[Mutation spectrum analysis of 23-site chip neonatal deafness genetic screening].

Objective:To analyze the mutation spectrum of 23-site chip newborn deafness genetic screening in Beijing, and to provide basis for genetic counseling and clinical diagnosis and treatment. Methods:The study included 21 006 babies born in Beijing from December 2022 to June 2023. All subjects underwent newborn deafness genetic screening in Beijing Tongren Hospital, covering 23 variants in 4 genes, the GJB2 gene（c.35delG, c.176_191del16, c.235delC, c.299_300delAT, c.109G>A, c.257C>G, c.512insAACG, c.427C>T, c.35insG）, SLC26A4 gene（c.919-2A>G, c.2168A>G, c.1174A>T, c.1226G>A, c.1229C>T, c.1975G>C, c.2027T>A, c.589G>A, c.1707+5G>A, c.917insG, c.281C>T）, Mt12SrRNA（m.1555A>G, m.1494C>T） and GJB3 gene（c.538C>T）. The mutation detection rate and allele frequency were analyzed. Results:The overall mutation detection rate was 11.516%（2 419/21 006）, with the GJB2 gene being the most frequently involved at 9.097%（1 911/21 006）, followed by the SLC26A4 gene at 2.123%（446/21 006）, the GJB3 gene at 0.362%（76/21 006） and Mt12SrRNA at 0.176%（37/21 006）. Among the GJB2 genes, c.109G>A and c.235delC mutation detection rates were the highest, with 6.579%（1 382/21 006） and 1.795%（377/21 006）, respectively. Of the SLC26A4 genes, c.919-2A>G and c.2168A>G had the highest mutation rates of 1.423%（299/21 006） and 0.233%（49/21 106）, respectively. Regarding the allele frequency, GJB2 c.109G>A was the most common variant with an allele frequency of 3.359%（1 411/42 012）, followed by the GJB2 c.235delC at 0.897%（377/42 012） and the SLC26A4 c.919-2A>G at 0.719%（302/42 012）. Conclusion:23-site chip newborn deafness genetic screening in Beijing showed that GJB2 c.109G>A mutation detection rate and allele frequency were the highest. This study has enriched the epidemiological data of 23-site chip genetic screening mutation profiles for neonatal deafness, which can provide evidence for clinical practice.

Predictors of the Outcome at 2 Years in Neonates With Congenital Cytomegalovirus Infection.

BACKGROUND: Approximately 20% of neonates with congenital cytomegalovirus (cCMV) develop long-term sequelae. The ability to accurately predict long-term outcomes as early as the neonatal period would help to provide for appropriate parental counseling and treatment indications. With this study, we aimed to identify neonatal predictive markers of cCMV long-term outcomes. METHODS: As this study's subjects, we chose neonates diagnosed with cCMV in 13 hospitals throughout France recruited from 2013 to 2017 and evaluated for at least 2 years with thorough clinical, audiology, and imaging evaluations and psychomotor development tests. RESULTS: A total of 253 neonates were included, and 3 were later excluded because of the identification of a genetic disorder. A total of 227 were followed up for 2 years: 187/227 (82%) and 34/227 (15%) were infected after a maternal primary or nonprimary infection, respectively, 91/227 (40%) were symptomatic at birth, and 44/227 (19%) had cCMV sequelae. Maternal primary infection in the first trimester was the strongest prognosis factor (odds ratio = 38.34 [95% confidence interval, 5.02-293], P < .001). A predictive model of no risk of sequelae at 2 years of age according to normal hearing loss at birth, normal cerebral ultrasound, and normal platelet count had 98% specificity, 69% sensitivity, and 0.89 area under the curve (95% confidence interval, 0.83-0.96). CONCLUSIONS: In the studied population, children with normal hearing at birth, normal platelet count at birth, and a normal cranial ultrasound had no risk of neurologic sequelae and a low risk of delayed unilateral sensorineural hearing loss. The use of this model based on readily available neonatal markers should help clinicians establish a personalized care pathway for each cCMV neonate.

Microstructural Changes in the Brainstem Auditory Pathway in Children With Hearing Loss.

