Epidemiology, Early Therapy and Sequelae Predictors in Congenital CMV: A Nationwide Cohort Study.

BACKGROUND: Congenital cytomegalovirus (cCMV) is the most common congenital infection, with approximately 17%-20% of infected neonates developing permanent sequelae. Early risk stratification remains challenging yet crucial for therapeutic decision-making. We aimed to characterize national epidemiology, identify early predictors of sequelae, and assess the impact of early antiviral treatment on outcomes in infants with cCMV. METHODS: We conducted a nationwide prospective observational study between 2017 and 2024, analyzing birth and 1-year follow-up data of infants with confirmed cCMV in Switzerland. RESULTS: Two hundred and nine cCMV-infected children were included. The most common findings at birth were microcephaly (35%), intrauterine growth restriction (34%) and neuroimaging abnormalities (36%). Antiviral treatment was administered to 36% (75/209) of patients, among whom 75% (56/75) had treatment initiation within the first month of life. Multivariate analysis identified hepatosplenomegaly (odds ratio 13.2, 95% confidence interval, 2.3-75.2) and hypotonia at birth (odds ratio 6.6, 95% confidence interval, 1.1-41.1) as independent predictors of late-onset sensorineural hearing loss (SNHL). At the 1-year follow-up assessment, early treatment initiation was associated with significantly lower rates of neurodevelopmental disorders compared with delayed treatment initiation (23% vs. 50%, P = 0.004). CONCLUSIONS: This Swiss nationwide study confirms the previously reported association between hepatosplenomegaly at birth and late-onset SNHL and identifies hypotonia as a new independent predictor of late-onset SNHL. The data also confirm the crucial role of early antiviral treatment, particularly for neurodevelopmental disorders, emphasizing the importance of prompt cCMV diagnosis and treatment when indicated.