Overview
Definition:
Congenital Cytomegalovirus (CMV) infection is the most common non-genetic cause of sensorineural hearing loss and neurodevelopmental disability in children
It occurs when a pregnant individual acquires a primary or recurrent CMV infection, and the virus is transmitted to the fetus in utero.
Epidemiology:
Worldwide, the prevalence of congenital CMV varies significantly by socioeconomic status and geographical region
In developed countries, it is estimated to occur in 0.2-0.7% of live births, with higher rates in developing countries
Approximately 10-15% of infected infants are symptomatic at birth
Primary maternal infection during pregnancy carries a higher risk of transmission (30-50%) compared to recurrent infection (0.4-1.5%).
Clinical Significance:
Congenital CMV is a major public health concern due to its potential for severe, long-term sequelae, including hearing loss, vision impairment, cognitive deficits, and cerebral palsy
Early diagnosis and appropriate management, particularly antiviral therapy in select cases, can significantly improve neurodevelopmental outcomes and prevent progressive hearing loss.
Clinical Presentation
Symptoms:
Infants with symptomatic congenital CMV may present with a wide spectrum of clinical manifestations
Common findings include petechiae or purpura ("blueberry muffin" rash)
Hepatosplenomegaly
Jaundice, often prolonged
Microcephaly or other intrauterine growth restriction
Chorioretinitis, which can lead to vision loss
Neurological abnormalities such as lethargy, hypotonia, seizures, or developmental delay
Thrombocytopenia
Elevated liver enzymes
Blueberry muffin rash.
Signs:
Physical examination may reveal petechiae, purpura, jaundice, hepatosplenomegaly, microcephaly, chorioretinal lesions, or neurological deficits
Examination of the eyes by an ophthalmologist is crucial for identifying chorioretinitis
Hearing screening (otoacoustic emissions or auditory brainstem response) should be performed in all newborns with suspected congenital CMV.
Diagnostic Criteria:
Diagnosis is confirmed by the detection of CMV DNA or virus in body fluids (saliva, urine, blood) of an infant less than 3 weeks of age
Recommended diagnostic samples include urine, saliva, and blood (for PCR)
Postnatally acquired CMV infection (occurring after 3 weeks of age) is not considered congenital and does not typically require antiviral treatment unless the infant is immunocompromised or severely ill.
Diagnostic Approach
History Taking:
Key history points include maternal primary CMV infection during pregnancy, particularly in the first or second trimester
A history of fever, rash, or mononucleosis-like illness in the pregnant individual
Family history of hearing loss or developmental delays
Screening pregnant women for CMV is not universally recommended but may be considered in high-risk populations or during outbreaks.
Physical Examination:
A thorough physical examination focusing on signs suggestive of disseminated viral infection, including skin (petechiae, purpura), liver, spleen, and neurological system
Ocular examination by an ophthalmologist is essential for detecting chorioretinitis
Formal audiologic evaluation is critical for assessing hearing function.
Investigations:
CMV DNA detection by quantitative PCR in blood, urine, or saliva is the preferred method for diagnosis
CMV IgM antibodies can be present but are less reliable in neonates
Serological testing (IgG and IgM) can help confirm maternal infection but is not diagnostic of congenital infection
Ultrasound may reveal intracranial calcifications, microcephaly, or hydrocephalus in utero
Postnatal imaging (MRI) can assess brain damage, especially white matter abnormalities and periventricular calcifications
Audiology: Hearing tests (e.g., auditory brainstem response - ABR)
Ophthalmology: Funduscopy for chorioretinitis
Complete blood count with differential and platelet count
Liver function tests.
Differential Diagnosis:
Other TORCH infections (Toxoplasmosis, Rubella, Herpes Simplex Virus, Syphilis)
Bacterial sepsis
Neonatal alloimmune thrombocytopenia
Hemolytic disease of the newborn
Genetic syndromes causing microcephaly or developmental delay
Congenital rubella syndrome
Neonatal herpes simplex virus infection.
Management
Initial Management:
Supportive care for symptomatic infants is crucial
This includes fluid and electrolyte management, nutritional support, seizure control if present, and monitoring for complications like liver dysfunction or respiratory distress
Close collaboration with ophthalmology and audiology services is paramount.
