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Hidden in Plain Sight: Understanding Congenital CMV
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Congenital cytomegalovirus (CMV) is the most common congenital infection worldwide, yet awareness is surprisingly low. We’re joined by Dr. Kaisha Gonzalez, Scientific Affairs Director at Diasorin, to unpack the complex spectrum of congenital CMV: from transmission during pregnancy to diagnostic challenges and long-term outcomes in newborns.
Hello and welcome to Diagnostics Decoded. In today's episode, we are diving into congenital cytomegalovirus or congenital CMV, which is the most common congenital infection worldwide and a leading infectious cause of hearing loss and developmental disabilities in children. And despite its prevalence, awareness remains surprisingly low, not only among the public, but also within the healthcare community. And today I am honored to be joined by Dr. Keisha Gonzalez, Scientific Affairs Director at Diasaurin. Keisha, thank you so much for joining me and taking the time to honestly educate us all today.
SPEAKER_03Thank you, Jessica, for having me. Very happy to be here and so looking forward to the conversation.
SPEAKER_02Yeah. So let's get started. So for listeners who might not be familiar, what is congenital CMV and how does it differ from the CMV infection that we honestly probably already all might know about?
SPEAKER_03That is a really great question and great way to start. So cytomegalovirus or CMV is actually a very, very common herpivirus. Most people are actually exposed to it at some point in our lives. It's very ubiquitous, so it's not very rare. CMV actually is spread through butterly fluids like saliva, urine, blood, even breast milk. So exposure is very common, especially if you are in environments close to daycare or even uh young children. And this is one of the reasons why, actually, around age of five, a lot of these children at school age, around 30%, they tend to be already seropositive. Wow. And yes, and not even that, like as we age and increase in our age, it is estimated around for adults around 40 years old, you will have some sort of seropositivity around 50%. Wow. And yes, and this is even worse for women because women now and then it's even closer to 60 and 80 percent in certain populations. So, like I said, it's not rare, it's very common. We get exposed all the time. And for your question in terms of how adults experience this infection, right? For healthy individuals, normally it's very mild or asymptomatic. Meaning, right, it's if it does have some symptoms, it's actually often like a flu-like symptom, you know, fatigue, maybe low-grade fever, nothing very specific. So it's not very easy to identify, oh, this is a CMV infection, right? When it comes to immunocompromise individuals, it's a different story. So I'm for sure you know, like CMV, it's very well recognized at the solid organ transplant space.
SPEAKER_02And that's always what I would think of when I would hear CMV is okay, transplant. Like I never considered or had heard of congenital CMV.
SPEAKER_03So yes, exactly. It's I mean, CMV EVB, which is another herpivirus, is very clinically significant uh for infections when we monitor, like we do like a viral low testing or quantitative testing for those immunocompromised individuals. So everyone hears about that and tests about that. Right. CMV then, right, because it's a herpivirus, it can reactivate under immunosuppression. This is why it's so important for this type of individuals, because it can actually cause a lot of invasive disease. So invasive disease like pneumonia, maybe sometimes uh even for systemic infections. So when it comes to transplant, right, has some indirect effects in terms of possible rejection of that organ or even grap dysfunction. This is why it's so very impactful when it comes to immunocompromised individuals. Now, when it comes to congenital CMV, which is the topic of today, right? This is when then infection happens during pregnancy and it's transmitted then by the mother to the fetus as a vertical transmission through the placenta. And this is then where actually becomes very different clinically of what you expect for immunocompetent individuals or even immunocompromised ones, because instead of a mild infection, this CMV infection can actually interfere with the fetal development. So, particularly for this type of infection, can cause a lot of issues to the brain and the auditory system. Wow. This is why it's so important, again, depending on the population, to understand the impact of CMB infection, which is varies as you can see in different individuals.
SPEAKER_02Yeah, yeah. How common is congenital CMV in newborns?
SPEAKER_03That is actually a really good question. And I think you share a little bit of the stats, right? It's one of the most common actually infectious causes of birth defects, especially here in the US. I think it's around one in 200 babies that will have some sort of impact of the CMB disease through the congenital CMB infection. It's also the leading cause of non-genetic cause of sensory neural hearing loss in children, which is when the inner ear actually uh or the auditory nerve, it's damaged. So it prevents then sound to actually be transmitted or being translated into the brain. So structurally, most of the time, those babies will have the middle ear fine and all that, but it's just nerve damage that causes this infection.
