Congenital Cytomegalovirus (CMV)-Related Hearing Loss: Pediatric Primary Care Guide

Diagnoses and follow-up care for children with CMV-related hearing loss

Other Names

cCMV hearing loss

Key Points

High prevalence
Congenital CMV infection is the most common non-genetic cause of sensorineural hearing loss (SNHL) in US children. SNHL may be the only manifestation of congenital CMV infection.

Diagnosis
Congenital CMV infection can be diagnosed prenatally or postnatally and be symptomatic or asymptomatic. CMV-related sensorineural hearing loss is the most common symptom.

Testing
If there is clinical suspicion of congenital CMV, urine or saliva PCR testing should be obtained within the first 3 weeks after birth. A positive saliva PCR should be followed by a urine culture due to the risk of false positives.

Treatment
Antivirals may be recommended for infants with moderate to severe symptomatic congenital CMV. There is less clear guidance about treatment for asymptomatic or mildly symptomatic infants, e.g., with isolated SNHL, due to the risks of the treatment (Rawlinson et al., 2017).  Treatment decisions are individualized and based on severity of symptoms, age of the infant, and presence of hearing loss or other neurological involvement.

Follow-Up
Given that CMV-related sensorineural hearing loss can be progressive, audiologic assessments should be performed serially throughout infancy and childhood (some research shows changes in hearing through the 18th year) for patients with symptomatic or asymptomatic congenital CMV infection (Pass, 2002).

Development
Affected children should be monitored closely for developmental delay and referred for services if concern arises.

Guidelines

Congenital cytomegalovirus infection in pregnancy and the neonate: consensus recommendations for prevention, diagnosis, and therapy.
Rawlinson, W. D., Boppana, S. B., Fowler, K. B., Kimberlin, D. W., et al. (2017). The Lancet. Infectious Diseases, 17(6), e177–e188.

Cytomegalovirus infection. Dollard SC, Dreon M, Hernandez-Alvarado N, & et al. (2024). In Red Book: 2024-2027 Report of the Committee on Infectious Diseases (32nd ed.). American Academy of Pediatrics.

Antiviral treatment of maternal and congenital cytomegalovirus (CMV) infections. Pinninti, S., & Boppana, S. (2023). Viruses, 15(10), 2116.

Diagnosis

Presentations

Congenital CMV infection is contracted through vertical transmission from the mother to the fetus via transplacental passage of the bloodborne virus (Dollard SC et al., 2024). Prenatal ultrasound may show intrauterine growth restriction, oligo- or polyhydramnios, microcephaly, periventricular calcifications or other abnormalities of brain development, ascites, hyperechogenic bowel, pericardial effusion, enlarged liver or spleen, or hydrops (Pass & Arav-Boger, 2018; Plosa et al., 2012).

Importantly, only 10% of infants with congenital CMV are symptomatic at birth (Pass & Arav-Boger, 2018). Symptomatic infants may demonstrate poor feeding and seizures. A physical exam may reveal microcephaly (Pass & Arav-Boger, 2018), hypotonia, jaundice, petechiae/purpura (“blueberry muffin rash”), and hepatosplenomegaly. The most common finding is isolated SNHL (Pass, 2002; Pinninti & Boppana, 2023). Additional clinical manifestations are listed in the following table.   

Table 1: Clinical Features of Congenital CMV Infection

Central Nervous System	Cerebellar hypoplasia, developmental delay, hypotonia, microcephaly, periventricular calcifications and pseudocysts, polymicrogyria, poor feeding, seizures, SNHL, spasticity, ventriculomegaly
Gastrointestinal	Direct hyperbilirubinemia, elevated liver enzymes, hepatomegaly
Hematologic	Anemia, hepatosplenomegaly, thrombocytopenia
Ophthalmologic	Chorioretinitis, cortical visual impairment, Mmcrophthalmia optic nerve atrophy, strabismus
Skin	Jaundice, petechiae/purpura (“blueberry muffin rash”)

Sensorineural hearing loss is seen in 30% of infants with symptomatic congenital CMV infection, but 40% who ultimately develop SNHL pass the initial hearing screening. Additionally, approximately 7-15% of infants with asymptomatic congenital CMV develop progressive SNHL during childhood (Boyle & Posada, 2022; Plosa et al., 2012). Infants with symptomatic congenital CMV may develop cerebral palsy, developmental delays, progressive SNHL, or vision loss. Symptomatic patients can develop severe complications, including myocarditis and hemophagocytic lymphohistiocytosis. Death from symptomatic congenital CMV infections occurs in approximately 3-10% (Boyle & Posada, 2022).

