Cranial Ultrasound Findings in Infants With Congenital Cytomegalovirus Infection in a Universal Newborn Screening Study in Minnesota

Abstract

Background: Congenital cytomegalovirus (cCMV) is the most common infectious cause of neurodevelopmental deficits in US children. To inform patient management, it is important to define whether central nervous system (CNS) manifestations are present at birth. This study characterized neuroimaging findings in infants with cCMV identified by a universal screening study in Minnesota during February 2016-December 2022.

Methods: Newborns with cCMV infection (confirmed by urine CMV polymerase chain reaction [PCR] testing, obtained following a positive screening saliva and/or dried blood spot result) underwent a diagnostic evaluation that included a cranial ultrasound (cUS) exam, laboratory studies, ophthalmological, and audiological evaluation. Neuroimaging findings and cCMV disease classification were interpreted based on international consensus guidelines.

Results: Among 87 newborns with confirmed cCMV, 76 underwent cUS. Of these, 53/76 (70%) had normal examinations, while 23/76 (30%) exhibited cUS findings: for 5 infants, these were clearly cCMV disease-defining, while for 18 infants, there were findings of uncertain significance. Magnetic resonance imaging (MRI) results (n = 10 infants) aligned with cUS cCMV disease-defining findings in 2 infants, while cCMV-specific abnormalities were noted by MRI in 2 of 6 infants with nondiagnostic/incidental cUS findings. Of 9 infants who had both cUS and MRI examination, the average time interval between studies was 220 days (range, 2-1061). Excluding infants with cCMV CNS disease-defining cUS abnormalities, incidental findings were observed more commonly in infants with clinical/laboratory features described in cCMV disease classification guidelines (9/13) than in newborns with completely asymptomatic infections (9/58; P < .0001).

Conclusions: Among infants with cCMV identified in a universal screening study, the majority had a normal cUS. CNS disease-defining abnormalities were present in 7%, while 24% had findings of uncertain significance. We propose that many cUS findings are incidental, and not diagnostic of symptomatic cCMV infection. Although these findings may not be sufficient to define the presence of symptomatic cCMV disease involving the CNS, in our study they were more commonly observed in infants with other clinical and/or laboratory findings associated with symptomatic cCMV infection.

Keywords: antiviral therapy; congenital CMV; cranial ultrasound; newborn screening; universal screening.