Cytomegalovirus Testing and Intervention Protocol for Newborn Nursery and Newborn Intensive Care Unit
| Status: | Completed |
|---|---|
| Conditions: | Hospital |
| Therapuetic Areas: | Other |
| Healthy: | No |
| Age Range: | Any |
| Updated: | 10/14/2018 |
| Start Date: | March 2016 |
| End Date: | May 2018 |
Objective:
Congenital cytomegalovirus (cCMV) is the most common non-genetic cause of pediatric
sensorineural hearing loss (SNHL) and an important cause of neurodevelopmental delay. Infants
with cCMV can be symptomatic, asymptomatic, or asymptomatic except for hearing loss.
Symptomatic infants may be more readily identified and quickly referred for intervention
because they may present with classic common clinical findings, but the majority of infants
(85-90%) with cCMV are asymptomatic at birth and do not have the classic clinical,
laboratory, or radiologic findings and therefore often have delayed identification and
intervention. 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.
The overall objective of this proposed research is to 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.
Eligibility Criteria:
Eligible participants will include newborns in the NBN or NICU who are less than 14 days of
life who fail the standard hearing screening.
Interventions and Evaluations Saliva samples will be obtained from participating infants with
a mouth swab according to an established protocol. The saliva will then be tested for CMV by
qualitative polymerase chain reaction by ARUP Laboratories. Infants who test positive for CMV
infection will then be referred for repeat audiology exam to confirm hearing loss and to
Pediatric Infectious Diseases for evaluation and treatment if necessary. Parents or guardians
of infants who test positive for cCMV will receive counseling on the importance of following
up with these specialists. The primary outcomes measured will be cCMV prevalence data and
time to referral and intervention.
Follow up:
Follow-up will be as clinically indicated and determined by the infant's primary care
provider, pediatric infectious disease physician, and audiologist. It will not be determined
by the study, referral to these services will be the study endpoint.
Congenital cytomegalovirus (cCMV) is the most common non-genetic cause of pediatric
sensorineural hearing loss (SNHL) and an important cause of neurodevelopmental delay. Infants
with cCMV can be symptomatic, asymptomatic, or asymptomatic except for hearing loss.
Symptomatic infants may be more readily identified and quickly referred for intervention
because they may present with classic common clinical findings, but the majority of infants
(85-90%) with cCMV are asymptomatic at birth and do not have the classic clinical,
laboratory, or radiologic findings and therefore often have delayed identification and
intervention. 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.
The overall objective of this proposed research is to 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.
Eligibility Criteria:
Eligible participants will include newborns in the NBN or NICU who are less than 14 days of
life who fail the standard hearing screening.
Interventions and Evaluations Saliva samples will be obtained from participating infants with
a mouth swab according to an established protocol. The saliva will then be tested for CMV by
qualitative polymerase chain reaction by ARUP Laboratories. Infants who test positive for CMV
infection will then be referred for repeat audiology exam to confirm hearing loss and to
Pediatric Infectious Diseases for evaluation and treatment if necessary. Parents or guardians
of infants who test positive for cCMV will receive counseling on the importance of following
up with these specialists. The primary outcomes measured will be cCMV prevalence data and
time to referral and intervention.
Follow up:
Follow-up will be as clinically indicated and determined by the infant's primary care
provider, pediatric infectious disease physician, and audiologist. It will not be determined
by the study, referral to these services will be the study endpoint.
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.
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.
Inclusion Criteria:
- Patient that fails initial hearing screen before 14 days of life.
Exclusion Criteria:
- Patient with passed hearing screen or patient older than 14 days of life.
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