Hearing Instability in Children with Congenital Cytomegalovirus: Evidence and Neural Consequences

Abstract

Objective/Hypothesis Sensorineural hearing loss (SNHL) is a common sequela of congenital cytomegalovirus (cCMV), potentially exacerbating neurocognitive delay. The objectives of this study were to assess: (1) age at which SNHL in children with cCMV; (2) stimulability of the auditory system in children with cCMV following cochlear implantation (CI); and (3) whether features of magnetic resonance imaging (MRI) potentially are predictive of hearing outcomes. Methods In this retrospective study of a prospectively acquired cohort, 123 children with cCMV who were referred for hearing loss at a single tertiary referral hospital over 20 years were compared with an unmatched comparative group of 90 children with GJB2‐related deafness. Outcome measures were results of newborn hearing screening (NHS), behavioral audiograms, and, in a subgroup of cochlear implant (CI) users, responses from the auditory nerve and brainstem evoked by CI at initial activation, as well as lesional volume of FLAIR‐hyperintense signal alterations on MRI. Results All but 3 of 123 children with cCMV had confirmed and persistent SNHL. At birth, 113 children with cCMV underwent NHS, 31 (27%) passed in both ears and 23 (20%) passed in one ear (no NHS data in 10 children). At the first audiologic assessment, 32 of 123 (26%) had normal hearing bilaterally; 35 of 123 (28%) had unilateral SNHL; and 57 of 123 (46%) had bilateral SNHL. More than half (67 of 123, 54%) experienced hearing deterioration in at least one ear. Survival analyses suggested that 60% of children who developed SNHL did so by 2.5 years and 80% by 5 years. In the children who passed NHS in one or both ears, 50% developed hearing loss by 3.5 years in the ear, which passed unilaterally (n = 23 ears), and 50% by 5 years in bilateral passes (n = 62 ears). Hearing loss was significant enough in all but one child with isolated high‐frequency loss for rehabilitation to be indicated. Hearing thresholds in individual ears were in the CI range in 83% (102 of 123), although duration of deafness was sufficient to preclude implantation at our center in 13 children with unilateral SNHL. Hearing aids were indicated in 16% (20 of 123). Responses from the auditory nerve and brainstem to initial CI stimulation were similar in children with cCMV‐related SNHL compared with GJB2‐related SNHL. Characteristic white matter changes on MRI were seen in all children with cCMV‐related SNHL (n = 91), but the lesion volume in each cortical hemisphere did not predict degree of SNHL. Conclusions cCMV‐related SNHL is often not detected by NHS but occurs with high prevalence in early childhood. Electrophysiological measures suggest equivalent stimulability of the auditory nerve and brainstem with CI in children with cCMV and GJB2‐related SNHL. Hyperintense white matter lesions on FLAIR MRI are consistently present in children with cCMV‐related SNHL but cannot be used to predict its time course or degree. Combined, the data show early and rapid deterioration of hearing in children with cCMV‐related SNHL with potential for...

Congenital cytomegalovirus infection diagnostics and management

“…Compared to infants with symptomatic cCMV, fewer children with asymptomatic cCMV have permanent sequelae – 10–15% with SNHL and much lower rates of ophthalmological and neurodevelopmental abnormalities compared to symptomatic cCMV [29,32,33,34 ▪ ]. SNHL in cCMV is variable with respect to time of onset, laterality, progression and fluctuance over time [31,32,35,36 ▪ ]. Approximately 33–50% of SNHL due to cCMV develops beyond the neonatal period (late-onset) with a later onset in asymptomatic compared to symptomatic cCMV.…”

Inconsistent Provider Testing Practices for Congenital Cytomegalovirus: Missed Diagnoses and Missed Opportunities

“…Examples of such programs include hearing-targeted cCMV testing, in which all infants who fail their newborn hearing screening are then tested for cCMV, and universal/routine screening programs, in which all infants are screened for cCMV regardless of apparent risk factors [ 40 , 44 , 45 ]. Such programs have been found to be effective and acceptable in several studies [ 46 , 47 , 48 , 49 , 50 ], although the debate about cost-effectiveness persists [ 51 ]. As a more nuanced understanding is being gained about the possible long-term outcomes of cCMV [ 43 , 50 , 52 ], as well as the effectiveness of early interventions [ 53 , 54 , 55 ], the risk–benefit analysis may be more clearly weighted towards systematic screening.…”

“…Such programs have been found to be effective and acceptable in several studies [ 46 , 47 , 48 , 49 , 50 ], although the debate about cost-effectiveness persists [ 51 ]. As a more nuanced understanding is being gained about the possible long-term outcomes of cCMV [ 43 , 50 , 52 ], as well as the effectiveness of early interventions [ 53 , 54 , 55 ], the risk–benefit analysis may be more clearly weighted towards systematic screening.…”

Congenital Cytomegalovirus Infection and Hearing Outcomes in Twins: A Systematic Review of Reported Cases

“…Although devices like cochlear implants are safe alternative treatment options for SNHL that allowed our patient to achieve normal hearing thresholds, antiviral therapies may directly mitigate SNHL severity. In patients with cCMV-associated single-sided deafness, unilateral cochlear implants can be highly beneficial, especially given the elevated risk of progressive contralateral hearing loss (58,59). Early detection and intervention may help avoid auditory deprivation during the critical period for language development (58).…”