Manifestation of Congenital CMV-Related Hearing Loss in Cohort Followed at Ear, Nose, and Throat Clinic

Molecular Screening for Children With Hearing Loss: Why Do It?

A Truncating Mutation in SERPINB6 Is Associated with Autosomal-Recessive Nonsyndromic Sensorineural Hearing Loss

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. To identify independent risk factors for cCMV-related congenital hearing loss and predictors of hearing loss severity at birth. 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. 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. 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). 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.

Aim of the Study: The aim of our study was to compare the impact of hearing loss in the life of adults who had congenital hearing loss with that of adults with acquired adult onset hearing loss (auditory neuropathy). Methodology: The quality of life scale questionnaire was administered on two groups. One group consisted of 10 adults with prelingual bilateral severe to profound hearing loss identified before the age of 3 years and who were using hearing aids and had received regular intervention for speech and language development by a qualified speech language pathologist. Second group consisted of 10 adults with auditory neuropathy. Results and Discussion: Wilcoxon rank sum test was used to compare the domains across the groups and the gender distributions between two groups were analyzed using Fisher's exact test. The results revealed that differences between the adults with early-onset hearing loss and late onset hearing loss was statistically significant for most of the domains. The results indicated the fact that accepting a hearing loss during adulthood leads to more psychological trauma than adjusting and living with the hearing loss from the early years of life. Loss of hearing is quite traumatic to adults. Psychological trauma that they undergo is as important as their physiological problem and psychological referral to a clinical psychologist may be beneficial to many of them.

Facial nerve anomalies in association with congenital hearing loss

The prevalence and risk factors for congenital hearing loss in neonates: A birth cohort study based on CHALLENGE study.

IN THIS ISSUE OF JAMA, BOPPANA AND COLLEAGUES 1 DEscribe their attempts to validate universal screening methods for congenital cytomegalovirus (CMV) infection, the most common congenital viral infection in the United States and many other regions, by using polymerase chain reaction (PCR) analysis of newborn dried blood spots. Congenital CMV infection remains an important public health problem not only because it has accounted for as much or more disability over the past 50 years than was associated with congenital rubella syndrome, but also because CMV infection, whether symptomatic or silent at birth, represents the most common nongenetic cause of permanent hearing loss among children in the United States. Congenital CMV infection causes a substantial proportion of sensorineural hearing loss even in regions with a low prevalence. Culture surveillance of nearly 4000 newborns in Utah revealed a congenital infection rate of 0.29%, corresponding to approximately 3 infected infants for every 1000 newborns or 165 infected newborns annually statewide, given the state’s current birth rate. Because as many as 10% of these infants will have CMV disease, a condition associated with a 30% to 50% prevalence of sensorineural hearing loss, and the remainder will have silent CMV infection, a condition conservatively associated with a 6% to 8% rate of sensorineural hearing loss, CMV accounts for hearing loss in 15 to 20 children each year in Utah, or approximately 20% of the 90 to 120 Utah children identified with permanent hearing loss annually (J. C. Carey, University of Utah School of Medicine, written communication, March 2010). Worldwide, thousands of infants have CMV-induced hearing loss annually. Universal newborn screening for many disorders has immense public health benefits. The history of phenylketonuria (PKU) illustrates the enormous benefit of such strategies. Universal screening of newborn hearing has led to improvement in language outcomes, with greater improvements when deaf infants are identified earlier and interventions are begun sooner. Thus, it seems logical to infer that if CMV-infected infants can be identified in the neonatal period, hearing could be tracked closely, interventions could begin early, and the hearing outcomes of congenital CMV infection might be improved. However, 2 challenges confront universal screening for congenital CMV infection. First, universal screening is only justified when an effective intervention exists that prevents adverse health outcomes, such as averting intellectual disability when infants who lack phenylalanine hydroxylase initiate a diet low in phenylalanine early in life. At present, no such solution exists for CMV. Although neonatal ganciclovir therapy improves hearing outcomes in some infants, the benefits are not universal and the risk/benefit ratio of ganciclovir therapy in infants with silent congenital CMV infection has not been sufficiently well-established to recommend such therapy for all CMV-infected infants. Nonetheless, knowing which infants are infected with CMV has benefit through early identification of infants at risk of CMVinduced hearing loss and may have additional benefits in the future when new and more effective antiviral strategies become available. The second challenge, the one addressed by Boppana et al, is the availability of a highly sensitive and specific screening method. Neonatal screening of hearing alone is insufficient to detect all CMV-infected infants because most infants with congenital CMV infection have normal hearing in the neonatal period. Fowler et al demonstrated that nearly 20% of the children with hearing loss due to silent congenital CMV infection have delayed onset of sensorineural hearing loss. In addition, most infants with congenital hearing loss do not have CMV infection. In 1996, when Barbi et al demonstrated that newborn dried blood spots and PCR assays could be used to detect CMV DNA in the blood of congenitally infected infants, there was optimism that the opportunity for universal screening for CMV had arrived. However, the study by Barbi et al was not population-based and did not have a sufficient sample size to establish convincingly the sensitivity and specificity of mass screening of newborn dried blood spots. In contrast, the large, prospective study by Boppana et al shows that even though real-time PCR has excellent specificity (approaching 100%), the sensitivity of the PCR