Diagnostic Criteria & Classifications

The consensus guidelines from Rawlinson et al. provide detailed definitions for the spectrum of congenital CMV disease, ranging from moderate to severe, mild, and asymptomatic (Rawlinson et al., 2017). Definitions are also present in the AAP Red Book (Dollard SC et al., 2024)).

• Moderate to severe congenital CMV infection: infant has either CNS manifestations of disease OR >2 features of congenital infection
• Mild congenital CMV infection: 1-2 features of congenital infection
• Asymptomatic congenital CMV infection with isolated SNHL: sensorineural hearing loss is present in the absence of other features of congenital infection
• Asymptomatic congenital CMV infection: normal hearing and no other features of congenital infection

Diagnostic Testing & Screening

There is ongoing controversy regarding universal or targeted CMV screening in pregnant women and infants.

Pregnant Women
At this time, universal screening of pregnant women for CMV infection is not recommended in the United States, although this is undergoing study. Instead, pregnant women with influenza-like illnesses “not attributable to another specific infection” or prenatal ultrasounds with fetal features concerning for CMV infection should be offered CMV serology testing (IgM, IgG, and IgG avidity) (Rawlinson et al., 2017). In situations of confirmed primary maternal infection during pregnancy or prenatal imaging concerning for features of congenital CMV, testing of the fetus via amniocentesis can be offered and postnatal testing of the neonate can be obtained (Boyle & Posada, 2022).

Newborns
The 2017 international consensus guidelines acknowledged the ongoing investigation into whether targeted screening for newborns who fail newborn hearing screening or universal newborn screening should be implemented. If screening is limited to infants who fail newborn hearing screening, 40% of infected newborns who develop hearing loss after the first month of life can be missed (Congenital Cytomegalovirus (cCMV), 2023.; Rawlinson et al., 2017).

Targeted screening relies on using predetermined risk factors, such as failed newborn hearing screening or microcephaly, to trigger testing in newborns (usually by urine or saliva PCR) in the first 3 weeks of life. Sensitivity is estimated at 79-88% (Schleiss et al., 2023). In Utah, a state that implemented targeted CMV screening for infants failing newborn hearing screens, 6% of the babies who failed newborn hearing screens tested positive for CMV, and 2.5% had confirmed SNHL. The Utah workgroup recommends targeted screening of infants with any of the following risk factors  (Congenital Cytomegalovirus (cCMV), 2023; Suarez et al., 2023):

• Maternal history of CMV infection
• Idiopathic elevated liver enzymes or bilirubin
• Failed hearing screen
• Abnormal central nervous system (CNS) imaging findings suggestive of cCMV (e.g., intracranial calcifications)
• Unexplained thrombocytopenia
• History of intrauterine growth restriction (IUGR)
• Small for gestational age (SGA)
• Microcephaly
• Intraabdominal calcifications
• Unexplained hepatomegaly, splenomegaly, or
• Petechial rash (Suarez et al., 2023)

Macrocephaly was removed from the original list of risk factors.

Universal newborn screening can mean either including CMV on the newborn bloodspot screening panel or testing the urine or saliva of all infants. Testing via newborn bloodspot screening has lower sensitivity (86%) than testing every infant’s urine or saliva (90%) but is more cost-effective (Congenital Cytomegalovirus (cCMV), 2023; Schleiss et al., 2023). Some advocacy groups have recommended that universal CMV screening be included in state newborn screening panels (Boyle & Posada, 2022; Congenital Cytomegalovirus (cCMV), 2023).  Minnesota became the first state to mandate universal newborn screening for congenital CMV and include it in the bloodspot panel. 

Consultation with specialists is recommended in cases of primary maternal infection or if there is concern for congenital CMV infection (Rawlinson et al., 2017).

Testing of Family Members
None is routinely advised

Labs

The presence of CMV DNA in amniotic fluid (obtained via amniocentesis after 21 weeks) or CMV immunoglobulin M (IgM) in fetal blood can be used to diagnose congenital CMV (Plosa et al., 2012).