OBJECTIVE: To assess the utility of diffusion tensor imaging of the auditory pathway in children with sensorineural hearing loss (SNHL). STUDY DESIGN: Retrospective cohort study. SETTING: A single academic tertiary children's hospital. PATIENTS: Sixteen pediatric patients with bilateral SNHL of at least moderate severity in the poorer ear (eight male; mean age, 5.3 ± 4.9 yrs). Controls consisted of age- and sex-matched children with normal hearing who were imaged for nonotologic, non-neurologic medical concerns and found to have normal magnetic resonance imaging (MRI). INTERVENTIONS: Three Tesla MRI scanners were used for diffusion tensor imaging. MAIN OUTCOME MEASURES: Quantitative diffusion tensor metrics were extracted from the superior olivary nucleus (SON), inferior colliculus (IC), and ipsilateral fiber tracts between the SON and IC delineated by tractography. RESULTS: We identified differences in fractional anisotropy of the SON between the SNHL cohort and controls (0.377 ± 0.056 vs. 0.422 ± 0.052; p = 0.009), but not in the IC. There were no differences in the mean diffusivity (MD) values in the IC and SON. Among younger children (≤5 yrs), MD was decreased in the SNHL cohort compared with controls in the IC (0.918 ± 0.051 vs. 1.120 ± 0.142; p < 0.001). However, among older children (>5 yrs), there were no differences in MD (1.124 ± 0.198 vs. 0.997 ± 0.103; p = 0.119). There were no differences in MD or fractional anisotropy in the white matter fibers of the IC-SON tract. CONCLUSIONS: Our results suggest abnormal neural tracts along the central auditory pathway among children with SNHL. Longitudinal studies should assess the prognostic value of these MRI-based findings for assessing long-term outcomes and determining intervention efficacy.

An eight-year follow-up on auditory outcomes after neonatal hearing screening.

OBJECTIVE: The aim of this study is to assess the neonatal click Auditory Brainstem Response (ABR) results in relation to the subsequently determined mean hearing loss (HL) over 1, 2 and 4 kHz, as well as over 2 and 4 kHz. METHODS: Between 2004-2009, follow-up data were collected from Visual Reinforcement Audiometry (VRA) at 1 and 2 years and playaudiometry at 4 and 8 years of newborns who had failed neonatal hearing screening in the well-baby clinics and who had been referred to a single Speech and Hearing center. Hearing Level data were compared with ABR threshold-levels established during the first months of life. The Two One-Sided Tests equivalence procedure for paired means was applied, using a region of similarity equal to 10 dB. RESULTS: Initially, in 135 out of 172 children referred for diagnostic procedures hearing loss was confirmed in the neonatal period. In 106/135 of the HL children the eight-year follow-up was completed. Permanent conductive HL was established in 5/106 cases; the hearing thresholds were predominantly stable over time. Temporary conductive HL was found in 48/106 cases and the loss disappeared by 4 years of age at the latest. Sensorineural hearing loss (SNHL) was found in 53/106 cases, of which 13 were unilateral and 40 bilateral. ABR levels were equivalent (within a 10 dB range) to VRA levels at age 1 and 2 and play audiometry levels at age 4 and 8, both when VRA and play audiometry were averaged over both frequency ranges. CONCLUSION: Long term follow-up data of children with SNHL suggest that the initial click ABR level established in the first months of life, are equivalent to the hearing threshold measured at the age of 1, 2, 4 and 8 years for both mean frequency ranges. Click ABR can reliably be used as starting point for long-term hearing rehabilitation.

The challenge of a mature final diagnosis of hearing loss severity and early cochlear implantation.

PURPOSE: Despite the recent trend of cochlear implantation (CI) at the age of six or even four months is prevalent in many centers around the world, clinicians should be cautious because perinatal risk factors of auditory neuropathy and/or delayed maturation carry the possibility of reversible hearing loss, yielding better auditory performance at the age of one year. The purpose of this study is to raise awareness that early CI may not be universal for all patients. In addition, we specify the factors to be considered in the pre-operative evaluation of CI in infants younger than one year. METHODS AND RESULTS: This study describes four cases provisionally diagnosed with severe to profound sensorineural hearing loss that were presented to the CI clinic to determine candidacy for implantation. Two cases had histories of prematurity, one had Down syndrome, and one had a family history of hearing loss. None of the study cases were candidates for CI, as they had varying degrees of hearing improvement. CONCLUSION: Although early CI may yield better auditory performance, the final diagnosis should be made only after repeated subjective and objective measurements as well as family feedback on the child's auditory performance, especially in preterm children. Early auditory brainstem response (ABR) prior to the age of one year in children with cognitive, neurologic, or developmental comorbidities should be interpreted with caution, as ABR "alone" could not accurately represent the child's true hearing ability in this patient population.