SPEAKER_02Okay. Thanks for sharing a little bit about what the virus is. Um, so let's start with during pregnancy. So say a mother has CMV, she might not know. I mean, we right, it's not something that's tested for. You test you talked a little bit about how it's transmitted, but could you kind of go into what if there's any particular risk factors that would cause the virus to transmit to the fetus?
SPEAKER_03Yes, there is actually in terms of risk factors, it's so many layers. And let me explain why. So you have the highest risk, it's when primary infection happens for that mother, meaning the mother is seronegative, right? So it's infected for the first time with CMV. In those cases, transmission to the fetus actually has been shown in a lot of studies to be up to 30 to 40 percent.
SPEAKER_00Wow.
SPEAKER_03So that layer of uh being a primary infection, it's uh really high risk in that sense. Now, it is very important then to understand the nuance of these infections because even when the women has been privileged exposed, so it's already seropositive, they can still have a reactivation or reinfection with C and B, which is known as a secondary infection. Sure. So they so they are not completely protected, even at that point, and because of that, then although it's not as high as risk as a primary infection, it can still lead to transmission, it's just a lower risk for those babies. Sure. And then and then here's another problem that I would say, right? Not only about the maternal immunostatus, it's is needed to understand the transmission, it's also timing matters too. So early infections in pregnancy tend to actually be associated with more severe outcomes, even though, right, in later pregnancy the transmission is actually higher. And this, yes, this is actually because of the human anatomy and how the pregnancy develops, very nuanced from that perspective, because just as you know, right early when early in the development, like the first trimester, organ systems are actually developing.
SPEAKER_02Right, the brain is like the scariest time of pregnancy.
SPEAKER_03Exactly. It is besides morning sickness and all that, from that fetus perspective, it's the development. So a lot of the brain developing, it's happening right there. And so if that infection happened at that stage, has a bigger impact for that baby, right? Later in pregnancy, the placenta, and this is again human anatomy, the the beautiful things of mother nature. The placenta is actually more mature, more developed. Right. That means functionally is connected to the fetus, connected to the mother, which then creates that transmission of the CMB more efficient. So this is why transmission is higher at later stage, but it's less impactful because right, the severity of that potential infection, the baby already it's more mature in the development stage, right? Third trimester, baby is already full form. So if that happens, then the impact is less. So this is why I say is like it's it's such a nuance when it comes to the transmission and the risk and the combination of things because it has to do with the mother immune status, then the timing of the infection, then exposure risk that drives everything in terms of the outcome of this disease for those babies.
SPEAKER_02Yeah. So say a mother has CMV and it's just dormant in her body, she has no idea, will the fetus always be born with CMV?
SPEAKER_03No.
SPEAKER_02Okay, so it's even more complicated.
SPEAKER_03It is more complicated because I would say, right, that not all maternal infections lead to fetal infection. So even if you are right there reactivated and having some sort of episode of CMV infection, not necessarily will that transmit to the baby. It has to do once again with the timing, whether the placenta is connected, and some other factors. So at that stage, even if you are positive and you're shedding CMV, the not necessarily you can pass that to the baby. And also important to understand, right, the risk, it's all about the primary and the secondary infection reactivation tends to be less impactful because your body is already accustomed to that infection. So the way that your body will react, cytokines going crazy, the inflammatory response and all that, it's lower. So that also creates some hopeful barrier on that transmission. So it can actually protect a little bit more that the body is not overproducing some of the stimulations to then cause the possible infection. So it's again, I wouldn't say that it's a flipping a coin, it's just too many variables that need to be happened at the same time in order to have a higher probability of that infection.
SPEAKER_02So during pregnancy, if an infection is suspected, how can a doctor test for it? Is that primarily coming up on an ultrasound or are there other testing methods?
SPEAKER_03So this is also when it gets very challenging because most because most maternal CMB infections are actually asymptomatic, there's not really often a clear clinical trigger to test for CMB. In some cases, though, CMB may be suspected. There's possible some abnormal ultrasound findings that it could be like growth restrictions, some babies, depending on that infection and how severe it can be, can have some microcephalia indications, some brain abnormalities, other fetal infection signs that can trigger some testing. But the unfortunate part here is like those are very still not specific for CMV. Right, right. Other infections can actually cause that.
SPEAKER_02Exactly. Yeah. So is CM like where does CMV fall in the diagnostic thought behind that? I mean, so say the baby the fetus is not meeting the developmental growth that you would expect. Where does CMV fall when you're testing or doing follow-up testing for that?