Screening for congenital cytomegalovirus infection: A tapestry of controversies

Introduction: Congenital sensorineural hearing loss is one of the most common sensory defects affecting 1-3 children per 1000 newborns. There are a lot of causes which result in congenital hearing loss, the most common is the genetic origin, but infection, cochlear malformation or other acquired causes can be reasons as well. Aim: The aim of this study was to establish the etiological factors of congenital profound sensorineural hearing loss in children who underwent cochlear implantation. Results: Our results show that the origin of the hearing loss was discovered in 62.9% of our patients. The most common etiological factor was the c.35delG mutation of the gap junction protein β-2 gene, the allele frequency was 38.7% in our cohort. Infection constituted to 10.1%, and meningitis and cytomegalovirus infection were the second most common cause. 79.9% of our patients received sufficient hearing rehabilitation before the end of the speech development's period (6 years old), but 11.2% of our cases were still diagnosed late. Conclusions: Based on our data we can state that genetic evaluation is crucial in the diagnostic process of congenital profound sensorineural hearing loss. Sufficient hearing rehabilitation affects the whole life of the child, and by late cochlear implantation the speech development falls behind. We can decrease the ratio of the late implantation with the new protocol of newborn hearing screening, and with sufficient information provided to the colleagues, so the children may be referred to the proper center for rehabilitation without delay. Orv Hetil. 2019; 160(21): 822-828.

Sensorineural hearing loss is the most common disease associated with systemic retinitis pigmentosa (RP). We have conducted an epidemiological study to assess the correlation of age at onset of visual symptoms and hearing loss associated with RP. Epidemiological data was derived from a questionnaire-based study of patients who are registered members of the Japanese Retinitis Pigmentosa Society (n = 3200). The questionnaire was mailed to these patients in 2002, and information was requested regarding age at onset of visual disturbance, awareness of hearing loss and the presence of progressive hearing loss, age at onset of hearing loss, awareness of tinnitus, and history of audiometric examination and hearing aid usage. 26.1% of the questionnaires were returned, and data for 828 patients with RP diagnosed by an ophthalmologist were evaluated. Cochlear symptoms were reported by 356 patients (43.0% of the total population), with hearing loss in 29.5%, tinnitus in 31.5% and hearing loss and tinnitus in 39.3% of the 356 patients. Of these 356 patients, progressive hearing loss was reported by 44.9% and was independent of age at onset of cochlear symptoms. The mean age at onset of visual symptoms was higher for patients with progressive hearing loss, and a significant correlation was found between the age at onset of visual symptoms and hearing loss for patients who were older at onset of the symptoms (>30 years of age). Onset of hearing loss occurs later and hearing loss is also more progressive for patients with late onset of RP. This suggests that particular care regarding hearing loss is necessary for this patient population, and that cooperation between opthalmologists and otologists is required for diagnosis of RP-hearing impairment-associated syndromes in this group of patients.

On the basis of strong research, universal newborn screening should be performed before age 1 month with repeat or follow-up testing for those who do not pass performed before age 3 months and intervention started before age 6 months. On the basis of strong research and consensus statement, tympanostomy tubes should be considered for individuals with bilateral persistent middle ear effusion for 3 months or greater and a documented conductive hearing loss. On the basis of consensus statement, all children with suspected hearing loss should have an age appropriate hearing test. On the basis of strong research, the most common form of congenital hearing loss is genetic. Most of this is nonsyndromic hearing loss.

