WEBVTT

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<v ->So our first plenary this morning</v>

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is the Elephant in our Living Room,

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and we're gonna be hearing

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from Dr. Gail Demmler-Harrison.

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And Dr. Harrison is a professor of pediatrics

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at Baylor College of Medicine

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and an infectious disease attending pediatrician

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who directs a CMV clinic

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at Texan Children's Hospital.

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She has studied biology, epidemiology,

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clinical manifestations,

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long-term outcomes, diagnosis,

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treatment and prevention of congenital CMV

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for over 40 years.

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And she's a staunch advocate

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of CMV awareness and education.

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And I know that her patients

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lovingly call her Dr. Gail.

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So I'm gonna turn the time over to her.

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(audience applauds)

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<v ->Thank you.</v>

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Thanks, Allison, and good morning, everybody.

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I am going to talk about congenital CMV.

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And the title of my talk is CMV 101,

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so it's gonna be an hour run through

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very quickly of all the contemporary issues

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associated with congenital CMV,

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sort of the warmup act

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for all the wonderful talks that are gonna go on.

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It's also notoriously called,

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you know, the elephant talk.

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Now, does everybody have their CMV Bingo card?

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Because I just may mention

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some of these words in my talk.

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Just for some disclosures,

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I'm gonna discuss some off-label,

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ganciclovir, valganciclovir and other antivirals

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and other biologics,

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but it will be supported by clinical trials

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and expert opinion and consensus panels.

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And I have received research support

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and have done consulting for a variety

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of that industry, all of which start

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with the letter M.

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So why elephants and why CMV?

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Well, CMV, as everybody in this room knows,

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is a big problem that really nobody talks about.

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CMV is the elephant in our living room,

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especially outside of this room.

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And, but most people don't know that elephants

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are also battling their own CMV-related virus,

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called elephant endotheliotropic herpesvirus,

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or EEHV, which threatens

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their elephant baby survivals as well.

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And I've had the pleasure of working

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with Baylor College of Medicine

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on developing diagnostic tests

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and antiviral therapies for EEHP.

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And I've asked a few of my elephant friends,

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these are some of the photos I've taken,

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to help us through this talk.

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So the objectives of CMV 101 is to cover

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just the basics of biology, epidemiology,

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clinical manifestations, diagnosis,

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treatment and prevention.

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So first, who is CMV?

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CMV means cytomegalovirus.

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Cyto, cell. Megalo, big.

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Virus, which is Latin for poison.

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It's a ubiquitous virus with protean manifestations.

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It's an opportunistic virus,

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it's a stealth virus,

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and it's the most common virus

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most people have never heard of.

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And it's the elephant in our living room.

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And here's an elephant here.

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I'm right here.

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No one even acknowledges me.

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(audience laughs)
That's not true

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of people in this room, of course.

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Your eyes are open to CMV,

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but outside this room,

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they cannot see the elephant.

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So if CMV was on Facebook

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and it had a profile picture,

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it'd looked like this,

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or if it was on facial recognition software,

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this is what CMV looks like.

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It's a large double-stranded DNA virus,

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240 KB genome, 162 capsomeres

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arranged in an icosahedral symmetry.

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And it's an enveloped virus.

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That means it's covered by a smooshy layer.

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You'll hear later from, I think,

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Dr. Martin Schleiss some of the details

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of the amazing biology of this virus.

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But some basics.

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It causes a primary or first infection,

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and second reinfections.

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It has the characteristics

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of latency and persistence,

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which is sort of a resting, dormant, asleep state,

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but also an expressive phase of infection.

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And the virus expresses

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numerous viral proteins and mRNAs, which mediate

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its amazing immune evasion capabilities.

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And it also infects a variety of human cells

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in our body.

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CMV can also reactivate.

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It can cause an active infection

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with full viral gene expression

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and production of those viral particles

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I just showed you.

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Now, CMV can also cause

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asymptomatic infections and symptomatic infections.

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Asymptomatic infection

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is an active viral infection

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that produces no obvious outward signs

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or symptoms in the person.

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And this is actually most CMV infections.

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Symptomatic infections

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are also active viral infections

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that produce symptoms and signs.

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There's many different signs and symptoms that can occur.

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And this is actually, though, the minority

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of CMV infections, which really makes it a challenge

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to study and to detect.

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CMV also can cause primary infections,

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which is your first experience with CMV,

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or recurrent infections or non-primary infections.

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Those can be reactivation,

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which is your own CMV, or your CMVs,

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if you're infected with multiple CMVs,

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endogenous in your body that reactivate

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and cause an infection.

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And most recurrent infections

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are probably reactivations.

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However, you can also be reinfected

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with a new CMV in your body,

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which adds to the ambiguity

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and the complexity of CMV.

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So that's just some basics of the biology.

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Let's now go into epidemiology.

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Who catches CMV?

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Well, you can catch CMV

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in a variety of different times in your life.

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We're talking about today,

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at this conference, congenital CMV,

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which is acquired from maternal transmission

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during pregnancy, in utero, to the baby.

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And the baby's born shedding large quantities

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of CMV in urine or saliva,

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or present in the blood.

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That's congenital CMV.

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But babies can also acquire CMV postnatally

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from mother's perinatal secretions

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during the birth process,

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from person to person, and very commonly

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from maternal breast milk reactivation of CMV.

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This is actually a very natural, normal way

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for babies to acquire CMV, at the time

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when they have their mother's antibody.

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It can be problematic in the neonatal intensive care unit,

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however, for some very extreme premature babies.

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Now, toddlers, they're hot zones for CMV.

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They acquire it from each other

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in daycare, playgroup, family.

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The sharing that toddlers do

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of about just about everything.

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Adolescence is another time of CMV acquisition,

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with their explorations of intimacy,

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shall I say,

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as well as sharing food and drink

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in the high school lunchroom,

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they can pass CMV.

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And then adulthood, of course.

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Intimacy of adulthood relationships,

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as well as sharing, and even more commonly,

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contact with young children in the home setting

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or in the work environment.

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So let's now talk about CMV

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in the fetus and the newborn.

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Now, these are US numbers here, and there's about,

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but you can, you know, apply them to any country.

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And there are approximately four million births annually

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in the US, and between 1 in 100

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to 1 in 200 babies are born with congenital CMV,

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which means tens of thousands of babies

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each year are born with congenital CMV.

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Now, if you look at one side,

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where there's symptomatic CMV,

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that's the minority of babies.

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Just about 10% or so

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will be symptomatic at birth.

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That is, you can tell that there's something

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not right with the baby,

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and the baby would warrant CMV testing.

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However, the vast majority of babies,

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the big silent majority of babies

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with congenital CMV,

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are actually asymptomatic at birth,

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yet they will go on to have hearing loss,

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some vision loss and maybe some developmental disabilities.

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Let's now look at pregnant persons

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or persons of childbearing age.

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My pointer is not working,

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so I'm just gonna sort of walk you through.

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If you first look over to the side

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where there's 55 to 85% CMV seropositive,

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that's the majority of people.

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So probably most people in this room had CMV.

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So if you're seropositive and you enter

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childbearing age, then you can experience

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a recurrent CMV infection,

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less than 1% of the time while you're pregnant,

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transmit the virus to your baby.

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Thankfully, most of those babies do not have symptoms

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or their symptoms are rarely manifested,

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though they can have a hearing loss

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that can be progressive.

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This area of recurrent maternal CMV infection

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producing congenital CMV is a big area

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of interest and a potential good opportunity

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to reduce or prevent

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some of the major number of sequelae

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of congenital CMV 'cause that's probably

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the majority of babies in many demographics.

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However, about 15 to 45% of babies

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of moms who are

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of a childbearing age

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will be CMV seronegative.

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They've never seen CMV.

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There's about a 4% annual seroconversion rate

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or primary CMV infection during pregnancy.

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And it ranges between 1 to 7%.

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Of these women who experience a primary

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or first infection with CMV, about 40%,

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and the range is about 25 to 55%,

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depending on the study methods and demographics,

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will transmit the virus to their baby.

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So the good news is, most of the time,

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even if you experience a primary CMV infection

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in pregnancy, you won't transmit,

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but sometimes you will.

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And then, as a result

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of a maternal infection with CMV,

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the baby can have symptoms at birth,

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the tip of the iceberg,

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or the silent majority

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of babies will be asymptomatic,

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but yet still at risk

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of later onset of sequelae.

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So that's some basics of biology and epidemiology.

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Now let's go to clinical manifestations.

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There in the red,

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we're gonna talk about these babies now.

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Congenital CMV can be symptomatic

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at birth, and the baby has symptoms

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that alert the doctor,

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and the mother and the father, too,

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that the baby may have congenital CMV.

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Symptomatic congenital CMV

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also may have central nervous system involvement

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or brain involvement as well.

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And those clinical signs can be evident

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with a small head, small brain,

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abnormal brain imaging or neurologic findings.

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And then some babies can be what I've termed

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the primary neurophenotype of symptomatic CMV,

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where only the brain is involved.

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The baby doesn't have any of the other somatic

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or body manifestations that may alert babies.

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So they may have sensory involvement, as well,

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with vision loss and hearing loss.

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And these babies often are missed

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or are not diagnosed early

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00:11:11.430 --> 00:11:12.993
in the newborn period.

278
00:11:14.910 --> 00:11:16.470
Here's a picture of a couple babies

279
00:11:16.470 --> 00:11:17.790
that I've taken care of

280
00:11:17.790 --> 00:11:21.090
with symptomatic congenital CMV at birth.

281
00:11:21.090 --> 00:11:22.380
One baby's a term baby.

282
00:11:22.380 --> 00:11:25.260
Obviously jaundice, petechiae, purpura,

283
00:11:25.260 --> 00:11:27.750
he had hepatosplenomegaly and also was deaf

284
00:11:27.750 --> 00:11:29.280
at birth, had retinitis

285
00:11:29.280 --> 00:11:31.710
and central nervous system involvement.

286
00:11:31.710 --> 00:11:35.130
So he had just about everything on the list.

287
00:11:35.130 --> 00:11:37.350
And the other baby is premature,

288
00:11:37.350 --> 00:11:38.940
but also manifested some

289
00:11:38.940 --> 00:11:42.337
of the classic signs of congenital CMV.

290
00:11:44.580 --> 00:11:46.650
But these babies are the tip of the iceberg.

291
00:11:46.650 --> 00:11:49.830
They're not all babies with congenital CMV.

292
00:11:49.830 --> 00:11:52.140
These are the classic signs and symptoms.

293
00:11:52.140 --> 00:11:54.870
But most of the time, babies with congenital CMV

294
00:11:54.870 --> 00:11:57.780
will just have one or two signs or symptoms,

295
00:11:57.780 --> 00:11:59.970
such as growth restriction or may be small

296
00:11:59.970 --> 00:12:01.920
for their gestational age.

297
00:12:01.920 --> 00:12:04.160
They may have jaundice with a direct hyperbilirubinemia,

298
00:12:04.160 --> 00:12:05.490
or some babies I've seen

299
00:12:05.490 --> 00:12:10.380
have an indirect hyperbilirubinemia as well.

300
00:12:10.380 --> 00:12:12.960
Skin rashes, like I talked about, enlarged liver and spleen,

301
00:12:12.960 --> 00:12:16.083
low platelets and abnormal liver enzymes.

