Congenital Cytomegalovirus Infection

Congenital cytomegalovirus (cCMV) infection is the commonest congenital infection. It is the leading non-genetic cause of sensorineural hearing loss and a major cause of neurodevelopmental disability. Birth prevalence is about 0.5 to 1% of live births (higher in populations with high maternal seroprevalence).

Transmission to the fetus occurs after primary maternal infection, with a transmission rate of about 30 to 40%. Risk is higher in the third trimester, but sequelae are more severe when infection occurs in the first trimester.

Transmission also occurs after non-primary infection (reactivation or reinfection with a new strain), with about 1 to 2% transmission. It can also occur from infected genital secretions, breast milk or blood.

About 10 to 15% of infected newborns are symptomatic at birth. Of asymptomatic infants, 10 to 15% develop late sequelae, mostly hearing loss.

• Symptomatic at birth: small for gestational age, microcephaly, petechiae and purpura, thrombocytopenia, jaundice (conjugated), hepatosplenomegaly, elevated transaminases, chorioretinitis.
• Also at birth: intracranial calcifications (periventricular), ventriculomegaly, cortical malformations (polymicrogyria, lissencephaly), seizures, hypotonia, and sensorineural hearing loss. "Blueberry muffin" rash is less common.
• Long term sequelae (even in infants asymptomatic at birth): sensorineural hearing loss, cerebral palsy, intellectual disability, seizures, vision impairment, and developmental disorders.
• The hearing loss is progressive, delayed onset or fluctuating. It occurs in 10 to 15% of asymptomatic and 40 to 60% of symptomatic infants.
• Prenatal ultrasound features: fetal growth restriction, microcephaly, ventriculomegaly, periventricular echogenic foci, hyperechoic bowel, hepatosplenomegaly, ascites, oligohydramnios or polyhydramnios, placentomegaly.

1. Confirm with CMV PCR (or culture) on urine or saliva within the first 21 days of life (diagnostic standard; after 3 weeks, postnatal infection cannot be distinguished). Stored dried blood spot PCR (from the newborn screen) can retrospectively diagnose congenital infection, but sensitivity is limited (about 70 to 80%).
2. In pregnancy: maternal CMV IgG, IgM, and IgG avidity. Low avidity within 12 to 16 weeks of infection suggests primary infection.
3. Fetal diagnosis is by PCR on amniotic fluid obtained by amniocentesis at least 6 to 8 weeks after maternal infection and after 21 weeks of gestation. Also fetal ultrasound and MRI.
4. Evaluation of infected infants: neurological examination, head ultrasound or MRI brain, ophthalmological exam (dilated), audiology (auditory brainstem response), complete blood count, liver function, bilirubin, and creatinine. Quantitative blood CMV PCR gives a baseline viral load.
5. Targeted newborn screening (for babies failing hearing screening) or universal screening is being adopted in some regions.

• Antiviral therapy for symptomatic congenital CMV with moderate to severe disease or central nervous system involvement: valganciclovir 16 mg/kg per dose orally twice daily for 6 months, started in the first month of life. This improves hearing outcomes and neurodevelopment.
• Alternative: ganciclovir 6 mg/kg IV every 12 hours for 6 weeks, in infants who cannot take oral therapy or are critically ill (then switch to oral valganciclovir).
• Neutropenia is the main toxicity (absolute neutrophil count below 500/microlitre). Check weekly for 6 weeks, then at 8 weeks, then monthly. Hold the drug until above 750/microlitre.
• Also monitor for thrombocytopenia, hepatotoxicity and renal function (adjust dose). Handle with care (teratogenic and carcinogenic; avoid contact with crushed tablets or liquid by pregnant caregivers).
• Isolated sensorineural hearing loss: treatment with valganciclovir for 6 months may be offered in selected infants (less than 1 month of age with confirmed cCMV and hearing loss).
• Asymptomatic infants: no antiviral treatment, but close follow up with audiological testing every 6 months until 3 years of age, then yearly until 6 years, and eye examination.
• Supportive care: hearing aids and cochlear implants, early intervention, physical, occupational and speech therapy, vision correction, antiepileptic drugs, and developmental assessments.
• Prevention in pregnancy: hygiene counselling (hand washing after contact with young children's saliva and urine and nappies, avoid sharing utensils and kissing on the mouth).
• Valacyclovir 8 g/day orally in divided doses, started early after primary infection in the first trimester, reduces vertical transmission in some trials. Give it only under specialist guidance and monitor for renal toxicity.
• Hyperimmune globulin has not been shown to be effective. There is no licensed vaccine.
• Breast milk: breastfeeding is encouraged in term infants with congenital infection. In preterm infants (under 30 weeks or under 1,500 g) of seropositive mothers, freezing or pasteurising milk reduces postnatal transmission.