies that are…when they test babies that are symptomatic, I think they treat those babies. When they screen babies, it’s harder to know what to do.
Dr. Fox: Right.
Dr. Gelber: Like, because if a baby isn’t symptomatic, some of them will get sick later. Most of them won’t. So, then you’re in the same situation. Do you want to give someone a medication that might be toxic? Or that might be inconvenient if everything is going to be okay.
Dr. Fox: Awesome. All right. Thank you for coming on the podcast. Great stuff. I appreciate it.
Dr. Gelber: Okay.
Dr. Fox: Thank you for listening to the “Healthful Woman” podcast. To learn more about our podcast, please visit our website at www.healthfulwoman.com. That’s healthfulwoman.com. If you have any questions about this podcast or any other topic you would like us to address, please feel free to email us at hw@healthfulwoman.com. Have a great day.
The information discussed in “Healthful Woman” is intended for educational uses only. It does not replace medical care from your physician. “Healthful Woman” is meant to expand your knowledge of women’s health and does not replace ongoing care from your regular physician or gynecologist. We encourage you to speak with your doctor about specific diagnoses and treatment options for an effective treatment plan.