302
00:12:17.400 --> 00:12:19.620
And then those with CNS involvement

303
00:12:19.620 --> 00:12:21.660
may have microcephaly at birth,

304
00:12:21.660 --> 00:12:23.640
or, very important,

305
00:12:23.640 --> 00:12:25.980
later on in infancy,

306
00:12:25.980 --> 00:12:27.840
the microcephaly may evolve.

307
00:12:27.840 --> 00:12:30.480
And the definition of microcephaly, in my opinion,

308
00:12:30.480 --> 00:12:33.360
is very dynamic and fluid.

309
00:12:33.360 --> 00:12:36.480
It's not just the head circumference at birth.

310
00:12:36.480 --> 00:12:38.970
They may have neurologic signs, seizures,

311
00:12:38.970 --> 00:12:41.070
some more severe involvement.

312
00:12:41.070 --> 00:12:44.613
They may have infantile spasms, hemiparesis.

313
00:12:45.510 --> 00:12:47.310
They may favor one side over the other.

314
00:12:47.310 --> 00:12:49.140
It's not normal for a three-month-old

315
00:12:49.140 --> 00:12:51.420
to show handedness at that age.

316
00:12:51.420 --> 00:12:54.540
It needs to wait 'til they're about three years of age.

317
00:12:54.540 --> 00:12:57.030
So hemiparesis may show up,

318
00:12:57.030 --> 00:12:59.040
or abnormal tone, either increased tone,

319
00:12:59.040 --> 00:13:01.623
hypertonia, or low tone, hypotonia.

320
00:13:02.760 --> 00:13:04.140
And then if you image their brain,

321
00:13:04.140 --> 00:13:07.170
you may find enlarged ventricles, calcifications,

322
00:13:07.170 --> 00:13:08.760
which are usually periventricular,

323
00:13:08.760 --> 00:13:11.310
around the fluid-filled sacs of the brain.

324
00:13:11.310 --> 00:13:12.660
There may be lucencies

325
00:13:12.660 --> 00:13:15.960
around ventricles, cerebral atrophy,

326
00:13:15.960 --> 00:13:17.640
cortical maldevelopment syndromes,

327
00:13:17.640 --> 00:13:19.650
such as polymicrogyria,

328
00:13:19.650 --> 00:13:22.980
or the very severe fetal brain disruption sequence

329
00:13:22.980 --> 00:13:25.680
that babies with congenital Zika can have.

330
00:13:25.680 --> 00:13:28.230
But I've seen more babies with congenital CMV

331
00:13:28.230 --> 00:13:30.183
have fetal brain disruption sequence.

332
00:13:31.047 --> 00:13:33.030
Lenticulostriate vasculopathy,

333
00:13:33.030 --> 00:13:34.620
which is some calcified blood vessels

334
00:13:34.620 --> 00:13:36.150
at the base of the brain,

335
00:13:36.150 --> 00:13:37.440
or cysts as well.

336
00:13:37.440 --> 00:13:40.830
So there's a wide variety of brain imaging findings

337
00:13:40.830 --> 00:13:42.450
that can be seen in babies

338
00:13:42.450 --> 00:13:43.860
with CNS involvement

339
00:13:43.860 --> 00:13:46.140
associated with congenital CMV.

340
00:13:46.140 --> 00:13:47.730
And then once again, I'd like to put a plug in

341
00:13:47.730 --> 00:13:52.620
for awareness of the primary neurophenotype of CMV.

342
00:13:52.620 --> 00:13:54.570
There is emerging recognition that CMV

343
00:13:54.570 --> 00:13:56.910
can just involve the brain of the baby

344
00:13:56.910 --> 00:14:01.173
with, once again, a variety of manifestations.

345
00:14:02.520 --> 00:14:04.860
And here's some head circumference plots.

346
00:14:04.860 --> 00:14:06.600
There's two of 'em here of babies

347
00:14:06.600 --> 00:14:08.160
that I took care of.

348
00:14:08.160 --> 00:14:10.387
And both of the times, the pediatrician says,

349
00:14:10.387 --> 00:14:11.220
"Well, don't worry about it.

350
00:14:11.220 --> 00:14:13.350
"Your baby's small."

351
00:14:13.350 --> 00:14:17.010
And they ended up having congenital CMV

352
00:14:17.010 --> 00:14:18.870
and cortical maldevelopment syndromes,

353
00:14:18.870 --> 00:14:22.293
even though they looked otherwise totally normal at birth.

354
00:14:24.090 --> 00:14:26.130
Here's a CT scan of a baby

355
00:14:26.130 --> 00:14:29.400
with severe fetal brain disruption sequence.

356
00:14:29.400 --> 00:14:31.440
The baby's skull was collapsed,

357
00:14:31.440 --> 00:14:33.840
so there's severe brain malformation,

358
00:14:33.840 --> 00:14:37.230
and periventricular calcifications that are very obvious.

359
00:14:37.230 --> 00:14:39.510
This is probably one of the most severe manifestations

360
00:14:39.510 --> 00:14:41.910
of CNS involvement from congenital CMV.

361
00:14:41.910 --> 00:14:43.440
This is the more classic one.

362
00:14:43.440 --> 00:14:45.000
If there's any medical students in the audience,

363
00:14:45.000 --> 00:14:47.970
this is the one that's gonna be on the board test,

364
00:14:47.970 --> 00:14:51.000
ventriculomegaly, linear periventricular calcifications,

365
00:14:51.000 --> 00:14:52.500
cerebral atrophy.

366
00:14:52.500 --> 00:14:53.580
If I had a pointer that works,

367
00:14:53.580 --> 00:14:54.573
I'd show you, but.

368
00:14:55.920 --> 00:14:57.510
And then, so more often than not,

369
00:14:57.510 --> 00:15:00.210
there's a mild to moderate involvement.

370
00:15:00.210 --> 00:15:02.190
You can have enlarged ventricles.

371
00:15:02.190 --> 00:15:04.980
You can have punctate or beaded calcifications.

372
00:15:04.980 --> 00:15:06.630
You see the little white dots

373
00:15:06.630 --> 00:15:09.000
around the ventricles.

374
00:15:09.000 --> 00:15:10.560
Or you can have what's called leukomalacia,

375
00:15:10.560 --> 00:15:12.930
where the brain

376
00:15:12.930 --> 00:15:16.350
is just a little bit thin from damage from CMV.

377
00:15:16.350 --> 00:15:18.090
And then cortical maldevelopment syndromes,

378
00:15:18.090 --> 00:15:20.580
which is polymicrogyria in general,

379
00:15:20.580 --> 00:15:22.260
you can have that as well.

380
00:15:22.260 --> 00:15:23.520
The larger MRI

381
00:15:23.520 --> 00:15:25.590
shows unilateral or one-sidedness.

382
00:15:25.590 --> 00:15:26.520
I think you can see that.

383
00:15:26.520 --> 00:15:27.570
On one side of the brain,

384
00:15:27.570 --> 00:15:29.340
there's a lotta little folds.

385
00:15:29.340 --> 00:15:31.440
On the other side of the brain, it's very smooth.

386
00:15:31.440 --> 00:15:33.930
And the ventricle, or the fluid-filled sac, is larger.

387
00:15:33.930 --> 00:15:36.240
That's unilateral PMG.

388
00:15:36.240 --> 00:15:37.890
On the other side is the baby

389
00:15:37.890 --> 00:15:39.420
that had severe microcephaly

390
00:15:39.420 --> 00:15:42.600
and bilateral PMG, where both sides

391
00:15:42.600 --> 00:15:44.550
of the brain are very smooth,

392
00:15:44.550 --> 00:15:46.140
it's atrophied and small,

393
00:15:46.140 --> 00:15:47.793
and the ventricles are large.

394
00:15:49.230 --> 00:15:51.180
Now, what about vision involvement

395
00:15:51.180 --> 00:15:53.280
with symptomatic congenital CMV?

396
00:15:53.280 --> 00:15:54.960
I think that the vision outcomes

397
00:15:54.960 --> 00:15:56.970
in congenital CMV are underappreciated

398
00:15:56.970 --> 00:15:59.160
and I think they're very important.

399
00:15:59.160 --> 00:16:01.260
Babies can have an active retinitis,

400
00:16:01.260 --> 00:16:03.810
where CMV is in the retina.

401
00:16:03.810 --> 00:16:05.430
They also can have inactive

402
00:16:05.430 --> 00:16:07.170
sort of chorioretinal scars.

403
00:16:07.170 --> 00:16:09.000
They can have optic nerve atrophy.

404
00:16:09.000 --> 00:16:10.530
They can have cortical blindness

405
00:16:10.530 --> 00:16:13.320
with central vision impairment, or CVI.

406
00:16:13.320 --> 00:16:15.150
And they can also have muscle imbalance

407
00:16:15.150 --> 00:16:16.833
in the eye, called strabismus.

408
00:16:18.150 --> 00:16:19.530
And then, of course, hearing loss,

409
00:16:19.530 --> 00:16:22.800
which is probably the most common

410
00:16:22.800 --> 00:16:26.040
long-term sequelae of congenital CMV.

411
00:16:26.040 --> 00:16:27.660
Now, the hearing loss can be conductive

412
00:16:27.660 --> 00:16:28.680
with middle ear effusion.

413
00:16:28.680 --> 00:16:31.380
We've shown that babies

414
00:16:31.380 --> 00:16:33.390
with congenital CMV disease

415
00:16:33.390 --> 00:16:35.970
are more likely than babies without congenital CMV

416
00:16:35.970 --> 00:16:39.180
to have hearing loss from middle ear effusions.

417
00:16:39.180 --> 00:16:40.920
So if you do have a baby with congenital CMV,

418
00:16:40.920 --> 00:16:44.160
make sure that you monitor their TMs

419
00:16:44.160 --> 00:16:46.740
and their middle ear function as well.

420
00:16:46.740 --> 00:16:49.920
And then, of course, sensorineural hearing loss.

421
00:16:49.920 --> 00:16:51.030
That's the big ticket.

422
00:16:51.030 --> 00:16:53.370
That's the one that we're most aware of.

423
00:16:53.370 --> 00:16:55.920
And that can be progressive,

424
00:16:55.920 --> 00:16:58.680
almost always, in my experience.

425
00:16:58.680 --> 00:17:01.020
Can be unilateral, one side, or bilateral.

426
00:17:01.020 --> 00:17:03.330
Can be congenital, that is, the baby's born

427
00:17:03.330 --> 00:17:06.303
with a hearing loss, or later onset.

428
00:17:08.040 --> 00:17:10.270
So now let's go over to the other side

429
00:17:12.380 --> 00:17:15.243
of the graph and look at the asymptomatic babies.

430
00:17:16.710 --> 00:17:19.000
Asymptomatic congenital CMV

431
00:17:20.010 --> 00:17:22.560
is no apparent symptoms at birth,

432
00:17:22.560 --> 00:17:24.126
normal hearing at birth,

433
00:17:24.126 --> 00:17:25.980
that is, they pass their newborn hearing screen,

434
00:17:25.980 --> 00:17:27.450
but yet they continue

435
00:17:27.450 --> 00:17:30.297
to be at risk for later onset hearing loss.

