Preparing for Otoferlin gene therapy trials: A survey of NHS Paediatric Audiology and Cochlear Implant services on diagnosis and management of Auditory Neuropathy Spectrum Disorder.

OBJECTIVES: Gene therapy for monogenic hearing loss is on the horizon. The first trials in patients with Auditory Neuropathy Spectrum Disorder (ANSD) due to pathogenic variants in the Otoferlin (OTOF) gene will open this year. In the UK, the new NHS Genomic Medicine Service (GMS) offers genetic testing in each child diagnosed with congenital or early onset sensorineural hearing loss. This survey study aims to map preexisting clinical pathways for the diagnosis and management of children with ANSD and identify opportunities for improvement in early identification of OTOF- related ANSD. METHODS: A Google form with 24 questions in English covering the ANSD clinical pathway was developed with clinicians involved in the diagnosis and management ANSD. The survey was disseminated via email to all Lead clinicians of NHS Tertiary Paediatric Audiology and Cochlear Implant Services within the UK. RESULTS: Data was received from 27 (34 %) NHS Tertiary Paediatric Audiology Services and 8 (n = 57 %) Paediatric Cochlear Implant Services. Services follow existing national guidance and provide multidisciplinary care with structured patient pathways for referral, diagnosis, and management of children with ANSD and multidisciplinary input throughout. Clinicians are aware of the genetic causes of ANSD and new processes for genetic testing, but do not uniformly refer children with ANSD for testing for OTOF pathogenic variants. As such, they had difficulty estimating numbers of children with OTOF pathogenic variants under their care. CONCLUSION: Those results highlight the urgency of implementing hearing gene panel sequencing for all children with ANSD to provide opportunities for early diagnosis and candidacy for OTOF gene therapy trials.

[Auditory neuropathy and prematurity: modern view of the issue (literature review)]. / Auditornaya neiropatiya i nedonoshennost': sovremennyi vzglyad na problemu (obzor literatury).

Auditory neuropathy spectrum disorder (ANSD) is a specific auditory disorder caused by dysfunction of periphery part of the auditory system, in which the function of the outer hair cells is preserved, but the afferent input at the cochlear level suffers due to the pathology of the inner hair cells, neurons of the spiral ganglion and/or the auditory nerve, as well as synaptic contact between them. As a result, a specific condition is formed, in which a patient's otoacoustic emissions and/or cochlear microphonics are present, auditory brainstem responses are abnormal or absent, the discrepancy between the hearing level and the electrophysiological data, poor speech perception which may not correlate with the hearing thresholds. ANSD is a multifactorial disease. One of the main risk factors is perinatal pathology and, in particular, prematurity. The possible factors associated with prematurity that provoke the onset of the disease, features of the pathogenesis, clinical and audiological peculiarities of ANSD in premature infants, contemporary approaches to the habilitation of such patients are discussed in the article. The necessity of an individual, patient-oriented approach to the treatment of premature infants with ANSD is substantiated; such an approach should be based both on the genesis of the disorder, taking into account possible points of lesion in the auditory system, and the developmental peculiarities of a premature baby considering the presence of concomitant diseases associated with prematurity. In the article attention is focused on the main directions of habilitation work with such children, including a multidisciplinary approach, regular careful monitoring of the auditory, speech and language skills, intensive psychological and speech therapist support, the choice of an adequate way of intervention and its improvement as necessary.

Characterization of an induced pluripotent stem cell line (UMi040-A) bearing an auditory neuropathy spectrum disorder-associated variant in TMEM43.

Hearing loss is one of the most common sensory disorders. TMEM43 is expressed in cochlear glia-like supporting cells (GLSs) and is known to be associated with late-onset auditory neuropathy spectrum disorder (ANSD) and progressive hearing loss. Here, we describe the derivation of an induced pluripotent stem cell (iPSC) line from a patient lymphoblastoid cell line (LCL) carrying a single heterozygous nonsense variant (p.Arg372Ter (c.1114C > T)) in TMEM43 that leads to a truncated protein lacking the 4th transmembrane domain. This cell line can serve as a tool for disease modelling and development of therapeutic approaches to restore inner ear function.

Diagnosis of Auditory Neuropathy Spectrum Disorder in the Neonatal Intensive Care Unit Population.

