Permanent Hearing Loss In Children Research Articles

Impaired AIF-CHCHD4 interaction and mitochondrial calcium overload contribute to auditory neuropathy spectrum disorder in patient-iPSC-derived neurons with AIFM1 variant

Auditory neuropathy spectrum disorder (ANSD) is a hearing impairment caused by dysfunction of inner hair cells, ribbon synapses, spiral ganglion neurons and/or the auditory nerve itself. Approximately 1/7000 newborns have abnormal auditory nerve function, accounting for 10%-14% of cases of permanent hearing loss in children. Although we previously identified the AIFM1 c.1265 G > A variant to be associated with ANSD, the mechanism by which ANSD is associated with AIFM1 is poorly understood. We generated induced pluripotent stem cells (iPSCs) from peripheral blood mononuclear cells (PBMCs) via nucleofection with episomal plasmids. The patient-specific iPSCs were edited via CRISPR/Cas9 technology to generate gene-corrected isogenic iPSCs. These iPSCs were further differentiated into neurons via neural stem cells (NSCs). The pathogenic mechanism was explored in these neurons. In patient cells (PBMCs, iPSCs, and neurons), the AIFM1 c.1265 G > A variant caused a novel splicing variant (c.1267-1305del), resulting in AIF p.R422Q and p.423-435del proteins, which impaired AIF dimerization. Such impaired AIF dimerization then weakened the interaction between AIF and coiled-coil-helix-coiled-coil-helix domain-containing protein 4 (CHCHD4). On the one hand, the mitochondrial import of ETC complex subunits was inhibited, subsequently leading to an increased ADP/ATP ratio and elevated ROS levels. On the other hand, MICU1-MICU2 heterodimerization was impaired, leading to mCa2+ overload. Calpain was activated by mCa2+ and subsequently cleaved AIF for its translocation into the nucleus, ultimately resulting in caspase-independent apoptosis. Interestingly, correction of the AIFM1 variant significantly restored the structure and function of AIF, further improving the physiological state of patient-specific iPSC-derived neurons. This study demonstrates that the AIFM1 variant is one of the molecular bases of ANSD. Mitochondrial dysfunction, especially mCa2+ overload, plays a prominent role in ANSD associated with AIFM1. Our findings help elucidate the mechanism of ANSD and may lead to the provision of novel therapies.

Infezione congenita da citomegalovirus e ipoacusia

Background - Cytomegalovirus (CMV) infection is the most common of congenital infections, with a prevalence of 0.3-1.2% in industrialized countries and is the most frequent non-genetic cause of permanent hearing loss in children, with an incidence ranging from 0.2 to 2%. Since there is no antenatal therapy or vaccine against CMV and since many patients with congenital CMV (cCMV) do not experience sequelae even in the absence of specific therapy, a universal screening programme has not been established. Current protocols provide test for the detection of cCMV in case of failure at newborn hearing screening. Aim - This article aims to analyze the pros and cons of the different screening approaches for cCMV, through an overview of the topic based on the most recent literature. Materials and Methods - The recent national and international literature on cCMV screening has been examined through a narrative review. Results - As part of the screening and early identification programmes for neonatal hearing loss, current procedures include a search for cCMV on urine or saliva within 3 weeks of life, following a positive result (Refer) at newborn audiological screening. This approach enables to recognize cCMV infection in newborns suffering from isolated hearing loss, which is already present at birth, however it does not allow cases of CMV-related hearing loss occurring in the postnatal period or late in childhood to be recognized. A universal newborn cCMV screening, in conjunction with audiological screening, would have the advantage of identifying all infants infected with cCMV, including 10%-15% of asymptomatic conditions at birth who may develop late hearing loss. One of the major obstacles to the establishment of universal cCMV screening is the unknown cost of its application and a clear understanding of the sensitivity and specificity of the cCMV test. Conclusions - Strategies are needed to identify children with congenital CMV infection at risk for developing late-onset hearing loss. A universal newborn screening to ensure timely recognition of children with cCMV, close audiological surveillance and possible early treatment at the onset of the first hearing symptoms should be provided.

Chronic suppurative otitis media causes macrophage-associated sensorineural hearing loss

BackgroundChronic suppurative otitis media (CSOM) is the most common cause of permanent hearing loss in children in the developing world. A large component of the permanent hearing loss is sensory in nature and our understanding of the mechanism of this has so far been limited to post-mortem human specimens or acute infection models that are not representative of human CSOM. In this report, we assess cochlear injury in a validated Pseudomonas aeruginosa (PA) CSOM mouse model.MethodsWe generated persisters (PCs) and inoculated them into the mouse middle ear cavity. We tracked infection with IVIS and detected PA using RT-PCR. We assessed cochlear damage and innate immunity by Immunohistochemistry. Finally, we evaluated cytokines with multiplex assay and quantitative real-time PCR.ResultsWe observed outer hair cell (OHC) loss predominantly in the basal turn of the cochlear at 14 days after bacterial inoculation. Macrophages, not neutrophils are the major immune cells in the cochlea in CSOM displaying increased numbers and a distribution correlated with the observed cochlear injury. The progression of the morphological changes suggests a transition from monocytes into tissue macrophages following infection. We also show that PA do not enter the cochlea and live bacteria are required for cochlear injury. We characterized cytokine activity in the CSOM cochlea.ConclusionsTaken together, this data shows a critical role for macrophages in CSOM-mediated sensorineural hearing loss (SNHL).

