Four-year neurodevelopmental outcomes in infants with symptomatic congenital cytomegalovirus disease treated with oral valganciclovir: A prospective follow-up study in Japan

Background: Congenital cytomegalovirus (CMV) infection is a leading cause of neurodevelopmental disabilities. Although oral valganciclovir (VGCV) treatment has shown short-term benefits, long-term outcomes beyond 3 years remain unclear. Objective: To evaluate 4-year neurodevelopmental outcomes in infants with symptomatic congenital CMV (SCCMV) disease treated with VGCV and identify predictors of adverse outcomes. Methods: This prospective follow-up study (VGCV-2) included 24 infants with SCCMV disease who received oral VGCV (16 mg/kg, twice daily for 6 months). Neurodevelopmental assessments were performed at 1, 2, 3, and 4 years of age using the Kyoto Scale of Psychological Development (KSPD). The primary outcome was developmental delay (developmental quotient [DQ] < 70) at 4 years. Secondary outcomes included diagnoses of neurodevelopmental disorders and results of autism spectrum disorder (ASD) screening. Results: Twenty-one participants (87.5%) completed the 4-year follow-up. Developmental delay was evident in 28.6% (6/21) of patients at 4 years. Neurodevelopmental disorders, including intellectual disability (28.6%), ASD (19.0%), and cerebral palsy (14.3%), were diagnosed in 42.9% (9/21) of patients. A poorer best-ear hearing assessment at baseline was a significant predictor of developmental delay. Shorter body length, smaller head circumference at birth, and poorer baseline hearing were significantly associated with the diagnosis of neurodevelopmental disorders. Early positive Modified Checklist for Autism in Toddlers screening at 2 and 3 years strongly predicted the diagnosis of neurodevelopmental disorders. Conclusion: Despite VGCV treatment, substantial neurodevelopmental impairment persisted for 4 years in children with SCCMV disease. Early clinical markers can help identify high-risk infants who require intensive developmental support. (Clinical trial registration: jRCT2051190075).