OBJECTIVE: To determine the incidence of auditory neuropathy spectrum disorder (ANSD) and its risk factors among the neonatal intensive care unit (NICU) population from 2009 to 2018 in the Pediatric Health Information System database. STUDY DESIGN: Retrospective national database review. SETTING: Population-based study. METHODS: The Pediatric Health Information System database was queried to identify patients ≤18 years old with NICU admission and ANSD diagnosis. Patient demographics, jaundice diagnosis, use of mechanical ventilation, extracorporeal membrane oxygenation, furosemide, and/or aminoglycosides were extracted. Multivariable linear regression was used to assess trends in incidence. Chi-square analysis was used to assess differences between patients with and without ANSD. Logistic regression was used to assess factors associated with ANSD. RESULTS: From 2009 to 2018, there was an increase in (1) NICU admissions from 14,079 to 24,851 (P < .001), (2) total ANSD diagnoses from 92 to 1847 (P = .001), and (3) annual total number of patients with ANSD and NICU admission increased from 4 to 16 (P = .005). There was strong correlation between the increases in total number of NICU admissions and total ANSD diagnoses over time (R = 0.76). The average ANSD incidence was 0.052% with no statistically significant change over 10 years. When compared with all NICU admissions, children with ANSD had a higher association with use of furosemide (P < .001) and ventilator (P < .001). CONCLUSION: Despite a statistically significant increase in NICU admissions and total ANSD diagnosis, the incidence of ANSD in the NICU population has not increased from 2009 to 2018. Furosemide and mechanical ventilator use were associated with increased likelihood of ANSD.

Prevalence, behavioural, and management outcomes of infants with auditory neuropathy spectrum disorder.

AIM: To provide an overview of electrophysiological and behavioural outcomes from a large UK centres data set on children diagnosed with auditory neuropathy (ANSD) between 2002 and March 2018. METHOD: A systematic audit was undertaken, collating the electrophysiological data from auditory brainstem response (ABR) follow-up, risk factors, and later behavioural results/management. These were then compared to look for trends between groups. The study sample consisted of 118 925 infants born, with 46 (0.039%, 0.39 per 1000 births) being diagnosed with congenital ANSD (39 bilateral, seven unilateral). RESULTS: Twenty-nine per cent of ears with ANSD had short latency components on ABR testing. Forty-four per cent of ears with present cochlear microphonics but absent transient-evoked otoacoustic emissions (TE-OAE) and no ABR went on to have profound behavioural hearing threshold levels. All but one child went on to show a hearing loss on behavioural testing. ANSD was not confined to the population from neonatal intensive care units: there were three bilateral and five unilateral cases in the typically developing infant population. INTERPRETATION: The incidence of ANSD is higher in this sample than that reported previously in the literature. Children who had cochlear microphonics with absent ABR and absent TE-OAE had significantly worse later behavioural outcomes than other patterns of electrophysiological results.

Perception of temporally enhanced and hearing aid processed speech in children with late-onset Auditory Neuropathy Spectrum Disorder.

OBJECTIVE: To investigate phrase perception and subjective quality preference of temporal enhancement-based speech processing strategies: Deep-band modulation and Stretching, and hearing aid processed speech in adolescents with late-onset Auditory Neuropathy. METHODS: 15 participants with Auditory Neuropathy Spectrum Disorder were involved. Speech perception was assessed using unprocessed, deep-band modulated, stretched, and hearing aid processed conditions. Subjective preference was also assessed using the pair-wise comparison technique. Gap detection test was done using broadband noise to investigate the possible correlation with benefit from processing strategies. RESULTS: As a group, no significant benefits were found with processed speech. Clinically relevant trends emerged on subdividing the group into good and poor performers. Deep-band modulation processing was significantly better than unprocessed speech in those with poorer speech recognition abilities. There was a trend for those with poorer temporal processing abilities to benefit more with deep-band modulation processing. In those with relatively better speech recognition abilities, processing showed no benefit, and hearing aid processed speech was inferior to unprocessed speech. Quality-wise, the unprocessed speech was preferred by all the participants. Among the processed conditions, deep-band modulation was preferred by most, followed by stretching and hearing aid processed speech. CONCLUSION: Results indicate that temporal enhancement strategies may be beneficial for a subset of individuals with ANSD with poorer temporal processing and speech perception abilities. However, processing strategies need to take into account the quality aspect and not just intelligibility.

Central auditory maturation and behavioral outcomes after cochlear implantation in prelingual auditory neuropathy spectrum disorder related to OTOF variants (DFNB9): Lessons from pilot study.

