Clinical Trial Details
— Status: Completed
Administrative data
| NCT number |
NCT02680743 |
| Other study ID # |
0828-15-EP |
| Secondary ID |
|
| Status |
Completed |
| Phase |
N/A
|
| First received |
|
| Last updated |
|
| Start date |
March 28, 2016 |
| Est. completion date |
May 1, 2018 |
Study information
| Verified date |
September 2023 |
| Source |
University of Nebraska |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Interventional
|
Clinical Trial Summary
Congenital cytomegalovirus (cCMV) is the most common non-genetic cause of pediatric hearing
loss and an important cause of neurodevelopmental delay. Symptomatic infants are readily
identified and quickly referred for treatment, but the majority of infants (85-90%) with cCMV
show no symptoms at birth and therefore do not receive timely treatment. Often, these
otherwise asymptomatic infants with cCMV may have early congenital hearing loss and therefore
fail the newborn hearing screen, but because they are not specifically identified as having
cCMV there is a delay in seeking further audiology exam and treatment of the CMV infection.
This study will investigate how testing newborns for congenital cytomegalovirus infection
(cCMV) after a failed newborn hearing screens can improve early identification of cCMV
infection and therefore reduce the delay in referral of the newborn to appropriate
specialists for intervention.
Description:
Specific Aim 1: Establish a cCMV testing protocol and demonstrate that this protocol is
successful at identifying infants with cCMV who present with hearing abnormality as the first
sign of infection.
Specific Aim 2: Demonstrate that a majority of infants who test positive for cCMV at the time
of failed hearing screen are referred within 14 days for appropriate confirmatory testing and
treatment.
Specific Aim 3: Improve cCMV prevalence data estimates for the State of Nebraska.
Congenital cytomegalovirus (cCMV) affects 20,000-40,000 infants in the United States annually
and is the most common congenital viral infection in newborns1. cCMV is the most common
non-genetic cause of sensorineural hearing loss (SNHL) in children and it is estimated that
the 1 in 10 children with SNHL have cCMV related hearing loss. SNHL is the most common
sequela of cCMV infection but the overall disease burden is much greater as cCMV is an
important contributor to neurodevelopmental delay2.
The most common physical exam findings for identification of cCMV include petechiae,
hepatosplenomegaly, microcephaly, hypotonia, hearing loss, purpura, chorioretinitis, and
seizure activity and the most common laboratory findings include elevated AST and ALT,
thrombocytopenia, conjugated hyperbilirubinemia, and elevated CSF protein3,4. Infants may
also be identified based on radiologic abnormalities including abnormal cranial ultrasound,
head CT, and brain MRI that may show cerebral calcifications and ventriculomegaly4. Infants
with cCMV infections are categorized as either symptomatic or asymptomatic based on the
physical exam, laboratory, and radiologic findings that are present at birth3. Approximately
10%-15% of cCMV cases are classified as symptomatic due to the any of these clinical findings
and the outcomes for these infants are poor with approximately half suffering from severe
neurologic sequelae including SNHL, mental retardation with IQs < 70, and microcephaly2,3.
Approximately 85-90% of children with cCMV do not have these clinical findings at birth and
are therefore considered asymptomatic3.However, some cases of otherwise asymptomatic cCMV do
have hearing loss as detected during newborn hearing test screening and these patients fall
into a sub-categorization of asymptomatic with a failed hearing screening.The hearing loss of
cCMV is significant as it is often severe to profound in both the symptomatic and
asymptomatic cases. In the asymptomatic children who had hearing impairment, 42% required
amplification and rehabilitation2.
There is currently no universal systematic screening of newborns for cCMV and while
symptomatic infants may be tested for CMV due to clinical suspicion, asymptomatic infants
present a greater challenge to early identification. Screening techniques are available and
these include urine or saliva cultures with and without PCR, as well as blood PCR that can be
run on dried blood samples (i.e. blood obtained as part of statewide newborn screening
exams)2. Recent studies have shown that CMV PCR assays of liquid and dried saliva samples
have a high sensitivity and specificity as compared to saliva cultures5. Although these tests
are available, they are not routinely used for neonatal universal screening either before or
after failed hearing screens even though it is known that detecting hearing loss early leads
to earlier intervention and therefore better long term hearing and developmental outcomes,
especially when the infants are treated with antiviral therapy such as ganciclovir or
valgancyclovir2,6.
Birth data collected from Nebraska Medicine (including Bellevue) for 2014 show 2,660 births
with 2,592 infants passing the hearing screen and 43 (1.6%) infants being referred There is
no system in place to track how many of these children then failed further testing, how many
were tested for cCMV, or how many were diagnosed with cCMV. The Nebraska Birth Defects
Registry, maintained by the Department of Health and Human Services (DHHS), has sparse data
on the number of babies identified with cCMV going back to 2007 and the data is as follows: 2
cases in 2007, 2 in 2009, 1 in 2011, and 1 in 2013. The mechanism by which the registry
receives the data is through birth certificate clerk entry and the data is most certainly not
complete.In order to be treated for cCMV with valgancyclovir diagnosis of cCMV must be made
within 14 days of birth and treatment initiated by 30 days of life; a timeframe currently not
feasible for the majority of infants currently identified by the current status quo with
follow-up hearing evaluation performed weeks and sometimes months after initial referral on
newborn hearing screen.
With this project we intend to institute testing for CMV in infants who fail their newborn
hearing screen in order to quickly identify those with cCMV. After identification, they will
be referred for further audiology testing and referred to Pediatric Infectious Diseases for
further diagnostic and confirmatory testing and treatment if indicated. Additionally, by
having a confirmed positive cCMV test, the parents and PCP can receive additional counseling
on the importance of proper follow up with early intervention specialists in order to improve
the infants long-term outcome. A secondary benefit will be improved data on cCMV prevalence
in Nebraska.
