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Melanie Cole (Host): There's no handbook for your child's health, but we do have a podcast, featuring world-class clinical and research physicians covering everything from your child's allergies to zinc levels.

Welcome to Kids Health Cast by Weill Cornell Medicine. I'm Melanie Cole. And joining me in this panel today are Dr. Christine Salvatore, she's an Associate Professor of Clinical Pediatrics at Weill Cornell Medicine and Dr. Sally Permar, she's the Chair of Pediatrics at Weill Cornell Medicine. Doctors, thank you so much for being with us today.

And Dr. Salvatore, I'd like to start with you, if you would give us a working definition of our topic today, which is congenital cytomegalovirus. Can you tell parents listening what that infection is and how common it is?

Christine Salvatore, M.D. (Guest): So congenital CMV, it's very common infection, but it's very underestimated. It is caused by this virus that is called cytomegalovirus. This has been around forever, and in adults and older kids gives no problems, like a flu. You have some fevers, you some malaise, but then it goes away. The problem is in when the moms gets the infection during pregnancy. And so the virus can go through the womb, through the placenta, to these babies, and they are born with this virus. And so that's when we call it congenital CMV.

It's very, very common. Like one every a hundred, one every 200 babies, is born with this infection in the United States. And we think actually in the world as well.

Host: Wow. That's so common, much more common than I think many of us realized. And Dr. Permar, tell us a little bit more about this virus. What are the symptoms that would raise red flags that could indicate CMV? How do we even know?

Sallie Permar, M.D., Ph.D (Guest): So as Dr. Salvatore said, it's an extremely common virus that generally doesn't cause too much of a problem unless you get it the first time or even are exposed to it again during pregnancy and potentially pass it to the fetus. And what it can result in is symptoms at birth potentially that can include a rash, can include some liver problems, can include some effects on the head circumference. So, the brain growth, in the fetal period. But many children can be born without any symptoms of the infection, but they may develop those over time, over the first few years of life. And some of the common impacts that this virus can result in is neurodevelopmental delays. So delays in speech and language development. A very common symptom of this virus is hearing loss.

And it's actually the cause of 25% of all infant hearing loss is due to this one virus. And even seizure disorders. Other, more subtle things like problems with your eyes and your balance. So, this virus is really more common than everything we test for on the newborn screen and causes so much, in the way of how our children are progressing, with their development and their neurologic, capabilities.

Dr. Salvatore: And definitely one of the things though that I wanted just to add is that like Dr. Permar said, the majority of these babies actually are born without any signs and symptoms. It's 90% of the babies. So, many times you would not know that they have this congenital infection because they have none of these red flags for which we would test these babies.

Host: Well, then I'd like to just follow up on something. Dr. Permar said, is this recent? Is this something we have known about for a long time? Being that it's so common, and nowadays we're hearing about viruses that we've never heard of before and various Coronaviruses that have been around for a while. But now we're learning about specific ones as you are educating us. Is this something new? Is it something in the last 10-20 years? Has this been time?

Dr. Salvatore: Yes, I don't know exactly when it was discovered. I don't know if you actually, Sally knows the exact time?

Dr. Permar: Well discovered in the sixties. I believe.

Dr. Salvatore: Right. So it's been there forever. Is just that the interesting part is almost nobody knows about how common a congenital infection is. And one of the things that I do, for example, ask in my clinic, when I see these parents that come with their baby that had just recent diagnosis. They ask me all the time why nobody ever told me about it because I never heard about this virus. But instead, has always been there. It's just that we just don't know. There is not that much education about the virus that is so common and has always been there.

Dr. Permar: Right. I always say it's a virus that has a PR problem because the people that need to know about it, which really is pregnant women or women planning a pregnancy or families planning pregnancies. It's not common to get education about it during your pregnancy or it's amongst all the things that you're hearing about all at once. And there's so many things to consider, when you learn you're pregnant. And it's a virus that, yeah, again, we've known about it for well over 50, 60 years. In fact, it's theorized that this virus has been evolving with the human population since the time of the dinosaurs even, is when they think the virus first started.

So since humans have been on this earth, they potentially have been walking around with this virus. And we've known about it as a common cause of congenital infections since at least the 1960s. And therefore it's been on the radar that we need a vaccine for this, infection for that many years.

And actually the, studies have been going on for at least more than 40 years towards the vaccine, which really puts it in perspective. Now that we've seen a new virus get a vaccine in less than a year. And so it is something that we continue to push that more education needs to happen and really solutions need to continue to develop for this, what we also refer to as a silent epidemic.

Host: Dr. Permar, I'd like you to speak and expand about the vaccine development. Because as I understand it, Moderna has launched their second, phase three trial over the CMV vaccine and your lab contributes to work around this. Speak to the listeners about that what's happening.

