What is the risk of perinatal transmission of Cytomegalovirus (CMV) infection when a maternal infection occurs in the first trimester?

Risk of Perinatal Transmission of CMV Maternal Infection in the First Trimester

Following primary maternal CMV infection in the first trimester, the rate of transmission to the fetus is approximately 30-40%. 1

Transmission Risk Based on Infection Type

The risk of perinatal transmission of cytomegalovirus (CMV) varies significantly depending on whether the maternal infection is primary (first-time) or non-primary (recurrent):

• Primary infection in first trimester: 30-40% transmission rate 1
• Non-primary infection (recurrent or reinfection): Much lower transmission rate of 0.15-1.0% 1

Factors Affecting Transmission

Timing of Infection

While the risk of transmission increases with advancing gestational age, the severity of fetal effects is inversely related:

• First trimester infections have lower transmission rates but higher risk of severe sequelae
• Severe fetal effects are more common when infection occurs before 20 weeks 2

Maternal Immune Status

• Previous CMV infection does not provide complete immunity
• Women with HIV and CMV coinfection have higher rates of CMV shedding (52-59% compared to 14-35% in HIV-uninfected women) 1
• HIV-infected women with CMV have an increased risk of transmitting CMV to their infants (4.5% in utero infection rate compared to <2% in general population) 1

Diagnostic Considerations

When primary CMV infection is suspected in the first trimester:

1. Serologic testing:

   • Diagnosis should be based on seroconversion (appearance of CMV-specific IgG in previously seronegative women)
   • Or detection of specific IgM and IgG antibodies with low IgG avidity 2

2. Prenatal diagnosis:

   • Amniocentesis is the gold standard for confirming fetal infection
   • Should be performed at least 6-8 weeks after presumed maternal infection
   • And after 17-21 weeks of gestation 2, 1

Risk of Adverse Outcomes

For fetuses infected following maternal primary infection in the first trimester:

• Approximately 10-15% of infected infants will be symptomatic at birth 1
• Symptomatic infants have a 30% mortality rate 1
• Of those who survive with symptomatic infection, 90% will develop long-term sequelae 1
• Even among asymptomatic infected infants, 10-15% will develop later complications 1

Management Considerations

Prevention

• Hygiene education is currently the most effective prevention strategy 2
• Women in contact with young children should be counseled about handwashing and avoiding contact with saliva and urine 3

Monitoring

• If maternal CMV infection occurs in the first trimester:
  • Regular ultrasound monitoring every 2-3 weeks is recommended 3
  • MRI of the fetal brain at 28-32 weeks can help assess for brain abnormalities 3
  • Testing of all babies born to women with confirmed or suspected CMV infection within first 21 days of life 3

Potential Interventions

• Some evidence suggests that hyperimmunoglobulin (HIG) administration may reduce transmission when started early:
  • In one study, biweekly HIG administration starting before 14 weeks reduced transmission to 2.5% compared to 35.2% in untreated controls 4
• For women with CMV IgG avidity in the "grey zone" during first trimester, transmission rates of 4.4% have been reported 5

Common Pitfalls in Management

1. Failure to recognize infection: CMV is often asymptomatic in pregnant women
2. Delayed diagnosis: Optimal intervention window may be missed if diagnosis is delayed
3. Inadequate follow-up: All infected infants require follow-up for at least 2 years to monitor for hearing loss and developmental issues 3
4. Overreliance on serology: Interpretation of CMV serology can be complex, particularly with "grey zone" avidity results

CMV remains the most common congenital viral infection and the leading non-genetic cause of sensorineural hearing loss. Early recognition of maternal infection and appropriate monitoring are essential to optimize outcomes.