Assessment of hearing in newborns with hyperbilirubinemia using otoacoustic emmisions and brainstem evoked response audiometry

The early linguistic age when language and speech skills develop is between 3-5 years. Speech is essential for communication and hence an important part of a normal life. Permanent hearing loss in children remains a public health problem and hence its prevention is an utmost important public health programme -The National Programme for Prevention and Control of Deafness. Neonatal hyperbilirubinemia is seen in about 2.3% of newborns. It is a common adverse effect that puts neonates at a high risk for hearing impairment. Bilirubin encephalopathy is due to raised unconjugated (indirect) bilirubin. Unconjugated bilirubin crosses the blood-brain barrier and, because it is lipid soluble, it penetrates neuronal and glial membranes too. Most of the tests used for assessing the hearing status in an individual require the cooperation of the subjects which is obviously not found in infants. Therefore, objective tests not requiring the infant’s cooperation can be used effectively. This study uses oto acoustic emissions (OAE) test as a screening test, and brain stem evoked response audiometry test (BERA) as a definite test for assessment of hearing in newborns with hyperbilirubinemia. To assess hearing impairment in newborns with hyperbilirubinemia.

Risk factors for hearing loss in children: a systematic literature review and meta-analysis protocol

BackgroundHearing loss in newborns and children is a public health concern, due to high prevalence and negative effects on their development. Early detection and intervention of childhood hearing loss may mitigate these negative effects. Population-based newborn hearing screening programs have been established worldwide to identify children at risk for congenital hearing loss and to follow children at risk for late onset or progressive hearing loss. This article presents the protocol for a systematic review that aims to review the risk factors associated with permanent hearing loss in children, including congenital, early, or late onset. Risk factors associated with progressive hearing loss will be investigated as a secondary aim.MethodsScientific literature from the following databases will be investigated: MEDLINE, Ovid MEDLINE(R) Daily and Ovid MEDLINE(R), Embase, and CINAHL. The primary outcome is a permanent bilateral or unilateral hearing loss with congenital onset or onset during childhood (birth to 18 years). The secondary outcome is progressive hearing loss. Studies must report data on risk factors associated with permanent hearing loss; risk factors may be present at birth or later and result in immediate or delayed hearing loss. Randomized controlled trials, quasi-experimental studies, nonrandomized comparative and non-comparative studies, and case series will be included. The risk of bias will be assessed using the Qualitative Assessment Tool for Quantitative Studies (McMaster University). If aggregation of data is possible for a subsection of studies, we will pool data using meta-analysis techniques. If aggregation of data is not possible, a qualitative synthesis will be presented. We will assess the quality and strength of the overall body of evidence using the Grading of Recommendations Assessment, Development and Evaluation (GRADE). The systematic review follows the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) recommendations.DiscussionThe resulting information will inform the update of a provincial audiological surveillance protocol for the Ontario Infant Hearing Program and will be applicable to early hearing detection and intervention (EHDI) programs worldwide.Systematic review registrationWe have registered the protocol in the International Prospective Register of Systematic Reviews (PROSPERO), registration number CRD42018104121.

Current Perspectives on Minimal and Mild Permanent Hearing Loss in Children

Over the last several decades, audiologists, speech-language pathologists (SLPs), and educators have learned a great deal about the impact of permanent minimal/ mild hearing loss (MMHL) on children. Once considered a problem that could be easily managed by preferential positioning of the listener relative to the talker of interest or, in the case of school-age children, preferential classroom seating, research has accumulated over the last several decades concluding that children with MMHL are at risk of significant educational and psychosocial challenges. Despite the term minimal, no longer is a MMHL viewed as being inconsequential. The following sections will describe our current knowledge about MMHL in children and what we have left to discover.

Pediatric Audiology in North America: Current Clinical Practice and How It Relates to the American Academy of Audiology Pediatric Amplification Guideline.

There is broad consensus that screening and diagnosis of permanent hearing loss in children must be embedded within a comprehensive, evidence-based, family-centered intervention program. Clinical practice guidelines (CPGs) for pediatric hearing assessment and hearing aid verification aim to reduce variability in practice and increase the use of effective evidence-based diagnostic and treatment options so that optimal outcomes may be achieved. To be of value, guidelines must be translated and implemented into practice and ongoing monitoring of their use in practice should occur. This paper provides the results of two studies that aim to examine current pediatric audiology and amplification practice in North America. A concurrent embedded mixed methods design was used. An electronic survey was distributed to North American audiologists who delivered pediatric audiology services with 350 audiologists participating in study 1 and 63 audiologists participating in study 2. A quantitative approach was the predominant method of data collection. Respondents were prompted to provide additional qualitative text and detail regarding their quantitative response choice. This qualitative text was used during the analysis phase and combined with quantitative results to assist understanding of respondents' knowledge, skills, and barriers/facilitators to implement best practice in pediatric amplification. Approximately 70% of audiologists reported using best-practice protocols for pediatric hearing aid fitting. Despite widespread knowledge and increased use of CPGs over the last 18 yrs, results of these studies show that variation in practice patterns continue to exist. Several examples of implementation challenges are discussed with recommendations provided. In order for audiologists working with children who are deaf or hard of hearing and their families to achieve the principles of family-centered early intervention, practice guidelines must continue to be developed, disseminated, and translated as they have a positive impact on the services provided. Researchers and clinical audiologists who deliver services must continue to collaborate to understand the "how" and "why" of implementing guidelines into practice and to identify the barriers/facilitators encountered in trying to do so.

