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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 with up to 4% of pregnant patients having a primary CMV infection. CMV remains the main non-genetic cause of congenital sensorineural hearing loss and neurological damage in pregnancy.

Vertical transmission occurs in 30-40% of cases of primary maternal infection. The frequency of vertical transmission increases with gestational age, yet more recent systematic neonatal screening yielded similar proportions of infected neonates following primary infection at all 3 trimesters. The most severe congenital CMV cases usually occur after a primary infection in the first trimester where neurologic morbidity is present in 40–50% of infected neonates. In Europe and the United States, primary infection in the first trimester is mainly seen in young parous women with a previous child younger than 3 years.

While CMV may present with maternal symptoms resembling a mononucleosis-like illness, most patients remain asymptomatic. The main prognostic factors in infected neonates are gestational age at maternal infection and the presence of neonatal symptoms. 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 infections die and sustain major neurologic morbidity. Infected infants who are asymptomatic at birth remain at risk for neurodevelopmental abnormalities with 15% developing hearing loss.

Secondary maternal infections occur from reactivation or reinfection with a new CMV strain with a vertical transmission rate of about 2%. In these cases, most newborns are asymptomatic at birth with congenital deafness being the most common severe complication.

There are two main circumstances prompting testing for fetal CMV infection:

• maternal primary infection diagnosed by either maternal symptoms and/or following prenatal serology screening.
• prenatal ultrasound findings indicative of fetal infection.

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.

Ultrasonographic findings include intracranial, abdominal or liver calcifications, hepatosplenomegaly, echogenic bowel, fetal growth restriction, cerebral ventriculomegaly, microcephaly, ascites, or hydrops. Serial ultrasound evaluations are recommended to monitor fetal growth and assess for features of fetal CMV infection. MRI may also demonstrated findings of encephalitis through CMV-related brain lesions and have been classified in stages of increasing severity.

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. Patients less than 20 weeks gestation with high avidity anti-CMV IgG are unlikely to have had primary infection during pregnancy. The 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.

Treatment for maternal infection is supportive. When antiviral treatment is used, ganciclovir or valganciclovir is preferred to prevent hearing deterioration and late-onset hearing loss.  European and US guidelines recommend against treatment in asymptomatic newborns.

Preexisting maternal CMV antibody is considered the most protective against transmission. Maternal IVIG and antiviral medications for prevention or treatment are considered investigational.

Further reading:

Leruez-Ville M, Chatzakis C, Lilleri D, et al. Consensus recommendation for prenatal, neonatal and postnatal management of congenital cytomegalovirus infection from the European congenital infection initiative (ECCI). Lancet Reg Health Eur. 2024 Apr 1;40:100892. doi: 10.1016/j.lanepe.2024.100892. PMID: 38590940; PMCID: PMC10999471.

Leruez-Ville M, Foulon I, Pass R, Ville Y. Cytomegalovirus infection during pregnancy: state of the science. American journal of obstetrics and gynecology. 2020 Sep 1;223(3):330-49.

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; Revised May 2024

 

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