436
00:17:30.297 --> 00:17:33.060
And then asymptomatic congenital CMV

437
00:17:33.060 --> 00:17:35.760
can also have isolated hearing loss.

438
00:17:35.760 --> 00:17:38.010
There's no clear symptoms at birth,

439
00:17:38.010 --> 00:17:40.800
yet they fail or refer on their newborn hearing screen.

440
00:17:40.800 --> 00:17:42.600
Audiologic evaluation confirms

441
00:17:42.600 --> 00:17:44.670
that they have a sensorineural hearing loss.

442
00:17:44.670 --> 00:17:47.850
And that hearing loss can be a congenital hearing loss.

443
00:17:47.850 --> 00:17:50.250
It can be unilateral or bilateral.

444
00:17:50.250 --> 00:17:52.290
And they are also at significant risk

445
00:17:52.290 --> 00:17:54.093
for the hearing loss progressing.

446
00:17:56.640 --> 00:17:58.800
Now, asymptomatic babies

447
00:17:58.800 --> 00:18:00.870
with congenital CMV

448
00:18:00.870 --> 00:18:03.060
may have brain imaging findings as well,

449
00:18:03.060 --> 00:18:04.740
and it may be very subtle,

450
00:18:04.740 --> 00:18:08.130
but it's sort of a light version

451
00:18:08.130 --> 00:18:10.380
of what some of the symptomatic babies have.

452
00:18:10.380 --> 00:18:11.947
So then you can get into discussions about,

453
00:18:11.947 --> 00:18:14.400
well, are they truly asymptomatic

454
00:18:14.400 --> 00:18:15.570
or are they symptomatic?

455
00:18:15.570 --> 00:18:17.970
You know, and you can sit over, you know,

456
00:18:17.970 --> 00:18:20.370
many bottles of wine

457
00:18:20.370 --> 00:18:22.890
discussing are they really asymptomatic or not?

458
00:18:22.890 --> 00:18:24.690
And I don't know the answer to that.

459
00:18:26.610 --> 00:18:28.530
Here are some imaging findings

460
00:18:28.530 --> 00:18:31.620
of babies that were born with congenital CMV

461
00:18:31.620 --> 00:18:33.180
that appeared normal at birth.

462
00:18:33.180 --> 00:18:36.870
And you can have very punctate calcifications,

463
00:18:36.870 --> 00:18:39.240
some periventricular leukomalacia,

464
00:18:39.240 --> 00:18:41.760
some mild enlargement of the ventricles.

465
00:18:41.760 --> 00:18:43.920
On head ultrasounds, you can have

466
00:18:43.920 --> 00:18:46.050
some subtle abnormalities,

467
00:18:46.050 --> 00:18:49.830
asymmetrical ventricles, some periventricular cysts.

468
00:18:49.830 --> 00:18:52.920
And on MRI, you can also see delayed myelination,

469
00:18:52.920 --> 00:18:56.340
small germinolytic cysts, slightly enlarged ventricles.

470
00:18:56.340 --> 00:18:59.400
So is this a asymptomatic baby totally

471
00:18:59.400 --> 00:19:01.890
or is this a baby with a mild neurophenotype?

472
00:19:01.890 --> 00:19:03.420
Are they symptomatic or not?

473
00:19:03.420 --> 00:19:05.310
With advanced imaging now

474
00:19:05.310 --> 00:19:07.860
and other advanced diagnostics,

475
00:19:07.860 --> 00:19:08.880
me as a clinician,

476
00:19:08.880 --> 00:19:10.290
sometimes there's a conundrum about

477
00:19:10.290 --> 00:19:12.633
is this baby asymptomatic or symptomatic?

478
00:19:14.520 --> 00:19:16.200
We do know long-term outcomes.

479
00:19:16.200 --> 00:19:18.476
The babies with asymptomatic congenital CMV

480
00:19:18.476 --> 00:19:21.270
are at risk for later onset hearing loss.

481
00:19:21.270 --> 00:19:23.680
But also, like one study

482
00:19:24.726 --> 00:19:26.400
that we published, asymptomatic babies

483
00:19:26.400 --> 00:19:28.230
identified through a newborn screening,

484
00:19:28.230 --> 00:19:30.120
where we screened 32,000 babies

485
00:19:30.120 --> 00:19:32.070
over a period of 10 years

486
00:19:32.070 --> 00:19:33.990
with normal hearing by age two,

487
00:19:33.990 --> 00:19:35.850
they didn't have any IQ differences

488
00:19:35.850 --> 00:19:37.800
or academic achievement differences

489
00:19:37.800 --> 00:19:40.590
at some of the key time points of five years and 18 years.

490
00:19:40.590 --> 00:19:43.290
However, if their hearing loss presented early,

491
00:19:43.290 --> 00:19:45.750
they did have lower full-scale IQs

492
00:19:45.750 --> 00:19:48.450
and receptive vocabulary scores,

493
00:19:48.450 --> 00:19:50.520
probably due to their sensorineural hearing loss.

494
00:19:50.520 --> 00:19:52.440
But a lot of babies who are asymptomatic

495
00:19:52.440 --> 00:19:53.550
with sensorineural hearing loss

496
00:19:53.550 --> 00:19:56.190
also have imaging abnormalities.

497
00:19:56.190 --> 00:19:59.610
So it might be a little bit hard to tease out.

498
00:19:59.610 --> 00:20:02.070
But can early detection of these babies

499
00:20:02.070 --> 00:20:05.160
and interventions minimize this impact

500
00:20:05.160 --> 00:20:06.543
on their learning ability?

501
00:20:08.160 --> 00:20:10.080
So that's biology, epidemiology,

502
00:20:10.080 --> 00:20:13.530
clinical manifestations of symptomatic and asymptomatic.

503
00:20:13.530 --> 00:20:17.220
Let's fly now to diagnosis.

504
00:20:17.220 --> 00:20:20.010
And we're gonna talk about all of these babies here

505
00:20:20.010 --> 00:20:21.510
in the red, about, you know,

506
00:20:21.510 --> 00:20:23.793
who may have congenital CMV.

507
00:20:24.960 --> 00:20:26.970
How do you diagnose congenital CMV?

508
00:20:26.970 --> 00:20:30.270
Well, it comes down to timing, specimen and method.

509
00:20:30.270 --> 00:20:31.560
The timing.

510
00:20:31.560 --> 00:20:33.690
Detection of the virus

511
00:20:33.690 --> 00:20:35.400
in the first 21 days of life,

512
00:20:35.400 --> 00:20:37.543
and some experts will extend that

513
00:20:37.543 --> 00:20:39.990
through the first 28 days of life,

514
00:20:39.990 --> 00:20:42.990
is the diagnosis of congenital CMV.

515
00:20:42.990 --> 00:20:44.640
You must detect the virus early

516
00:20:44.640 --> 00:20:47.190
in the newborn period because after that time,

517
00:20:47.190 --> 00:20:48.990
remember in one of my earlier slides,

518
00:20:48.990 --> 00:20:50.700
CMV is very commonly acquired

519
00:20:50.700 --> 00:20:53.790
during many times in your life.

520
00:20:53.790 --> 00:20:54.870
So timing.

521
00:20:54.870 --> 00:20:56.550
Second is specimen.

522
00:20:56.550 --> 00:20:59.790
Saliva, urine, blood plasma,

523
00:20:59.790 --> 00:21:03.270
dried blood spot, tissue biopsy

524
00:21:03.270 --> 00:21:06.960
can all be used to diagnose congenital CMV.

525
00:21:06.960 --> 00:21:08.250
And you'll hear a lot of talks

526
00:21:08.250 --> 00:21:10.770
and discussions about what's the best specimen,

527
00:21:10.770 --> 00:21:14.160
saliva, urine, dried blood spot?

528
00:21:14.160 --> 00:21:15.840
They all can be used.

529
00:21:15.840 --> 00:21:20.490
Which is best I think depends on the application

530
00:21:20.490 --> 00:21:21.870
and what you're doing.

531
00:21:21.870 --> 00:21:23.040
And then finally, the method.

532
00:21:23.040 --> 00:21:24.300
How do you detect CMV?

533
00:21:24.300 --> 00:21:27.420
Well, the traditional way we used to do,

534
00:21:27.420 --> 00:21:30.750
before all the molecular diagnostics, is culture,

535
00:21:30.750 --> 00:21:33.660
or now an enhanced shell vial culture,

536
00:21:33.660 --> 00:21:34.770
some labs still offer,

537
00:21:34.770 --> 00:21:37.350
but quite honestly, contemporary-wise,

538
00:21:37.350 --> 00:21:39.000
PCR-based diagnostics

539
00:21:39.000 --> 00:21:43.590
or other nucleic acid diagnostics are available.

540
00:21:43.590 --> 00:21:46.810
And one of our exhibitors

541
00:21:47.790 --> 00:21:50.910
does have some information

542
00:21:50.910 --> 00:21:54.240
on nucleic-acid-based amplification methods

543
00:21:54.240 --> 00:21:56.013
for the detection of CMV.

544
00:21:58.410 --> 00:22:01.170
Now, newborn diagnosis also

545
00:22:01.170 --> 00:22:02.610
has other timings,

546
00:22:02.610 --> 00:22:04.830
diagnostic, targeted and universal.

547
00:22:04.830 --> 00:22:07.520
So diagnostic testing for congenital CMV.

548
00:22:07.520 --> 00:22:08.910
So here and the now.

549
00:22:08.910 --> 00:22:10.620
Newborns with signs and symptoms

550
00:22:10.620 --> 00:22:12.543
of congenital CMV are tested.

551
00:22:13.560 --> 00:22:14.790
But are they?

552
00:22:14.790 --> 00:22:17.970
If they have the classic signs and symptoms, yeah.

553
00:22:17.970 --> 00:22:19.170
Most don't.

554
00:22:19.170 --> 00:22:22.740
Many, maybe most, are still missed

555
00:22:22.740 --> 00:22:27.210
with the traditional diagnostic testing paradigm.

556
00:22:27.210 --> 00:22:28.650
How about targeted newborn screening?

557
00:22:28.650 --> 00:22:29.610
That's evolving.

558
00:22:29.610 --> 00:22:30.870
There's a lotta interest in that.

559
00:22:30.870 --> 00:22:31.703
There's gonna be a lotta talks.

560
00:22:31.703 --> 00:22:34.260
I know Dr. Park's gonna talk about it,

561
00:22:34.260 --> 00:22:36.510
and a lot of other speakers will be talking about

562
00:22:36.510 --> 00:22:38.010
targeted newborn screening.

563
00:22:38.010 --> 00:22:38.970
It's evolving.

564
00:22:38.970 --> 00:22:41.310
It's actually catching fire.

565
00:22:41.310 --> 00:22:42.870
And that's where normal newborns

566
00:22:42.870 --> 00:22:44.580
with failed to refer newborn hearing screens

567
00:22:44.580 --> 00:22:45.413
are tested for CMV,

568
00:22:45.413 --> 00:22:47.370
'cause congenital CMV is one

569
00:22:47.370 --> 00:22:50.490
of the many causes of congenital hearing loss.

570
00:22:50.490 --> 00:22:52.353
Then universal newborn screening.

