Impact of Maternal Valaciclovir Therapy on Early Neurodevelopment in Congenital CMV Infection: A Retrospective Pilot Study

Background/Objectives: Maternal valaciclovir therapy is increasingly used to reduce fetal viral replication in cases of primary cytomegalovirus (CMV) infection during pregnancy. However, data on its impact on early neurodevelopmental outcomes remain limited. This study aimed to evaluate the association between prenatal valaciclovir exposure and early neurodevelopment in infants with confirmed congenital CMV infection (cCMV). Methods: In this retrospective monocentric cohort study, 30 infants with PCR-confirmed cCMV infection were assessed at 4–8 months of age using the Bayley Scales of Infant and Toddler Development, Third Edition (Bayley-III). Infants were stratified according to prenatal exposure to maternal valaciclovir. Univariate analyses and multivariable linear regression models were performed to evaluate the association between prenatal antiviral exposure and cognitive outcome, adjusting for brain MRI findings and selected clinical variables. Results: Fifteen infants (50%) were exposed to prenatal valaciclovir. Exposed infants demonstrated higher cognitive composite scores compared with unexposed infants (median 105 [IQR 100–110] vs. 90 [85–110]; p = 0.030). In multivariable analysis, prenatal valaciclovir exposure remained significantly associated with higher cognitive scores (β = 11.89, 95% CI 2.86–20.92; p = 0.012), while neonatal MRI abnormalities were not independently associated with outcome. No significant differences were observed in language or motor domains. The final model explained 30% of the variance in cognitive scores (R2 = 0.30). Conclusions: Prenatal valaciclovir exposure was associated with higher cognitive composite scores after adjustment for selected covariates. Although causality cannot be inferred, these findings suggest a potential association with early neurodevelopmental outcomes and support the inclusion of functional neurodevelopmental endpoints in future prospective studies. These results should be considered exploratory and hypothesis-generating