ROUGH EDITED COPY

EHDI

FEBRUARY 28, 2017, 9:00 a.m. PT

GRAND HALL A

Hearing Targeted Congenital Cytomegalovirus Screening as Part of a Universal

Newborn Hearing Screening Program

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This is being provided in a rough-draft format. Communication Access Realtime Translation (CART) is provided in order to facilitate communication accessibility and may not be a totally verbatim record of the proceedings.

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>> DR. ALBERT PARK: Good morning, everyone can hear me. My name is Albert Park. Pediatric otolaryngology at University of Utah. And I've been honored to present with just to get a sense of the audience, if you're a parent, can you raise your hand? Then what about ed di. What about a provider, pediatrician, neonatal, audiology? Did I miss anybody? Students. Okay. Very good. A lot of students. Great. Well, thank you very much for attending. And so what I thought I would do is talk hopefully relatively briefly about the rationale of early targeted early CMV testing.And if you have questions, don't hesitate to raise your hand and this is just hopefully be an interactive session, too. But, if not, I have plenty to talk about.So I do need you to present some non-disclosures so I do have grants. Third word doesn't seem clear but that's collaborator. I do have NIH grants. Second is somewhat related to what I'll present and I'll be talking about valganciclovir which is not FDA approved for congenital CMV. Before this story but I thought this would be an interesting story to present to you. This happened back in 2012. So quite a few years ago. By this time we'd been implementing CMV screening or testing for a lot of our hearing impaired children. So this child was like many who presented later so she -- by

the time she came to us, she was 19 months of age. She had failed her newborn hearing screening. She also under wept a click which showed elevations in thresholds but the audiologists recommended just observation and reassessment in nine months. In terms of her history, when she was a fetus she had an ultrasound that showed enlargement of ventricles and had a subsequent that showed changes consistent with inutero insult. So when presented her otologic examination was fine but at 19 months or so she started developing right profound loss and left moderate sensorineural hearing loss. So we were doing CMV testing at this time. We did saliva. Now I would probably do urine. Positive. We did a dry blood spot neonatal -->> What can you not see.>> Oh, sorry.Okay. Let' see if I can fix it. Bring it down here. Would that work? Okay. Thank you. Thank you for bringing that to my attention. Sorry.So we had the dry blood spot PCR test. So that confirms diagnosis for congenital CMV. In 2012 there wasn't a lot of data in terms of anti-viral therapy but we discussed it with the family and elected to do 6 weeks. On therapy her left hearing thresholds continued to worsen to the point she developed profound loss so bilateral cochlear implant. She required a revision and is current currently doing well.Let's see, it's not advancing, I wonder if the Skype did something.Congenital CMV. We know it's the most common non-hereditary cause for congenital hearing loss. Because of progressive nature it can actually account for up to 20, 25% of pediatric hearing loss in the older child.So at least in my field a lot has been emphasized when you evaluate children are hearing loss in terms of performing genetic testing or imaging, but CMV has not been in the general picture for our evaluation. It is not at all in the workup. So around 2008, 2007, we started implementing CMV testing early I had an interesting conversation with Amy Donohue at an EHDI conference and she lead the fact there is not a lot being done in terms of understanding how CMV works in hearing loss. So I said well that's interesting. I don't really test for it. So why don't we start testing for it. So we did. This is the results. We did CMV testing early. We used following criteria for the diagnosis of CMV. Confirmed diagnosis is those who had positive urine or saliva were less than three weeks of age or positive cry blood spot in the older child. Probable where the conditions are old are which is often but had progressive sensorineural hearing loss consistent with congenital CMV. We looked at kids in terms of negative test we looked at imaging, genetic testing or ancillary tests and looked at costs. We have a standardized multi hospital standardized cost accounting system so we can track the cost for these children when they're undergoing threes sort of evaluations. So in 111 children over a 5 year period we had a wide range of types of hearing loss as you can see here where some of them had mild, moderate, severe, profound and most bilateral hearing loss. What we found which I was surprised at was the most come etiology that we war able to determine is congenital CMV, even more ton than those with inner ear cochlear vestibular desmoplasia. 16 of them had confirmed diagnosis. Six were able to obtain a diagnosis through dry blood spot testing and 9 had ray probable diagnosis. Average age kids came to attention was almost one year of age. In fact only five of the

