Secondary Prevention of Fetal Cytomegalovirus Infection Through Valacyclovir Administration in Maternal Primary Infections During the Periconceptional Period and First Trimester of Pregnancy

Objective: Oral administration of valacyclovir at 8g/day significantly reduces the rate of vertical transmission of CMV in women with a primary CMV infection acquired during the periconceptional period or the first trimester. The aim of this study is to expand the findings of previously published studies by including all recent cohorts on the subject.

Methods: The MEDLINE, Scopus, Cochrane Central Register of Controlled Trials (Central), and "clinical trial" registry (www.

Results: gov) were consulted. Randomized controlled trials and cohort studies administering oral valacyclovir at 8g/day to pregnant women with a primary CMV infection acquired during the periconceptional period or the first trimester were included. Cochrane's Risk of Bias 2 and ROBINS-I tools were used to assess the risk of bias. The result of the CMV PCR in the amniotic fluid was the primary outcome. A two-step individual patient data meta-analysis was conducted, and a subgroup analysis was performed, evaluating periconceptional and first-trimester infections separately. Results: Four studies (1 RCT and 3 cohorts) were included in the analysis (n=860 women). A significant reduction in the rate of the CMV vertical transmission was observed in the Valacyclovir group (aOR=0.39, 95% CI 0.25-0.59). This reduction was significant for both the periconceptional period (aOR=0.30, 95% CI 0.13-0.68) and the first trimester (aOR=0.47, 95% CI 0.28-0.78). Valacyclovir also reduced the rate of neonatal infections, aOR=0.45 (95% CI 0.25-0.83), for both periods considered (aOR=0.42, 95% CI 0.20-0.90, and aOR=0.54, 95% CI 0.29-0.99).

Conclusions: The current evidence suggests that oral valacyclovir (8g/day) is associated with reduction of the rate of vertical transmission of CMV following maternal primary infection acquired during the periconceptional period or the first trimester of pregnancy.