BACKGROUND AND OBJECTIVE: Hearing loss caused by congenital cytomegalovirus (cCMV) infection was first observed in 1964. Today cCMV is the most common cause of nonhereditary sensorineural hearing loss in childhood. Our objective was to provide an overview of the prevalence of cCMV-related hearing loss, to better define the nature of cCMV-associated hearing loss, and to investigate the importance of cCMV infection in hearing-impaired children. METHODS:Two reviewers independently used Medline and manual searches of references from eligible studies and review articles to select cohort studies on children with cCMV infection with audiological follow-up and extracted data on population characteristics and hearing outcomes. RESULTS:Thirty-seven studies were included: 10 population-based natural history studies, 14 longitudinal cohort studies, and 13 retrospective studies. The prevalence of cCMV in developed countries is 0.58% (95% confidence interval, 0.41-0.79). Among these newborns 12.6% (95% confidence interval, 10.2-16.5) will experience hearing loss: 1 out of 3 symptomatic children and 1 out of 10 asymptomatic children. Among symptomatic children, the majority have bilateral loss; among asymptomatic children, unilateral loss predominates. In both groups the hearing loss is mainly severe to profound. Hearing loss can have a delayed onset, and it is unstable, with fluctuations and progression. Among hearing-impaired children, cCMV is the causative agent in 10% to 20%. Despite strict selection criteria, some heterogeneity was found between selected studies.CONCLUSIONS: This systematic review underscores the importance of cCMV as a cause of sensorineural hearing loss in childhood. Pediatrics 2014;134:972-982

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In 2007, a prospective multicentre registry was set up to collect data on incidence and outcome of children with congenital cytomegalovirus infection in Flanders. A consensus was reached about management and follow up of cytomegalovirus-infected children. With this registration we aimed at gathering information on congenital cytomegalovirus infection in Flanders and evaluating the consensus on management and therapy. Children with proven congenital cytomegalovirus infection were eligible for registration in the database. Information on prenatal and neonatal management, therapy and follow up until 6 years was obtained. Between 2007 and 2017, 686 children were registered. Data on the prenatal and neonatal characteristics in children with congenital cytomegalovirus infection are reported. ConclusionIn this article we report on our experience of conducting a registry for cCMV in Flanders. Eleven years of collecting data on CMV in a multicenter setting has shown us some pitfalls and opportunities. We address some of the problems and aim at improving our data gathering. We encourage other groups to share their data. Better knowledge of the burden of the disease will be important to guide future management strategies.

ImportanceWith a prevalence between 0.2% and 6.1% of all live births, congenital cytomegalovirus (cCMV) infection is a major cause of congenital nonhereditary sensorineural hearing loss. Despite the large amount of research on cCMV-related hearing loss, it is still unclear which newborns are at risk of hearing loss.ObjectiveTo identify independent risk factors for cCMV-related congenital hearing loss and predictors of hearing loss severity at birth.Design, Setting, and ParticipantsThis cross-sectional study of newborns with cCMV infection used data included in the Flemish CMV registry that was collected from 6 secondary and tertiary hospitals in Flanders, Belgium, over 15 years (January 1, 2007, to February 7, 2022). Data were analyzed March 3 to October 19, 2022. Patients were included in the study after confirmed diagnosis of cCMV infection and known hearing status at birth. Patients who presented with other possible causes of sensorineural hearing loss were excluded.Main Outcomes and MeasuresPrimary outcome was hearing status at birth. Clinical, neurological, and laboratory findings along with the timing of seroconversion and blood viral load were separately considered as risk factors. Binary logistic regression was performed to identify independent risk factors for congenital hearing loss in newborns with cCMV. Effect sizes were measured using Hedges g, odds ratio, or Cramer V.ResultsOf the 1033 newborns included in the study (553 of 1024 [54.0%] boys), 416 (40.3%) were diagnosed with symptomatic cCMV infection and 617 (59.7%) with asymptomatic cCMV infection. A total of 15.4% of the patients (n = 159) presented with congenital hearing loss; half of them (n = 80 [50.3%]) had isolated hearing loss. The regression model revealed 3 independent risk factors for congenital hearing loss: petechiae at birth (adjusted odds ratio [aOR], 6.7; 95% CI, 1.9-23.9), periventricular cysts on magnetic resonance imaging (MRI; aOR, 4.6; 95% CI, 1.5-14.1), and seroconversion in the first trimester (aOR, 3.1; 95% CI, 1.1-9.3). Lower viral loads were seen in patients with normal hearing compared with those with congenital hearing loss (median [IQR] viral load, 447.0 [39.3-2345.8] copies per milliliter of sample [copies/mL] vs 1349.5 [234.3-14 393.0] copies/mL; median difference, −397.0 [95% CI, −5058.0 to 174.0] copies/mL).Conclusions and RelevanceFindings of this cross-sectional study suggest that newborns with cCMV infection and petechiae at birth, periventricular cysts on MRI, or a seroconversion in the first trimester had a higher risk of congenital hearing loss. Clinicians may use these risk factors to counsel parents in the prenatal and postnatal periods about the risk of congenital hearing loss. Moreover, linking clinical features to hearing loss may provide new insights into the pathogenesis of cCMV-related hearing loss. The importance of viral load as a risk factor for congenital hearing loss remains unclear.

