Universal saliva PCR screening for congenital cytomegalovirus identifies asymptomatic infections with neuroimaging abnormalities in a prospective neonatal cohort.

Congenital cytomegalovirus (cCMV) infection is the leading non-genetic cause of sensorineural hearing loss and an important cause of neurodevelopmental impairment [1-3, 6-14]. Targeted screening strategies frequently fail to detect infected infants who are asymptomatic at birth but remain at risk for late sequelae [9]. This study aims to evaluate the diagnostic yield of universal saliva PCR screening compared with targeted screening strategies and to describe neuroimaging findings in identified cases. We conducted a prospective observational cohort study including 4000 neonates born at ARNAS Civico di Palermo, Italy, between July 2023 and September 2025. All neonates underwent saliva PCR screening on the second day of life. Positive results were confirmed by urine PCR. Infants with confirmed infection underwent cranial ultrasound, brain MRI, ophthalmologic examination, and audiological assessment. The prevalence of cCMV infection was 0.2% (8/4000). Using targeted screening criteria based on symptoms or failed hearing screening, only 62.5% (5/8) of infections would have been detected. Consequently, 37.5% (3/8) represented infections in asymptomatic infants who passed hearing screening. Neuroimaging abnormalities were observed in all confirmed cases.

conclusionUniversal screening improves diagnostic yield and identifies clinically asyntomatic infections with early neuroimaging abnormalities, supporting broader neonatal surveillance strategies. WHAT IS KNOWN: • cCMV infection is a leading non-genetic cause of childhood hearing loss and neurodevelopmental impairment. Only ~10% of infected neonates are symptomatic at birth; targeted screening often misses asymptomatic infants. Saliva PCR is a practical and accurate diagnostic tool for early detection. WHAT IS NEW: • Universal saliva PCR screening detected 37.5% more infections than targeted strategies. All infected infants, including asymptomatic cases, showed early neuroimaging abnormalities, highlighting neurological involvement.