571
00:22:53.760 --> 00:22:55.680
Just last month when I gave this talk,

572
00:22:55.680 --> 00:22:58.320
I had the word waiting,

573
00:22:58.320 --> 00:23:00.780
but what word did I put now?

574
00:23:00.780 --> 00:23:02.520
Evolving.

575
00:23:02.520 --> 00:23:04.440
Because universal newborn screening

576
00:23:04.440 --> 00:23:05.610
is gaining traction,

577
00:23:05.610 --> 00:23:07.650
and that's where all newborns

578
00:23:07.650 --> 00:23:10.830
are screened and tested for congenital CMV.

579
00:23:10.830 --> 00:23:12.000
And that's probably the only way

580
00:23:12.000 --> 00:23:13.683
we're going to find all the babies

581
00:23:13.683 --> 00:23:15.063
with congenital CMV.

582
00:23:17.100 --> 00:23:18.720
So what about targeted newborn screening

583
00:23:18.720 --> 00:23:20.430
for congenital CMV,

584
00:23:20.430 --> 00:23:22.410
failed newborn hearing screening in the US?

585
00:23:22.410 --> 00:23:24.540
There are many states that I've listed there

586
00:23:24.540 --> 00:23:27.720
that have state-based targeted testing.

587
00:23:27.720 --> 00:23:28.980
Many birthing hospitals,

588
00:23:28.980 --> 00:23:31.620
my own included, in many other states

589
00:23:31.620 --> 00:23:33.690
will test babies who fail to refer

590
00:23:33.690 --> 00:23:36.270
on the newborn hearing screen for congenital CMV.

591
00:23:36.270 --> 00:23:37.440
So if you're expecting a baby,

592
00:23:37.440 --> 00:23:39.840
you can find out if your birthing center

593
00:23:39.840 --> 00:23:41.370
does test babies.

594
00:23:41.370 --> 00:23:43.890
You can also go to the National CMV website

595
00:23:43.890 --> 00:23:45.900
and look for hospitals

596
00:23:45.900 --> 00:23:48.720
that may do targeted testing

597
00:23:48.720 --> 00:23:50.460
for congenital CMV.

598
00:23:50.460 --> 00:23:51.660
Now, here in Canada,

599
00:23:51.660 --> 00:23:54.270
now, Canadians, help me if I didn't get it right,

600
00:23:54.270 --> 00:23:56.460
but there's at least two provinces

601
00:23:56.460 --> 00:23:58.410
where there's province-wide targeted testing,

602
00:23:58.410 --> 00:24:00.180
British Columbia and Manitoba.

603
00:24:00.180 --> 00:24:02.850
Many birthing hospitals in other provinces as well.

604
00:24:02.850 --> 00:24:04.770
And you can go to CMV Canada, sorry,

605
00:24:04.770 --> 00:24:07.410
I forgot the A in the middle of Canada,

606
00:24:07.410 --> 00:24:09.093
for a list of these hospitals.

607
00:24:10.650 --> 00:24:12.600
What about universal screening?

608
00:24:12.600 --> 00:24:13.650
Where are we on that?

609
00:24:13.650 --> 00:24:16.890
Well, the recommended universal screening panel application

610
00:24:16.890 --> 00:24:18.810
was submitted, and resubmitted

611
00:24:18.810 --> 00:24:20.550
in March of the 2019,

612
00:24:20.550 --> 00:24:24.720
by the National CMV RUSP Multidisciplinary Nomination Team.

613
00:24:24.720 --> 00:24:25.980
And to my knowledge,

614
00:24:25.980 --> 00:24:27.750
it's still under review.

615
00:24:27.750 --> 00:24:30.060
If you wanna learn more about this effort

616
00:24:30.060 --> 00:24:30.893
or to support it,

617
00:24:30.893 --> 00:24:33.123
go to the nationalcmv.org website.

618
00:24:35.370 --> 00:24:37.140
Now, what about strategies

619
00:24:37.140 --> 00:24:38.430
for universal newborn screening?

620
00:24:38.430 --> 00:24:39.960
You're gonna hear a lotta talks

621
00:24:39.960 --> 00:24:42.060
about what's the best strategy?

622
00:24:42.060 --> 00:24:44.190
I don't know the answer to that,

623
00:24:44.190 --> 00:24:45.390
but the important thing is at least

624
00:24:45.390 --> 00:24:46.890
we're trying and discussing.

625
00:24:46.890 --> 00:24:48.810
So you can detect CMV in the urine

626
00:24:48.810 --> 00:24:50.820
by old, traditional viral culture.

627
00:24:50.820 --> 00:24:52.200
Nobody's doing that much anymore.

628
00:24:52.200 --> 00:24:54.150
DNA PCR.

629
00:24:54.150 --> 00:24:56.315
I think we should look at more R and D

630
00:24:56.315 --> 00:24:57.720
for CMV antigen.

631
00:24:57.720 --> 00:24:59.040
And I think we should look more

632
00:24:59.040 --> 00:25:01.440
for rapid point of care testing in the newborn nursery.

633
00:25:01.440 --> 00:25:02.580
I think that would be awesome.

634
00:25:02.580 --> 00:25:03.960
Then every baby, when they get

635
00:25:03.960 --> 00:25:05.310
the newborn hearing screen,

636
00:25:05.310 --> 00:25:07.290
can also get a point of care test

637
00:25:07.290 --> 00:25:10.650
for CMV, and they know before they leave home

638
00:25:10.650 --> 00:25:12.450
if they have congenital CMV or not.

639
00:25:12.450 --> 00:25:13.620
We're not there yet.

640
00:25:13.620 --> 00:25:16.110
You can detect CMV in the saliva, once again,

641
00:25:16.110 --> 00:25:18.870
by all of these different methods.

642
00:25:18.870 --> 00:25:20.460
Breast milk feeds may produce

643
00:25:20.460 --> 00:25:22.470
a low false positive result.

644
00:25:22.470 --> 00:25:24.960
And most CMV experts feel that you should confirm

645
00:25:24.960 --> 00:25:28.290
all saliva positives with a urine CMV test.

646
00:25:28.290 --> 00:25:30.420
And then detection of CMV in newborn screening

647
00:25:30.420 --> 00:25:32.810
by dried blood spots, by DNA PCR,

648
00:25:32.810 --> 00:25:37.410
is also a very, you know, popular way

649
00:25:37.410 --> 00:25:38.580
that's being evaluated.

650
00:25:38.580 --> 00:25:39.930
And I know in Minnesota,

651
00:25:39.930 --> 00:25:44.040
and with Dr. Schleiss' efforts,

652
00:25:44.040 --> 00:25:45.090
this has been adopted

653
00:25:45.090 --> 00:25:46.390
in the state of Minnesota.

654
00:25:47.310 --> 00:25:49.320
Speaking of Minnesota,

655
00:25:49.320 --> 00:25:51.420
universal newborn screening for congenital CMV

656
00:25:51.420 --> 00:25:53.640
in the US, Minnesota was the first state

657
00:25:53.640 --> 00:25:56.430
to adopt routine newborn screening for congenital CMV.

658
00:25:56.430 --> 00:25:58.067
It's gonna start in 2023,

659
00:25:58.067 --> 00:26:00.690
and it will use the newborn dried blood spot,

660
00:26:00.690 --> 00:26:02.370
which is a platform that is used

661
00:26:02.370 --> 00:26:03.990
for newborn screening.

662
00:26:03.990 --> 00:26:05.280
And so the ease

663
00:26:05.280 --> 00:26:07.770
of that sample collection

664
00:26:07.770 --> 00:26:09.780
and process that's already in place,

665
00:26:09.780 --> 00:26:11.310
I think helped ease that.

666
00:26:11.310 --> 00:26:13.950
And then in Canada, Ontario was the first

667
00:26:13.950 --> 00:26:15.960
sort of geographic area to adopt

668
00:26:15.960 --> 00:26:18.150
universal newborn screening for congenital CMV,

669
00:26:18.150 --> 00:26:19.674
and you're right here.

670
00:26:19.674 --> 00:26:20.507
(audience applauds)

671
00:26:20.507 --> 00:26:21.967
Yes, a round of applause.

672
00:26:21.967 --> 00:26:23.940
Yes.
(audience applauds)

673
00:26:23.940 --> 00:26:25.620
And Saskatchewan, I believe,

674
00:26:25.620 --> 00:26:28.980
and I think Manitoba, might be pending soon.

675
00:26:28.980 --> 00:26:31.680
So universal newborn screening for congenital CMV

676
00:26:31.680 --> 00:26:33.030
is no longer awaiting.

677
00:26:33.030 --> 00:26:34.053
It's evolving.

678
00:26:36.240 --> 00:26:37.770
Now, you can also go back in time.

679
00:26:37.770 --> 00:26:39.810
So say your three-month-old baby has hearing loss,

680
00:26:39.810 --> 00:26:40.643
you're trying to figure out

681
00:26:40.643 --> 00:26:42.600
if it's congenital CMV or not.

682
00:26:42.600 --> 00:26:46.050
You can can retrieve your baby's newborn dried blood spot

683
00:26:46.050 --> 00:26:48.690
and have it tested for CMV DNA.

684
00:26:48.690 --> 00:26:51.080
So if your baby had significant viremia

685
00:26:51.080 --> 00:26:54.180
at the time that he or she was born,

686
00:26:54.180 --> 00:26:56.400
you can diagnose congenital CMV

687
00:26:56.400 --> 00:26:57.240
that way as well.

688
00:26:57.240 --> 00:26:59.880
So if it's positive, it does confirm congenital CMV.

689
00:26:59.880 --> 00:27:01.800
But if it's negative, it doesn't exclude it

690
00:27:01.800 --> 00:27:04.650
'cause there is a false negative rate.

691
00:27:04.650 --> 00:27:06.360
And there might be limitations of storage.

692
00:27:06.360 --> 00:27:09.333
I know in Texas, after one year, they throw it out.

693
00:27:11.070 --> 00:27:13.593
Okay, now, let's go to treatment.

694
00:27:15.090 --> 00:27:15.923
Right there.

695
00:27:15.923 --> 00:27:17.670
What about the symptomatic babies?

696
00:27:17.670 --> 00:27:19.800
What if we can help make their life

697
00:27:19.800 --> 00:27:21.690
a little bit better, can we?

698
00:27:21.690 --> 00:27:23.550
Well, antiviral treatment does provide

699
00:27:23.550 --> 00:27:24.970
some benefits, and actually

700
00:27:26.340 --> 00:27:27.848
in the early '90s,

701
00:27:27.848 --> 00:27:30.300
all the way from 10 years, 1991 to '99,

702
00:27:30.300 --> 00:27:32.700
there was a phase III randomized clinical trial

703
00:27:32.700 --> 00:27:34.380
of IV ganciclovir.

704
00:27:34.380 --> 00:27:36.210
Some of us in this room

705
00:27:36.210 --> 00:27:38.820
participated in that clinical trial

706
00:27:38.820 --> 00:27:40.890
with some of our babies that we identified.

707
00:27:40.890 --> 00:27:42.120
And it was for six weeks,

708
00:27:42.120 --> 00:27:44.610
and only babies that were the tip, tip of the iceberg,

709
00:27:44.610 --> 00:27:46.920
symptomatic with CNS involvement,

710
00:27:46.920 --> 00:27:48.420
were enrolled in this clinical trial.