The cortical auditory evoked potential (CAEP)-based P1 component acts as a biomarker for cochlear implantation (CI) outcomes in children with auditory neuropathy spectrum disorder (ANSD). To date, early intervention primarily before the age of two years and six months of CI usage is necessary and sufficient to achieve age-appropriate cortical maturation and good prognosis. However, varying degrees of neural dyssynchrony, resulting from the etiological heterogeneity of ANSD, may preclude uniform application of this hypothesis to ensure auditory cortical maturation. Thus, a focused evaluation of those carrying OTOF variants, which may be the salient molecular etiology of prelingual ANSD, would circumvent the issue of heterogeneity. Here, we sought to provide a much better understanding of the brain perspectives (i.e., P1 maturation) in OTOF-associated ANSD subjects and set the stage for an optimal strategy to enhance language development. We conducted a preliminary study comprising 10 subjects diagnosed with OTOF-related ANSD who underwent CI by a single surgeon and subsequently underwent measurements of the P1 component. We observed that DFNB9 subjects who received CI after 2 years of age exhibited "absent" or "anomalous" P1 components that correspond to delayed language development. However, timely implantation, as early as 12 months of age per se, might be insufficient to achieve age-appropriate cortical maturation of DFNB9 in cases with six to seven months of device use. This suggests the importance of sustained rehabilitation in DFNB9 than in other etiologies. Indeed, an additional follow-up study showed that a reduction in P1 latency was linked to an improvement in auditory performance. Collectively, our results suggest that central auditory maturation and successful outcome of CI in DFNB9 may have more demanding requirements, that is, earlier implantation and more sustained rehabilitation. We believe that the current study opens a new path toward genome-based neuroimaging in the field of hearing research.

Mitochondrial Dysfunction and Therapeutic Targets in Auditory Neuropathy.

Sensorineural hearing loss (SNHL) becomes an inevitable worldwide public health issue, and deafness treatment is urgently imperative; yet their current curative therapy is limited. Auditory neuropathies (AN) were proved to play a substantial role in SNHL recently, and spiral ganglion neuron (SGN) dysfunction is a dominant pathogenesis of AN. Auditory pathway is a high energy consumption system, and SGNs required sufficient mitochondria. Mitochondria are known treatment target of SNHL, but mitochondrion mechanism and pathology in SGNs are not valued. Mitochondrial dysfunction and pharmacological therapy were studied in neurodegeneration, providing new insights in mitochondrion-targeted treatment of AN. In this review, we summarized mitochondrial biological functions related to SGNs and discussed interaction between mitochondrial dysfunction and AN, as well as existing mitochondrion treatment for SNHL. Pharmaceutical exploration to protect mitochondrion dysfunction is a feasible and effective therapeutics for AN.

The limitation of risk factors as a means of prognostication in auditory neuropathy spectrum disorder of perinatal onset.

OBJECTIVE: The management of hearing loss due to auditory neuropathy spectrum disorder (ANSD) in neonates and infants is challenging because speech and language development prognosis cannot be directly inferred from early audiometric hearing thresholds. Consequently, appropriate intervention with hearing aids or cochlear implantation (CI) can be delayed. Our objective was to determine whether any features of patient history could be used to identify CI candidates with ANSD at an earlier age. METHOD: A database was maintained over 11 years to monitor cases of perinatal onset ANSD. Risk factors associated with the perinatal time period considered pertinent to hearing outcomes were assessed, including prematurity, birth weight, APGAR score, ototoxic drugs, and hyperbilirubinemia. Children with cochlear nerve aplasia and genetic mutations were excluded. Hearing outcome was determined according to mode of auditory rehabilitation beyond 30 months of age: A) no hearing device; B) hearing aid; C) CI. RESULTS: Of twenty-eight children with ANSD, nine (32%) had behavioural thresholds and language development sufficient to require no assistive device, 9 (32%) were fitted with hearing aids and 10 (36%) had CIs. The average age at CI (3.45 ± 2.07 years) was significantly older than the age at CI of other children in our program with prelingual hearing loss (2.05 ± 1.14 years; p = 0.01 Mann-Witney U Test). None of the putative risk factors for hearing loss reliably predicted the need for subsequent CI. CONCLUSION: The small sample size in this study is sufficient to confirm that clinical history alone does not reliably predict which young children with perinatal-onset ANSD will require CI. Consequently, timing for CI remains delayed in these children, potentially affecting speech and language outcome. The pathogenesis of perinatal-onset ANSD remains undetermined and novel means of assessment are required for prognostication in affected infants.

