Congenital and Perinatal Cytomegalovirus Infection (CMV)

Congenital CMV infection, which occurs in approximately 5 in 1000 live births worldwide, may result from transplacental acquisition of either a primary or recurrent maternal infection (1). Clinically apparent disease in the neonate is much more likely to occur after a primary maternal infection, particularly in the first half of pregnancy. In the United States, approximately 40% of women age 20 to 49 lack antibody to CMV, making them susceptible to primary infection (2).

Perinatal CMV infection is acquired by exposure to infected cervical fluid, human milk, or blood products. Maternal antibody is thought to be protective, and most exposed term infants are asymptomatic or not infected. In contrast, preterm infants (who have received less maternal antibody to CMV) can develop serious infection or can die, particularly when transfused with CMV-positive blood. Efforts should be made to transfuse these infants with only CMV-negative blood or components or to use blood that has been filtered to remove leukocytes, which carry CMV. Such leukoreduced blood is considered by many experts to be CMV safe.

Many people who become infected with CMV during pregnancy are asymptomatic, but some develop a mononucleosis-like illness.

Approximately 13% of infants with congenital CMV infection have symptoms, signs, or complications at birth, including (1) the following:

• Intrauterine growth restriction

• Preterm delivery

• Microcephaly

• Jaundice

• Petechiae

• Hepatosplenomegaly

• Periventricular calcifications

• Chorioretinitis

• Hepatitis

• Pneumonitis

• Sensorineural hearing loss

Infants who acquire CMV during or after birth, especially if they are preterm, may develop a sepsis-like syndrome, pneumonia, hepatosplenomegaly, hepatitis (which can lead to liver failure), thrombocytopenia, and atypical lymphocytosis. However, if transmission is via human milk, the risk of severe symptomatic disease and long-term sequelae is low.

• Polymerase chain reaction (PCR) testing using urine, saliva, blood, or tissue

• Viral culture using urine, saliva, or tissue

Symptomatic congenital CMV infection must be distinguished from other congenital infections, including toxoplasmosis, rubella, lymphocytic choriomeningitis, and syphilis.

In neonates, viral detection using culture or PCR of urine, saliva, blood, or a tissue sample is the primary diagnostic tool; maternal diagnosis can also be made by serologic testing or PCR (see Diagnosis of CMV). Congenital CMV infection is diagnosed if the virus (or viral nucleic acid) is identified in urine, saliva, or other body fluids obtained within the first 3 weeks of life; urine and saliva have the highest sensitivity. After 3 weeks, viral detection may indicate postnatal infection. Infants may shed CMV for several years after either type of infection.

Fetal CMV infection can be confirmed by PCR testing for CMV in the amniotic fluid.

Congenital Cytomegalovirus Infection

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By permission of the publisher. From Demmler G: Congenital and perinatal infections. In Atlas of Infectious Diseases: Pediatric Infectious Diseases. Edited by CM Wilfert. Philadelphia, Current Medicine, 1998.

A complete blood count (CBC) with differential and liver tests may be helpful but are not specific. Cranial ultrasound or CT and an ophthalmologic evaluation should also be performed. Periventricular calcifications are commonly found on CT.

Hearing tests should be routinely performed at birth in all infected neonates, and continued close monitoring is required because hearing loss may develop after the neonatal period and be progressive.

• Ganciclovir or valganciclovir for symptomatic neonatesGanciclovir or valganciclovir for symptomatic neonates

Symptomatic neonates are given antiviral medications. Oral valganciclovir for 6 months decreases viral shedding in neonates with congenital CMV and modestly prevents hearing deterioration and improves neurodevelopmental outcomes at 12 and 24 months of age (Symptomatic neonates are given antiviral medications. Oral valganciclovir for 6 months decreases viral shedding in neonates with congenital CMV and modestly prevents hearing deterioration and improves neurodevelopmental outcomes at 12 and 24 months of age (1); parenteral ganciclovir can be used if gastrointestinal absorption is unreliable. ); parenteral ganciclovir can be used if gastrointestinal absorption is unreliable.

In utero treatment of affected fetuses with acyclovir or In utero treatment of affected fetuses with acyclovir orvalacyclovir may also improve neonatal outcomes, but large studies with long-term follow up are lacking.

The main toxicity of these medications is neutropenia.

Symptomatic neonates have a mortality rate of up to 5 to 10% (1). Approximately 30 to 65% of survivors of symptomatic congenital CMV develop sensorineural hearing loss (2).

Among asymptomatic neonates, 5 to 15% eventually develop neurologic sequelae; hearing loss is the most common (3).

Nonimmune pregnant patients should attempt to limit exposure to the virus. For instance, because CMV infection is common among children attending day care centers, pregnant patients should always wash their hands thoroughly after exposure to urine and oral or respiratory secretions from children.

Pasteurization of donated human milk can decrease CMV transmission to severely immunocompromised neonates, who are at increased risk of severe postnatal CMV infection.

Transfusion-associated perinatal CMV disease can be avoided by giving preterm neonates blood products from CMV-seronegative donors or leukoreduced products.

Vaccines to prevent congenital CMV infection are in development. Maternal antiviral therapy with acyclovir or valacyclovir to prevent fetal transmission is being investigated (Vaccines to prevent congenital CMV infection are in development. Maternal antiviral therapy with acyclovir or valacyclovir to prevent fetal transmission is being investigated (1).

CMV hyperimmune globulin given to pregnant patients with primary CMV infection did not show a reduction in congenital infection in a randomized, controlled trial (2).