SPEAKER_03Yeah, so during that pregnancy, it is all about risk or suspicion. So if you are already a mother with high risk, could be like HIV positive, as an example, or already have some maternal exposure for CMV, or some sort of already information on maternal serology suggesting that there's a recent infection that may trigger to have some testing for that fetus, besides the abnormalities surrounding that ultrasound. So they normally they can have options on doing like amnio and amniosynthesis where they can do some CMB testing if it's needed. There's a BDD testing as well, that's more for Europe's side, but again, it's otherwise. I mean, if there's not really a risk of suspicion during pregnancy based on some abnormalities found in that ultrasound or the high risk of suspicion from that mother, the infection actually just pretty much can't fly under the radar. Like it's not gonna be able to actually detect it on time. Yeah.
SPEAKER_02Yeah. Say that the infection is detected. Is there any management that can be done while the mother is pregnant, or will that be all kind of postnatal management?
SPEAKER_03So I know there has been some studies trying to manage those during pregnancy, like do antivirals to protect as much as you can. The problem is those are very toxic, right? Especially for that for a fetus who will, depending on this development stage, can't cause even more toxicity and more damage than the course of the infection. And because there are so many nuance on just because that mother's CMB positive not necessarily will transmit that infection. I mean, it's a lot of conversation with the with the parents to figure it out if you want to treat. Treatment not necessarily happens usually here in the US. It's very, I would say off-label or more research driven outside here the US. A lot of Europe, I've seen some publications. But beyond that, if that fetus already has some abnormalities, I mean, antivirals will not do as much. It's just trying to mitigate more of the symptoms, right? Alleviate the symptoms, but not really beyond that, unfortunately.
SPEAKER_02Yeah, yeah. Okay, so now we're let's fast forward to birth. So can you kind of explain the spectrum of symptoms if a baby is born with CMV?
SPEAKER_03Yes.
SPEAKER_02I mean, that's also again, so yeah. No, I mean it's a complicated disease, right? Or a complicated infection.
SPEAKER_03It's yes, exactly, exactly. And and the wording of spectrum, it's the right word. And I'm glad that you used that one because it really exists on that spectrum. So at the end, uh one end, right, you have infants with clear clinical disease at birth. Right. And in the other hand, infants who look completely healthy, even with the infection present. Okay. I think one important thing to understand is that 90% of infants with congenital CMV will have the infection, but will appear asymptomatic, healthy babies. 90%. Wow. 90%, 90%. So they will look healthy, you know, they will have nothing really clinical to stand out that there's something wrong with them beyond even what they have the infection. Okay. The remaining 10% will then have what we call they are going to be symptomatic because they will have a CMB disease. The CMB disease can be the pathicle rash, which they call it, which is kind of like the hallmark of a CMB disease and infection at birth, which is uh they call it most of the time blueberry babies because they will have those uh vessels very uh purplish, and they will have some microcephalia, they will have some neurological presentations, seizures, some of that, they will have juntas babies who have that disease, but it's only 10% out of the whole spectrum of babies. And even with those who actually appear asymptomatic with the CMB infection, right, which is 90% of them, I wanna to make mention this is that they still are risk because some will go and develop late onset hearing loss or even narrow uh developmental delays.
SPEAKER_02And what is the timing you typically see on that? It is that a few years, can that be seven years, or is it does it just depend?
SPEAKER_03It all depends, unfortunately, and each baby is different. Most of the time when you start seeing that late onset happening, it's around that six months to up to a two-year, I've seen in some publications. So this is why it's so important to actually identify even those 90% of CMV infections babies, because identification matters to monitor progressively how these babies will go within the next couple of years, just to make sure that there's no other late onset progression.
SPEAKER_02So I know historically CMV testing has been very targeted and often only performed if the baby fails his or her hearing test, the universal hearing screening. Is that typically still the standard approach that we see today?
SPEAKER_03Yes. And in many places, unfortunately, in many places, and I will explain why I say unfortunate. This is still the most common approach. Any approach I will say is great, right? It's better than not. Right.
SPEAKER_02But when only 90% of those babies do not have symptoms, that's not being set up for great success to catch that, right?