infants of 25 were evaluated when they were one month of age or younger so this was a significant challenge that we identified through this study. When you look at cost, regardless of the type of hearing loss which shows on the bottom. Mild, moderate severe. Unilateral. Bilateral. In all those categories if you implement CMV testing first the cost is less than if you were to implement genetic testing or imaging, only auditory neuropathy inspection disorder and in those children it was less cost to perform imaging first. We found a diagnostic paradigm has a high yield, that you can actually diagnose the older child through dry spot blood testing. The average age of initial evaluation is a significant challenge because kids were close to a year of age when they come to our attention and earlier CMV testing has a lower cost imaging, the child I presented to you was daisy. I remember the day that I met daisy and her mom, Sarah. Sarah told me I don't know what this CMV thing is and I can't believe this is something -- I'm educated. I've been involved in healthcare issues. So what is this thing? We talked a little and she said my mother is actually quite involved in child and women's health issues. I had this conversation with other parents before. So I actually personally was appreciative of that but I didn't think too much of that.Until about two weeks later when I got a phone call telling me that I am going to be going to this Department of Health meeting in about a day or two. Which I did go to.And when I was there, Mark Verner. Jim Bale and a number of other specialists were at this meeting which was astounding to me because I'd never been able to get these guys in one room together. But representative Menlo was there and she did that. We had a brainstorming session where we talked about congenital CMV. The things we talked about were issues of awareness. She again also mentioned that she'd never heard of this condition which wasn't surprising to me because this was a study from the CDC showing that compared to all these other conditions such as toxoplasmosis, strep, spina bifida, the awareness in this national survey is least in terms of those who know about congenital CMV. Astounding but true. Still true today, unfortunately. And then we also talked about the paradigm that we used. On the left when I was showing you that retrospective study of five years or so, this is the way that we approached these kids. Essentially I show this to you to show you that it's not very straightforward. That you have a child who presents with hearing loss. I can't even see the type and I'm sure you can't either. But you do CMV testing and these children are other three weeks of age and you do a dry blood spot and that's about 34% in that sort of landmark paper by Saresh. So you do imaging study but that's not very sensitive -- so you're left with a quandary of a child you think may have congenital CMV but you're not sure. We talked about hearing targeted screenings because as we know here universal newborn screening has been practiced in the United States and been successful with a high success rate in screening all those children. So the thought was we were to pig tee back on an successful hearing screening program maybe we could capture children who we've not been able to capture. We talked about universal screening which I'll talk about later too. You can see the figure to the right is a lot easier. Essentially you have a child who fails newborn screening. If they fail, you get CMV testing and try to do it early before three weeks of age so that you don't have the confounding results of post natal infection that can come about in the older child. This is the bill. The bill is that the Department of Health was tasked to inform caregivers about CMV and then potentially

the most controversial issue was that it also mandated that medical practitioners test infants who are under three weeks of age who fail newborn hearing screening and inform those parents of the results and implications.And so in 2013, unite ah unanimously got this passed. And became the first state in the country to implement a hearing targeted early CMV testing approach for kids. That's changed in four years. So in four years, there's been a lot of change going on. Now Texas, Illinois, Tennessee, Rhode Island, and Hawaii have implemented some sort of mandate some of this involving awareness, others involving actual screening or testing of children based on universal newborn hearing as well as a number of states that have enacted or looked into this issue. So this is rally evolving. In fact, I've been involved in this sort of nationally. If you look at hospitals, almost 1/3 hospitals have already implemented early CMV testing through the United States. I'm showing hod beds of areas where this has been started. In this environment in December response letter from Department of Practice and division and response to these legislative efforts that are throughout the United States. So this is what the newsletter had come out with. It stated that there's no evidence that supports treatment of newborns who test positive for CMV but are otherwise asymptomatic. The treatment is valganciclovir which is carrying potential risks and clinicians practicing in the best up to date fashion face medical liability and if states continue it may affect our ability to practice medicine in a manner consistent with the best available science. These laws may drive treatment in a way that parents and providers often feel they must do something and we may harm the children we're trying to help. So I guess the AAP was not very supportive of these efforts. If you look at definition of treatment, that's what I did when I came across this newsletter is went to Wikipedia which is the origin of all sorts of questions whenever I have issues that I'm trying to figure out. If you go to Wikipedia, it mentions treatment is the management and care of the patient. It's the combating of a disease or disorder and so I don't see how treatment really equates with anti-viral therapy which I think is a mistake in that sort of viewpoint from the AAP. In fact, in my humble opinion, treatment for early CMV testing addresses these issues: It helps the family of the hearing impaired child. It increases the detection rate for the symptomatic child. So these are children with much more disseminated severe disease -- it protects at risk populations, it focuses attention on CMV affected infants for progressive hearing loss. And this is a recent result from a pediatrics paper that Marissa Dean Hart in our group just had published in February of 2015. A surprising result. And we found that a hearing targeted early CMV testing approach actually improves the time to diagnosis hearing loss for all CMV tested infants and I'll talk about this in a moment. It may also improve the hearing out comes of CMV hearing impaired infants where the AAP was focused on and it's a reasonable cost approach.So how does it help the family? This is I think a great quote from Helen Keller where she mentioned that blindness separates people from things but deafness separates people from people.And if you ask the family because I've unfortunately or fortunately been involved in situations where a child comes to my attention with hearing loss, the come on response is surprise, sadness and concern and the parents in the room if I'm wrong with that, let me know. But that's at least what I've noticed when I'm seeing kids in my clinic and

