Improvement of pregnancy outcome following primary CMV infection after the introduction of valacyclovir in the clinical practice in Italy, updated data from a large real-life multicenter study.

BACKGROUND: Congenital cytomegalovirus infection (cCMV) is a leading cause of neurodevelopmental impairment and congenital sensorineural hearing loss (SNHL). Since December 2020, valacyclovir (VCV) is reimbursed by the Italian National Health System to reduce maternal-fetal CMV transmission following primary CMV maternal infection.

OBJECTIVE: The aim of this study is to evaluate the effectiveness of VCV in preventing fetal CMV infection, termination of pregnancy, miscarriage, congenital CMV infection at birth and presence of signs/symptoms of cCMV in newborns.

STUDY DESIGN: The current study provides an update on previously published data from a large multicenter observational Italian study including women with primary CMV infection acquired during the periconceptional period and up to 24 gestational weeks between January 2010 and June 2025. Primary outcomes are CMV transmission at amniocentesis, termination of pregnancy, miscarriage, transmission at birth (positive CMV DNA on newborn's urine), symptomatic cCMV, and a composite outcome (occurrence of transmission at amniocentesis or at birth or termination of pregnancy or miscarriage).

RESULTS: Overall, 832 women were included (826 singletons and 8 sets of twin pregnancies, total 842 fetuses); 588 fetuses received prenatal VCV (576 singletons and 6 twins) and 254 were untreated (248 singletons and 4 twins). CMV-positive amniocentesis occurred in 17.2% (64/373) of VCV-treated fetuses compared with 27.9% (38/136) of untreated one (p=0.007, aOR 0.53 [95%CI 0.34, 0.85]).Termination of pregnancy and miscarriage occurred in 4.7% (26/555) and 0.7% (4/555) of treated fetuses versus 10.0% (25/250) and 1.6% (4/250) of untreated one, respectively (p=0.004, aOR 0.46 [95%CI 0.25, 0.78] and p=0.24, aOR 0.45 [95%CI 0.11, 1.80]). Neonatal CMV DNA in urine was detected in 23.7% (124/525) and 27.1% (60/221) of newborns from treated and untreated pregnancies, respectively (p=0.31, aOR 0.83 [95%CI 0.58, 1.19]). The prevalence of symptomatic congenital infection at birth was significantly less frequent in the VCV group (3.6% 19/525 vs. 9.9% 22/221, p=0.001, aOR 0.34 [95%CI 0.18, 0.64]). The composite outcome occurred less frequently in treated pregnancies (27.2% vs. 35.8%, p = 0.012, aOR 0.67 [95%CI 0.49, 0.91]). VCV-related adverse events were reported in 6.7% of cases and were mild or moderate. The diagnosis of cCMV infection at birth following a negative amniocentesis was not significantly different among treated and untreated pregnancies (12.9%, 36/280 versus 7.3%, 7/96; p = 0.139). In the group of treated pregnancies with negative amniocentesis the proportion of newborn with cCMV diagnosed at birth was 23.2% (19 of 63), 10.9% (11 of 90) and 6.3% (6 of 90) among those with seroconversion, positive lgG-IgM and low IgG avidity and positive lgG-IgM and intermediate IgG avidity and positive molecular test respectively (p=0.003).

CONCLUSIONS: Large scale real-life data confirm that VCV improves the outcome of pregnancy with CMV primary infection with a good safety profile.