Sensorineural hearing loss in children: The association with Apgar score. A registry-based study of 392 371 children in Norway

ObjectivesThe causes of congenital permanent hearing loss in children are insufficiently understood. We studied the association of Apgar score 5min after birth with sensorineural hearing loss diagnosed before the age of 5years. MethodsWe performed an epidemiological cohort study with data obtained by linkage between The Medical Birth Registry of Norway and the Norwegian County Registry of Children with Hearing Loss. Cases were 327 children born in Norway during the period 1978–1998 with sensorineural hearing loss. Controls were all children in Norway without sensorineural hearing loss born in the same counties and during the same period as the cases (n=392044). The associations of Apgar score 5min after birth with sensorineural hearing loss were estimated as odds ratios (OR) with 95% confidence intervals (CI) by applying logistic regression analyses. ResultsAmong children with sensorineural hearing loss 0.9% (3/327) had Apgar score <3, whereas that was true for 0.1% (304/392044) of children without hearing loss (p=0.001, chi square test). The aOR for sensorineural hearing loss was 7.5 [95% CI 2.3–, 24.2] comparing Apgar score <3 to Apgar score 10, after adjustment for birthweight and concurrent birth defects. Most children with sensorineural hearing loss (90%) had Apgar score >8 five minutes after birth. ConclusionsLow Apgar score was associated with childhood sensorineural hearing loss. However, most children with sensorineural hearing loss, had Apgar score >8.

Age of identification of hearing impairment in Mumbai—A trend analysis

Implementation of Universal Newborn Hearing Screening (UNHS) has led to lowering the age of identification of congenital hearing loss in children. In the absence of UNHS in Mumbai (India), it is pertinent to establish a data base on the age of identification of permanent hearing loss in children to facilitate affirmative action. Objective To study the trend in age of identification (AOI) of hearing impairment in children studying in special schools. Methods This retrospective study was a survey conducted on a convenient sample. The authentic data about date of birth and age of identification (AOI) of 510 children were collected through parental interview, and scrutiny of documents like birth certificates, first audiological report maintained in special schools/institutes/hospitals. Results Time series analysis of the data concluded that from 1989 to 2008, AOI has reduced by 9.59 months. AOI has not reached one year even by 2008 and is much below the target of three months of age as per the recommendation of Joint Committee on Infant Hearing (2007). Conclusion In absence of Universal Newborn Hearing Screening (UNHS) in Mumbai (India) the present efforts do not seem to be enough in lowering the age of identification of hearing loss and policy decision is warranted.

German registry for hearing loss in children: results after 4 years

Since April 1996 the German Registry for Hearing Loss in Children has been collecting and recording various data on permanent hearing loss in children. Up to now, the data of 3882 children have been gathered nation-wide. A particularly remarkable aspect of data so far collected is the alarmingly high age at the time of diagnosis (mild hearing loss is on average only diagnosed at 6; 2 years, moderate loss at 4; 4 years, severe at 2; 5 years and profound with 1; 9 years). The German Registry for Hearing Loss in Children provides the first reliable source of epidemiological data on permanent hearing loss in children in Germany. A constantly growing number of currently 112 co-operating partners takes part in the data acquisition. The periodical reports of results to the co-operating partners and the first publications have heightened the awareness of the importance of early diagnosis and therapy. A minimum standard for patient history was established by the primary examination report. Thus, an important contribution has been made to the prevention of avoidable secondary damage.

Is diagnosis of persistent pediatric hearing loss still made too late?

Since 1994, the German Registry for hearing Loss in Children has registered data of 1500 children and by now can present results concerning the age at diagnosis of permanent hearing loss in children in Germany. The mean age at diagnosis is still very high. There is a strong correlation between age at diagnosis and degree of hearing loss, i.e., severe and profound hearing loss, is diagnosed distinctly earlier than mild and moderate hearing loss. On average, mild hearing loss is diagnosed with 6.2 years, moderate h.l. with 4.4 years, severe hearing loss with 2.5 years and profound hearing loss with 1.9 years. This corresponds with the results of regional German studies. At least regionally, in other European countries the age at diagnosis is known to be distinctly lower. In 36% of the children registered in Germany the delay between first suspicion and diagnosis of permanent hearing loss is 1 year or more.