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8/1/2016

Cytomegalovirus Infection in Pregnancy

Author: Michael Adler, MD

Mentor: Pamela D. Berens, MD
Editor: David Chelmow, MD

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Cytomegalovirus (CMV) is the most common congenital viral infection, occurring in 0.2 – 2.2% of neonates. Up to 4% of women have a primary CMV infection during pregnancy. CMV may present as a mononucleosis-like illness, although most women are asymptomatic.

Vertical transmission occurs in approximately 30-40% of cases of primary maternal infection. The frequency of vertical transmission increases with gestational age, though the most severe congenital CMV cases usually occur with primary infection in the first trimester.

Twelve to 18% of infected fetuses have evidence of infection at birth and up to 25% have sequelae including small for gestational age, microcephaly, ventriculomegaly, hepatosplenomegaly, hepatitis, chorioretinitis, and thrombocytopenia. Approximately 30% of infants with severe infection die, and the majority of survivors have severe neurologic morbidity. Infected infants who are asymptomatic at birth remain at risk for developing neurodevelopmental abnormalities.

Secondary maternal infections occur from reactivation or reinfection with a new CMV strain. The vertical transmission rate is up to 2%. In these cases, most newborns are asymptomatic at birth. Congenital deafness is the most common severe complication.

Testing pregnant women for CMV is indicated in women with mononucleosis-like illness or when fetal CMV infection is suspected based on suggestive sonographic findings such as intracranial, abdominal or liver calcifications, hepatosplenomegaly, echogenic bowel, fetal growth restriction, cerebral ventriculomegaly, microcephaly, ascites, or hydrops. These findings are non-specific.

Universal screening for CMV in pregnancy is not recommended. Seronegative childcare workers and families with young children are at risk for seroconversion. Measures to prevent CMV infection including frequent hand-washing may be discussed, although no measures can eliminate risk and the efficacy of such practices is unproven.

Primary maternal infection is diagnosed by testing samples drawn 3-4 weeks apart for anti-CMV IgG and noting seroconversion through detection of antibodies in a previously seronegative woman or a greater than four-fold increase in titer. In the absence of documented seroconversion or significant titer increase, the presence of anti-CMV IgG and anti-CMV IgM may represent primary or secondary infection. Many women with anti-CMV IgM will not have primary infection, but rather a re-exposure, a reactivation, or a false positive result. CMV IgG avidity testing is useful in these cases. During acute primary CMV infection, low avidity immature anti-CMV IgG is produced. Two to four months later, high avidity anti-CMV IgG is produced. Patients less than 20 weeks gestation with high avidity anti-CMV IgG are unlikely to have had primary infection during pregnancy. Presence of low avidity anti-CMV IgG suggests recent primary infection.

Prenatal testing should be offered when CMV infection is suspected. Referral to a maternal fetal medicine specialist should be considered. Amniocentesis is ideally performed after 21 weeks gestation and at least six weeks after maternal infection. Amniotic fluid is sent for PCR testing to detect CMV DNA. Serial ultrasound evaluations are recommended to monitor fetal growth and assess for features of fetal CMV infection. Normal ultrasound does not exclude risk for sequelae or neurodevelopmental abnormalities.

Treatment for maternal infection is supportive. There is no known effective treatment for congenital CMV infection. Preexisting maternal CMV antibody is thought to be the most protective factor against transmission. Currently, maternal IVIG and antiviral medications for prevention or treatment of fetal CMV infection are considered investigational.

Further reading:

Centers for Disease Control and Prevention, Cytomegalovirus (CMD) and Congenital CMV Infection. https://www.cdc.gov/cmv/

American College of Obstetricians and Gynecologists, Practice bulletin no. 151: Cytomegalovirus, parvovirus B19, varicella zoster, and toxoplasmosis in pregnancy. Obstet Gynecol. 2015 Jun;125(6):1510-25. doi: 10.1097/01.AOG.0000466430.19823.53.

Initial Approval September, 2013; Revised May 2016, Reaffirmed November 2017 and May 2019

 

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