Medical Management:
Antiviral therapy with valganciclovir is recommended for infants with symptomatic congenital CMV infection
The standard regimen is 16 mg/kg per dose orally every 12 hours for 6 weeks
Valganciclovir is a prodrug of ganciclovir and offers better oral bioavailability
Dosage should be adjusted for renal impairment
Monitoring for neutropenia and thrombocytopenia is essential during treatment
Intravenous ganciclovir (5 mg/kg per dose every 12 hours for 6 weeks) may be used if oral valganciclovir cannot be tolerated or absorbed, though oral valganciclovir is now preferred due to ease of administration and equivalent efficacy.
Surgical Management:
Surgical management is generally not indicated for congenital CMV itself, but may be required for specific complications such as severe hydrocephalus requiring shunting, or for management of consequences of chorioretinitis.
Supportive Care:
Aggressive supportive care is vital for all neonates diagnosed with congenital CMV, especially those who are symptomatic
This includes meticulous monitoring of vital signs, fluid balance, and laboratory parameters
Nutritional support with appropriate feeding methods and caloric intake is essential for growth
Physical, occupational, and speech therapy should be initiated early for infants with neurological deficits.
Complications
Early Complications:
Seizures
Thrombocytopenia
Hemolytic anemia
Hepatitis
Pneumonitis
Disseminated intravascular coagulation (DIC)
Neurological deterioration
Sensorineural hearing loss (initial).
Late Complications:
Progressive sensorineural hearing loss, which can occur even in previously asymptomatic infants or those with mild initial symptoms
Vision impairment due to chorioretinitis
Cognitive deficits and learning disabilities
Developmental delay
Cerebral palsy
Executive function deficits
Attention deficits.
Prevention Strategies:
Prevention of primary maternal CMV infection is challenging
Strategies include meticulous hand hygiene, especially after contact with children (daycare centers, schools), avoiding contact with saliva and urine of young children
Universal screening of newborns for congenital CMV is not currently recommended by all organizations, but is debated and implemented in some regions
Prenatal education on CMV prevention for pregnant women is important.
Prognosis
Factors Affecting Prognosis:
The prognosis is significantly influenced by the presence and severity of symptoms at birth, the gestational age at infection, and whether antiviral therapy is initiated
Symptomatic infants have a higher risk of long-term sequelae
Infants infected earlier in gestation may also have worse outcomes
Early diagnosis and treatment of symptomatic infants can improve neurodevelopmental outcomes and prevent progressive hearing loss.
Outcomes:
Symptomatic infants who receive antiviral therapy have a reduced risk of developing progressive hearing loss and may experience improved neurodevelopmental outcomes compared to untreated symptomatic infants
However, some degree of neurodevelopmental disability or hearing impairment may still persist
Asymptomatic infants generally have a good prognosis, but a small percentage may develop hearing loss later in life.
Follow Up:
Infants diagnosed with congenital CMV, symptomatic or asymptomatic, require lifelong follow-up
This includes regular audiological assessments (every 6-12 months for the first several years of life) and developmental monitoring
Ophthalmological examinations are crucial for those with chorioretinitis or other ocular findings
Neurodevelopmental assessments should be performed at regular intervals.
Key Points
Exam Focus:
Congenital CMV is the leading non-genetic cause of sensorineural hearing loss
Diagnosis in neonates requires detection of CMV DNA in urine, saliva, or blood within the first 3 weeks of life
Valganciclovir 16 mg/kg/dose PO BID for 6 weeks is the standard antiviral therapy for symptomatic infants
Symptomatic infants have poorer outcomes and require early intervention.
Clinical Pearls:
Always consider congenital CMV in neonates with microcephaly, petechiae, hepatosplenomegaly, jaundice, or chorioretinitis
Do not miss progressive hearing loss in previously asymptomatic infants
Valganciclovir is preferred over IV ganciclovir for oral administration due to convenience and comparable efficacy
Regular audiology and developmental follow-up are critical, even for initially asymptomatic infants.
Common Mistakes:
Diagnosing congenital CMV based on maternal serology alone without neonatal testing
Relying solely on urine CMV PCR for diagnosis, as viral shedding can be intermittent
multiple sample types are recommended
Delaying antiviral therapy in symptomatic infants due to concerns about side effects
benefits often outweigh risks
Failing to perform adequate long-term audiological and developmental follow-up for all affected infants.