Increased Risk of Long-Term Disabilities Following Childhood Bacterial Meningitis in Sweden.

Importance: Few studies have examined the incidence of long-term disabilities due to bacterial meningitis in childhood with extended follow-up time and a nationwide cohort. Objective: To describe the long-term risks of disabilities following a childhood diagnosis of bacterial meningitis in Sweden. Design, Setting, and Participants: This nationwide retrospective registry-based cohort study included individuals diagnosed with bacterial meningitis (younger than 18 years) and general population controls matched (1:9) by age, sex, and place of residence. Data were retrieved from the Swedish National Patient Register from January 1, 1987, to December 31, 2021. Data were analyzed from July 13, 2022, to November 30, 2023. Exposure: A diagnosis of bacterial meningitis in childhood recorded in the National Patient Register between 1987 and 2021. Main Outcomes and Measures: Cumulative incidence of 7 disabilities (cognitive disabilities, seizures, hearing loss, motor function disorders, visual disturbances, behavioral and emotional disorders, and intracranial structural injuries) after bacterial meningitis in childhood. Results: The cohort included 3623 individuals diagnosed with bacterial meningitis during childhood and 32 607 controls from the general population (median age at diagnosis, 1.5 [IQR, 0.4-6.2] years; 44.2% female and 55.8% male, median follow-up time, 23.7 [IQR, 12.2-30.4] years). Individuals diagnosed with bacterial meningitis had higher cumulative incidence of all 7 disabilities, and 1052 (29.0%) had at least 1 disability. The highest absolute risk of disabilities was found for behavioral and emotional disorders, hearing loss, and visual disturbances. The estimated adjusted hazard ratios (HRs) showed a significant increased relative risk for cases compared with controls for all 7 disabilities, with the largest adjusted HRs for intracranial structural injuries (26.04 [95% CI, 15.50-43.74]), hearing loss (7.90 [95% CI, 6.68-9.33]), and motor function disorders (4.65 [95% CI, 3.72-5.80]). The adjusted HRs for cognitive disabilities, seizures, hearing loss, and motor function disorders were significantly higher for Streptococcus pneumoniae infection (eg, 7.89 [95% CI, 5.18-12.02] for seizure) compared with Haemophilus influenzae infection (2.46 [95% CI, 1.63-3.70]) or Neisseria meningitidis infection (1.38 [95% CI, 0.65-2.93]). The adjusted HRs for cognitive disabilities, seizures, behavioral and emotional disorders, and intracranial structural injuries were significantly higher for children diagnosed with bacterial meningitis at an age below the median. Conclusions and Relevance: The findings of this cohort study of individuals diagnosed with bacterial meningitis during childhood suggest that exposed individuals may have had an increased risk for long-term disabilities (particularly when diagnosed with pneumococcal meningitis or when diagnosed at a young age), highlighting the need to detect disabilities among surviving children.

Communicating Emotion: Vocal Expression of Linguistic and Emotional Prosody in Children With Mild to Profound Hearing Loss Compared With That of Normal Hearing Peers.

OBJECTIVES: Emotional prosody is known to play an important role in social communication. Research has shown that children with cochlear implants (CCIs) may face challenges in their ability to express prosody, as their expressions may have less distinct acoustic contrasts and therefore may be judged less accurately. The prosody of children with milder degrees of hearing loss, wearing hearing aids, has sparsely been investigated. More understanding of the prosodic expression by children with hearing loss, hearing aid users in particular, could create more awareness among healthcare professionals and parents on limitations in social communication, which awareness may lead to more targeted rehabilitation. This study aimed to compare the prosodic expression potential of children wearing hearing aids (CHA) with that of CCIs and children with normal hearing (CNH). DESIGN: In this prospective experimental study, utterances of pediatric hearing aid users, cochlear implant users, and CNH containing emotional expressions (happy, sad, and angry) were recorded during a reading task. Of the utterances, three acoustic properties were calculated: fundamental frequency (F0), variance in fundamental frequency (SD of F0), and intensity. Acoustic properties of the utterances were compared within subjects and between groups. RESULTS: A total of 75 children were included (CHA: 26, CCI: 23, and CNH: 26). Participants were between 7 and 13 years of age. The 15 CCI with congenital hearing loss had received the cochlear implant at median age of 8 months. The acoustic patterns of emotions uttered by CHA were similar to those of CCI and CNH. Only in CCI, we found no difference in F0 variation between happiness and anger, although an intensity difference was present. In addition, CCI and CHA produced poorer happy-sad contrasts than did CNH. CONCLUSIONS: The findings of this study suggest that on a fundamental, acoustic level, both CHA and CCI have a prosodic expression potential that is almost on par with normal hearing peers. However, there were some minor limitations observed in the prosodic expression of these children, it is important to determine whether these differences are perceptible to listeners and could affect social communication. This study sets the groundwork for more research that will help us fully understand the implications of these findings and how they may affect the communication abilities of these children. With a clearer understanding of these factors, we can develop effective ways to help improve their communication skills.