Dr. Permar: Yeah. So, it is an exciting time towards the development of a vaccine for cytomegalovirus to really, eliminate it as a cause of infant hearing loss and neurodevelopmental impairment. It's something achievable that we could end this cause of children losing opportunity to have their greatest potential in life.

And, I have been involved in CMV vaccine development since really I started my career as a Pediatric Infectious Disease Fellow, where I saw that in congenital infection clinic, I kept seeing, it was like, I had my own Zika virus epidemic going on in front of me because I saw so many patients with the same virus and I just thought who is making a vaccine for this virus. At the time I was working in HIV vaccine development, but noticed that there weren't a lot of researchers in academia who were working towards CMV vaccine. So really took that on as an area in my own research. But luckily there are a number of programs in companies that we now know of as household names like Moderna and Pfizer that are making vaccines for CMV and are in various stages of testing. And the one that's furthest along right now is Moderna. Moderna's lead product before the SARS COV2 pandemic was a CMV vaccine. And so I'm proud that they have carried that forward even after the SARS COV2 vaccine pursued, that it's now their second, phase three trial is ongoing right now with a CMV vaccine based on their mRNA technology. So I do have great hope that a vaccine is coming for CMV.

Host: And when that happens, I'd like you to come back on and let us all know about that. Now, Dr. Salvatore, as you see all newborns in clinic, I'd like you to tell us about your goals to create a congenital infection clinic and in particular for CMV, what would that look like? Because I think that parents are going to have a lot of questions and certainly as diagnoses are made, they're going to want to know about transmission, the risks to already born babies and even their caregiver.

Dr. Salvatore: So our congenital clinic and congenital infection clinic, particularly in CMV, because I think that is the one we are seeing the most is the congenital CMV; has to be a multidisciplinary because it's not just me, as an Infectious Diseases Specialist. There would be in association with the audiologists. That is extremely important because as we have been saying, hearing loss is one of the most important things. So, there has to be a collaboration with the long-term follow-up with these babies. Me seeing these babies for the first time in clinic and then referring to them for the long-term follow-up. The other person that would be very important, would be a developmentalist. Because again, as we said, their development can be affected by having congenital CMV. So it's a sort of multidisciplinary team that we would have to put together to have the expertise to see, evaluate the small little nuances probably of congenital CMV. Of course, what is important when they come, it would be to have a counseling because the parents will need a lot of counseling.

And do I receive a lot of questions. Do we have treatment? Do we don't have treatment? How is the chance that he will develop all these things? And so that is something that we will have to do is be able to talk and reassure also, parents, but of course also telling them the facts of what we have experienced during all these years.

And considering that my goal would be to do universal screening. As I said, we are missing many, many babies and diagnoses. So universal screening would be to test every single baby at birth. So, we are not going to miss any potential baby with congenital CMV and we could right away, channel him to the right follow-ups.

So that could be with the audiologist, for example, with the ophthalmologist for an eye exam, and all the rest of the workup that needs to be done. That is sort of my goal and what I would like to create with the clinic and how I approach it usually with the parents.

Host: Well, Dr. Salvatore, is there treatment? mentioned this parents listening are going to go well is there treatment? about that.

Dr. Salvatore: We do offer treatment. There are different scenarios, let's say. There is not complete understanding of how treatment really works or not in these babies. One of the things that for sure, as of now, every probably, pediatric infectious disease specialist would, treat babies that do have CNS involvement. That means involvement of the central nervous system. And in those cases, definitely, treatment with valgancyclovir. This is one of the medications, the antiviral that we use. We do, advise strong. This did show in blinded randomized trial that are the most correct trials, show that actually there is improvement in hearing, at one point. Not in every single baby, but in the majority of the babies, there was an improvement, or at least there was no worsening of the hearing loss. And also there was improvement in the cognitive development, especially the receptive communication, how they are able to hear and also to communicate.

In those cases, in babies less than one month of age, we do offer treatment. For the other babies that are completely without sign of symptoms, or they are a little bit older than one month of age, there is a lot of debates of what to do and in my opinion, I think that especially if they do have hearing loss, I do tend to offer, strongly to the parents to start treatment.

But it's a long treatment because it's a six month treatment. It's not something they say 10 day course, and that is over. That's why there has to be a common decision with me giving advice on what we know at this time about the infection and about what is available about the treatment.

Host: Dr. Permar, we would be remiss in this podcast, not to mention your groundbreaking work on mother to child transmission of viruses, including HIV and CMV that earned you the prestigious 2020 - 2021 Society of Pediatric Research Award in honor of E. Mead Johnson. Tell us about that. did that feel? How cool is that?