SPEAKER_03Exactly, exactly. So, you know, we have that what you mentioned, right? The targeted, it's what we also call it hearing-targeted screening, right? That's when the infants are tested for CMV and are only the ones who fail the newborn hearing screen. The challenge is that, as you mentioned, right, many of these cases, the majority of cases will be missed. Because, like I said, many of these infants that were with congenital CMV infection will pass the hearing screen at birth, but later develop that late onset. Okay, so at birth, they do within the next 48 hours, the hearing test, they pass, but then six months later, maybe at two years, they start progressively losing their hearing. Because of that, I would say that there has been a shift in thinking, thankfully, and there are some programs that are moving towards what we call expanded target testing. And this is where infants are actually tested based on additional risk factors like the abnormal clinical findings like low birth, maybe they have some dipitechia. And this is uh also whether the mother has some suspected um CMB infection. Now, this is still unfortunately limited because it still requires a clinical symptom. And we talk about right that not a lot of will have clinical symptoms. So it's still great because it's adding additional besides hearing loss, they're adding additional criteria to include for testing, but it's just still limited to symptomatic babies, unfortunately.
SPEAKER_02And if a baby fails his or her hearing loss, where is CMV kind of in that physician's mind on like where does CMV fall in that diagnostic workflow?
SPEAKER_03That is a good question. And that depends on that physician or uh pigot. Which is scary.
SPEAKER_02Which is scary. And I say that only because, and we've talked about it, but not on the podcast. But it I mean, I I mentioned it before that it's just not a well thought of um infection among the healthcare community. And I talked to my OB about it um recently to be like, hey, what do you know about this disease? And she knew nothing. And I don't fault her for that because you can't test or educate against something you don't know, right? And if your primary doctor that's caring for your pregnancy doesn't know, and you know, when I had my daughter, it never came up during her our care when we were in the hospital. Thankfully, she doesn't that we that we know of, she does not have it, but it never came up in a discussion with her pediatrician in the days that we visited post-delivery. So it's scary.
SPEAKER_03It is scary, and I always share this story with me, with everyone, because it's similar to what you just told me, right? And we were discussing is I as my role, right? I'm scientific affairs, so I need to be educated in some of the topics that I have to uh handle internally and externally to educate people. And when I started diving into congenital CMV, obviously scared me the Jesus out of me because I'm like, what is this infection I never heard of? And I was six months pregnant with my second. Oh gosh.
SPEAKER_02So, as if you need something else to worry about.
SPEAKER_03Exactly, exactly. So I did the same thing as you did. I did ask my OBGYN, and I'm like, hey, you know, why you have not told me about this infection? This is my second child, and I'm six months pregnant, which I'm in the high risk category because my child, my first one was already in preschool, which that is that age of the five-year-old who has a really high serum positivity starting acquisition of CMB because a lot of children. I mean, they share everything.
SPEAKER_02I mean, what are you supposed to do? Like say hi, don't come and give mommy a hug, right?
SPEAKER_03Yeah, don't kiss me, don't hug me. Yeah, it's exactly. I can, obviously. And she she responded similar to what you encounter. She's like, Well, Kaisha, unfortunately, I'm in Maryland, so it's like there's no legislation here. So unfortunately, I cannot provide you with any tools, and I cannot, I don't have to talk about it. Yeah, and it's I completely understand her point of view because she doesn't have the tools to talk about it because there's no legislation under Maryland. But I'm like, as an expectant mother, right? We are told to avoid sushi, avoid cold pressure. Right, don't have cold-pressed drinks. Like, yes, and you know, just just make sure you are not at high risk and avoid eating delicious sushi and drink your water. And I'm like, we are told to protect that fetus, right? To protect our baby as much as we can, with a lot of precautions around on how to handle even to avoid certain things and scenarios. And us, of course, as parents, we're gonna do that because we want the best for our children. So it is very unfortunately that we don't talk about it. And to your point, right, if it doesn't matter, it's unfortunately if your pediatrician at that time or OVGYN doesn't know it or doesn't have the tools to talk about it during delivery, if that happens, right? The the only thing that it's put in place, they probably usually, and this is also part of my story. So when I started learning during my delivery, I my second baby actually failed first time the hearing. The the yes, which imagine me, scientists, everything spiraling. Yeah, yes. I am like, I was already in the phone with my OBGYN to I need a CMB test, and they're like, no, no, no, just wait, maybe it can be liquid, and most of the time, you know, this is why it requires to uh they need to fail twice because sometimes during if it's especially uh vaginal delivery, they're sometimes liquid and things like that, that it can affect the results. And I'm like, okay, I'm gonna give it. They have to wait 24 hours in order to retest. And I'm like, of course, I'm already like speed dial is like if this fails once again, like I will perform the assay myself, okay? Yes, I will exactly. I was like about to do that, and fortunately enough, for my scenario, right? My baby passed the hearing there, although I was so cautious about it because, right, we know that it can pass the hearing test, and then later on can have that onset. So I was monitoring my baby like crazy, making sure that you know, with the pediatrician, it's like, can we check once again the auditory, like just make sure that everything. So from my side, I was doing the due diligence to do it. But imagine parents who don't have that information, who do not have that knowledge, and then you don't have the support system, unfortunately, from the OBG or or for the pediatricians because they don't have also the tools. So it's very nerve-wracking knowing how patchy it is when it comes to CMV.