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.

Speech, Sign, or Both? Factors Influencing Caregivers' Communication Method Decision Making for Deaf/Hard of Hearing Children.

PURPOSE: Caregivers of deaf/hard of hearing infants are faced with challenging decisions regarding their child's communication method. The purpose of the current research note is to characterize the advice that caregivers receive and value as well as the factors that influence caregivers' decision making. METHOD: The current study enrolled 105 caregiver-child dyads, including children between 12 and 18 months of age with bilateral, congenital hearing loss. All children were exposed to spoken language, and 63.81% of children were also exposed to sign language. Caregivers completed the "Making Decisions About Sign, Speech, and Multilingualism Survey" (Crowe et al., 2014). RESULTS: Caregivers most frequently received advice to use both speech and sign and highly valued advice from speech-language pathologists. When considering the use of speech, the factors that caregivers most frequently rated as very important were "My child's future academic success" (96.19%), "My child's future literary success" (95.24%), and "My child's future access to higher education" (95.19%). When considering the use of sign, the factors that caregivers most frequently rated as very important were "My child's ability to form friendships and future relationships" (82.52%), "My child's future literary success" (81.37%), and "My child's future academic success" (81.37%). CONCLUSIONS: Results of the current study suggest that throughout the decision-making process, caregivers' highest priority is understanding how their decisions will influence their child's future access to opportunities and relationships. Providers may consider discussing these factors early in the decision-making process to support caregivers' ability to make an informed choice regarding their child's communication method.

The Association of Race With Decreased Access to Pediatric Hearing Healthcare in the United States.

Successful intervention to support a child with congenital hearing loss requires early identification and consistent access to frequent professional services. In the early 2000s, the United States implemented an initiative, Early Hearing Detection and Intervention (EHDI), to provide timely identification and treatment of congenital hearing loss. This national program aims to screen hearing by 1 month of age, diagnose hearing loss by 3 months of age, and provide intervention to infants with hearing loss by 6 months of age. To date, the United States is successfully implementing hearing screening by 1 month of age but continually struggling to diagnose and treat congenital hearing loss promptly for many infants. This article begins by exploring the current state of American children and families, focusing on social determinants of health, specifically race and poverty. The objective is to understand how race affects social determinants of health, and ultimately hearing healthcare access for children. A narrative literature review spanning public health, sociology, and hearing research was completed to inform this work. The current body of literature supports the conclusion that race and racism, separate from poverty, lead to decreased access to pediatric hearing healthcare. Interventions targeting these issues are necessary to improve timely access to hearing loss diagnosis and treatment for American children.

Risk Factors Associated with Delays in Hearing Loss Identification in Pediatric Patients.