Dr. Permar: That was really a career highlight for me, because this is an award given by, the primary society that celebrates and fosters pediatric research. It's their top award and really some, really amazing pediatrician scientists who have gone on to develop other really successful vaccines or treatments for childhood diseases, are amongst those that have been recognized.

And really, I think it was, partly in recognition of the importance of the virus that we're talking about. The importance of CMV as a cause of neurodevelopmental impairments in children. Every pediatrician recognizes how important ending that virus as a cause, a preventable cause of neurologic impairment in kids is just so clear.

And so I would like to think that in partly, it was also, to recognize the importance of the work around developing a vaccine for CMV. Similar to how we have a vaccine that really has eliminated congenital rubella syndrome as a cause of impairment in children. And one of the award winners is the developer of that vaccine for this award as well. So I think it's actually partly a nod to the importance of the work.

Host: Well, it certainly is. And I'd like to give you each a chance for a final thought. This is such an interesting topic. And when I was doing my research and I've done a lot of these, I must tell you that I was surprised at what I learned about something that as you said, has this PR problem, right? It's one of those viruses. Some things get a lot of PR and some not so much. So that's what we're here doing today. And Dr. Salvatore, I'd like you to give us some prevention or mitigation strategies for parents and caregivers to reduce that risk of infection. Is there anything that we can do when women are pregnant, before they get pregnant or even after the are born to reduce that transmission?

Dr. Salvatore: One of the major risk factors, in a sort of way with somebody is pregnant or planning to become pregnant, is having actually toddlers at home. And the reason is the transmission. The transmission it's so easily transmissible because it's through the saliva, the droplets that you may be have it in, this sample of our body that is so common, you sneeze. And toddlers actually have a high amount of virus. And one thing that we tend to do as parents, because of course I am a mom, I realize sometimes I do that mistake, or I did actually that mistake, like not washing my hands or to clean the utensils sometimes that I gave to the toddler. I've seen it sometimes that you clean it with your mouth or the pacifier falls on the floor and sometimes you clean it yourself. You don't have water next to you.

And those are actually the things that have shown to increase the incidence of congenital CMV. So all moms who are planning really to have babies, and they do have toddlers, but in general, wash your hands always. Do not share utensils. Do not share pacifers. Do not do these simple things. Trying not to kiss on the mouth your toddler, your children. And I know that I do that mistake. However, some studies that showed actually that moms who were aware of this or potential mom, if you are pregnant women, actually, that knew about it. So that is where the information is very important. And the knowledge of it actually had a decreased chance of transmission compared to moms and pregnant women who were not aware of any preventive and we're not giving any instruction on how to prevent. So even though it's extremely hard, but really can prevent congenital CMV. And so that's what I usually really advise.

Host: That's a great takeaway message. Dr. Permar, last word to you. You've been working with government affairs towards advocating for state legislation around CMV education. And as Dr. Salvatore said earlier about universal testing, I'd like you to finish podcast telling us how's that going? Any progress that has been made and your final thoughts for parents listening?

Dr. Permar: It is really important as Dr. Salvatore brought up, for us to work towards testing every baby for congenital CMV, just like we test them for number of other diseases again, that all added up together are less common than CMV and then we would know ahead of time, whether we should screen for their hearing, screen for potential developmental delays, potentially put them on treatment.

So all these things we can go into knowing, if we do that screening at birth. And that's what we're working towards through state legislation. There is some exciting work in certain states that have expanded their testing and even in Minnesota is the first state that will start testing every baby, as a new state law.

So we are working in New York state towards a CMV education bill this year that will require that providers talk to the pregnant women about CMV. But it also needs to go further than that, into the universal testing. And really it's an exciting time, I think, in that, yes, everyone knows what a virus is now. Everyone knows about the importance of vaccines and how it can really end epidemics and work towards preventing disease. And that's the type of understanding that we need to move forward in the fight against CMV and it's cause for preventing a child from really reaching their full potential.

And this is cause that, of disease in children that we know we can defeat. We can do it through the methods that we know have worked for other similar infections, like congenital rubella syndrome. And I think we can do it here for CMV.

Host: And that's why we're talking about it. And I thank you both so very much for coming on and sharing your incredible expertise on a topic that I think like other parents like me, we're just not as familiar with. So thank you so much for educating us and telling us about all the great work that you're doing to help babies and caregivers. And Weill Cornell Medicine continues to see our patients in-person as well as through video visits. And you can be confident of the safety of your appointment at Weill Cornell Medicine. That concludes today's episode of Kids Health Cast. We'd like to invite our audience to download subscribe, rate, and review Kids Health Cast on Apple podcasts, Spotify and Google podcasts.

For more health tips, please visit weillcornell.org and search podcasts. And don't forget to check out our Back to Health. Lots of interesting podcasts there. I'm Melanie Cole.

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