Congenital CMV infection and central nervous system involvement: mechanisms, treatment, and long-term outcomes

Congenital Cytomegalovirus (cCMV) infection is the leading infectious cause of non-genetic sensorineural hearing loss and a significant cause of neurodevelopmental disability in infants. This narrative review aims to describe the mechanisms by which CMV disrupts fetal brain development in early gestation, the importance of neonatal neuroimaging in predicting prognosis, and the optimal intervention for preventing neurologic sequelae. We performed a literature search on PUBMED on this topic and selected the most relevant results, including studies describing neurologic outcomes, neuroimaging, hearing loss, treatment efficacy, or follow-up recommendations in infants with cCMV, prioritizing randomized controlled trials (RCTs), systematic reviews, and expert consensus guidelines. The pathogenesis of cCMV infection is the result of various mechanisms that the virus uses to replicate in the developing fetal central nervous system; the major cause of structural damage to the brain is aberrant migration of neuronal precursors. Recent literature stresses the importance of neuroimaging and the role of neuroradiologic scores to predict neurologic sequelae. The management of infants with isolated SNHL, especially those diagnosed after the neonatal period, remains controversial, though emerging evidence suggests a potential therapeutic window up to 12 weeks of age. Follow-up protocols should be tailored based on clinical presentation, with close audiologic and developmental surveillance.

Despite recent advances, key knowledge gaps persist regarding the mechanisms of CNS injury, optimal screening for vestibular dysfunction, neonatal biomarkers of prognosis, and treatment indications for isolated SNHL. Targeted research and standardized follow-up models are essential to improve outcomes in this vulnerable population.

• Congenital Cytomegalovirus infection is the leading infectious cause of non-genetic sensorineural hearing loss and a significant cause of neurodevelopmental disability in infants. • Neurological complications remain the most significant contributors to morbidity in cCMV infection.

• Beyond classical neurological manifestations, cCMV infected babies show a high prevalence of vestibular dysfunction; neurodevelopmental sequelae are frequent, including autism, attention deficit, and learning difficulties, and may occur even in asymptomatic cases. Neuroradiologic scoring systems proved to be predictive of developmental outcomes. • This review proposes a structured follow-up model tailored to clinical and imaging findings and discusses prognostic factors that may help identify children at increased risk for late-onset sequelae.