OBJECTIVE: To identify sociodemographic factors associated with pediatric late-identified hearing loss (LIHL) and classify novel subgroups within the LIHL population. STUDY DESIGN: Retrospective cohort. SETTING: Tertiary children's hospital. METHODS: Our cohort included children with permanent hearing loss (HL) between 2012 and 2020 (n = 1087). Patients with early-identified HL were compared to patients with LIHL (>6 months of age at diagnosis), and 3 subgroups: (1) late-identified congenital HL: failed NHS but had a diagnostic audiogram >6 months old; (2) late-onset HL: passed NHS and identified with HL after 6 months old; (3) late-identified, unknown-onset: unknown NHS results, identified after 6 months old. Geospatial analysis was performed using ArcGIS Pro. RESULTS: Compared with early-identified children, children with LIHL were more likely to have more comorbidities (odds ratio [OR] = 1.12, [1.01, 1.23]), be an under-represented minority (URM) (OR = 1.92, [1.27, 2.93]) and have a higher social vulnerability index (SVI) (adjusted odds ratio [AOR] = 2.1, [1.14, 3.87]). However, subgroups in the LIHL cohort had variable associations. Children with late-identified unknown onset hearing loss were uniquely associated with a primarily non-English speaking household (AOR = 1.84, [1.04, 3.25]), whereas children with late-onset hearing loss were less likely to have public insurance (AOR = 0.47, [0.27, 0.81]. There were no significant associations for children with late-identified congenital hearing loss. Neighborhood disadvantage, as measured by SVI, had an increased association with late-identified unknown onset HL (AOR = 4.08, [2.01, 8.28]) and a decreased association with late-onset HL (AOR = 0.40, [0.22, 0.72]). CONCLUSION: Sociodemographic factors serve as proxies for health care access, and these factors vary across LIHL pathways. Understanding the risk factors associated with each LIHL subgroup may help address disparities in pediatric HL identification.

Longitudinal Analysis of Early Hearing Detection and Intervention Program Performance.

OBJECTIVES: Early hearing detection and intervention (EHDI) is a newborn hearing screening system created to detect infants with hearing loss (HL) and intervene to reduce language and communication impairment. Early hearing detection (EHD) consists of three sequential stages: identification, screening, and diagnostic testing. This study longitudinally reviews each stage of EHD in each state and proposes a framework to improve utilization of EHD data. DESIGN: A retrospective public database review was conducted, accessing publicly available data from the Centers for Disease Control and Prevention. Summary descriptive statistics were utilized to generate a descriptive study of EHDI programs in each U.S. state from 2007 to 2016. RESULTS: Data over 10 years from 50 states as well as Washington, DC were included in this analysis, creating up to 510 data points per analysis. Hundred percent (85 to 105) (median [min to max]) of newborns were identified by and entered EHDI programs. Ninety-eight percent (51 to 100) of identified infants completed screening. Of the infants who screened positive for HL, the proportion that received diagnostic testing was 55% (1 to 100). The overall proportion of infants who failed to complete EHD was 3% (1 to 51). Of the infants who fail to complete EHD 70% (0 to 100) are from missed screenings, 24% (0 to 95) are from missed diagnostic testing, and 0% (0 to 93) are from missed identification. Although there are more infants missed at screening, it was estimated, with limitations, that there is an order of magnitude more infants with HL among those who did not complete diagnostic testing compared with those who did not complete screening. CONCLUSIONS: Analysis demonstrates high completion rates at both identification and screening stages, whereas the diagnostic testing stage demonstrates low and highly variable completion rates. The low completion rates at diagnostic testing create a bottleneck in the EHD process and the large variability impedes the comparison of HL outcomes across states. Analysis also demonstrates that among all stages of EHD, whereas the largest number of infants are missed at screening, the largest number of children with HL are likely missed at diagnostic testing. Therefore, a focus by individual EHDI programs on addressing causes of low diagnostic testing completion rates would yield the greatest increase in the identification of children with HL. Potential causes of low diagnostic testing completion rates are further discussed. Finally, a new vocabulary framework is proposed to facilitate further study of EHD outcomes.

Spectral Resolution and Speech Perception in Cochlear Implanted School-Aged Children.

OBJECTIVE: Cochlear implantation of prelingually deaf infants provides auditory input sufficient to develop spoken language; however, outcomes remain variable. Inability to participate in speech perception testing limits testing device efficacy in young listeners. In postlingually implanted adults (aCI), speech perception correlates with spectral resolution an ability that relies independently on frequency resolution (FR) and spectral modulation sensitivity (SMS). The correlation of spectral resolution to speech perception is unknown in prelingually implanted children (cCI). In this study, FR and SMS were measured using a spectral ripple discrimination (SRD) task and were correlated with vowel and consonant identification. It was hypothesized that prelingually deaf cCI would show immature SMS relative to postlingually deaf aCI and that FR would correlate with speech identification. STUDY DESIGN: Cross-sectional study. SETTING: In-person, booth testing. METHODS: SRD was used to determine the highest spectral ripple density perceived at various modulation depths. FR and SMS were derived from spectral modulation transfer functions. Vowel and consonant identification was measured; SRD performance and speech identification were analyzed for correlation. RESULTS: Fifteen prelingually implanted cCI and 13 postlingually implanted aCI were included. FR and SMS were similar between cCI and aCI. Better FR was associated with better speech identification for most measures. CONCLUSION: Prelingually implanted cCI demonstrated adult-like FR and SMS; additionally, FR correlated with speech identification. FR may be a measure of CI efficacy in young listeners.

