Urinary Cytomegalovirus Load at Birth as a Predictor of Sequelae in Congenital Cytomegalovirus Infection

Congenital cytomegalovirus infection (cCMV) is the most common congenital infection worldwide. Identifying early prognostic markers of sequelae is crucial for improving follow-up protocols, especially for asymptomatic patients at birth. We aimed to determine the association of urine cytomegalovirus (CMV) viral load (VL) at birth with symptomatic disease and the development of sequelae in a cohort of Spanish patients with cCMV.

Patients for whom a positive quantitative CMV urine VL was available in the neonatal period were included. Exclusion criteria were urine VL performed beyond day 28 of life, having initiated antiviral treatment and concomitant primary or secondary immunodeficiency disorders. Sequelae were assessed in children with at least 6 months of follow-up.

Overall, 357 patients were included and sequelae were assessed in 282 (79.0%). At birth, 30.2% were asymptomatic, 11.8% had mild and 58.0% had moderate-to-severe cCMV disease. Higher urine CMV VL at birth was associated with thrombocytopenia, chorioretinitis and neuroimaging abnormalities, but not with disease severity. At the last available follow-up (median age: 30.1 months), 68 (24.1%) children presented with sequelae, mainly sensorineural hearing loss (n = 60). Sequelae were more common among children with moderate-to-severe cCMV disease at birth. In multivariate analysis, hepatomegaly [adjusted odds ratios (aOR): 7.9, 95% confidence intervals (CI): 1.5-63.3], hypotonia (aOR: 4.4, 95% CI: 1.2-18.3), abnormalities in cranial ultrasound (aOR: 3.3, 95% CI: 1.9-5.7) and urine CMV VL at birth (aOR: 1.3 per 1 log 10 increase, 95% CI: 1.1-1.6) were associated with a higher risk of sequelae.

Urine CMV VL at birth was associated with some symptoms and signs of cCMV and positively correlated with the risk of sequelae.