questions that often asked to me are what is the cause of my child's hearing loss. What is the likely impact to my child, and what are the options for treatment? And these are substantiated by a number of papers in the literature. This is an interesting paper from the CDC where they surveyed families about CMV and they found that 84% of respondents would like to know if their -- would like to have their child tested for CMV even if the hospital or Dr. Did not do it routinely. 84% of them would want to know if she has it even if he or she never develops problems and 84% would like to pay for this test. They're saying $20 but they're willing to pay for the test for their child.Another issue you need to be aware of ask that CMV testing is time sensitive. So you need to obtain the test in a child who is three weeks of age or younger or you have the issue of could this be post natal infection and we know that in an otherwise healthy child does not cause hearing loss or other sequelae. Unlike other testing which is newer field is discussed and often times performed you cannot wait until the child is older to make a diagnosis. So that's the quandary with this condition.Now what about this issue of increasing detection rate of symptomatic CMV infected infants? You would think a child who presents like shown on the right would be relatively straightforward to diagnosis. A lot of children can pass away. Multiple organs can be affected by this more severe condition. But surprisingly in a number of studies the minority of children with symptomatic CMV are diagnosed. In the recent paper in Vancouver group they found less than 10% of children who should be diagnosed with CMV are diagnosed. We found that in our two to three year period since implementation of the law we've been able to dying diagnose five children with symptomatic CMV who would not about an diagnosed without this approach. The reason this is important is because David Kimberling came out with an important paper where he shows in symptomatic more severely infected children a longer duration of therapy of six months of valganciclovir improved hearing and neurocognitive outcomes compared to children treated for just six weeks. This shows the neurocognitive outcomes, significant language composite and language skills are better in the children treated for longer therapy of valganciclovir.So there's a general consensus in the community that this group would benefit with anti-viral therapy and thus, if we can improve the detection of these children, that certainly would benefit this important group who are afflicted by this infection. And in my opinion and what we found is that a hearing targeted approach does improve our ability to protect these children? What about protection of at risk children. We know they'll shed share the virus for months or years and it's contagious and people at risk are pregnant mothers and those immunocompromised. So this enables us to know which children are at risk to transmit and we know simple, relatively straightforward approaches for hygiene can improve transition. Hand washing, kissing on lips, lack of sharing of utensils. There's a number of studies who showed reduction through projections of the conversion rate of mothers at risk to develop CMV. We know preventive measures can be helpful in reducing transmission. CMV. you will of us are aware of issues of limited resources. It would be wonderful if we could test every child every three months for time and certainly this audience would agree with that but that's an issue of cost. So, if we're able to identify those children at greatest risk of progressive hearing loss we can focus limited resources. We know

through a number of longitudinal studies that CMV children have a chance of developing progressive hearing loss. We know children with initial normal hearing have a 15% chance. So these are children we can target through resources to determine if their hearing were to change and this is a graphical representation of a child who initially had normal hearing but then in 2011 started -- or 202012 started developing elevation of thresholds so this is a child we're able to detect worsening hearing in a speedy fashion.Now what about this issue of timely diagnosis evaluation? This is a paper published in pediatrics. We found that the timely diagnostic evaluation of children with hearing impairment was 66% which is in keeping with the national results. But after implementation it increased to 77% and then if you kind of hone down on the groups that were tested 90% of children underwent evaluation I wanted to show a hearing targeted approach benefits the CMV affected cohorts but also all children who fail newborn hearing screening.Now why is that important? This is a seminal paper by Hatani showing earlier intervention of a child with hearing loss before six months of age improves their language outcomes compared to the children who are diagnosed or treated after six months of this challenge is an existing issue in this day and age where in this survey 52% is highlighted in red are those who undergo the evaluation in a national survey. This is ab area where there's a lot of room for improvement. What about anti-viral therapy. This is a child presented to me a little under a month of age, failed her newborn hearing screening. We were identified having congenital CMV through this targeted hearing approach. Right neural left profound sensorineural hearing loss. This is around 2013 so again not a tremendous amount of data on anti-virals but we elected to treat her for six weeks, I've followed her for four to five years and her hearing has been stable and her speech and language is progressing normally. So this is the big question. If we are able to identify children and intervene in a way we can affect or mitigate they infection of CMV, that's the million dollar question. When we looked at our results we have 11 children who actually had this picture of CMV infected hearing impaired only. Average age of initial treatment is a little over a month of age. Duration is a little over a month to up to six months. One of them required surgical drainage and emissions. So certainly these drugs are not without risk. Four of them had an elevation in liver function test and we followed these children for almost two years. This is not a valid comparison but I'll show it anyway. It's compelling. On the left is a survey of the New England journal of medicine showing stabilization over time. On the far right is our Utah results, a very small sample size but it does show you over 80% of these children who are treated with a follow-up of almost two years had either stable or improvement in hearing results comparable to what David Kimberling showed in the New England journal of medicine paper. This is a randomized clinical trial we hope to embark in the summer. It's going to be hearing impaired children with CMV but don't have other conditions. It will be anti-viral versus placebo for six months and we'll look at hearing outcomes and farm 0 kinetic data. We already have about 32 sites that have agreed to collaborate with us on this. I'm still looking and open to any other sites that are interested in collaborating because this is a big study, we're trying enroll about 110 children. Take home message for you is I believe there is evidence that supports treatment of newborns buff the treatment is not just limited to anti-viral. Treatment is