Neonatal hearing screening - does failure in TEOAE screening matter when the AABR test is passed?

PURPOSE: Newborns who fail the transient evoked otoacoustic emissions (TEOAE) but pass the automatic auditory brainstem response (AABR) in universal newborn hearing screening (UNHS), frequently have no further diagnostic test or follow-up. The present study aimed to investigate whether hearing loss might be missed by ignoring neonatal TEOAE failure in the presence of normal AABR. METHODS: A retrospective analysis was conducted in newborns presenting between 2017 and 2021 to a tertiary referral centre due to failure in the initial UNHS. The main focus was on infants who failed TEOAE tests, but passed AABR screening. The clinical characteristics and audiometric outcomes were analysed and compared with those of other neonates. RESULTS: Among 1,095 referred newborns, 253 (23%) failed TEOAE despite passing AABR screening. Of the 253 affected infants, 154 returned for follow-up. At 1-year follow-up, 46 (28%) achieved normal audiometric results. 32 (21%) infants had permanent hearing loss (HL) confirmed by diagnostic ABR, 58 (38%) infants had HL solely due to middle ear effusion (MEE), and for 18 (12%) infants HL was suspected without further differentiation. The majority of permanent HL was mild (78% mild vs. 13% moderate vs. 9% profound). The rate of spontaneous MEE clearance was rather low (29%) leading to early surgical intervention in 36 children. The profile of the risk factors for hearing impairment was similar to that of newborns with failure in both, TEOAE and AABR; however, there was a stronger association between the presence of risk factors and the incidence of HL (relative risk 1.55 vs. 1.06; odds ratio 3.61 vs. 1.80). CONCLUSION: In newborns, the discordance between a "refer" in TEOAE and a "pass" in AABR screening is associated with a substantial prevalence of hearing impairment at follow-up, especially in the presence of risk factors.

Clinical and molecular characteristics of two Italian kindreds with hypoparathyroidism, deafness and renal dysplasia (HDR) syndrome.

PURPOSE: Hypoparathyroidism, deafness, and renal dysplasia (HDR) syndrome, also known as Barakat syndrome, is a rare autosomal dominant disease characterized by the triad of hypoparathyroidism, deafness, and renal abnormalities. The disorder is caused by the haploinsufficiency of the zinc finger transcription factor GATA3 and exhibits a great clinical variability with an age-dependent penetrance of each feature. We report two unrelated kindreds whose probands were referred to our outpatient clinic for further evaluation of hypoparathyroidism. METHODS: The proband of family 1, a 17-year-old boy, was referred for severe hypocalcemia (5.9 mg/dL) incidentally detected at routine blood tests. Abdomen ultrasound showed bilateral renal cysts. The audiometric evaluation revealed the presence of bilateral moderate hearing loss although the patient could communicate without any problem. Conversely, the proband of family 2, a 19-year-old man, had severe symptomatic hypocalcemia complicated by epileptic seizure at the age of 14 years; his past medical history was remarkable for right nephrectomy at the age of 4 months due to multicystic renal disease and bilateral hearing loss diagnosed at the age of 18 years. RESULTS: Based on clinical, biochemical, and radiologic data, HDR syndrome was suspected and genetic analysis of the GATA3 gene revealed the presence of two pathogenetic variants in exon 3, c.404dupC and c.431dupG, in the proband of family 1 and 2, respectively. CONCLUSION: HDR syndrome is a rare cause of hypoparathyroidism and must be excluded in all patients with apparently idiopathic hypoparathyroidism. A correct diagnosis is of great importance for early detection of other HDR-related features and genetic counseling.

Congenital Cytomegalovirus-Associated Sensorineural Hearing Loss in Children: Identification Following Universal Newborn Hearing Screening, Effect of Antiviral Treatment, and Long-Term Hearing Outcomes.