SPEAKER_02Okay, could you talk about the available assays and the sample types that they require and just any sort of consideration that should be taken into account when testing?
SPEAKER_03So, right now, right, the standard of diagnosing congenital CMV, it's PCR-based testing. And this is within the first 21 days of life of that baby or after being born. Timing is critical because we want to make sure that it's within that window just to understand to make sure that it's a congenital CMV and not a post-natal acquisition of CMB because CMB can be shed through breast milk. So it's very important to test within that window. Typically, right now, there's some available molecular PCI PCR assays for that detection. I mean, we have laboratories using laboratory developed tests or LDTs, but there's also FDA clear assays in the market. There's currently two available. One is the Alethea CMB assay from Meridian, which it's clear for saliva testing. And then there's the Simplexa congenital CMB direct from DSorin, which is for both saliva and urine. And in terms of the sample, this is a really good question as well and perspective to put into when we are testing for congenital CMB because it's very important the type of specimen that you use. Saliva is typically used for screening, right? It's not invasive, it's easy to collect, and has actually a very high sensitivity. CMV sheds through the glands of saliva like very high viral load, typically for this babies who have the infection. Urine, urine is also then a very useful and very use the specimen more for confirmatory testing because it offers actually the more specificity among some of the sample types that you can use. Because if you already systemically, right, if you're shedding urine, CMV in the urine, that actually tells you that it's an internal infection. And then there is also the third specimen that has been used broadly and especially recently more is the dry blood spots. And this is very good for retrospective diagnosis, and also it's their preferred specimen or most commonly used for public health as part of the newborn screening programs. I will say that when I say it right, specimen isn't very important when it comes to congenital CMB, besides that window of 21 days, because there's a lot of practical considerations. Not to make it even more complicated for congenital CMB, but as an example, right, with saliva, timing actually matters when you're collecting that sample because of breastfeeding and CMB shedding, you know, you can get actually false positive.
SPEAKER_02I was gonna ask, right?
SPEAKER_03Yeah, do due to that shedding through the breast milk. So in terms of uh trying to collect, there has to be a really good collection protocols for that type of specimen, like wait an hour after breastfeeding and things like that, just to make sure to avoid any false positivity. And there's also then this is why then urine gets to use for confirmatory testing. Gotcha. But here's the problem again that urine, although it's a great sample, then they have the issues of logistically collecting because newborns don't always void on demand. You cannot tell them, okay, pee in the cup, right? It's very difficult. Also, the discharge workflows or discharge the hospital once you give birth. I mean, that also you have to kind of coordinate very well because even even that you cannot actually collect with uh void on demand for the babies, when they are born, they actually the urine volume is so limited, they are like actually dehydrated when they're born. So the the amount of urine that you can collect is also minimal, it's also very difficult. So it's a lot of logistics behind things in terms of collecting. And then you have dry blood spots, which, although very convenient for public health, there is also an issue when it comes to this type of specimen. It has to do with the sensitivity, it's a very low sensitivity compared to urine and saliva. I would say that the sensitivity doesn't have to, it doesn't come from the methodology that you're using or the type of assay that are you using. It has to come with that most CMB babies, congenital CMB babies, actually don't have detectable biremia at birth. Oh, okay. The virus actually might not be present.
SPEAKER_02Wow. So this is very complicated to diagnose.
SPEAKER_03It is, it is, it is, because I think uh if the infection happened early at the first trimester, by the time that baby gets to born, I mean the infection might be clear already in the system, right? So the viramia and it's not present. Usually, when the infection happens at the third trimester, which is closer to giving birth, that's where you have the possibility to actually detect it in the blood. So this is why I'll tell you that dry blood spots don't really rule out infection. Only urine saliva actually can do that, and it's one of the the recommendations that to use for that reason. Again, not only complicates transmission, not only is very complicated when it comes to the risks and uh the type of outcomes of that baby, it's also then trying to detect the infection.
SPEAKER_02Yeah. So you've mentioned the 21-day window. Why is that so important?