also providing providers and parents etiology for child's hearing loss. Increasing the opportunity of diagnosing the symptomatic more severely infected child. The opportunity to educate families, try to reduce transmission risk for those at risk, focus limited resources for children who are at risk to develop progressive hearing loss. Improves the ability to diagnose hearing loss for all infants who fail newborn hearing screening. Preliminary data is promising for anti-viral therapy and it's affordable.>> What about universal? I'm actually a proponent of universal testing. However, I don't know how to get there. And I think that's the big challenge right now. To the left shows you the universal approach to the right is the hearing targeted approval. And the real big question is this group in agreement of who are initially found not to have hearing loss. This is an interesting paper that Karen Fowler -- and it's either published or about to be published through the Chime study. They looked at over 100,000 children through a multi institutional study and they found 400 or so infants with congenital CMV and those children performed newborn screening for hearing as well as diagnostic AVR testing. They found nearly 60% of those were detected through newborn hearing screening. This is not an issue that I've seen myself in Utah and unfortunately, although it's a really great paper and very interesting. They didn't present any methodology in terms of how they did the newborn hearing screening, diagnostic and no validation because it's relatively early follow-up of how these children did in terms of behavioral testing. So this is an interesting result but something that needs to be reassessed and validated.In terms of cost effectiveness, this is an important paper by Sor an Gant. If you look at the cost, the cost on the left for universal screening is about $90,000 assuming about a $50 charge for the test.Versus targeted which is almost $4,000 and this is an important -- there's an important paper by Karen et al in 2002 looking at the cost for universal hearing screening which is comparable. About 21,000.I think in many ways, our current situation with CMV is like what we were in the 1990s with universal hearing screening. Most everybody was doing targeted hearing screening and the issue was obviously we're missing many of these children through that approach and thus that -- and there was data supporting that early intervention will help these children and I think that kind of pushed the movement in a nutshell, for universal hearing screening. We're at that juncture now with CMV where what I'm trying to do is push for hearing targeted CMV testing with the hope that we'll have enough data at some point hopefully soon for universal.But right now there's no program that currently uses universal CMV screening as a standard of care. As I showed you before several institutions have been targeted CMV testing. Why is no one implementing universal screening? It's difficult. It's very costly, in fact, what I just found out recently was that the 10-$50 Officer costs that are projected, in Utah the cost to families is between 250 and $300 for the test. So for us to implement a universal screening for 55,000 children in Utah is just not doable.I hope it will be, but at least with that current cost I don't think it can be done. Logistically it's difficult to implement a whole new screening process. It's also difficult to know what to do with the kids who have normal hearing. Even now with a much more modest hearing targeted approach, a third of the children we identify actually have

