#22 Does Cranial Ultrasound Differentiate Asymptomatic Congenital CMV (cCMV) Infection from cCMV with Central Nervous System Disease in Infants? Results from a Universal Screening Study in Minnesota, USA

Abstract

Abstract Background Congenital cytomegalovirus (cCMV) is the most common infectious cause of neurodevelopmental deficits, including sensorineural hearing loss (SNHL). With the passage of a universal cCMV screening bill by the Minnesota legislature in 2021, it is imperative to define the optimal diagnostic approach for identified cases, particularly for asymptomatic infants. Cerebral ultrasound (US) is a safe, non-invasive technique to examine neonatal brains, and has been advocated by an international consensus panel as a modality for cCMV disease classification. This analysis described clinical manifestations of cCMV in infants identified by universal screening and characterized cranial US findings obtained during diagnostic evaluation. We correlated viral load in the newborn CMV screening saliva samples with clinical and US findings. Method Newborns were screened for cCMV at six Twin Cities nurseries by PCR of dried blood spots (DBS) obtained for routine newborn screening, and saliva collected 1-2 days after birth. Screen-positive infants had a confirmatory urine PCR test within 3 weeks of birth, and clinical evaluation that included cranial US. Results Through September 1, 2021, 19,017 newborns were screened for cCMV. 76 cases were identified (prevalence of 0.4%) by saliva or DBS, confirmed by urine CMV PCR testing. 76% (58/76) had asymptomatic cCMV; the remaining 24% were infants with cCMV disease. Nine had congenital or delayed-onset SNHL, of which 7 had abnormal US; 1 had normal US, and 1 did not have US performed. Median saliva viral load differed between infants with cCMV disease (3.3×104 IU/ml) and asymptomatic infants (8.6×106 IU/ml; p< 0.05, Fig. 1). Cranial US exams were available for 68 infants (51 asymptomatic, 17 with cCMV disease). 50 (74%) infants had normal US; 18 infants had abnormal US (Table 1). Of the 17 infants with cCMV disease, 12 had abnormal US, of which 4 showed cCMV disease-defining lesions. Of 51 asymptomatic infants, 6 had abnormal, and 45 normal, cranial US. Saliva viral loads did not vary between infants with normal vs. abnormal US (p=0.7). Conclusion PCR of newborn DBS and/or saliva revealed a prevalence of 4.0 per 1000 in a universal cCMV screening study. Surprisingly, an inverse relationship was observed between saliva viral load at birth and cCMV disease classification. Among babies with cCMV, the majority had normal cranial US, and most abnormalities were not pathognomonic for cCMV disease. Clarification is needed regarding which cranial US findings require detailed follow-up, including MRI, as universal cCMV screening programs move forward in clinical practice.