Valacyclovir was effective in reducing the rate of fetal cytomegalovirus (CMV) infection after maternal primary infection early in pregnancy, according to data from a prospective, randomized, double-blind, placebo-controlled trial published in The Lancet (Clinicaltrial.gov, NCT02351102).
Pregnant women aged 18 years or older with serological evidence of CMV infections acquired periconceptionally or within the first trimester were included. 92 participants were randomized to receive either oral valacyclovir 4g twice daily or placebo from time of enrollment until time of amniocenteses at 21 or 22 weeks. Baseline characteristics between groups were similar, and primary endpoint was rate of vertical transmission of CMV.
The median gestational age at initiation was 76 days (interquartile range [IQR], 69-95). In the valacyclovir group, 11% of amniocenteses (5/45) were positive for CMV compared to 30% of amniocenteses (14/47) in the placebo group (odds ratio [OR], 0.29; 95% CI, 0.09-0.90; P =.027). Among all women with a CMV infection in the first trimester, 11% of women (2/19) in the valacyclovir group had a positive amniocentesis compared to 48% of women (11/23) in the placebo group (P =.02). For women with periconceptional CMV infections, there was no difference between groups (P =.91).
Patients infected during the first trimester began treatment significantly earlier compared with patients with periconceptional infections in both valacyclovir (P =.0026) and placebo (P <.0001) groups. Women with a positive amniocentesis in the valacyclovir group began treatment significantly later compared with mothers with a negative amniocentesis (75.60 vs 50.75 days; P =.0047). One pregnancy in the valacyclovir group and 2 pregnancies in the placebo group was terminated at a late stage due to CMV-related fetal damage. In the valacyclovir group, 1 infant had hearing loss and 1 had subependymal cysts without any other manifestations. The valacyclovir group had lower odds of any CMV-related morbidity compared to placebo (OR, 0.38; 95% CI, 0.09–1.56).
Limitations of this study include small sample size, primary use of serological assays to determine the timing of maternal infection, and the use of a per-protocol analysis. A total of 6 infants, 2 from the placebo group and 4 from the valacyclovir group, were positive for CMV at birth despite negative amniocenteses, which suggests the possibility of late fetal infections.
According to investigators, this is the first study to investigate the efficacy of valacyclovir in preventing vertical transmission of CMV after first trimester primary maternal infection. “Adoption of this strategy could reduce rate of symptomatic congenital cytomegalovirus in neonates,” investigators concluded.
Shahar-Nissan K, Pardo J, Peled O, et al. Valaciclovir to prevent vertical transmission of cytomegalovirus after maternal primary infection during pregnancy: a randomised, double-blind, placebo-controlled trial. Lancet. 2020;396(10253):779-85. doi:10.1016/S0140-6736(20)31868-7.