normal hearing. And those are the kids who actually aren't following up. They're not getting the serial otologic testing. It's understandable for parents. Maybe we're not doing a good job illustrating and counseling and these kids are fouling through the cracks. If we implement universal until we have a better infrastructure to work with these families, that's going to fail.So what can you do now? I think if your institution has not started hearing targeted early CMV testing you should do it now. The way you do it is talk to audiologists. Talk to the newborn medical directors. Again, almost 100 hospitals have already started doing this in just four years.You should be able to implement dry blood spot testing. Every state has a dry blood spot program and I can send this to you. I have a listing of every contact person in the state where you can obtain dry blood spot testing if you wish to. Those of you interested in participating in the clinical trial, there's my email. Don't hesitate to contact me. I go want to acknowledge the numerous collaborators who worked on clinical projects here. Without them none of this could be done. Thank you very much.(Applause.)I'm. >> ANGELA SHOUP: And. >> KRIS OWEN: And I are going to give you our experience with hearing targeted CMV at the Parkland Hospital in Dallas, Texas. The history of our program started if 1986 as most of you are aware. Marian downs was promoting the idea of hearing screening from the 60s. High risk register in special care nurseries and well baby nurseries in 1986 and this happened due to the national Council of supplies and with screenings we continued with that process until 1991, 92 which h they started screening all babies in special care nursery and continued to hearing loss. In 1997 we get newborn hearing screening. This committee very importantly was a joint effort. It was a collaborative team that excluded people from across the entire nursery. This included people from the nursing leadership, from the wish women infants health services administration. The medical directors of both the special care nursery and the well baby nursery as well as audiology. Very importantly woe talked with other stakeholders in the nursery including infectious disease neonatology represented by Pablo Sanchez. One thing any of you familiar with old park land we have a beautiful new parkland. This is our new hospital. If you get a chance go look at the old hospital. It's quite a difference from what we used to see in the past. This opened last August.So our screening program very similar to most screening programs we focus a lot on our data for babies that are identified with hearing loss. We're able to screen 99% of our babies, the only babies we do not capture are those who are transferred out for surgical procedures, ECMO, those who do not survive the birth admission and those who may be on comfort care or palliative care when they discharge we have a .9% refer rate. .2% chance of follow-up. We have found that over the last couple years we had two years with zero% loss to follow-up and last year we lost one baby. We've confirmed hearing loss in.thee 3% of the babies screened and 38% of the refers. One of the lessons learned for hearing targeted CMV is we move into discussing Kris is going to touch on some of the reasons this is extremely important. But our champion was Pablo Sanchez, an infectious disease physician working heavily in the newborn nursery.

When we were planning the program he was the one who thought of the idea he was passionate about CMV back in the 90s and said why don't we do screening on the babies that don't pass screening. This is because he'd been advocating for universal newborn CMV screening and hadn't been successful. As part of a kickoff to newborn hearing screening program in 1999 we had hearing targeted CMV screening. So our flow chart looks similar to the those of all programs we have inpatient hearing screening. In our case it's by a tech that is trained by audiologist and overseen very closely. If a baby passes screening they then are analyzed for risk factors for delayed on set of hearing loss. The way we implemented this since 1999 is the physicians and providers responsible for the history and physical and discharge physical also ask other questions about hearing history and they mark anything that's associated with delayed onset of hearing loss into the child's chart. Audiology is alerted and they give the family information about delayed onset of hearing loss instead of a regular pass letter and we give them information to give to their primary care provider when they leave the hospital to get them referred in for six month check for delayed onset risk factor. In they're not at risk they get a regular pass letter. If they don't pass the newborn hearing screening this is where we diverge a little bit. They get an inpatient hearing screen by an audiologist and we timed this as close as possible to discharge so we can give a little bit of time from initial screen. Another thing I wanted to bring up is our program is 100% screening ABR and has been since 1989. The audiologist goes back in right before discharge. We rescreen the baby to verify it wasn't a technical referral and maybe the baby now has had time to clear completely so we may get a pass result. If the baby passes the audiologist looks to see if there are risk factors for delayed onset and the baby either is or is not and follows that path. If they do not pass the inpatient screen by the audiologist, this smaller subset of infants will receive the CMV screen. The audiologist alerts the provider. An order is put in for CMV screening and we get it completed before they leave the hospital.The baby then returns in about 10-12 days for outpatient screening at the hospital where they initially were screened by an audiologist. If they pass this, once again, they go through the analysis for at risk delayed onset of hearing loss. If they refer, they get their diagnostic evaluation. There's a small subset of babies, very, very sick babies or babies with atrocia that go diagnostic and come back for outpatient rescreening. We found out in the Earl' days what drastically improved our return for follow-up is moving the first visit for the family back to the birth hospital. In addition to screening babies that don't pass the newborn hearing screening, we screen the babies of H IV that's mother's HIV positive will also receive a screen before they leave the hospital even if don't have signs. In a cohort of babies we found that 3% of HIV exposed babies are positive. It's an important addition to managing these patients and families. What is the purpose of our hearing targeted congenital CMV screening? The purpose is to identify infants that refer at park land. We want to determine if they are positive for congenital CMV. And if so, which of those that have congenital hearing loss may have congenital hearing loss that's etiology is directly linked to congenital CMV. It assists us that we might not otherwise pick up. All of those babies that did not receive a congenital CMV screen would be put into a group of they get a pass letter, go home, parents are not counseled that they have a specific risk factor that needs to make them more alert to potential