Objectives: Congenital cytomegalovirus (cCMV) infection is the leading cause of nonhereditary sensorineural hearing loss in childhood and is also associated with CNS abnormalities. The main objective is to investigate the prognostic value of neonatal cranial ultrasound (cUS) and cranial magnetic resonance imaging (cMRI) in predicting long-term hearing outcome in a large cohort of cCMV-infected symptomatic and asymptomatic patients. Design: Data were prospectively collected from a multicentre Flemish registry of children with cCMV infection born between 2007 and 2016. Neonatal cUS and cMRI scans were examined for lesions related to cCMV infection. Audiometric results at different time points were analyzed. The imaging and audiometric results were linked and diagnostic values of cUS and cMRI were calculated for the different hearing outcomes. Results: We were able to include 411 cCMV patients, of whom 40% was considered symptomatic at birth. Cranial ultrasound abnormalities associated with cCMV infection were found in 76 children (22.2% of the cUS scans), whereas cMRI revealed abnormalities in 74 patients (26.9% of the cMRI scans). A significant relation could be found between the presence of cUS or cMRI abnormalities and hearing loss at baseline and last follow-up. Cranial ultrasound and cMRI findings were not significantly correlated with the development of delayed-onset hearing loss. Specificity and sensitivity of an abnormal cUS to predict hearing loss at final follow-up were 84% and 43%, respectively compared with 78% and 39% for cMRI. Normal cUS and cMRI findings have a negative predictive value of 91% and 92%, respectively, for the development of delayed-onset hearing loss. Conclusions: Neuroimaging evidence of CNS involvement in the neonatal period is associated with the presence of hearing loss in children with a cCMV infection. Imaging abnormalities are not predictive for the development of delayed-onset hearing loss.

Whether or not cranial ultrasound (crUS) and cerebral magnetic resonance imaging (MRI) have both a place in the assessment of children with congenital cytomegalovirus infection (cCMV) remains a topic of discussion between research groups. Literature suggests that MRI is indicated only in children with abnormal crUS. In Flanders, Belgium, combined crUS and MRI was performed on 639 children with cCMV, referred for diagnostic assessment. Cranial US was classified as abnormal in the presence of striatal vasculopathy, calcifications, cysts, cystic germinolysis, and/or ventriculomegaly. MRI findings were classified as abnormal in the presence of gyration disorders, cerebellar abnormalities, ventriculomegaly, cysts, or pathologic white matter lesions. One in five children (93/480) with normal crUS showed abnormal findings on MRI. Of them, 85 (91.4%) were classified as symptomatic. In 37 of those 93 children (39.8%), classification as severely symptomatic was made based on MRI lesions alone. MRI and crUS proved to be complementary in the assessment of CNS involvement in children with cCMV. Long-term studies are needed to evaluate the importance of this finding with respect to outcome and benefit of therapy in this particular subgroup of patients with cCMV infection.Conclusion: Our findings support an enhanced role of MRI in the diagnosis of CNS involvement in children with cCMV infection. The ideal assessment should include both imaging techniques, as the strengths of each test compensate for the other's weaknesses. What is Known:• Congenital CMV infection involves the central nervous system with direct injury to and possible disruption of brain development.• Experts suggest that MRI is indicated only in children with abnormal crUS. What is New:• In almost 20% of our children with a normal cranial ultrasound, abnormalities were detected on MRI.• Our results suggest that performing both MRI and cranial US is important to obtain a complete assessment of central nervous system involvement in children with cCMV.

Objectives: Congenital cytomegalovirus (cCMV) can affect vestibular function, which is an important cornerstone for early motor development. This study aims to identify risk factors for early vestibular dysfunction with severe repercussions on the motor outcome.Methods: This prospective cohort study included 169 cCMV-patients with complete vestibular assessment (lateral video Head Impulse Test and cervical Vestibular Evoked Myogenic Potentials) before the age of 18 months (mean 8.9, standard deviation 3.27 months). Motor results using the Alberta Infant Motor Scale were collected in 152 of these patients. Logistic and linear regression models were applied to identify risk factors for the vestibular and motor outcomes, respectively.Results: The odds of developing early vestibular dysfunction were 6 times higher in patients presenting with hearing loss at birth compared to those born with normal hearing (p = .002). Within the latter group, significant predictors for vestibular dysfunction were (delayed-onset) hearing impairment at the time of vestibular testing (p = .003) and the presence of periventricular cysts on magnetic resonance imaging (p = .005). Remarkably, none of the patients infected during the third trimester of pregnancy (n = 14) developed early vestibular dysfunction. On average, vestibular-impaired patients had a z-score on the Alberta Infant Motor Scale that was 1.17 points lower than patients without vestibular deficit (p < .001).Conclusion: Early vestibular loss can have a significant adverse effect on motor development. Hearing and cranial imaging findings could facilitate the widespread implementation of a (targeted) vestibular assessment approach in the cCMV-population.