Long-term treatment outcomes in children with auditory neuropathy spectrum disorder (ANSD).

INTRODUCTION: The present article shows long-term results in the hearing and speech development of children with auditory neuropathy spectrum disorder (ANSD). Some children were followed up for nearly 20 years, monitoring their progress through childhood into adulthood. METHODS: This retrospective study examined data from 10 children who were diagnosed and treated at our tertiary referral center. All children were provided with hearing aids and/or cochlear implants. The children's hearing and speech development and their social and educational development were evaluated. RESULTS: Seven children were provided with cochlear implants on both sides; three children, one of which had single-sided deafness, received hearing aids. All children with cochlear implants on both sides used their devices full-time. Speech perception ranged between 100% and 0% on one side. Five children attended a school for the hearing impaired; four children attended a regular school. Four children attended vocational training. CONCLUSIONS: At present, there is a lack of literature on the long-term outcomes of treatment in children with ANSD. The data presented show that the hearing and speech development in children with ANSD are significantly heterogeneous. Regular school education and social integration of children with ANSD can be achieved with intensive and supportive rehabilitative methods.

Music and psychoacoustic perception abilities in cochlear implant users with auditory neuropathy spectrum disorder.

OBJECTIVE: Auditory neuropathy spectrum disorder (ANSD) is a condition wherein the pre-neural or cochlear outer hair cell activity is intact, but the neural activity in the auditory nerve is disrupted. Cochlear implant (CI) can be beneficial for subjects with ANSD; however, little is known about the music perception and psychoacoustic abilities of CI users with ANSD. Music perception in CI users is a multidimensional and complex ability requiring the contribution of both auditory and nonauditory abilities. Even though auditory abilities lay the foundation, the contribution of patient-related variables such as ANSD may affect the music perception. This study aimed to evaluate the psychoacoustic and music perception abilities of CI recipients with ANSD. STUDY DESIGN: Twelve CI users with ANSD and twelve age- and gendermatched CI users with sensorineural hearing loss (SNHL) were evaluated. Music perception abilities were measured using the Turkish version of the Clinical Assessment of Music Perception (T-CAMP) test. Psychoacoustic abilities were measured using the spectral ripple discrimination (SRD) and temporal modulation transfer function (TMTF) tests. In addition, the age of diagnosis and implantation was recorded. RESULTS: Pitch direction discrimination (PDD), timbre recognition, SRD, and TMTF performance of CI users with ANSD were concordant with those reported in previous studies, and differences between ANSD and SNHL groups were not statistically significant. However, the ANSD group performed poorly compared with SNHL group in melody recognition subtest of T-CAMP, and the difference was statistically significant. CONCLUSION: CI can prove beneficial for patients with ANSD with respect to their music and psychoacoustic abilities, similar to patients with SNHL, except for melody recognition. Recognition of melodies requires both auditory and non-auditory abilities, and ANSD may have an extensive but subtle effect in the life of CI users.

Evaluation and therapy outcome in children with auditory neuropathy spectrum disorder (ANSD).

OBJECTIVES: The aims of the present study are to: describe diagnostic findings in patients with auditory neuropathy spectrum disorder (ANSD); and demonstrate the outcomes of different therapies like hearing aids (HAs) or cochlear implantation. METHODS: 32 children were diagnosed and treated at our tertiary referral center and provided with HAs or cochlear implants (CIs). All of them underwent free-field or pure-tone audiometry. Additionally, otoacoustic emissions (OAEs), impedance measurements, auditory brainstem responses (ABRs), auditory steady-state responses (ASSR), electrocochleography, and cranial magnetic resonance imaging (cMRI) were all performed. Some patients also underwent genetic evaluation. Following suitable provision pediatric audiological tests, psychological developmental diagnostic and speech and language assessments were carried out at regular intervals in all the children. RESULTS: OAEs could initially be recorded in most of the children; 17 had no ABRs. The other eight children had a poor ABR morphology. Most of the children had typical, long-oscillating cochlear microphonics (CMs) in their ABRs, which was also observed in all of those who underwent electrocochleography. Eight children were provided with a HA and 17 received a CI. The functional gain was between 32 and 65 decibel (dB) with HAs and between 32 and 50 dB with CI. A speech discrimination level between 35 and 100% was achieved during open-set monosyllabic word tests in quiet with HA or CI. With the Hochmair-Schulz-Moser (HSM) sentence test at 65 dB SPL (sound pressure level), 75% of the children with a CI achieved a speech discrimination in noise score of at least 60% at a signal to noise ratio (SNR) of 5, and four scored 80% or higher. Most of the children (72%) were full-time users of their devices. All the children with a CI used it on a regular basis. CONCLUSION: Only a few case reports are available in the literature regarding the long-term outcomes of ANSD therapy. The present study reveals satisfactory outcomes with respect to hearing and speech discrimination in children with CIs or HAs. The nearly permanent use of the devices reflects a subjective benefit for the children. Provision with a suitable hearing device depends on audiological results, the speech and language development of an individual child, and any accompanying disorders. Repeated audiological evaluations, interdisciplinary diagnostics, and intensive hearing and speech therapy are essential for adequate rehabilitation of this group of children.