delayed onset of hearing loss. They may get the same milestones that everybody else gets but they don't have that heightened awareness. It provides support for families. We're interested in providing parent education and another important component of this we'll find and you'll find as you work with the CMV population is provider education. If you talk to a lot of our parents here that are involved with national CMV, they'll tell you that they spend a lot of time on provider education because it is not necessarily happening at the pediatrician's office or OB/GYN's office. We want to assist with making appropriate treatments and referrals because even if you have a provider who is motivated to work with CMV baby, they don't know what the necessary workup is. So providing that additional support. Institute an appropriate monitoring plan for those that have congenital hearing loss due to CMV or a monitoring plan for those at risk prognostic information for the families. Dr. Park touched on this but part of the Joint Committee on Infant Hearing statement is portions such as urine culture leading cause of hearing loss might begin in the birth hospital particularly for those spending time in the NICU. Just like Dr. Park mentioned if we miss a certain window of time, we can't effectively diagnose a child with congenital CMV. So we follow across our hospital if you obtain a sample before three reeks weeks of age, you can determine if it is positive for congenital CMV. If the specimen was taken before three weeks of aiming, they're considered indeterminate. Then you have to rely on other signs and symptoms and head Sono show something to suggest CMV. Do he they have other possible physical indicators that may have been missed because they're mild? We know it's acquired if they had a culture positive CMV on an infant that was screened after three weeks of age but who had a negative CMV culture previously. I'm going to turn this over to Kris Owen. She's going to talk to you about some of the lesson learned and challenges in instituting hearing targeted CMV.>> >> KRIS OWEN: Good morning. Thank you for giving me the opportunity or allowing me to come tell you a little bit about parklands. I want to tell you about how we do it in the hospital. If a baby doesn't pass with a hearing technician, audiology will repeat the at the time. We try to do it close to discharge. Our moms with vaginal delivery with no complications are in the hospital for a minimum of 36 hours and we try to complete the test with the last 12 hours of birth. We try to do it in plenty of time if they do need a CMV hearing there will be plenty of time. If the baby doesn't pass, I'll contact the provider taking care of the baby. I'll text page or call her and ask her to put in an order for CMV. By the time I'm taking the mom back to the room. The nurse is waiting for me to go ahead and bag the baby. We try to get a urine sample if possibility or we'll revert to saliva sample if we need to. I will go in and counsel the mom. All of our counseling is done by audiology. I'll let the mom know that the baby didn't pass the screen. I'll talk to her and give her follow-up appointment and I'll discuss a little of CMV with her. How I tell her about it is that every baby that doesn't pass the hearing test we need to do another test to make sure our baby didn't have infection called cytomegalovirus the chances of your baby having the infection are very small so I don't want you to worry. I also tell her that it takes a few days for us to get the results back. We send the results to the lab. So when you come back and see me for your outpatient appointment, I'll go over the results. It's important for her to know that. I'll explain we're putting a little bag

on your baby. If you see urine call the nurse and she'll take the bag off and that's what we'll send to the lab to get results for the screen. Most moms are very comfortable with that. A few moms will ask me more questions but most of okay with that explanation. On the ow patient visit, we will repeat the hearing screen first. In the meantime we do our outpatient visit 10-12 days post discharge. During that time audiology is the one monitoring the CMV results checking to see when the results are back. And then if the results are negative, we don't do anything. But, if the results are positive ahead of time before the appointment. We contact the in-patient provider and discuss the CMV are positive. We make arrangements for the in-patient provider to be the one there during the outpatient appointment to counsel the family about the positive CMV results and talk to them about what the follow-up plan will be.Also our in-patient provider will contact tact the outpatient provider and let them know the results are positive and these are things they're recommending to the family so everybody knows what's going on before the family comes in. When the family comes in we'll do the hearing screen. If the results were negative. Audiology will give that information to the family. If they're positive after we do the hearing screen, the provider will come talk to the family about that. We have a handout we give the family so they're not trying to remember all the information they're given right then and there. If for some reason during the inpatient stay they were -- we weren't able to get a viable sample we'll repeat the CMV screen on the outpatient window. Then we'll make a phone call to the family and to the provider about the results of the test regardless if it's negative or positive. And what happens when the provider comes in and she talks to the family about CMV, she gives the handout and then she also -- our recommendations are to have a head Sono and ophthalmology consultation. She begins that process and makes those referrals for that. We also refer them to infectious disease clinic to make sure they're connected with that clinic. And for intervention down the road. Challenges and issues that we have. First of all, collecting the urine sample. Some babies are not cooperative with this. And we do urine. That's our gold standard for our hospital. It can be quite challenging. So we try to do the best we can and try to give the nurse plenty of time to get that sample. We encourage the mom to feed the baby when we bring them back and know that needs to be done just so we can hopefully get that sample. Also circumcision. For us it's extremely uncomfortable for a baby to get a urine sample after they've had a circumcision. If we have boy babies on our list that day, we talk to the providers and find out when their having their circumcision and try to work with them on making sure the hearing screening and if we need a CMV screen that's done ahead of time. And sometimes it takes a while to get a urine receive CMV screen so we try to give them plenty of time but sometimes that's not possible. So there are alternative we do so we do not delay discharge and that's saliva. We do foul back on that. We don't want to delay discharge. So, if we try every other means of getting a urine sample then we'll do saliva. Other challenges we have are providers not really thinking it's really necessary to do a CMV. A lot of times if for example there's an obvious reason the baby didn't pass, they had oral atresia they're like why would you need a CMV screen we know why they didn't pass. We educate them and talk about how they can have more than one thing going on and importance of doing CMV screening they're very good. Once you explain the rationale. Reason for it, we don't have any problems with

