Risk Factors for Natural Hearing Evolution in Newborns With Congenital Cytomegalovirus Infection.

Importance: Congenital cytomegalovirus (cCMV) is the major cause of congenital nonhereditary sensorineural hearing loss in children. Currently, criteria to identify infants at increased risk for unfavorable hearing outcome are lacking. Objective: To identify risk factors associated with cCMV-related hearing improvement, hearing deterioration, and late-onset hearing loss. Design, Setting, and Participants: This multicenter cohort study included patients from 6 secondary and tertiary hospitals enrolled in the Flemish CMV registry (Belgium). Newborns with untreated cCMV infection with at least 4-year audiological follow-up were included. Patients who presented with other possible causes of sensorineural hearing loss were excluded. Data were collected for 15 years (January 1, 2007, to February 7, 2022) and analyzed from September 26, 2022, to January 16, 2023. Main Outcomes and Measures: Primary outcome was hearing evolution (per-ear analysis; described as stable hearing, improvement, or deterioration). The association of gestational characteristics, clinical findings, timing of seroconversion, viral load, and hearing status at birth with hearing evolution was investigated using effect sizes (Cramer V, odds ratio [OR], or Hedges g). Results: Of the 387 children, 205 of 385 with nonmissing data were male (53.2%), 113 (29.2%) had a symptomatic infection, and 274 (70.8%) had an asymptomatic infection. Every child was 4 years or older at final hearing evaluation. A total of 701 of 774 ears (90%) showed stable hearing (normal hearing or stable hearing loss since birth) over time. Late-onset hearing loss (normal hearing at birth followed by hearing loss) was present in 43 of 683 ears (6.3%). Among children with hearing loss present at birth, 24 of 34 ears (70.6%) had hearing deterioration, and 6 of 91 ears (6.6%) had hearing improvement. Prematurity was associated with a higher chance of hearing improvement (OR, 12.80; 95% CI, 2.03-80.68). Late-onset hearing loss was more prevalent in a first trimester infection (OR, 10.10; 95% CI, 2.90-34.48). None of the 104 ears of children with a third trimester seroconversion developed late-onset hearing loss. Conclusions and Relevance: Findings of this cohort study support that ongoing audiological follow-up for untreated children with congenital hearing loss is important, as the majority of patients had hearing deterioration. The timing of seroconversion was associated with the risk of developing late-onset hearing loss. These insights can aid in parental counseling, patient stratification, and follow-up. Future research should focus on the effect of treatment, the influence of determined risk factors, and the study of eventual new risk factors in patients at high risk to develop hearing loss.

Risk Factors for Hearing Loss at Birth in Newborns With Congenital Cytomegalovirus Infection.

Importance: With 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. Objective: To identify independent risk factors for cCMV-related congenital hearing loss and predictors of hearing loss severity at birth. Design, Setting, and Participants: This 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 Measures: Primary 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. Results: Of 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 Relevance: Findings 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.

Congenital CMV-Associated Hearing Loss: Can Brain Imaging Predict Hearing Outcome?

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.

Hearing in Children with Congenital Cytomegalovirus Infection: Results of a Longitudinal Study.

OBJECTIVES: To evaluate hearing outcome, to characterize the nature of symptomatic and asymptomatic congenital cytomegalovirus (cCMV) infection and associated hearing loss, and to compare results with data from previous studies. STUDY DESIGN: A prospective multicenter registry was set up in 2007. Six centers participated in the development of a standardized protocol for diagnosis, treatment, and follow-up. Data were gathered in an online registry. Children (n = 379) with a documented cCMV infection and at least 2 separate audiologic evaluations were included. Audiometric results from a multicenter cohort study of children with cCMV infection with longitudinal observation were examined. RESULTS: Results from 123 children with a symptomatic and 256 children with an asymptomatic cCMV infection were analyzed. In the group with symptomatic cCMV, 63% had hearing loss, compared with 8% in the group with asymptomatic cCMV. Delayed-onset hearing loss occurred in 10.6% of symptomatic cCMV and in 7.8% of asymptomatic cCMV. In the group with symptomatic cCMV, 29.3% of children used some kind of hearing amplification; 1.6% in the group with asymptomatic cCMV used hearing amplification. CONCLUSIONS: Symptomatic and asymptomatic cCMV infections are a major cause of hearing loss in childhood. Reliable estimates of the long-term outcome of cCMV infection are mandatory to increase vigilance, especially among pregnant women and to draw attention to preventive measures, vaccine development, and prenatal and postnatal therapy. Universal screening of newborns for cCMV infection should be initiated and combined with longitudinal audiometric follow-up.