Auditory Neuropathy: Bridging the Gap Between Hearing Aids and Cochlear Implants.

Auditory neuropathy spectrum disorder (ANSD) is a complex and heterogeneous disorder associated with altered neural synchrony with respect to auditory stimuli. Patients have characteristic auditory findings including normal otoacoustic emissions in the setting of abnormal auditory brainstem response. Patients with ANSD have a high incidence of comorbid developmental delay that may impact speech outcomes. Treatment options for ANSD include hearing amplification and cochlear implantation. The article highlights issues and controversies with the diagnosis and treatment of this complex disorder.

ATP1A3 mutations can cause progressive auditory neuropathy: a new gene of auditory synaptopathy.

The etiologies and prevalence of sporadic, postlingual-onset, progressive auditory neuropathy spectrum disorder (ANSD) have rarely been documented. Thus, we aimed to evaluate the prevalence and molecular etiologies of these cases. Three out of 106 sporadic progressive hearing losses turned out to manifest ANSD. Through whole exome sequencing and subsequent bioinformatics analysis, two out of the three were found to share a de novo variant, p.E818K of ATP1A3, which had been reported to cause exclusively CAPOS (cerebellar ataxia, areflexia, pes cavus, optic atrophy, and sensorineural hearing loss) syndrome. However, hearing loss induced by CAPOS has never been characterized to date. Interestingly, the first proband did not manifest any features of CAPOS, except subclinical areflexia; however, the phenotypes of second proband was compatible with that of CAPOS, making this the first reported CAPOS allele in Koreans. This ANSD phenotype was compatible with known expression of ATP1A3 mainly in the synapse between afferent nerve and inner hair cells. Based on this, cochlear implantation (CI) was performed in the first proband, leading to remarkable benefits. Collectively, the de novo ATP1A3 variant can cause postlingual-onset auditory synaptopathy, making this gene a significant contributor to sporadic progressive ANSD and a biomarker ensuring favorable short-term CI outcomes.

The management of pediatric hearing loss caused by auditory neuropathy spectrum disorder.

PURPOSE OF REVIEW: Auditory neuropathy spectrum disorder (ANSD) is a condition in which auditory testing reveals normal otoacoustic emissions, but auditory brainstem testing is abnormal or absent and speech discrimination is poor. This constellation of findings ostensibly suggests that the cochlea is healthy and an abnormality of conduction or processing of sound occurs along the nerve fibers. As more is learned about this condition, it is becoming clear that ANSD describes heterogeneous, distinct clinical entities that must be taken into account when devising treatment modalities. RECENT FINDINGS: Modern auditory testing, genetic testing, and neuroimaging can allow for an accurate understanding of the location of the lesion causing ANSD in the auditory pathway. Contributing causes can include genetic mutations, absent or deficient cochlear nerve, hypoxia and jaundice among others. Hearing aids can be successful in the management of ANSD. Several studies suggest that cochlear implantation can lead to successful hearing outcomes in a subset of this patient population. SUMMARY: Auditory neuropathy spectrum disorder represents a relatively rare but important diagnosis for clinicians. Treatment for this condition includes hearing aids and FM systems in more mild cases, and cochlear implants in severe cases. Cochlear implantation for many patients can lead to a good hearing outcomes but the outcome can vary greatly depending on the underlying etiology of ANSD.

Modiolar ossification in paediatric patients with auditory neuropathy.

