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8/1/2016

Cytomegalovirus Infection in Pregnancy

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 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.

About 10% of infected fetuses are symptomatic at birth with rash, jaundice, microcephaly, low birth weight, hepatosplenomegaly, seizures, or retinitis.  Approximately 30% of infants with severe infection die, and the majority of survivors have neurologic morbidity including hearing or vision loss, intellectual disability, microcephaly, lack of coordination or weakness, or seizures. Infected infants who are asymptomatic at birth remain at risk for neurodevelopmental abnormalities. Approximately 15% of babies with congenital CMV will be asymptomatic at birth but will later develop isolated hearing loss.

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 for CMV is indicated in patients with mononucleosis-like illness or when fetal infection is suspected based on sonographic findings such as intracranial, abdominal or liver calcifications, hepatosplenomegaly, echogenic bowel, fetal growth restriction, cerebral ventriculomegaly, microcephaly, ascites, or hydrops. Universal screening for CMV in pregnancy is not recommended. Seronegative childcare workers and families with young children are at increased risk of exposure to CMV.

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 patient 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 because anti-CMV IgM may represent re-exposure, 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.

CMV DNA in amniotic fluid obtained with amniocentesis ideally performed after 21 weeks gestation and at least six weeks after maternal infection indicates fetal infection. 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. Antiviral medications such as ganciclovir or valganciclovir may improve hearing and developmental outcomes, however should be weighed against potential serious side effects. Preexisting maternal CMV antibody is considered most protective against transmission. 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; Revised January 2021; Revised July 2022

 

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