711
00:27:48.420 --> 00:27:50.490
And it did show that it reduced the risk

712
00:27:50.490 --> 00:27:51.990
of hearing loss progression,

713
00:27:51.990 --> 00:27:53.850
improved head circumference

714
00:27:53.850 --> 00:27:55.800
and improved developmental milestones

715
00:27:55.800 --> 00:27:57.990
in the first years of life.

716
00:27:57.990 --> 00:27:59.190
It laid the groundwork then

717
00:27:59.190 --> 00:28:02.310
to another phase III randomized clinical trial

718
00:28:02.310 --> 00:28:04.290
of oral valganciclovir

719
00:28:04.290 --> 00:28:06.210
every 12 hours for six weeks,

720
00:28:06.210 --> 00:28:08.130
which was the standard at the time,

721
00:28:08.130 --> 00:28:09.330
to six months.

722
00:28:09.330 --> 00:28:12.060
And the results of this clinical trial,

723
00:28:12.060 --> 00:28:13.440
headed by David Kimberlin,

724
00:28:13.440 --> 00:28:15.510
and I think many of us in the room

725
00:28:15.510 --> 00:28:19.080
helped patients enroll

726
00:28:19.080 --> 00:28:20.250
in this study,

727
00:28:20.250 --> 00:28:21.690
it once again confirmed

728
00:28:21.690 --> 00:28:24.360
that six months of antiviral treatment

729
00:28:24.360 --> 00:28:26.880
improved hearing loss outcomes,

730
00:28:26.880 --> 00:28:28.080
improved head size

731
00:28:28.080 --> 00:28:30.240
and improved developmental outcomes,

732
00:28:30.240 --> 00:28:32.730
especially speech/language outcomes.

733
00:28:32.730 --> 00:28:37.210
So treatment for symptomatic congenital CMV

734
00:28:40.410 --> 00:28:42.420
is now recommended

735
00:28:42.420 --> 00:28:44.640
by the American Academy of Pediatrics

736
00:28:44.640 --> 00:28:48.570
and many international consensus guidelines and groups.

737
00:28:48.570 --> 00:28:50.730
So neonates with symptomatic CMV,

738
00:28:50.730 --> 00:28:52.530
with or without CNS involvement,

739
00:28:52.530 --> 00:28:54.180
'cause that second clinical trial had babies

740
00:28:54.180 --> 00:28:55.860
without CNS involvement,

741
00:28:55.860 --> 00:28:57.810
should receive oral valganciclovir,

742
00:28:57.810 --> 00:28:59.370
especially if they have a moderate

743
00:28:59.370 --> 00:29:01.380
to severe symptomatic CMV.

744
00:29:01.380 --> 00:29:04.260
It should go on for six months.

745
00:29:04.260 --> 00:29:06.360
And then you really do need to start

746
00:29:06.360 --> 00:29:09.180
the treatment within the first month of life.

747
00:29:09.180 --> 00:29:11.520
After that, there's no evidence-based medicine

748
00:29:11.520 --> 00:29:14.280
to show that it has

749
00:29:14.280 --> 00:29:15.720
the benefit that's been shown

750
00:29:15.720 --> 00:29:18.090
if you start it in the first month of life.

751
00:29:18.090 --> 00:29:20.493
In order to avoid neutropenia,

752
00:29:22.560 --> 00:29:24.840
the babies must have their CBC diff

753
00:29:24.840 --> 00:29:27.090
and platelets monitored,

754
00:29:27.090 --> 00:29:28.470
as well as their hepatic function

755
00:29:28.470 --> 00:29:30.060
and their renal function.

756
00:29:30.060 --> 00:29:32.820
The dosing needs to be adjusted with weight gain.

757
00:29:32.820 --> 00:29:34.590
But it made outpatient treatment

758
00:29:34.590 --> 00:29:36.930
of these babies feasible and affordable.

759
00:29:36.930 --> 00:29:38.490
It revolutionized the treatment

760
00:29:38.490 --> 00:29:40.140
of CMV infection in the newborn,

761
00:29:40.140 --> 00:29:42.033
as well as in the transplant setting.

762
00:29:44.100 --> 00:29:45.750
Now, those of y'all who have babies

763
00:29:45.750 --> 00:29:47.130
with congenital CMV or care for them,

764
00:29:47.130 --> 00:29:50.130
you know that antiviral treatment is just one

765
00:29:50.130 --> 00:29:52.170
of the arms of the treatment.

766
00:29:52.170 --> 00:29:54.600
There's many other interventions that are helpful.

767
00:29:54.600 --> 00:29:56.220
Hearing aids, cochlear implants,

768
00:29:56.220 --> 00:29:58.530
speech/language therapy,

769
00:29:58.530 --> 00:29:59.910
sign language if they choose

770
00:29:59.910 --> 00:30:01.080
to be in the deaf community,

771
00:30:01.080 --> 00:30:02.850
educational accommodations,

772
00:30:02.850 --> 00:30:05.040
orthopedic and orthotics

773
00:30:05.040 --> 00:30:06.090
and mobility aids,

774
00:30:06.090 --> 00:30:08.220
seizure treatments, vision aids,

775
00:30:08.220 --> 00:30:10.440
strabismus surgery, nutritional interventions.

776
00:30:10.440 --> 00:30:12.060
It goes on and on.

777
00:30:12.060 --> 00:30:13.710
There's a lot

778
00:30:13.710 --> 00:30:16.563
to treating a baby with congenital CMV.

779
00:30:18.720 --> 00:30:20.850
But there's a lotta unanswered questions, as well,

780
00:30:20.850 --> 00:30:23.250
especially with antiviral treatment.

781
00:30:23.250 --> 00:30:26.490
Follow-up in the randomized clinical trials

782
00:30:26.490 --> 00:30:27.810
that were very well-designed

783
00:30:27.810 --> 00:30:29.850
was only for anywhere from six months

784
00:30:29.850 --> 00:30:31.470
to two to three years.

785
00:30:31.470 --> 00:30:34.500
Now, congenital CMV is a lifelong condition

786
00:30:34.500 --> 00:30:36.810
as babies continue to grow,

787
00:30:36.810 --> 00:30:38.040
and into adulthood.

788
00:30:38.040 --> 00:30:40.560
And so the apparent short-term benefits

789
00:30:40.560 --> 00:30:42.750
of antiviral therapy in the newborn period

790
00:30:42.750 --> 00:30:44.850
may not last long term.

791
00:30:44.850 --> 00:30:46.143
And we certainly have,

792
00:30:47.580 --> 00:30:51.330
you know, published some of that data.

793
00:30:51.330 --> 00:30:54.270
And I wonder, do we need to treat longer?

794
00:30:54.270 --> 00:30:56.190
Do we need better antivirals?

795
00:30:56.190 --> 00:30:59.583
Or are antivirals not the permanent solution?

796
00:31:01.200 --> 00:31:02.650
So now let's go over

797
00:31:03.510 --> 00:31:05.670
to asymptomatic babies.

798
00:31:05.670 --> 00:31:07.110
Should we treat those babies?

799
00:31:07.110 --> 00:31:09.260
They're at risk for long-term hearing loss.

800
00:31:10.560 --> 00:31:12.540
Do we have any evidence-based medicine

801
00:31:12.540 --> 00:31:13.803
to support that?

802
00:31:14.970 --> 00:31:17.070
Asymptomatic newborns with congenital hearing loss,

803
00:31:17.070 --> 00:31:19.980
will antiviral treatment prevent progressive hearing loss

804
00:31:19.980 --> 00:31:22.650
in both the affected ear and the unaffected ear?

805
00:31:22.650 --> 00:31:26.940
Dr. Park spearheaded the ValEAR clinical trial

806
00:31:26.940 --> 00:31:29.670
to try and see,

807
00:31:29.670 --> 00:31:32.013
through good evidence-based medicine,

808
00:31:32.880 --> 00:31:33.930
do we treat babies

809
00:31:33.930 --> 00:31:37.830
with congenital CMV and just hearing loss?

810
00:31:37.830 --> 00:31:39.630
And then how about asymptomatic babies

811
00:31:39.630 --> 00:31:40.950
with normal hearing?

812
00:31:40.950 --> 00:31:42.210
Will antiviral treatment prevent

813
00:31:42.210 --> 00:31:43.350
their later onset hearing loss?

814
00:31:43.350 --> 00:31:46.860
Dr. Kimberlin spearheaded a trial about that,

815
00:31:46.860 --> 00:31:49.410
which is also on hold right now.

816
00:31:49.410 --> 00:31:51.720
So we may not, at least anytime soon,

817
00:31:51.720 --> 00:31:54.780
have the answer to those questions.

818
00:31:54.780 --> 00:31:57.030
Currently, this approach is not recommended

819
00:31:57.030 --> 00:31:59.130
by most experts, for these babies

820
00:31:59.130 --> 00:32:01.080
to routinely receive antiviral treatment.

821
00:32:01.080 --> 00:32:03.330
However, you know, in my own experience,

822
00:32:03.330 --> 00:32:05.760
we do do a family-centered approach

823
00:32:05.760 --> 00:32:08.070
to treatment options

824
00:32:08.070 --> 00:32:09.660
and do discuss those options.

825
00:32:09.660 --> 00:32:12.090
But it is frustrating, from the clinical perspective,

826
00:32:12.090 --> 00:32:13.840
to not have good

827
00:32:15.240 --> 00:32:17.643
evidence-based medicine to tell us what to do.

828
00:32:19.200 --> 00:32:21.090
But what we do know that we can do

829
00:32:21.090 --> 00:32:23.400
with asymptomatic congenital CMV and management

830
00:32:23.400 --> 00:32:24.810
is anticipatory guidance,

831
00:32:24.810 --> 00:32:25.890
'cause we know that they're at risk

832
00:32:25.890 --> 00:32:27.150
for progressive hearing loss

833
00:32:27.150 --> 00:32:28.770
and later onset hearing loss.

834
00:32:28.770 --> 00:32:30.780
So they should have regular hearing evaluations.

835
00:32:30.780 --> 00:32:32.160
Everybody in this room knows that.

836
00:32:32.160 --> 00:32:34.083
But outside this room, not so much.

837
00:32:35.100 --> 00:32:37.230
In my clinic, we do every six months for three years,

838
00:32:37.230 --> 00:32:38.550
and then annually thereafter.

839
00:32:38.550 --> 00:32:41.910
Or if there's a clinical suspicion, more often.

840
00:32:41.910 --> 00:32:44.430
Speech/language therapy, educational accommodations

841
00:32:44.430 --> 00:32:47.730
and sign language education awareness and inclusion

842
00:32:47.730 --> 00:32:50.130
of all children with hearing loss

843
00:32:50.130 --> 00:32:51.690
is very important in the management

844
00:32:51.690 --> 00:32:52.683
of these babies.

845
00:32:53.910 --> 00:32:54.900
So those are the babies.

846
00:32:54.900 --> 00:32:57.120
What about the moms?

847
00:32:57.120 --> 00:32:58.530
Prenatal testing or screening

848
00:32:58.530 --> 00:33:00.810
to diagnose maternal CMV infection during pregnancy.