that. With them being willing to order the CMV. A lot of them come from other hospitals that don't do a CMV screen when their baby doesn't pass. So we're educating them on the importance of it and wouldn't it be a good idea to do at your other hospital too. First of all, education, we try to educate our providers about it. Every week CMV comes up and we talk about our protocol and CMV why we do it. Sometimes I'm the very first person to talk to them about CMV. So it's a great opportunity for us to get to share that with them. One thing I will encourage you is we have the CMV protocol in our hospital protocol. So it's in our hearing screening protocol that if a baby doesn't pass, they need a CMV screen prior to discharge. That is very helpful when queer talking with providers who aren't necessarily on board. If it's in your policy and procedures and it's a hospital policy and procedure, if they don't do it, if anything happens down the road, they have to have a rationale for why they didn't do it. It's important that's in your policies and procedures. We don't usually have resistance. If you give them rationale and reasons for it, they will follow through. I'm going to turn it over [to Angela. >> About 17 years now. Some babies identified with congenital CMV. 9% of our babies are referred on universal newborn hearing screening. 89% have received a screen and most of the ones that we did not get a CMV screen were in the early days. Surprisingly or maybe it won't surprise you based on what Kris just said the ones most resistance in the Earl' days were providers in the NICU. They feel like these are sick babies we know why they have hearing loss, we don't need a CMV screen and this is where your physician champion comes in because Dr. Sanchez would talk to providers and be more positive providing a screen. We have three percent who have been found to be positive for congenital CMV and 97% negative. This is from an article we published in 2008 talking about results from our CMV screening program. It's probably a little small for people in the back of the room to see and I apologize for that. Essentially what we found is that that at that point in time 7% of the babies screened had not passed the hearing screening. And of these 84% were screened for CMV and five percent were CMV positive. Most important to note here is that 16 or 67% of the infants confirmed with auditory impairment were in this cohort in this group. Let me find -- and 25% of these had clinical signs prom, CMV screening and 75% fell to hearing screening prompted -- the failed hearing screening prompted the congenital screen itself. When we go back and reanalyze the test results we find if you do very, very careful chart review there were 33% of this group that were screened for congenital CMV strictly due to the hearing screening refer that should have received a CMV screen due to other clinical signs but they'd been missed in the history and physical. Like Dr. Park mentioned you can pick up sick tomorrow attic CMV kids with congenital screening you might do with hearing targeted program. 25% of these infant ended up having normal hearing.So these were infants that would not have been picked up otherwise if they hadn't had the refer on the newborn hearing screening and I used to talk about this as being due to possibly transient conductive pathology that triggered this screen. But now I recognize that it could have been fluctuating sensorineural hearing loss and we picked them up because of congenital CMV not because of transigent conductive pathology. If we go a comparison looking at recent data. 240,000 babies we screened on the left side of the screen you see results from the first five years of the program and now you see from