OBJECTIVES: Congenital cytomegalovirus (cCMV) is the most common cause of nongenetic sensorineural hearing loss (SNHL) in children. We examined the longitudinal hearing outcomes of children with cCMV in relation to their newborn hearing screening findings, and their use of antiviral therapy. DESIGN: The study was based on a retrospective chart review using a database of pediatric patients (N = 445) seen at the University of Minnesota Lions clinic. Chart review identified infants with cCMV, and records were reviewed for information about universal newborn hearing screen (UNHS) results, the clinical course of SNHL, and the use of antiviral therapy. RESULTS: A total of 44 children were identified with cCMV. In this group, 33 (75%) had SNHL of varying degree and age at onset. Notably, 17 (39%) children passed UNHS bilaterally. Of those children, 6 (35%) ultimately acquired bilateral or unilateral SNHL, detected at a mean age of 20 months (median age, 12 months). Five out of 10 children (50%) that did not pass UNHS in one ear acquired late-onset hearing loss in the contralateral ear, identified at a mean age of 24 months (median age, 4 months). Eleven (25%) children passed UNHS bilaterally and continued to demonstrate normal hearing in both ears at their most recent follow-up visit at a mean age of 19 months (SD, 18 months). Of the 33 children with cCMV and SNHL, 18 (55%) received antiviral medication (ganciclovir and/or valganciclovir). While, on average, both treated and untreated ears experienced a progression of hearing loss over time, the group that received antiviral treatment experienced less overall hearing change compared with the untreated group (baseline-adjusted expected mean difference, -10.5 dB; 95% confidence interval, -28.1 to 7.2 dB). CONCLUSIONS: Among children with cCMV included in this study who passed UNHS in both ears, 35% demonstrated delayed-onset SNHL. Notably, of those children who referred unilaterally, 50% later demonstrated SNHL in the contralateral ear. These findings have implications for audiological monitoring, and potentially antiviral therapy, of children with cCMV. As implementation of universal cCMV screening moves forward, a key aspect of follow-up will be appropriate long-term audiologic monitoring.

Genetic screening of 15 hearing loss variants in 77,647 neonates with clinical follow-up.

BACKGROUND: To analyze the genotype distribution and frequency of hearing loss genes in newborn population and evaluate the clinical value of genetic screening policy in China. METHODS: Genetic screening for hearing loss was offered to 84,029 neonates between March 2019 and December 2021, of whom 77,647 newborns accepted the screening program with one-year follow-up. The genotyping of 15 hot spot variants in GJB2, GJB3, SLC26A4, and MT-RNR1 was performed on microarray platform. RESULTS: A total of 3.05% (2369/77,647) newborns carried at least one genetic hearing loss-associated variant, indicated for early preventive management. The carrier frequency of GJB2 gene was the highest, at 1.48% (1147/77,647), followed by SLC26A4 gene at 1.07% (831/77,647), and GJB3 gene at 0.23% (181/77,647). GJB2 c.235delC variant and SLC26A4 IVS7-2A>G variant were the most common allelic variants with allele frequency of 0.6304% (979/155,294) and 0.3992% (620/155,294), respectively. 10 children are identified as homozygous or compound heterozygous for pathogenic variants (4 in GJB2, 6 in SLC26A4), and 7 of these infants had passed the hearing screening. Following up of the genetically screened newborns revealed that genetic screening detected more hearing-impaired infants than hearing screening alone. Genetic screening helped identify the infants who had passed the initial hearing screening, and reduced time for diagnosis and intervention of hearing aid. In addition, we identified 234 newborns (0.30%, 234/77,647) susceptible to preventable aminoglycoside antibiotic ototoxicity undetectable by hearing screening. CONCLUSION: We performed the largest-scale neonatal carrier screening for hearing loss genes in Southeast China. Our results indicated that genetic screening is an important complementation to conventional hearing screening. Our practice and experience may facilitate the application and development of neonatal genetic screening policy in mainland China.

Arachnoid Cyst of the Cerebellopontine Angle: A Systematic Literature Review.