849
00:33:00.810 --> 00:33:03.030
I'm gonna open that Pandora's box, okay?

850
00:33:03.030 --> 00:33:05.013
Any obstetricians in the audience?

851
00:33:06.330 --> 00:33:07.163
Oh, oh, good.

852
00:33:08.100 --> 00:33:09.923
Or not good? You know.

853
00:33:10.790 --> 00:33:11.910
We need to reach them.

854
00:33:11.910 --> 00:33:13.620
Maternal serology.

855
00:33:13.620 --> 00:33:16.503
It's not routine, but it is routinely available.

856
00:33:17.490 --> 00:33:20.550
So if you have your CMV antibody tested

857
00:33:20.550 --> 00:33:22.500
early in pregnancy or before pregnancy,

858
00:33:22.500 --> 00:33:24.330
if you're CMV IgG positive, it means

859
00:33:24.330 --> 00:33:26.400
you acquired CMV infection at some time.

860
00:33:26.400 --> 00:33:28.230
You could have been born with CMV,

861
00:33:28.230 --> 00:33:29.430
had it when you were a teenager

862
00:33:29.430 --> 00:33:31.020
or had it last month.

863
00:33:31.020 --> 00:33:33.393
The IgG antibody can't tell you any timing.

864
00:33:34.410 --> 00:33:37.620
You can then have a CMV IgM antibody test done.

865
00:33:37.620 --> 00:33:39.300
And if that's positive, it may mean

866
00:33:39.300 --> 00:33:41.280
a recent primary infection.

867
00:33:41.280 --> 00:33:42.420
That's where everybody goes.

868
00:33:42.420 --> 00:33:44.370
But this antibody test

869
00:33:44.370 --> 00:33:47.310
is fraught with ambiguity and difficulties.

870
00:33:47.310 --> 00:33:49.080
It could mean a recurrent infection.

871
00:33:49.080 --> 00:33:50.610
It could mean a false positive

872
00:33:50.610 --> 00:33:52.410
from an autoimmune disorder.

873
00:33:52.410 --> 00:33:54.030
Or some women

874
00:33:54.030 --> 00:33:57.270
and men have prolonged positive IgM serostatus,

875
00:33:57.270 --> 00:33:58.953
sometimes for a year or two,

876
00:34:00.310 --> 00:34:02.160
and so, and you can't really tell.

877
00:34:02.160 --> 00:34:04.440
You can sort of get a tiebreaker test,

878
00:34:04.440 --> 00:34:07.140
called the CMV IgG avidity index.

879
00:34:07.140 --> 00:34:08.850
That can help timing in a little bit.

880
00:34:08.850 --> 00:34:11.400
So if it's low, it means you had a recent infection,

881
00:34:11.400 --> 00:34:13.500
less than about four months ago.

882
00:34:13.500 --> 00:34:15.210
But if it's high, it means it happened

883
00:34:15.210 --> 00:34:17.910
probably at least four to six months ago.

884
00:34:17.910 --> 00:34:19.410
And that's sort of the state of the art

885
00:34:19.410 --> 00:34:21.810
of CMV serologic testing.

886
00:34:21.810 --> 00:34:23.730
And you can kinda understand why it's not routine.

887
00:34:23.730 --> 00:34:27.720
There is a lot of ambiguity and uncertainty

888
00:34:27.720 --> 00:34:30.390
with serologic testing in pregnant women.

889
00:34:30.390 --> 00:34:31.920
And so for that reason,

890
00:34:31.920 --> 00:34:34.590
the American College of Obstetrics and Gynecology

891
00:34:34.590 --> 00:34:36.810
does not recommend prenatal testing

892
00:34:36.810 --> 00:34:37.950
or screening to diagnose

893
00:34:37.950 --> 00:34:40.590
maternal CMV infection during pregnancy.

894
00:34:40.590 --> 00:34:43.320
However, the Society of Obstetrics and Gynecology

895
00:34:43.320 --> 00:34:46.680
in Canada does sort of open the door a little bit,

896
00:34:46.680 --> 00:34:48.000
and their big toe's through,

897
00:34:48.000 --> 00:34:49.650
going in the room.

898
00:34:49.650 --> 00:34:53.670
And they say, in their 2021 guidance,

899
00:34:53.670 --> 00:34:56.310
that in provinces where IgG avidity testing

900
00:34:56.310 --> 00:34:58.860
is available, the screening for CMV primary infection

901
00:34:58.860 --> 00:35:00.480
in the first trimester

902
00:35:00.480 --> 00:35:02.820
can be offered, especially in women

903
00:35:02.820 --> 00:35:04.800
that are high risk.

904
00:35:04.800 --> 00:35:06.720
In other international consensus reports,

905
00:35:06.720 --> 00:35:08.190
it's not recommended,

906
00:35:08.190 --> 00:35:10.110
primarily because of the ambiguity

907
00:35:10.110 --> 00:35:11.280
of all the testing

908
00:35:11.280 --> 00:35:14.790
and also the lack of clear guidance

909
00:35:14.790 --> 00:35:15.963
and interventions.

910
00:35:16.890 --> 00:35:18.270
But what is done routinely?

911
00:35:18.270 --> 00:35:19.500
And those of you who are pregnant

912
00:35:19.500 --> 00:35:20.670
or were recently pregnant know

913
00:35:20.670 --> 00:35:24.570
that second trimester fetal anatomy ultrasounds are routine.

914
00:35:24.570 --> 00:35:25.833
And this is how many babies

915
00:35:25.833 --> 00:35:28.770
with congenital CMV are picked up.

916
00:35:28.770 --> 00:35:30.873
They may have echogenic bowel,

917
00:35:32.160 --> 00:35:34.470
intrauterine growth restriction,

918
00:35:34.470 --> 00:35:36.540
hydrops, brain abnormalities.

919
00:35:36.540 --> 00:35:38.880
Those may be the first indication

920
00:35:38.880 --> 00:35:41.310
of a CMV infection in utero.

921
00:35:41.310 --> 00:35:43.620
And if your baby has any of these,

922
00:35:43.620 --> 00:35:46.290
in my opinion, warrants CMV testing.

923
00:35:46.290 --> 00:35:48.720
Here's one example of a baby

924
00:35:48.720 --> 00:35:50.720
and her mother.

925
00:35:50.720 --> 00:35:52.816
A 24-year-old mom, gravida 2, par 1,

926
00:35:52.816 --> 00:35:54.930
had a toddler at home, never heard of CMV.

927
00:35:54.930 --> 00:35:57.240
She had her routine ultrasound at 20 weeks,

928
00:35:57.240 --> 00:35:59.100
and then when they saw some abnormalities,

929
00:35:59.100 --> 00:36:00.240
repeated it again,

930
00:36:00.240 --> 00:36:02.400
and she had thickened placenta,

931
00:36:02.400 --> 00:36:04.470
cerebral echogenic foci in the fetus,

932
00:36:04.470 --> 00:36:06.570
fetal ascites and hepatosplenomegaly,

933
00:36:06.570 --> 00:36:08.370
enlarged liver and spleen.

934
00:36:08.370 --> 00:36:11.370
Maternal studies showed CMV IgG was positive.

935
00:36:11.370 --> 00:36:13.324
So she had been infected with CMV.

936
00:36:13.324 --> 00:36:14.340
CMC IgM was positive.

937
00:36:14.340 --> 00:36:16.920
So maybe recent, but her avidity was high,

938
00:36:16.920 --> 00:36:18.330
which means it probably happened

939
00:36:18.330 --> 00:36:20.040
at least four months ago.

940
00:36:20.040 --> 00:36:21.510
Is that a recent primary infection

941
00:36:21.510 --> 00:36:23.268
during her pregnancy

942
00:36:23.268 --> 00:36:24.330
if her screening was done at five

943
00:36:24.330 --> 00:36:25.620
to six months of age?

944
00:36:25.620 --> 00:36:27.270
So maybe or not.

945
00:36:27.270 --> 00:36:30.030
So the baby was tested through an amniocentesis,

946
00:36:30.030 --> 00:36:32.850
and the amniocentesis did have CMV

947
00:36:32.850 --> 00:36:34.020
in the amniotic fluid.

948
00:36:34.020 --> 00:36:36.570
So the baby had in utero CMV infection.

949
00:36:36.570 --> 00:36:38.910
Here's the placenta, very enlarged.

950
00:36:38.910 --> 00:36:41.610
That's pretty characteristic of in utero congenital CMV.

951
00:36:41.610 --> 00:36:43.920
Here's some fetal ascites.

952
00:36:43.920 --> 00:36:46.560
Here's a cut of the brain

953
00:36:46.560 --> 00:36:48.750
showing echogenic foci

954
00:36:48.750 --> 00:36:51.750
or ventricular calcifications.

955
00:36:51.750 --> 00:36:53.130
And so this baby had in utero

956
00:36:53.130 --> 00:36:55.350
symptomatic congenital CMV.

957
00:36:55.350 --> 00:36:57.180
And this is a graph that I borrowed

958
00:36:57.180 --> 00:36:59.850
from the the Canadian Society

959
00:36:59.850 --> 00:37:02.430
of Obstetrics and Gynecology 2021 guidance.

960
00:37:02.430 --> 00:37:04.080
And it shows that the risk

961
00:37:04.080 --> 00:37:07.950
of long-term sequelae drops

962
00:37:07.950 --> 00:37:09.960
through the trimesters of pregnancy.

963
00:37:09.960 --> 00:37:13.893
The risk of transmission goes up.

964
00:37:15.420 --> 00:37:18.090
And so can we influence that at all?

965
00:37:18.090 --> 00:37:19.910
Well, this is more

966
00:37:19.910 --> 00:37:22.020
of a historical interest slide now,

967
00:37:22.020 --> 00:37:24.870
but when we were doing CMV hyperimmune globulin,

968
00:37:24.870 --> 00:37:27.123
it was a very hot topic.

969
00:37:28.200 --> 00:37:29.700
And originally,

970
00:37:29.700 --> 00:37:31.830
there were four prospective observational studies

971
00:37:31.830 --> 00:37:33.780
that were very promising.

972
00:37:33.780 --> 00:37:35.250
Randomized clinical trials,

973
00:37:35.250 --> 00:37:37.500
at least two of them, have not demonstrated

974
00:37:37.500 --> 00:37:40.710
significant benefit, and did show some side effects.

975
00:37:40.710 --> 00:37:42.150
And so it's still investigational

976
00:37:42.150 --> 00:37:44.100
in research at this time.

977
00:37:44.100 --> 00:37:46.410
Some moms in this room

978
00:37:46.410 --> 00:37:49.200
may have even had this treatment.

979
00:37:49.200 --> 00:37:51.090
I know that the woman in the slides

980
00:37:51.090 --> 00:37:52.140
I just showed you,

981
00:37:52.140 --> 00:37:53.250
she did have the treatment,

982
00:37:53.250 --> 00:37:56.250
and we saw the placenta shrink down

983
00:37:56.250 --> 00:37:59.040
and some of the symptoms improve.

984
00:37:59.040 --> 00:38:00.570
But it's not standard at this time.

985
00:38:00.570 --> 00:38:01.710
It's not recommended.

986
00:38:01.710 --> 00:38:03.813
It's not being done anymore, period.