SPEAKER_03It has to do with the importance of multiple things. One is to make sure it's congenital CMB and not postnatal, but also it's so critical to have as much as you can that early window of diagnosis because it can then define possible treatments and possible follow-ups for that baby. As fast as you can identify a potential CMB infection, especially within those first few weeks of life, it opens the door of antiviral therapy in certain cases, then also audiology monitoring, any other follow-ups, especially development follow-ups. So for treatment standpoint, right, it's important because it can it would not cure it, right? But it will it will help minimize possible more severe outcomes if it's not treated.
SPEAKER_02And that's what the antiviral?
SPEAKER_03That is with the antiviral. There's only, as of now, I know there's some studies trying to see if there's some help with asymptomatic or with CMB infection babies. But right now the recommendations only to severe, to medium symptomatic babies, meaning they have some hearing loss and some additional outcomes, severe outcomes to give antiviral. It used to be again cycle beer, but that had some now study have shown alcoholcyclomir, which is it's easier to administrate and has better treatment course for those babies. So it gets metabolize even better. The current guidelines is all about, unfortunately, symptomatic babies in terms of training.
SPEAKER_02In the lab, how can you differentiate an infection that was acquired during pregnancy or postnatal? You can't. Can the baby get CMV and have it show up positive on a test?
SPEAKER_03Yeah. Congenital CMV has it has to be that acquires that infection and utero. Postnatal infection doesn't have the implications that will have if it's congenital CMV. So, in terms of trying to distinguish, like if there is a test to do it, I mean PCR, which is the recommended, it would not be able to distinguish. Within within that 21 days, it helps to establish the recourse of that infection. And it's expected that if if it's acquired after birth through the breast milk, it has to have um for that baby, right? It will have some sort of immunoresponse. So you will start seeing that baby with some sort of typically flu-like symptoms, which are babies, so you're not gonna have more than non-specific symptoms like possible low-grade um fever and things like that.
SPEAKER_02So scary, but and again, like when you you're when your baby has that, you're not thinking CMV. Like, if that were me, I would be like, oh my gosh, did my is my baby like having RSV? Is this a COVID-19 infection? I would never think about CMV.
SPEAKER_03Exactly, exactly. And that that's pretty much some of the very typical symptoms, like flu like symptoms, like which is very hard to distinguish through flu, RSV, or SARS-CoV-2, like you're mentioning. So it's it's all about timing. It's all about timing in order to you need to test within that 21 days to have more indication whether it's congenital CMV versus postnatal because the implications are very different, like I said. So, but there is not a way with a test, PCR test, to tell you which one is which. It's CMV detected plus or minus. That's it. Wow, unfortunately.
SPEAKER_02It's just crazy because it seems like everything is really pointing to universal screening, and there's so many diseases that newborns are screened for that I had never heard of when I gave birth. Um, when my daughter, when I had my daughter, I heard them say, Oh, she's Coombs positive. And I'm like, What is that? You know, so it's just crazy because there's all of these diseases, like I said, that are tested for. So why not add something else? Can you talk a little bit about what the cost behind like implementing universal screening is and any sort of considerations that should be taken into account? Yeah, there's or is there even anywhere doing universal screening right now? I guess maybe I should have started out asking that.
SPEAKER_03Yeah, yeah. There's definitely places doing universal screening, which is a good thing. Yeah, I am for the audience, just to uh explain what universal screening means, right? It means that all babies, right, all newborns are tested regardless of symptoms or hearing results, right? We're talking about the approach capture, which captures pretty much the majority of the infections and will allow then early identification of even CMB infection healthy babies, uh, or at least the asymptomatic babies, right? Right. Which is 90% of the babies. It's right now the only two places that are having universal screening, it's Minnesota, which passed around 2022 and started 2023 full speed ahead. They're using dry blood spots and they're using the newborn screening um system from the public health. And then recently, as of I'll say June, summer 2025, Connecticut also passed legislation in terms of a mandate of universal screening. And universal screening, when I say that, it includes a lot of educational tools and monitoring and supporting tools for families. So it's just not only testing, it's also the supportive structure.
SPEAKER_02And that's so important just to be able to help give that family a care management team and just help set them up with all of the resources that they need. And it's crazy because I've looked into some of the legislation, and it's not just by state. You know, it gets broken down into counties or it's it's crazy. It's really crazy. And so you might be giving birth in a state, but then like the county next to you, the physicians might not be educated on that. And again, no fault to them, but it's just it's scary, right? It's really sad for these families.