OBJECTIVE: The role of surgical management of arachnoid cyst (AC) of the cerebellopontine angle (CPA) is uncertain. This topic has remained controversial with varying contradictory recommendations in the literature, which is limited to mostly case reports. We aimed to provide a comprehensive summary and analysis of symptoms, operative techniques, outcomes, and recurrence of all available surgical cases of AC of the CPA to date. METHODS: A systematic literature search was performed in May 2022 querying several scientific databases. Inclusion criteria specified all studies and case reports of patients with AC located at the CPA for which any relevant surgical procedures were performed. RESULTS: A total of 55 patients from the literature and 5 treated at our institution were included. Mean patient age was 29 years (range, 0.08-79 years), with nearly twice (1.7×) as many female as male patients (37 female, 22 male). Headaches (35%), hearing loss (30%), vertigo (22%), and ataxia (22%) were the most common presentations. Following surgery, 95% experienced symptom improvement, with complete resolution in 64%. Of patients with hearing loss, 44% reported a return to normal. The rate of mortality was 1.69%, and 10% of tumors recurred (mean follow-up 2.3 years [range, 0-15 years]. CONCLUSIONS: Symptomatic AC of the CPA is rare. It exhibits a proclivity for females and commonly manifests with headache, hearing loss, vertigo, and ataxia. While careful selection for surgical candidacy is needed and intervention should be reserved for patients with severe symptoms, surgical decompression is an effective tool for symptom alleviation and recovery.

Cochlear Implantation in Children Under 9 Months of Age: Safety and Efficacy.

OBJECTIVE: To assess the safety of cochlear implants (CIs) in children under 9 months of age to better understand expected postoperative complication rates, and to provide a preliminary look at efficacy. STUDY DESIGN: Single-center retrospective review. SETTING: Tertiary referral center. PATIENTS: Children 5 to 8 months of age who received a CI between 2011 and 2021. INTERVENTIONS: Therapeutic-CI. MAIN OUTCOME MEASURES: The primary outcome was 6-month postoperative complication rate. Secondary outcomes included length of stay, device explantation/reimplantation, rehabilitation supports, and hearing and language outcomes. Complications of children implanted under than 9 months of age was compared with a cohort of children implanted 9 to 18 months of age between the years 2011 and 2016 using a chi-squared test ( p < 0.05). RESULTS: One hundred six children under 9 months of age were implanted (204 CIs) at a mean age of 6.6 months (range: 5-8). Postoperative complications occurred in 28 patients (26%) and were often minor. There were no mortalities. There was no statistically significant difference in complications, including reimplantation rates, between patients implanted under 9 months of age and those implanted 9 to 18 months of age. Speech discrimination outcomes were excellent, and mean spoken language outcomes were near normative for typically developing children. CONCLUSIONS: Cochlear implantation can be a safe and effective treatment option for children 5 to 8 months of age. Early hearing screening and referral for infants to receive appropriate intervention will continue to play a critical role in optimizing speech and language outcomes.

Postmeningitic pediatric hearing loss from non-type b Haemophilus influenzae.

BACKGROUND: Postmeningitic hearing loss from Haemophilus influenzae (H. influenzae) is increasingly due to encapsulated serotypes other than type b (Hib) and nontypeable strains (collectively, nHiB H. influenzae). Pediatric hearing loss after nHib H. influenzae meningitis remains poorly described. METHODS: Retrospecive case series of nHiB H. influenzae meningitis cases identified from a microbiologic database at Children's Hospital Colorado from 2000 to 2020. Literature regarding nHiB H. influenzae and H. influenzae postmeningitic hearing loss was also reviewed. RESULTS: Eleven cases of nHib H. influenzae meningitis (median age 15.9 months) were identified due to serotype f (36 %), serotype a (27 %), and nontypable strains (36 %). Seven (64 %) patients were male, 55 % were white and 18 % were Hispanic or Latino. Hearing loss was initially identified in 4 children (40 %), with two patients with moderate conductive hearing loss (CHL) and one child with unilateral moderate sensorineural (SNHL) hearing loss patients recovering normal hearing. One patient with bilateral profound sensorineural hearing loss and associated labyrinthitis ossificans required cochlear implantation. All children (4) with identified hearing loss were noted to have additional intracranial sequelae, which included empyema (2), sinus thrombosis (2), and seizures (2). Of patients receiving steroids, 25 % had hearing loss on initial testing, compared to 66 % of those who did not receive steroids. CONCLUSIONS: nHib H. influenzae can cause both transient and permanent postmeningitic hearing loss. Steroids may offer otoprotection in nHib H. influenzae meningitis similar to Hib meningitis. Given the limited literature, further study is needed to better characterize hearing outcomes after nHib H. influenzae meningitis.