987
00:38:05.010 --> 00:38:07.320
But there may be some ongoing research.

988
00:38:07.320 --> 00:38:08.460
So what are we doing now?

989
00:38:08.460 --> 00:38:09.450
What do you do if you think you may have

990
00:38:09.450 --> 00:38:10.710
a primary CMV infection?

991
00:38:10.710 --> 00:38:12.900
Well, there's a lot of excitement now

992
00:38:12.900 --> 00:38:15.540
from a randomized clinical trial

993
00:38:15.540 --> 00:38:17.520
using high-dose valacyclovir,

994
00:38:17.520 --> 00:38:19.500
which is an antiviral.

995
00:38:19.500 --> 00:38:20.970
It was randomized double-blind,

996
00:38:20.970 --> 00:38:22.890
placebo-controlled study of pregnant women

997
00:38:22.890 --> 00:38:25.470
who had serologic evidence of a primary

998
00:38:25.470 --> 00:38:28.140
or first infection early in pregnancy.

999
00:38:28.140 --> 00:38:30.420
They were randomized to get a high dose,

1000
00:38:30.420 --> 00:38:33.540
eight grams daily, of valacyclovir or placebo.

1001
00:38:33.540 --> 00:38:35.910
And this reduced the rate of fetal infection,

1002
00:38:35.910 --> 00:38:38.790
that is transmission, by 71%.

1003
00:38:38.790 --> 00:38:41.370
In their study, placebo had 30%.

1004
00:38:41.370 --> 00:38:42.600
Remember, the transmission rate

1005
00:38:42.600 --> 00:38:44.820
is anywhere from 25 to 50%,

1006
00:38:44.820 --> 00:38:46.050
with a mean of about 40,

1007
00:38:46.050 --> 00:38:48.840
so within range, versus 11%

1008
00:38:48.840 --> 00:38:50.517
of those who were treated with antiviral therapy.

1009
00:38:50.517 --> 00:38:52.140
And this was a significant difference.

1010
00:38:52.140 --> 00:38:54.480
So there's a lot of excitement

1011
00:38:54.480 --> 00:38:56.873
from maternal fetal medicine specialists

1012
00:38:56.873 --> 00:38:58.500
and OBs and women

1013
00:38:58.500 --> 00:39:00.810
who are infected with CMV about this antiviral.

1014
00:39:00.810 --> 00:39:02.700
And I think you may hear more about it

1015
00:39:02.700 --> 00:39:04.290
here at this meeting.

1016
00:39:04.290 --> 00:39:05.160
It appears safe.

1017
00:39:05.160 --> 00:39:07.170
It's used for HSV in pregnancy.

1018
00:39:07.170 --> 00:39:08.310
There are reports, though,

1019
00:39:08.310 --> 00:39:10.140
of reversible acute renal failure.

1020
00:39:10.140 --> 00:39:11.040
So if you take it,

1021
00:39:11.040 --> 00:39:13.053
you need to have your labs monitored.

1022
00:39:13.950 --> 00:39:15.900
But it's still considered research at this time,

1023
00:39:15.900 --> 00:39:18.180
and it's not routinely recommended

1024
00:39:18.180 --> 00:39:20.520
by any of the societies.

1025
00:39:20.520 --> 00:39:23.370
However, the Society of OBGYN in Canada

1026
00:39:23.370 --> 00:39:26.490
does say that it can be considered,

1027
00:39:26.490 --> 00:39:28.200
both in primary infections

1028
00:39:28.200 --> 00:39:30.120
to reduce transmission

1029
00:39:30.120 --> 00:39:33.060
and in established congenital CMV infection

1030
00:39:33.060 --> 00:39:34.380
during pregnancy.

1031
00:39:34.380 --> 00:39:36.060
So there's, like I said,

1032
00:39:36.060 --> 00:39:37.890
there's a lot of interest in this.

1033
00:39:37.890 --> 00:39:40.290
And I think if this really

1034
00:39:40.290 --> 00:39:41.820
is shown to be effective

1035
00:39:41.820 --> 00:39:43.833
and readily available and safe,

1036
00:39:44.940 --> 00:39:46.680
recommendations for routine screening

1037
00:39:46.680 --> 00:39:50.490
for CMV in pregnancy may evolve and change.

1038
00:39:50.490 --> 00:39:52.020
So that's a lot, right?

1039
00:39:52.020 --> 00:39:53.490
Treat, diagnose the babies,

1040
00:39:53.490 --> 00:39:55.170
treat the babies, diagnose the moms,

1041
00:39:55.170 --> 00:39:56.250
treat the mom, all right?

1042
00:39:56.250 --> 00:39:58.320
What if it could all go away?

1043
00:39:58.320 --> 00:39:59.583
We'd be happy, right?

1044
00:40:01.050 --> 00:40:03.628
We'd come together for some other reasons, yeah.

1045
00:40:03.628 --> 00:40:05.643
(audience laughs)
Prevention.

1046
00:40:07.350 --> 00:40:09.570
So CMV vaccine, right, the holy grail,

1047
00:40:09.570 --> 00:40:11.340
to prevent maternal CMV infection

1048
00:40:11.340 --> 00:40:14.070
and CMV infection in the baby.

1049
00:40:14.070 --> 00:40:15.690
CMV vaccine research has been going on

1050
00:40:15.690 --> 00:40:17.940
since the '70s, so there's been many candidates.

1051
00:40:17.940 --> 00:40:19.230
I've lived through all of this.

1052
00:40:19.230 --> 00:40:21.540
Many of you in the audience have lived through

1053
00:40:21.540 --> 00:40:24.120
hope after hope, of they've been evaluated,

1054
00:40:24.120 --> 00:40:26.520
but none have been successful so far.

1055
00:40:26.520 --> 00:40:28.770
CMV vaccine was actually a priority

1056
00:40:28.770 --> 00:40:30.060
for the 21st century.

1057
00:40:30.060 --> 00:40:31.893
We're now, what, 22 years into that,

1058
00:40:32.940 --> 00:40:35.040
in the US, and I'm sure in other countries,

1059
00:40:35.040 --> 00:40:37.140
by the Institute of Medicine.

1060
00:40:37.140 --> 00:40:39.300
There's been many CMV vaccine candidates

1061
00:40:39.300 --> 00:40:42.540
under evaluation with active R and D pipelines.

1062
00:40:42.540 --> 00:40:45.840
And there's currently some early clinical trials

1063
00:40:45.840 --> 00:40:48.240
from a variety of industries.

1064
00:40:48.240 --> 00:40:51.540
There's a phase III clinical trial

1065
00:40:51.540 --> 00:40:53.250
underway with the mRNA platform.

1066
00:40:53.250 --> 00:40:54.450
If you wanna learn more

1067
00:40:54.450 --> 00:40:56.400
about Moderna's mRNA platform,

1068
00:40:56.400 --> 00:40:58.320
you can go to clinicaltrials.gov,

1069
00:40:58.320 --> 00:41:00.990
you can go to CMV Victory website

1070
00:41:00.990 --> 00:41:02.820
or you can watch their video

1071
00:41:02.820 --> 00:41:05.970
on their flat screen outside as well.

1072
00:41:05.970 --> 00:41:07.650
It's an amazing technology,

1073
00:41:07.650 --> 00:41:09.060
and it will probably revolutionize

1074
00:41:09.060 --> 00:41:11.130
many areas of medicine.

1075
00:41:11.130 --> 00:41:13.650
But as hopeful as we are,

1076
00:41:13.650 --> 00:41:16.533
there's no licensed CMV vaccine available yet.

1077
00:41:17.550 --> 00:41:19.110
Our babies are still waiting.

1078
00:41:19.110 --> 00:41:21.420
So what can we do in the meantime

1079
00:41:21.420 --> 00:41:23.790
to prevent maternal CMV infection

1080
00:41:23.790 --> 00:41:24.990
through other ways?

1081
00:41:24.990 --> 00:41:26.430
We know that CMV is transmitted

1082
00:41:26.430 --> 00:41:27.900
through close contact with others

1083
00:41:27.900 --> 00:41:30.450
who have CMV-infected body fluids.

1084
00:41:30.450 --> 00:41:33.870
We know toddlers are hot zones for CMV.

1085
00:41:33.870 --> 00:41:36.030
We know that annual seroconversion rates

1086
00:41:36.030 --> 00:41:37.950
are higher in daycare center workers,

1087
00:41:37.950 --> 00:41:41.400
and can approach 50% in households

1088
00:41:41.400 --> 00:41:43.520
where toddlers are actively shedding CMV

1089
00:41:43.520 --> 00:41:45.183
in their urine or their saliva.

1090
00:41:46.050 --> 00:41:48.360
And we can reduce this risk

1091
00:41:48.360 --> 00:41:52.200
by reducing contact with CMV-infected secretions.

1092
00:41:52.200 --> 00:41:54.540
So this is what I dubbed the CMV knowledge vaccine,

1093
00:41:54.540 --> 00:41:57.030
or others have called the information vaccination.

1094
00:41:57.030 --> 00:41:58.680
It's an ounce of CMV awareness.

1095
00:41:58.680 --> 00:42:01.380
You first have to know CMV exists.

1096
00:42:01.380 --> 00:42:04.350
And then three simple precautions.

1097
00:42:04.350 --> 00:42:06.420
Don't kiss young children on or near the mouth.

1098
00:42:06.420 --> 00:42:07.950
Don't share their food or drink

1099
00:42:07.950 --> 00:42:10.620
or pacifiers or toothbrushes.

1100
00:42:10.620 --> 00:42:13.410
And wash your hands after all diaper changes.

1101
00:42:13.410 --> 00:42:14.730
Not just poopy diapers,

1102
00:42:14.730 --> 00:42:15.900
but wet diapers as well.

1103
00:42:15.900 --> 00:42:18.033
And after wiping runny noses and drool.

1104
00:42:18.960 --> 00:42:20.520
These simple precautions, however,

1105
00:42:20.520 --> 00:42:22.710
are not recommended routinely

1106
00:42:22.710 --> 00:42:25.560
by obstetricians and by the American College

1107
00:42:25.560 --> 00:42:27.363
of Obstetricians and Gynecology.

1108
00:42:28.200 --> 00:42:30.930
In their 2015 guidance, they,

1109
00:42:30.930 --> 00:42:33.390
and I quote, it's too burdensome or unproven,

1110
00:42:33.390 --> 00:42:34.860
but I heard some wild rumors

1111
00:42:34.860 --> 00:42:37.770
that they may be reconsidering this,

1112
00:42:37.770 --> 00:42:40.140
these recommendations, in the light

1113
00:42:40.140 --> 00:42:43.140
of some current events.

1114
00:42:43.140 --> 00:42:44.850
So maybe.

1115
00:42:44.850 --> 00:42:46.590
It is recommended by CMV experts

1116
00:42:46.590 --> 00:42:48.510
in this room, by parents,

1117
00:42:48.510 --> 00:42:50.070
international consensus guidelines,

1118
00:42:50.070 --> 00:42:51.510
by the Academy of Pediatrics,

1119
00:42:51.510 --> 00:42:54.480
by the Society of OBGYN in Canada,

1120
00:42:54.480 --> 00:42:57.300
as well, and supported by clinical trials.

1121
00:42:57.300 --> 00:42:58.290
So who should know?