SPEAKER_03It is, and it's like a I I think I mentioned it's like a patchwork because you know the majority of the states, right? It's it's following that hearing target itself. Okay, that's that's I would say the most common one that uh as we mentioned. Universal screening only so far, soap two. But one thing I want to say is that because of what you even said, right? Like there is some counties that they are even following their own protocols and procedures and even internal decisions to actually do better in terms of the testing since there's no federal law right now. So I've seen, I will tell you, I've seen hospital-led legislation where hospital-specific hospitals and different states are leading their own uh ways of screening. And most of the time, what they do is that universal screening. So they they usually, I mean, for that is very difficult just to logistically do it because you need that clinical champion, and then you need the laboratory champion as well to drive that initiative inside the hospital because you have to figure it out logistic of collection, transport, testing. It's so many things to consider. Definitely, it's unfortunately that, like I said, there's no really federal mandate, although there was one introduced, which is Stop CMB Act by in 2025, to put some more uh Legislation on the federal level. But right now, I have not seen anything moving towards that or uh bringing into I know like CMB Foundation is continue fighting for that type of initiative because it brings a lot of support for screening and universal screening and then additional educational materials, research, and all that. So, but unfortunately nothing is has been approved yet, and hopefully soon. But yeah, it's everything unfortunately very patchy at this point.
SPEAKER_02Some studies have explored possible links between congenital CMV and neurodevelopmental conditions like autism. Can you talk a little bit about those studies and what you've read?
SPEAKER_03Yes, this is a very good area that is actually growing up interest. And a lot of the work that has been done under this has been from Dr. Megan Pesche and colleagues. They did several studies, and there has been some really good publication where they're looking through the broader narrow development impact of congenital CMV. Their work actually, along with others, has shown actually a really good association between congenital CMV and the increase of risk of that narrow development conditions, including the autism spectrum disorder. Now, some studies even suggest that around two to three-fold increase risk estimated, which is around 5% of the children that develop congenital CMB will have also part of this spectrum. Now, I want to make clear, right, that association is no causation, right? I don't wanna I don't want to alarm anyone because congenital CMB, it's possible many of the many factors, right, that can influence neurodevelopment of the baby. So, but it's very interesting that their hypothesis that they are creating around these studies is that it's which is very biological plausible, right? Because we know CMB does like to affect a lot of development brain, right? Triggers that inflammatory response from the mother and that during that critical period of development, which can then have impact on the on the neural pathways formed from that fetus. So I know there's a lot of research still evolving on that, and this is also then reinforced that CMB is just not about hearing loss. Right. There's a lot of again, the spectrum of that infection can also have a more narrow development impact. And this is why, once again, I will say it once again identification is so important and follow up those with CMB infection because again, it will help monitor those babies and the narrow development moving forward.
SPEAKER_02And just help um educate the families on possible symptoms or what to expect, right?
SPEAKER_03Exactly, exactly. It's it's a high risk. Um, and again, it's not a causation, but when you start looking into a lot of the symptoms that uh within the autism spectrum, those babies have, and then CMV uh disease um babies have as well, they have similarities, like it's unable to have eye contact, they they have issues with speech delays and all that. So they they do have a lot of overlap symptoms within that spectrum, and then CMB um disease that that's why they did an amazing job in trying to look into it, and yeah, there's some sort of possible link. Gotcha.
SPEAKER_02Okay, so looking ahead, do you see any opportunities for new diagnostic approaches, maybe like a multiplex newborn screening panel that could include CMV?
SPEAKER_03That's it's a really good question. So I think I mean CMV now being part of the newborn screening, it's it I wouldn't say it's a multiplex, but it's part of that testing, right? Among other typically testing that has been done, genetic testing that is done for that baby when it's born. I would say that possible should be. I think we have to think a little bit bigger, honestly, when it comes to trying to test for this baby's. I think definitely part of the solution is to have more access on testing, right? It's very important. But I think what I start seeing more is building better the right system around that test. Gotcha. Meaning, meaning, right? Getting the right specimen, right? Knowing what saliva can provide, knowing what urine can provide, knowing the limitation on tri blood spots. So it's very important to then try and then to have a more operationalized system around the right specimen because I know we can do better in the terms of testing. Right. There's also issues with that infrastructure because that means we need to figure out a way to collect at the bedside. We need to collect. Um, I'd um try to then also think about how are we going to transport that? How are we gonna have rapid turnaround time before it gets discharged? How are we going to have better follow-up around that testing? Right. So there's so many ways that I think we need to first think about in terms of how to really build the right system around that test, then just go for a multiplex because it's more about the infrastructure side of things in the the right test to do it in order to then make it more impactful and more actionable.