Following birth, CMV-specific PCR (or, less efficiently, by viral culture) can be performed on neonatal urine, blood, saliva, or CSF samples. Urine can be obtained by placing cotton balls in the diaper and, once wet, squeezing the fluid into the collection vial; there is no need to catheterize the baby. Importantly, postnatal testing must be performed in the first 3 weeks following birth to allow for accurate diagnosis of congenital infection (Plosa et al., 2012).

The AAP Red Book reports that the sensitivity of saliva PCR tests for infants is >95%, although the results may be affected if the infant drinks human milk CMV (Dollard SC et al., 2024). For that reason, obtaining a confirmatory urine CMV PCR or culture within the first 3 weeks of life for any newborn with a positive saliva CMV test can be useful (Dedhia et al., 2018; Rawlinson et al., 2017; Dollard SC et al., 2024).

Studies obtained after 3 weeks of age often cannot differentiate between congenital and postnatal infection. Testing of neonatal archived dry blood spots for CMV offers an option for later diagnosis of an older child with congenital CMV. However, a landmark study by Boppana et al. detected only 34% of infected children (Boppana et al., 2010).

Infants with a positive PCR for CMV are recommended to undergo additional lab evaluation with a complete blood cell count and liver function tests, including evaluation for direct hyperbilirubinemia. This evaluation will allow stratification of the infant into a symptomatic category that will then guide treatment ( Boyle & Posada, 2022).

Imaging

Infants with a positive PCR for CMV are recommended to undergo neuroimaging to help with risk stratification and treatment planning (Boyle & Posada, 2022). A head ultrasound can be useful in risk stratification; consult with experts before obtaining an MRI.

Other (sensory, genetic, other)

Infants with a positive PCR for CMV are recommended to undergo ophthalmologic and audiologic evaluations to help with risk stratification and treatment planning ( Boyle & Posada, 2022). See Treatment for additional guidance about repeat audiologic evaluations during infancy and childhood.

Genetics

Congenital CMV is caused by infection and is not a genetic condition.

Incidence and Prevalence

Congenital CMV infection is the most common non-genetic cause of SNHL in US children (Goderis et al., 2014). Globally, approximately 1 in 150 live-born infants (0.7%) are affected, with approximately 40,000 cases per year in the United States, 5,000 of whom manifest permanent sequelae (Boyle & Posada, 2022). In the United States, prevalence varies by the race of newborn infants, with it being highest in Black children (9.5/1000 live births), followed by non-Hispanic white children (2.7/1000 live births), and lowest in Hispanic children (3.0/1000 live births) (Dollard SC et al., 2024).

Vertical transmission from mother to fetus during pregnancy can occur either secondary to primary infection or non-primary infection, in which case there is either latent virus re-activation or infection by another CMV strain (Dollard SC et al., 2024). In the case of primary infection, the transmission rate from mother to fetus is 40% compared to 1% in the case of re-activation (Plosa et al., 2012). Although fetal infection in the first trimester is associated with more severe sequelae, transmission can occur during maternal infection at any time of pregnancy and is more likely later on in pregnancy in the case of primary infection (Chatzakis et al., 2020; Dollard SC et al., 2024). Risk factors for congenital CMV infection include exposure of the pregnant woman to young children, premature delivery, young maternal age, NICU admission, and maternal HIV infection (Goderis et al., 2014; Kenneson & Cannon, 2007).

Differential Diagnosis

In the case of more severely affected infants, consider other TORCH infections, particularly toxoplasmosis, sepsis, and erythroblastosis fetalis. In cases of isolated SNHL, consider other causes of hearing loss, including genetic causes and ototoxic medications, e.g., aminoglycosides).

Comorbid Conditions

• CNS abnormalities, including periventricular calcifications and pseudocysts
• Seizures
• Chorioretinitis
• Developmental delays
• Optic nerve atrophy
• Strabismus

Please see Table 1 for more.

Prognosis

In children with SNHL due to congenital CMV, it is estimated that 50% will have progression of their SNHL over time, making routine audiologic evaluation imperative for early detection (Dollard SC et al., 2024).  