Sudden hearing loss associated with tacrolimus in a liver transplant recipient

Background Congenital cytomegalovirus (CMV) occurs in about 1 in 200 babies and is the leading non-genetic cause of sensorineural hearing loss (SNHL) in children in the United States. Approximately 50% of children with SNHL secondary to CMV have progression of their hearing loss. Data on the effectiveness of valganciclovir in the treatment of infants with congenital CMV with isolated hearing loss at birth is limited. Methods All newborns who did not pass their newborn hearing screening at birth between 2019-2023 were included and tested for CMV by a nucleic acid test from saliva and if positive confirmed from urine. All infants with CMV detected in urine had a Brainstem Auditory Evoked Response (BAER) test by 2-3 weeks of life and if hearing loss was confirmed, offered treatment with valganciclovir for 6 months. Infants who only had CMV detected in the saliva were not included. Results 204,680 newborns received hearing screens between 2019-2023. 7147 (3.5%) did not pass their hearing screening. 509 (7.1%) had hearing loss confirmed on BAER testing. 46 of the 7147 infants who did not pass their initial hearing screen had CMV detected in saliva and 17 of those had CMV detected in urine. 5 patients never received a urine test and were lost to follow-up. Among 17 cases with confirmed congenital CMV, 9 had confirmed hearing loss, 7 had normal hearing, and one lost to follow-up. 12 of the 17 cases were treated with valganciclovir, 8 with confirmed hearing loss, 3 with normal hearing, and one unknown. Among the 8 treated with hearing loss, 3 had progression of hearing loss, one improved, one was unchanged, and 3 lost to follow-up. Among the 7 with congenital CMV and normal hearing at birth, 3 were treated with valganciclovir and 2 remain with normal hearing with one to be determined. Among the 4 not treated, 3 remain with normal hearing and one was lost to follow-up. Among the 6638 with normal hearing on follow-up, 7-13 had congenital CMV (1 in 511-948). Among the 509 with confirmed hearing loss, there were 9 (1.8%) who had congenital CMV. Conclusion Congenital CMV was found in only 1.8% of newborns with hearing loss and about 0.15% of newborns without hearing loss. Treatment with valganciclovir did not appear to be beneficial in preventing the progression of hearing loss in some newborns but the numbers were too small to reach a conclusion. Disclosures All Authors: No reported disclosures

To investigate the natural progression of hearing loss in patients with high-frequency hearing loss whose audiograms met the criteria for a hybrid cochlear implant (CI). Retrospective database review. We retrospectively identified patients who met the criteria for a hybrid CI from our audiometric database. We also recorded the etiology of hearing loss in each patient and excluded patients with retrocochlear etiologies, those age <6 years, duration of observation <1 year, or those with a mixed or conductive hearing loss. We calculated the pre-CI progression of residual low-frequency (LF) hearing level in decibels per year and investigated the risk factor of the progression of hearing loss. A total of 1,083 ears of 944 patients were included in this study. The average rate of hearing loss progression for all etiologies was 1.70 ± 0.10 dB/yr at an average of 250 Hz, 500 Hz, and 1 kHz in the affected ear(s). The progression of hearing loss was 5.0 ± 0.93 dB/yr in patients with Meniere's disease and 3.5 ± 0.76 dB/yr in those with autoimmune disease, both of which were significantly faster than progression rates in other etiologies. In patients with idiopathic, genetic/hereditary, and congenital hearing loss, the progression of hearing loss was 1.46 ± 0.10 dB/yr. Patients with steeply sloping hearing loss experienced significantly faster progression in the ipsilateral ear compared to patients with another audiometric type. It is suggested that Meniere's disease, autoimmune-mediated inner ear disease, and steeply sloping hearing loss in the ipsilateral ear are risk factors for faster progression of residual LF hearing level. 4 Laryngoscope, 130:1299-1303, 2020.

To conduct a scoping review on etiologic investigation of prelingual hearing loss among children <2 years of age in the era of universal newborn hearing screening (UNHS). PubMed, Embase, PsycInfo, CINAHL, and Cochrane Library databases. We searched for articles published from January 1, 1998, to February 19, 2020. We reviewed studies that (1) included children identified with either congenital or delayed-onset hearing loss before 2 years of age among cohorts who had undergone UNHS and (2) investigated ≥1 etiologies of hearing loss. We defined hearing loss as congenital when confirmed after UNHS failure and as delayed onset when diagnosed after ≥1 assessments with normal hearing. Among 2069 unique citations, 115 studies met criteria for full-text assessment, and 20 met our inclusion criteria. Six studies tested children diagnosed with hearing loss for genetic etiology, 9 for congenital cytomegalovirus (CMV) infection, and 5 for both. Among 1787 children with congenital hearing loss and etiologic investigation, 933 (52.2%) were tested for genetic mutations and 1021 (57.1%) for congenital CMV infection. The proportion of congenital hearing loss cases attributable to genetic etiology ranged between 7.7% and 83.3% and to congenital CMV infection between 0.0% and 32.0%. Data are lacking on the identification and etiology of delayed-onset hearing loss in children <2 years of age in the UNHS era. The proportion of congenital hearing loss cases attributable to genetic etiologies and congenital CMV infection appears to vary widely.