A Neonatal Prognostic Score for Infants with Congenital Cytomegalovirus Infection (cCMVnet Score)

Objectives: To identify risk factors for long-term sequelae in children with congenital cytomegalovirus (cCMV) infection and to develop a prognostic scoring system (cCMVnet score) to support individualized management. Study design: This retrospective study was conducted within the prospective European Registry of Children with cCMV and included 570 children born between 2011 and 2024 in 11 countries. Eligible participants had confirmed cCMV, early cranial ultrasound and brain MRI (≤90 days of life), and at least six months of follow-up. The primary outcome was sequelae, defined as sensorineural hearing loss (SNHL), motor impairment, epilepsy, or visual impairment. Predictors were identified using multivariable logistic regression with Elastic-Net selection, followed by development and internal validation of the score. Results: Overall, 63.2% were symptomatic at birth and 28.9% developed sequelae, mainly SNHL (24.7%), motor impairment (8.2%), epilepsy (4.0%), and visual impairment (2.6%). Splenomegaly, severity of hearing loss, and neuroimaging abnormalities (white matter changes, calcifications, ventriculomegaly, migration disorders) were significant predictors. The cCMVnet score showed strong discrimination (AUC 0.870). At a 3.6-point cut-off, sensitivity was 81.3%, specificity 85.3%, and negative predictive value 90.6% Conclusions The cCMVnet score enables accurate risk stratification beyond symptomatic status integrating clinical, audiological, and neuroimaging findings. External validation is needed before widespread implementation.