Can Valaciclovir in Early Pregnancy Prevent Vertical Transmission of CMV?

Valaciclovir treatment in early pregnancy is effective at preventing vertical transmission of cytomegalovirus (CMV), according to study findings published in the journal Clinical Infectious Diseases.

The most common cause of congenital viral infection is CMV. Congenital CMV is associated with risk for serious sequelae, especially when it occurs in the first trimester. Evidence from a previous study indicated that valaciclovir treatment prevented vertical viral transmission better than placebo; however, it appeared that the efficacy of treatment relied on the amount of time that elapsed between infection and treatment. In reaction to these findings, the protocol for valaciclovir treatment was amended.

For the study, researchers assessed outcomes of the revised valaciclovir treatment schedule. Pregnant women (n=178) with primary early CMV infection who received 8 grams per day valaciclovir until amniocentesis, within 8 or 9 weeks of presumed infection at Rabin Medical Center in Israel between 2020 and 2022, were evaluated for vertical viral transmission assessed via amniocentesis. The rate of vertical transmission was compared with the control group in the original study (n=47).

The women who were infected with CMV in the periconception period (n=59) or first trimester (n=119) were mean age, 30.47 (SD, 3.73) and 31.42 (SD, 4.38) years; 82.6% and 70.6% had a parity of 1 and underwent amniocentesis at a gestational age of 21.28 (SD, 0.59) and 21.44 (SD, 0.55) weeks, respectively.

The self-reported adherence rate was over 90% in this study.

Overall, no vertical transmission events were observed among the subset of women who received treatment during periconception, compared with 11.8% of women who received treatment in their first trimester (P =.014).

In a pooled analysis, the vertical transmission rate in this study was 7.9%, compared with 30% among the historical control group (P <.001). Among only women who were infected in the periconception period, the amniocentesis positivity rate was lower in the treatment group than control individuals (odds ratio [OR], 0.000; 95% CI, 0-0.97; P =.02).

The time from infection to treatment was significantly shorter among the periconception subgroup (mean, 46.98 vs 66.5 d; P <.001) and the first trimester subgroup (mean, 39.08 vs 46.98 d; P <.001), compared with the historical control individuals, respectively.

One adverse event of a transient increase in creatinine level occurred, which was resolved after a 4-day suspension of treatment.

The major limitation of this study was the retrospective design and the use of a historical cohort.

The findings revealed that valaciclovir was effective at preventing vertical transmission of CMV to fetuses of pregnant women with infections.

The researchers concluded, “The revised protocol dramatically improved the results in women infected in the periconception period compared to the original protocol. For better implementation of this strategy of secondary prevention, early screening of CMV serology in seronegative women is needed, including frequent serological follow-up in the first 3 months of pregnancy.”