Treatment & Management

Unfortunately, antiviral treatment does not eliminate CMV from the body as it establishes “lifelong persistent infection” (Dollard SC et al., 2024). As a result, patients are at risk of viral re-activation and shedding of viral particles. Even asymptomatic newborns with congenital CMV may develop symptoms over time, most commonly SNHL. This leads to the need for ongoing vigilance by the primary care clinician to monitor for progressive hearing loss, developmental delays, and other possible long-term effects.

Infectious Disease

Research supports the treatment of newborns with moderate to severe symptomatic congenital CMV infection to prevent or mitigate SNHL and other complications. The AAP Red Book recommends starting oral valganciclovir within the first month of life (Dollard SC et al., 2024). Careful monitoring is required due to the high risk of neutropenia. Long-term risks of treatment include carcinogenicity and gonadal dysgenesis (Rawlinson et al., 2017). Treatment is recommended for 6 months and should be weight-adjusted monthly. While on treatment, it is recommended to monitor the absolute neutrophil count weekly for the first 6 weeks, then at 8 weeks, and then monthly until treatment is completed. Additionally, while on treatment, it is recommended to monitor serum transaminases, specifically alanine aminotransferase, monthly (Rawlinson et al., 2017; Dollard SC et al., 2024). Intravenous ganciclovir may be used in certain situations under the direction of a neonatologist or infectious disease specialist.

At this time, given the lack of evidence and risks associated with the antiviral medication, treatment for congenital CMV infection is not recommended for:

• Asymptomatic infants
• Infants with only sensorineural hearing loss
• Infants with mildly symptomatic disease (Rawlinson et al., 2017)

If, per clinician discretion, which may include factors such as prematurity, such patients are started on antiviral therapy, data should be gathered to inform efficacy and safety and thus guide future similar decision-making (Rawlinson et al., 2017). A clinical trial is exploring the efficacy of oral valganciclovir in preventing progression of hearing loss in infants with congenital CMV infection and SNHL. There is also a lack of evidence regarding the efficacy of starting antiviral treatment after the first month following birth (Rawlinson et al., 2017).

Audiology

Long-term management of patients with congenital CMV infection depends on whether or not the infant is symptomatic. In both asymptomatic and symptomatic infants, it is important to obtain:

• Serial audiologic examinations: The American Academy of Pediatrics recommends hearing screening/assessment at 4, 6, 9, 12, 15, 18, 24, and 30 months of age for children with congenital CMV, in addition to the standard hearing testing recommended for all children at 4, 5, 6, 8, and 10 years of age (Hagan et al., 2017; Dollard SC et al., 2024).

Children with SNHL should be referred early to otolaryngology and audiology for appropriate treatment and management, which may include hearing aids or cochlear implants. For infants following up with an audiologist, the audiologist typically determines the recommended frequency for follow-up evaluations, and the primary care clinician can help remind the family of the monitoring schedule. Furthermore, any time a family has concerns regarding a change in hearing, the child should have a hearing test.

Ophthalmology

Symptomatic infants should obtain serial ophthalmologic examinations.

Development

Although many infants with congenital CMV do not end up with developmental delays, there is increased risk. Monitor for developmental delays using the American Academy of Pediatrics recommended screening and surveillance intervals for primary care. Refer to early intervention and developmental therapists as appropriate.

Neurology

Due to the effects on fetal brain development, seizures and cerebral palsy are possible long-term complications. If suspected, refer to Neurology to assist with diagnosis and management. For children with spasticity, refer to physical therapy and to physical medicine and rehabilitation.

Prevention

Prevention of congenital CMV through pre-conception vaccination has been an elusive goal for decades (Schleiss et al., 2023). Currently, it is not recommended that pregnant women with primary CMV infection receive CMV immunoglobulin or antiviral therapy to prevent vertical transmission (Pinninti & Boppana, 2023; Rawlinson et al., 2017). Perhaps a more practical recommendation is to provide information to potential mothers and have them follow simple handwashing measures and behavioral modifications to reduce infection risk (Din et al., 2011; Rawlinson et al., 2017; Stowell et al., 2012). Pregnant women can be counseled to avoid contact with the saliva of young children, such as by not placing children’s pacifiers in their mouths and avoiding sharing utensils or food and beverages (Rawlinson et al., 2017).

Referrals

• Audiology
• Early intervention (if developmental delay is present)
• Neurology
• Otolaryngology
• Ophthalmology

Patient Education

• Congenital CMV and Hearing Loss (CDC)
• CMV in Newborns (CDC)

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