about 17 years of the program is that the percentages have stayed pretty much the same. 99% have been screened. The babies not screened are those too ill or transferred out for other procedures. .9% refer rate with .33% of the infants with having confirmed hearing impairment auditory impairment of those screened and six percent of these at 5 year mark and 17 year Mark have been positive for congenital receive CMV. Of those 16 started within normal limits or 34%. 62% had auditory impairment and 44% were loss to follow-up. Of those who started with a normal limit, we have found that we've had progression of hearing loss in at least three of these.We have 8 that we don't know, many of these are being monitored elsewhere. They moved away from where we've been able to follow them. Five have stayed normal within -- three have been identified as progressing to sensorineural. 15 were initially unilateral. This is small to see. Most of these have either progressed or in many cases they've become bilateral over time. So it is important from the standpoint even if your hospital isn't really vigilant with unilateral to recognize that this can rapidly progress to a bilateral hearing impairment. 14 were bilateral to start with. We have this pieced into different degrees of hearing loss. You can see many of these infants had progression in their auditory impairment over time. What have we learned in 15 years? We think a CMV screen is helpful for all infants who refer on hearing screening can provide information for those with hearing loss. It also can provide appropriate monitoring and managements for those who don't initially pass a newborn hearing screening but may pass one later and are found to be positive for congenital CMV. We do recognize and are concerned that we will miss a number of positive CMV babies by doing a hanger targeted approach. Many hospitals aren't willing to take that step yet. Our hospital has been hearing targeted for 17 years. We are part of the chime study and had a wonderful window where we got to do almost universal but as soon as that ended our hospital went back to hearing targeted. We are able to I'd any a number of babies. My concern with the fact we're not universal is we may be giving a false sense of security to some parents. We don't give a delayed onset of hearing loss letter unless there's another letter. They get the pass letter that gives them milestones and they don't know the babe tee is at increased risk for adult on set of hearing loss. Six percent of infants with confirmed hearing loss are positive for CMV. Some of the tips that Kris alluded to is ensure you have strong provider support. Have a written protocol in place. Press fizz the individuals responsible for monitoring test results and notifying providers of positive outcomes. This is something we see a lot of times. Somebody is doing testing but nobody is responsible for find being out the results unless you identify a person in that role. And you also need to find out who is going to be responsible for following the infants and families positive for congenital CMV. You want somebody impassion end about CMV from a medical provider standpoint. Have educational materials available. Establish a protocol for follow-up. Make sure everybody is clear. Have a contingency plan for an additional -- contingency plan. Just to touch on another key factor for trying to promote hearing targeted CMV and that is awareness. You have heard at other sessions about different state programs we just heard about Utah and saw many other states have implemented CMV legislation. In Texas we did called the Madeline Lee Armstrong act. I will tell you once education, collaboration are extremely important but so is awareness and the most important key players in getting the awareness out

making sure everybody is aware of congenital CMV and is promoting education for families is your families. Forming a tight network with your parent group is extremely helpful. One other thing to keep in mind is that you don't necessarily always get what you wanted when you first start a process. Some people will wait forever to do something because they don't have it perfect and I'm one of those people I'll wait too long to do something because that's not the way I want to present it. I'm too embarrassed. I tell my daughter the things I regret in my life are not the things I did poorly or did wrong, what I regret are the things I never did because I was afraid to get started. This is an example of that. Passionate families got together and worked hard and they got a bill passed which is almost impossible. But the bill that they enrolled to was for testing for CMV as well as education. What I got passed is the education component which is powerful but not what they initially set out to do. At the national CMV and public policy conference there is a poll see speaker from US Austin and he used this quote and I think it mostly cloudy skies well to this situation and that is General Patton said a good plan violently executed now is better than a perfect plan next week. So making some progress forward is helpful. I'd like to refer you if you have interest in congenital CMV. If you want resources, go to the national CMV foundation Web site. This is an outstanding Web site kept up to indicate. Parents have worked very hard on get egg this education out there will update you on what stays have legislation in place. What movement is being made within various states. And so you can use that information to talk to your facilities as well. So take advantage of those resources.We really appreciate you coming today and listening to what we had to say. This is actually my daughter running cross country and the important thing about this is it really is not a sprint, it is a long distance run. We've been at this for many years and we're making progress very slowly. It's very similar to what we started out with Marian downs in the 60s saying we need to screen all babies by the 80s, many hospitals like our hospital were doing hearing targeted or risk factor targeted hearing screening now they moved to universal because we recognized we were missing a lot of babies with risk factor targeted hearing screening and same is going on now with national CMV I think with congenital hearing screen. Thank you all so much.(Applause.)We may have time for a couple questions if anybody has any. Yes.>> One of your slides said a baby born with CMV (off mic).>> They does viral titres over time. But as soon as you discontinue the anti-virals, they come back up. So whether it reduces the overall duration, I guess no one knows that issue. >> AUDIENCE MEMBER: (off mic). >> ALBERT PARK: I don't know if I can answer that question well. I don't think there's a long-term issue with that. But might be best to discuss that or I can certainly ask my pediatric GI docs on that too. Thank you very much, everybody.(Applause.)