Hearing status in children with congenital cytomegalovirus: up-to-6-years audiological follow-up.

OBJECTIVE: To evaluate the audiological outcome of children with congenital cytomegalovirus infection. METHODS: In a prospective study, the hearing of ninety seven congenitally cytomegalovirus-infected children, born between January 2003 and July 2009, was systematically evaluated until the age of six, applying the Flemish CMV protocol. Depending on the age of the child, the protocol provides hearing evaluation by objective-, play- or conventional audiometry. Symptomatic children with hearing loss at birth were treated with ganciclovir, if parents consented. RESULTS: Seventy children had a pass on initial screening, 27 had unilateral or bilateral hearing loss. Within the normal hearing group, one asymptomatic and two symptomatic children developed late-onset hearing loss. Within the group with hearing loss, 8 children received ganciclovir, while 8 symptomatic and 11 asymptomatic children did not receive ganciclovir. As for the treated group, 37.5% of the children had stable hearing loss, one child had progressive and one child had fluctuating hearing loss. Improvement of hearing threshold occurred in 37.5% of the children. Among the untreated symptomatic children, hearing loss remained stable in 50%, while progression occurred in 37.5%. In the group of asymptomatic children with hearing loss, hearing loss was most commonly stable (72.7%). Within the group of normal hearing ears at birth (n=156), there is a significant better progression in pure tone average for ears of asymptomatic subjects in comparison to ears of symptomatic subjects (p≤0.0001). As for the group of ears with hearing loss at birth (n=38), analysis shows no evidence for a difference in pure tone average progression between the different groups (p=0.38). CONCLUSIONS: Cytomegalovirus infection may cause hearing loss, in both symptomatic and asymptomatic children. Our data show a significant difference, between both groups, in the progression of pure tone average of normal hearing ears at birth, in favor of the asymptomatic children. This is not the case for ears with hearing loss at birth. However, this may be due to the small number of ears in this group. Our data show the tendency that treatment with ganciclovir increases the likelihood of improvement and reduces the likelihood of deterioration of the hearing.

SVD-based optimal filtering for noise reduction in dual microphone hearing aids: a real time implementation and perceptual evaluation.

In this paper, the first real-time implementation and perceptual evaluation of a singular value decomposition (SVD)-based optimal filtering technique for noise reduction in a dual microphone behind-the-ear (BTE) hearing aid is presented. This evaluation was carried out for a speech weighted noise and multitalker babble, for single and multiple jammer sound source scenarios. Two basic microphone configurations in the hearing aid were used. The SVD-based optimal filtering technique was compared against an adaptive beamformer, which is known to give significant improvements in speech intelligibility in noisy environment. The optimal filtering technique works without assumptions about a speaker position, unlike the two-stage adaptive beamformer. However this strategy needs a robust voice activity detector (VAD). A method to improve the performance of the VAD was presented and evaluated physically. By connecting the VAD to the output of the noise reduction algorithms, a good discrimination between the speech-and-noise periods and the noise-only periods of the signals was obtained. The perceptual experiments demonstrated that the SVD-based optimal filtering technique could perform as well as the adaptive beamformer in a single noise source scenario, i.e., the ideal scenario for the latter technique, and could outperform the adaptive beamformer in multiple noise source scenarios.