What is the percentage-wise comparison of transplacental (in utero) transmission for Cytomegalovirus (CMV), Rubella (German measles), Hepatitis B (HBV), and Herpes Simplex Virus (HSV) from most to least likely in a pregnant individual?

Transplacental Transmission Rates: Ranked from Highest to Lowest

Rubella has the highest transplacental transmission rate at 80-90% during primary maternal infection in early pregnancy, followed by CMV at 30-40%, Hepatitis B at 5-15% (in HBeAg-positive mothers with high viral load), and HSV with the lowest rate at <5%. 1

Detailed Transmission Rate Breakdown

1. Rubella (German Measles): 80-90%

• Primary maternal infection during early pregnancy carries the highest transplacental transmission risk at 80-90%. 1
• The CDC emphasizes the critical importance of verifying maternal immunity status before or early in pregnancy due to this exceptionally high transmission rate. 1
• Vaccination is contraindicated during pregnancy but essential for non-immune women postpartum. 1

2. Cytomegalovirus (CMV): 30-40%

• CMV transmission occurs transplacentally during primary maternal infection at rates of 30-40%. 1
• Reactivation or reinfection poses a substantially lower risk of approximately 1-2%, making primary infection the critical concern. 1
• Treatment with ganciclovir or valganciclovir may be considered for maternal end-organ disease, though primarily for maternal benefit rather than prevention of transmission. 1

3. Hepatitis B Virus (HBV): 5-15%

• In utero transmission risk is 5-15% in HBeAg-positive mothers with high viral load. 1
• The WHO recommends screening all pregnant women for HBsAg to identify at-risk pregnancies. 1
• HBeAg-positive mothers have significantly higher transmission risk compared to HBeAg-negative carriers (2-15% transmission rate). 1, 2
• The transplacental passage of HBeAg may make the infant tolerant to HBV, which partially explains the lower in utero transmission compared to intrapartum transmission. 2
• Most HBV transmission (70-90% of cases) actually occurs during delivery rather than in utero, making this primarily a peripartum rather than transplacental infection. 3

4. Herpes Simplex Virus (HSV): <5%

• In utero transmission of HSV is rare, occurring in less than 5% of cases. 1
• HSV is primarily transmitted perinatally during passage through an infected birth canal rather than transplacentally. 1, 4
• The ACOG recommends focusing prevention efforts on avoiding exposure during delivery through cesarean section if active genital lesions are present at labor onset. 1
• Maternal acyclovir suppression in late pregnancy reduces viral shedding and the need for cesarean delivery. 1

Critical Clinical Caveats

Timing of Maternal Infection Matters

• For Rubella and CMV, primary maternal infection during pregnancy poses the highest risk, while reactivation carries minimal risk. 1
• The gestational age at which maternal infection occurs significantly impacts transmission rates, particularly for Rubella where early pregnancy infection has the highest rates. 1

Viral Load as a Key Determinant

• For both HBV and CMV, maternal viral load is the single most important modifiable risk factor for transmission. 1, 5
• HBeAg-positive status in HBV serves as a marker for high viral replication and increased transmission risk. 1, 2

Prevention Strategies Differ Dramatically

• Rubella prevention relies entirely on pre-pregnancy vaccination, as no intervention exists once pregnancy occurs. 1
• HBV has the most effective prevention strategy with postexposure prophylaxis (hepatitis B immunoglobulin plus vaccine) achieving >90% protective efficacy. 2
• HSV prevention focuses on delivery management rather than in utero transmission. 1
• CMV has limited prevention options beyond hygiene measures to prevent primary infection. 1