1122
00:42:58.290 --> 00:42:59.580
Probably everybody,

1123
00:42:59.580 --> 00:43:01.470
but pregnant persons with contact

1124
00:43:01.470 --> 00:43:03.933
with young children especially should know.

1125
00:43:05.880 --> 00:43:07.157
But do they?

1126
00:43:07.157 --> 00:43:08.236
(audience laughs)

1127
00:43:08.236 --> 00:43:10.560
This is a actual sign in Texas.

1128
00:43:10.560 --> 00:43:11.970
When you drive in Texas,

1129
00:43:11.970 --> 00:43:14.070
you are asked about CMV.

1130
00:43:14.070 --> 00:43:15.533
There's an inspection station.

1131
00:43:15.533 --> 00:43:16.410
(audience laughs)

1132
00:43:16.410 --> 00:43:19.053
Not really, but this is a sign in Texas.

1133
00:43:19.890 --> 00:43:22.620
Do we pass inspection for CMV awareness?

1134
00:43:22.620 --> 00:43:23.610
We don't.

1135
00:43:23.610 --> 00:43:25.950
This is a graph from the National CMV website

1136
00:43:25.950 --> 00:43:28.980
and it's the compilation of several surveys

1137
00:43:28.980 --> 00:43:31.050
of people walking in the street,

1138
00:43:31.050 --> 00:43:32.700
about do you know about these things?

1139
00:43:32.700 --> 00:43:34.830
And most people have heard of HIV/AIDS,

1140
00:43:34.830 --> 00:43:36.660
Down, sudden infant death, spina bifida,

1141
00:43:36.660 --> 00:43:38.220
fetal alcohol syndrome.

1142
00:43:38.220 --> 00:43:39.750
And the awareness of, yeah,

1143
00:43:39.750 --> 00:43:42.060
I've heard of that, is commensurate

1144
00:43:42.060 --> 00:43:44.490
with the incidence in the US.

1145
00:43:44.490 --> 00:43:46.590
But congenital infections in general

1146
00:43:46.590 --> 00:43:49.170
don't get the same awareness and respect.

1147
00:43:49.170 --> 00:43:50.490
And you go to the top,

1148
00:43:50.490 --> 00:43:54.420
congenital CMV is, really needs a lot of work.

1149
00:43:54.420 --> 00:43:55.920
There's very low awareness.

1150
00:43:55.920 --> 00:43:57.240
Probably, you know, less than 10%

1151
00:43:57.240 --> 00:43:59.610
of people walking the street have even heard of CMV.

1152
00:43:59.610 --> 00:44:00.513
Once again, the most common virus

1153
00:44:00.513 --> 00:44:02.250
that most people have never heard of.

1154
00:44:02.250 --> 00:44:04.260
Yet if you look at US incidence

1155
00:44:04.260 --> 00:44:06.270
and you look in the other countries,

1156
00:44:06.270 --> 00:44:07.600
it's not at all

1157
00:44:08.610 --> 00:44:10.740
in relation to what we should know.

1158
00:44:10.740 --> 00:44:13.473
We need to make CMV a household word.

1159
00:44:15.960 --> 00:44:17.130
Even medical students.

1160
00:44:17.130 --> 00:44:18.720
This is a study that I did with a medical student

1161
00:44:18.720 --> 00:44:20.190
at Baylor College of Medicine.

1162
00:44:20.190 --> 00:44:21.780
You know, medical students, they have degrees,

1163
00:44:21.780 --> 00:44:23.160
they have advanced degrees,

1164
00:44:23.160 --> 00:44:25.230
you know, they're kinda smart,

1165
00:44:25.230 --> 00:44:26.580
they're starting their families.

1166
00:44:26.580 --> 00:44:28.203
But when we surveyed them,

1167
00:44:29.250 --> 00:44:30.930
most entering medical school

1168
00:44:30.930 --> 00:44:32.760
had never even heard of CMV.

1169
00:44:32.760 --> 00:44:33.593
Isn't that amazing?

1170
00:44:33.593 --> 00:44:35.790
And even by the time they left medical school,

1171
00:44:35.790 --> 00:44:37.950
most of 'em were not very familiar with CMV.

1172
00:44:37.950 --> 00:44:39.780
And I'm sure that's been your experience

1173
00:44:39.780 --> 00:44:41.580
with some doctors, of you parents,

1174
00:44:41.580 --> 00:44:44.407
that many of your own doctors have never heard of CMV

1175
00:44:44.407 --> 00:44:45.750
or, yeah, it's rare.

1176
00:44:45.750 --> 00:44:47.340
I've never really see it.

1177
00:44:47.340 --> 00:44:48.440
Don't know what to do.

1178
00:44:49.590 --> 00:44:52.830
Those of us in medical education

1179
00:44:52.830 --> 00:44:54.303
need to change that as well.

1180
00:44:56.400 --> 00:44:57.720
Now, grassroots efforts.

1181
00:44:57.720 --> 00:44:59.703
Like many people in this room,

1182
00:45:00.720 --> 00:45:02.130
just taking things in your own hands.

1183
00:45:02.130 --> 00:45:03.780
And how are we gonna change this?

1184
00:45:03.780 --> 00:45:06.870
And one way that's been very successful.

1185
00:45:06.870 --> 00:45:08.835
It almost brings tears to my eyes 'cause,

1186
00:45:08.835 --> 00:45:11.220
you know, the passion of parents and the doctors

1187
00:45:11.220 --> 00:45:13.770
and the legislators that support them.

1188
00:45:13.770 --> 00:45:14.850
You know, this is also lifted

1189
00:45:14.850 --> 00:45:17.310
from the National CMV website,

1190
00:45:17.310 --> 00:45:20.790
is laws have been enacted in many states

1191
00:45:20.790 --> 00:45:25.080
for CMV awareness, either education

1192
00:45:25.080 --> 00:45:28.983
or testing or screening.

1193
00:45:29.880 --> 00:45:31.170
And it would be nice to see

1194
00:45:31.170 --> 00:45:33.303
that entire map filled in.

1195
00:45:35.100 --> 00:45:37.260
And also, just grassroots efforts.

1196
00:45:37.260 --> 00:45:39.180
There's a lot of CMV advocacy groups.

1197
00:45:39.180 --> 00:45:40.200
I've listed some there.

1198
00:45:40.200 --> 00:45:42.240
If I didn't list yours, please come up and tell me.

1199
00:45:42.240 --> 00:45:43.500
I'll add it to the list.

1200
00:45:43.500 --> 00:45:44.910
Social media as well.

1201
00:45:44.910 --> 00:45:46.590
But we're probably talking to each other

1202
00:45:46.590 --> 00:45:47.970
more than we're reaching out.

1203
00:45:47.970 --> 00:45:49.800
But still, there's a lot more chatter

1204
00:45:49.800 --> 00:45:53.430
than we had a couple decades ago about CMV.

1205
00:45:53.430 --> 00:45:54.390
Moms.

1206
00:45:54.390 --> 00:45:56.240
Have our own, Lisa Saunders is here

1207
00:45:56.240 --> 00:45:58.410
in the front table here.

1208
00:45:58.410 --> 00:46:01.320
Other moms, Brielle's mom, also have written books

1209
00:46:01.320 --> 00:46:02.590
about what life

1210
00:46:03.630 --> 00:46:05.880
with children with congenital CMV.

1211
00:46:05.880 --> 00:46:07.297
Dr. Paul Griffiths wrote a book,

1212
00:46:07.297 --> 00:46:09.390
"The Stealth Virus," as well.

1213
00:46:09.390 --> 00:46:12.030
Many of us in this room publish about CMV.

1214
00:46:12.030 --> 00:46:13.560
One very inspiring story

1215
00:46:13.560 --> 00:46:16.110
was that the medical student there, see that,

1216
00:46:16.110 --> 00:46:18.270
the medical student wearing that sign?

1217
00:46:18.270 --> 00:46:21.600
She did a month elective with me on congenital CMV.

1218
00:46:21.600 --> 00:46:23.610
And she was just so impressed

1219
00:46:23.610 --> 00:46:25.140
with how common it was,

1220
00:46:25.140 --> 00:46:27.090
but how uncommon awareness was.

1221
00:46:27.090 --> 00:46:28.380
And many of her friends in medical school

1222
00:46:28.380 --> 00:46:30.600
were thinking of starting their family or were pregnant.

1223
00:46:30.600 --> 00:46:32.910
So during her lunch hour,

1224
00:46:32.910 --> 00:46:34.920
while she did a monthlong elective with me,

1225
00:46:34.920 --> 00:46:36.390
she wore this sign.

1226
00:46:36.390 --> 00:46:39.450
Walked around, handed out pamphlets

1227
00:46:39.450 --> 00:46:41.400
to try, in her own unique way,

1228
00:46:41.400 --> 00:46:43.230
to raise CMV awareness

1229
00:46:43.230 --> 00:46:46.773
to, you know, a vulnerable group of parents.

1230
00:46:48.000 --> 00:46:50.343
So I'm gonna end with like, what elephant?

1231
00:46:51.300 --> 00:46:52.503
When we leave this room,

1232
00:46:53.741 --> 00:46:55.170
this is what we face, okay?

1233
00:46:55.170 --> 00:46:56.463
This is why we're here.

1234
00:46:57.990 --> 00:47:00.133
We wanna face the congenital CMV challenge.

1235
00:47:00.133 --> 00:47:02.160
I know many of you face it every day.

1236
00:47:02.160 --> 00:47:03.390
To take next step forwards.

1237
00:47:03.390 --> 00:47:05.590
And here's a quote that I think

1238
00:47:05.590 --> 00:47:06.423
is very important.

1239
00:47:06.423 --> 00:47:08.310
It's if we stumble, it won't be because

1240
00:47:08.310 --> 00:47:10.980
we lack for technology, vision or motivation.

1241
00:47:10.980 --> 00:47:13.290
There's plenty of that here in this room.

1242
00:47:13.290 --> 00:47:15.180
It will be because we cannot set

1243
00:47:15.180 --> 00:47:17.760
a direction and march collectively,

1244
00:47:17.760 --> 00:47:19.863
underlined, into the future.

1245
00:47:20.820 --> 00:47:23.130
And so we need to have maternal CMV screening

1246
00:47:23.130 --> 00:47:24.300
in pregnancy, in my opinion.

1247
00:47:24.300 --> 00:47:27.390
We need to have more CMV awareness.

1248
00:47:27.390 --> 00:47:29.040
We need to have newborns screened

1249
00:47:29.040 --> 00:47:30.720
for congenital CMV.

1250
00:47:30.720 --> 00:47:33.270
We need more and better antiviral treatments.

1251
00:47:33.270 --> 00:47:34.803
And we need the CMV vaccine.

1252
00:47:35.768 --> 00:47:36.601
<v Audience Member>Yes.</v>

1253
00:47:36.601 --> 00:47:39.300
<v ->Because it's time to say goodbye</v>

1254
00:47:39.300 --> 00:47:41.050
to the elephant in our living room.

1255
00:47:42.360 --> 00:47:45.240
And for that, I'd like to say thank you.

1256
00:47:45.240 --> 00:47:46.970
And the end.

1257
00:47:46.970 --> 00:47:49.970
(audience applauds)