PURPOSE:

• Valaciclovir has been used in pregnancy to treat herpes simplex infections
• Shahar-Nissan et al. (Lancet, 2020) sought to determine if valaciclovir administered to pregnant women with a primary cytomegalovirus infection is effective in preventing vertical transmission of cytomegalovirus (CMV)

METHODS:

• Prospective, randomized, double-blind, placebo-controlled trial
• Participants
  • Pregnant women ≥18 years
  • Primary CMV based on serologic evidence | Acquired periconceptionally or first trimester
  • Opted for amniocentesis to confirm diagnosis
• Randomized to one of two groups from enrolment until amniocentesis at 21 or 22 gestational weeks
  • Oral valaciclovir: 8 g per day, twice daily
  • Placebo
• CMV testing done on amniocentesis specimens
  • If patients declined amniocentesis, CMV positive infants assumed to be positive at time of amnio and CMV infants assumed to be negative
• Sample size of 38 for each group
  • Detect reduction in CMV transmission from 40% in the placebo group to 10% in the valaciclovir group
  • 80% power by two-sided test at a 5% significance level
• Primary outcome
  • Rate of vertical CMV transmission

RESULTS:

• 45 patients in the valaciclovir group (singletons) | 45 patients in placebo group (43 singletons and two sets of twins)
• First trimester and periconceptional infections combined (positive CMV detected in amniocentesis specimens)
  • Rate of vertical transmission was lower in the valaciclovir group (p=0.027)
    • Valaciclovir: 11%
    • Placebo: 30%
    • Odds ratio (OR) 0·29 (95% CI, 0.09 to 0.90)
• First trimester infection (positive CMV detected in amniocentesis specimens)
  • Rate of vertical transmission was lower in the valaciclovir group (p=0.020)
    • Valaciclovir group: 11%
    • Placebo: 48%  
• Post-hoc analysis to exclude patients who declined amnio
  • Effect of valacyclovir on vertical transmission reduction remained (p=0.038)
• No adverse effects were observed

CONCLUSION:

• Valaciclovir appears to reduce vertical transmission of CMV in women who acquired the infection early in pregnancy
• The authors state that

Combined with appropriate screening and further strengthening in larger trials, this strategy might safely and effectively alleviate neonatal short and long-term cytomegalovirus-related morbidity 

Learn More – Primary Sources:

Valaciclovir to prevent vertical transmission of cytomegalovirus after maternal primary infection during pregnancy: a randomised, double-blind, placebo-controlled trial

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