OBJECTIVE: To describe our finding of increased ossification of the modiolus in paediatric patients with auditory neuropathy who met criteria for cochlear implantation. METHODS: A retrospective case series with a comparison group at a tertiary referral centre is described. Seven paediatric patients with auditory neuropathy who met criteria for and underwent cochlear implantation were identified. Fifteen paediatric implantees with bilateral profound sensorineural hearing loss were included as the comparison group. All patients underwent pre-operative computed tomography. Attenuation at the modiolus was measured in all subjects by a neuroradiologist blinded to clinical information. RESULTS: Attenuation values in the modiolus in the auditory neuropathy patients (mean ± standard deviation = 796.2 ± 53.0 HU) was statistically significantly higher than in the comparison sensorineural hearing loss patients (267.1 ± 45.6 HU; p < 0.05, t-test). CONCLUSION: Patients with auditory neuropathy who meet criteria for cochlear implantation demonstrate significantly higher modiolar attenuation on computed tomography imaging, consistent with increased ossification at the modiolus.

Gender Differences in Audiological Findings and Hearing Aid Benefit in 255 Individuals with Auditory Neuropathy Spectrum Disorder: A Retrospective Study.

BACKGROUND: There are many studies reported in the literature that have summarized audiological findings and possible rehabilitation in individuals with auditory neuropathy spectrum disorder (ANSD). However, there are very few studies that have attempted to delineate the gender differences in audiological characteristics and hearing aid benefit in individuals with ANSD. PURPOSE: The study aimed to explore the differences between males and females in terms of demographic details, audiogram, speech identification scores, otoacoustic emissions, acoustic reflexes, long latency responses, and hearing aid benefit. RESEARCH DESIGN: A retrospective study. STUDY SAMPLE: A total of 255 individuals diagnosed with ANSD were selected for the study. The study included 137 females and 88 males. DATA COLLECTION AND ANALYSIS: The demographic details, results of diagnostic audiological testing, and hearing aid benefit were analyzed retrospectively. The differences in findings across gender were compared. RESULTS: The study shows that females have a relatively higher degree of hearing loss and that the majority of females show a rising type of audiometric configuration. The study shows that females have poorer speech perception abilities and experience limited benefits from hearing aids compared to males. CONCLUSIONS: The results of the study show that there are gender differences in audiological findings and hearing aid benefits in individuals with ANSD. However, well-controlled prospective studies are essential to confirm the results obtained and to identify the possible mechanisms underlying the gender differences.

Children with Auditory Neuropathy Spectrum Disorder Fitted with Hearing Aids Applying the American Academy of Audiology Pediatric Amplification Guideline: Current Practice and Outcomes.

BACKGROUND: Up to 15% of children with permanent hearing loss (HL) have auditory neuropathy spectrum disorder (ANSD), which involves normal outer hair cell function and disordered afferent neural activity in the auditory nerve or brainstem. Given the varying presentations of ANSD in children, there is a need for more evidence-based research on appropriate clinical interventions for this population. PURPOSE: This study compared the speech production, speech perception, and language outcomes of children with ANSD, who are hard of hearing, to children with similar degrees of mild-to-moderately severe sensorineural hearing loss (SNHL), all of whom were fitted with bilateral hearing aids (HAs) based on the American Academy of Audiology pediatric amplification guidelines. RESEARCH DESIGN: Speech perception and communication outcomes data were gathered in a prospective accelerated longitudinal design, with entry into the study between six mo and seven yr of age. Three sites were involved in participant recruitment: Boys Town National Research Hospital, the University of North Carolina at Chapel Hill, and the University of Iowa. STUDY SAMPLE: The sample consisted of 12 children with ANSD and 22 children with SNHL. The groups were matched based on better-ear pure-tone average, better-ear aided speech intelligibility index, gender, maternal education level, and newborn hearing screening result (i.e., pass or refer). DATA COLLECTION AND ANALYSIS: Children and their families participated in an initial baseline visit, followed by visits twice a year for children <2 yr of age and once a yr for children >2 yr of age. Paired-sample t-tests were used to compare children with ANSD to children with SNHL. RESULTS: Paired t-tests indicated no significant differences between the ANSD and SNHL groups on language and articulation measures. Children with ANSD displayed functional speech perception skills in quiet. Although the number of participants was too small to conduct statistical analyses for speech perception testing, there appeared to be a trend in which the ANSD group performed more poorly in background noise with HAs, compared to the SNHL group. CONCLUSIONS: The American Academy of Audiology Pediatric Amplification Guidelines recommend that children with ANSD receive an HA trial if their behavioral thresholds are sufficiently high enough to impede speech perception at conversational levels. For children with ANSD in the mild-to-severe HL range, the current results support this recommendation, as children with ANSD can achieve functional outcomes similar to peers with SNHL.