SPEAKER_02Sure. Yeah, that makes total sense. So you've shared so much great information, um, and this has been very educational. So, with all of this said, what would you say is the biggest misconception that somebody has about congenital CMV?
SPEAKER_03I think one of the biggest misconceptions that I hear, that I see in all these years, you know, around this infection and the disease and learning more and more every year, is that idea somehow protecting families by not having the conversation. I think there's often this hesitation, almost a sense of wanting to spare parents, right, from worry if a baby might have congenital CMB. In reality, I'll say that I think that hesitation comes more from the provider side, because those can be a very difficult conversation to have.
SPEAKER_02Sure, but I mean, so is if a mother gets an NIPT test, that's going to be a difficult conversation, right?
SPEAKER_03Exactly, exactly. And I'll tell you, you know, what I've seen and heard all this year is that family consistently say, I want to know. Yeah, I would love to know. They want information, they want answers, they want opportunity to act. If there's something that should be monitored, right? Like I I did when I I knew I have enough information to do it. So I I will tell you before I go, like I I have to share this because I did a talk last year about congenital CNB. And after the talk, this person actually came to me, and she shared this that her son, now in 30, in his 30s, has been neurodivergent in the spectrum and has hearing loss in one year. And she has never thought of a congenital CMB. And when she learned about the potential links right between neurodivergence and then congenital CMB, again, it's a link, but it's not conclusive. But she's like, I feel like I have a possible answer. And she told me, like, I spent all my decades, you know, wondering if something that I did, which is it's a great guilt. Yeah, it's it's like 30 years of guilt, and I feel so bad. And she she that really stuck so much with me because again, right, it goes to the point that knowledge doesn't really create anxiety, it actually kind of like relieves it, right? Like does provide you potential answers. So I just gonna say, right, like having the conversation is never easy, but not having it at all, it's even worse.
SPEAKER_02You're setting that family up for failure. It is, it is.
SPEAKER_03So again, I understand when there's no ways to support and give the support system because the legislation doesn't allow it because there's no tools to education, but it's still important for the family perspective. And again, I hear it all the time and on the conferences that I go and the conversations that I get, it's like I wanted answers, I should have answers, and I feel so guilty that people don't have them, unfortunately, and have to carry some of the guilt that they did something wrong. And I'm gonna say this like there's nothing wrong from the mother perspective, there's nothing that you did wrong about it, so that's also important to communicate. So that's the biggest misconception. It's families don't want to hear it, that is not right. Family doesn't want to know, like that's not right, right?
SPEAKER_02Right. Well, it seems like really at the end of the day, all we can do is educate ourselves and our care team, right? Um, because if they don't know, then how are they supposed to help? Where would you recommend that somebody could go to find more educational resources on congenital CMV?
SPEAKER_03Yeah, CMV Foundation, it's a great uh resource. Uh, they do have all information by state, what type of legislation, if there's any. I mean, they have resources from infographics, from educational tools. They are the best, I would say, resources to go. There's also the CDC where there's a lot of recommendations that goes more for the clinical side and from the clinician side for the recommendation on the right specimens, how to collect logistically, all the operational side of things. The European, there is a European consortium as well that does have really good recommendations. So there's no guidelines, unfortunately, but there's places that you can find from different sources. Also, the American American Academy of Pediatrics, the Red Book. There's a lot of good resources on congenital CMB as well. So there's resources out there. Families, CMB Foundation, clinicians, laboratorians. There's plenty from the CTC, from the Red Book, and in some of the consortiums that are towards the congenital CMB.
SPEAKER_02All right, Keisha, well, thank you so much for sharing all of this information with us. I really hope our listeners found value in it and learned something. I know I did, and this has been such um an interesting topic. And thank you again for sharing this with us.
SPEAKER_03No, thank you for having me. And hopefully, at least, like I always say, if I at least reach out to one person and learn something about it, that's that's enough for me. So thank you again for having me. Thank you.
SPEAKER_01Thank you for joining us for today's episode of Diagnostics Decoded. We'll be back each month with new conversations diving into the science, challenges, and innovations shaping diagnostics. If you would like to learn more about zeptometrics and the resources we offer, visit us at www.zepdometrics.com. Until next time, thank you so much for listening. Toodles
