Outcome of Preterm Infants With Postnatal Cytomegalovirus Infection.

OBJECTIVES: To assess whether preterm infants with postnatal cytomegalovirus infection develop neurologic sequelae in early childhood. METHODS: Infants <32 weeks' gestation were prospectively screened for cytomegalovirus (CMV) at term-equivalent age. Neurodevelopment was compared between CMV-positive and CMV-negative infants by using the Griffiths Mental Development Scales (GMDS) at 16 months' corrected age (CA); the Bayley Scales of Infant and Toddler Development, Third Edition or the GMDS at 24 to 30 months' CA; and the Wechsler Preschool and Primary Scale of Intelligence, Third Edition and Movement Assessment Battery for Children, Second Edition at 6 years of age. At 6 years old, hearing was assessed in CMV-positive children. RESULTS: Neurodevelopment was assessed in 356 infants at 16 months' CA, of whom 49 (14%) were infected and 307 (86%) were noninfected. Infected infants performed significantly better on the GMDS locomotor scale. There were no differences at 24 to 30 months' CA on the Bayley Scales of Infant and Toddler Development, Third Edition or GMDS. At 6 years of age, infected children scored lower on the Wechsler Preschool and Primary Scale of Intelligence, Third Edition, but mean scores were within normal range, reaching significance only in verbal IQ (96 [SD 17] vs 103 [SD 15] points; P = .046). Multiple regression indicated no impact of CMV status but significant influence of maternal education and ethnicity on verbal IQ. No significant differences in motor development were found and none of the infected children developed sensorineural hearing loss. CONCLUSIONS: In this cohort study, postnatal cytomegalovirus infection in preterm children did not have an adverse effect on neurodevelopment within the first 6 years of life.

From Neonatal Hearing Screening to Intervention: Results of the Dutch Program for Neonatal Hearing Screening in Well Babies.

In the Netherlands, Youth Health Care services (YHC) have been carrying out neonatal hearing screening (NHS) in newborns since 2006. The aim of the NHS is to identify children with permanent hearing loss, so that intervention can be started before the age of 4 months. Early detection of hearing loss is important, as children who start intervention early have been shown to develop better. This article describes the structure and performance of the NHS carried out by the YHC, the quality of the program, and the timeliness of the start of intervention. Since its implementation, the NHS has been audited annually in order to monitor the program's quality. Monitoring reports and data from the Dutch Foundation for the Deaf and Hard of Hearing Child were used in this study. For many years, results have shown the NHS to be a stable screening program of high quality. The participation rate is high, refer percentage low, and the timeliness of the program is continually improving. Although the timeliness of post screening diagnostics and intervention need most improvement as they do not always meet the target times, this has improved over recent years.

The effectiveness of bilateral cochlear implants for severe-to-profound deafness in adults: a systematic review.

OBJECTIVE: Assessment of the clinical effectiveness of bilateral cochlear implantation compared with unilateral cochlear implantation or bimodal stimulation, in adults with severe-to-profound hearing loss. In 2007, the National Institute for Health and Clinical Excellence (NICE) in the U.K. conducted a systematic review on cochlear implantation. This study forms an update of the adult part of the NICE review. DATA SOURCES: The electronic databases MEDLINE and Embase were searched for English language studies published between October 2006 and March 2011. STUDY SELECTION: Studies were included that compared bilateral cochlear implantation with unilateral cochlear implantation and/or with bimodal stimulation, in adults with severe-to-profound sensorineural hearing loss. Speech perception in quiet and in noise, sound localization and lateralization, speech production, health-related quality of life, and functional outcomes were analyzed. DATA EXTRACTION: Data extraction forms were used to describe study characteristics and the level of evidence. DATA SYNTHESIS: The effect size was calculated to compare different outcome measures. CONCLUSION: Pooling of data was not possible because of the heterogeneity of the studies. As in the NICE review, the level of evidence of the included studies was low, although some of the additional studies showed less risk of bias. All studies showed a significant bilateral benefit in localization over unilateral cochlear implantation. Bilateral cochlear implants were beneficial for speech perception in noise under certain conditions and several self-reported measures. Most speech perception in quiet outcomes did not show a bilateral benefit. The current review provides additional evidence in favor of bilateral cochlear implantation, even in complex listening situations.

Hearing in preterm infants with postnatally acquired cytomegalovirus infection.

Cytomegalovirus is an important cause of sensorineural hearing loss in children. In contrast to congenitally infected infants, little is known about hearing in preterm infants with postnatal cytomegalovirus infection. We studied the hearing in 64 preterm infants during the first year of life and in 18 during the second year of life. None of the infants developed sensorineural hearing loss.

The effectiveness of bilateral cochlear implants for severe-to-profound deafness in children: a systematic review.

OBJECTIVE: To assess the clinical effectiveness of bilateral cochlear implantation compared with unilateral cochlear implantation alone or with a contralateral hearing aid (bimodal stimulation), in children with severe-to-profound hearing loss. Recently, the National Institute for Health and Clinical Excellence (NICE) in the U.K. has conducted a systematic review on cochlear implantation. We decided to update the pediatric part of the NICE review. DATA SOURCES: The electronic databases MEDLINE and Embase were searched for European, North American, and Australasian studies published between October 2006 and June 2009. Reference lists of the included articles were also searched for relevant articles. STUDY SELECTION: Studies were included if they comprised data on comparisons between bilateral cochlear implantation and unilateral cochlear implantation and/or bilateral cochlear implantation and bimodal stimulation, in children with severe-to-profound sensorineural hearing loss. The following outcome measures were analyzed: audiological, speech perception, speech production, functional capacities, health-related quality of life, and/or educational outcomes. DATA EXTRACTION: Characteristics of the participants, interventions, outcomes, and methodological comments were entered into data extraction forms and the level of evidence was assessed. DATA SYNTHESIS: Results were standardized for each outcome measure by calculating a standardized mean difference (effect size). CONCLUSION: Effect sizes could not be pooled because of the heterogeneity of the studies. Therefore, we presented the results qualitatively. Although the level of evidence was low, the advantages of bilateral cochlear implants corresponded with the primary benefits of bilateral hearing, that is, improved speech perception in quiet and noise. Localization results were less consistent. No data on audiologic, speech production, or educational outcomes were available.

Measuring disease-specific health-related quality of life to evaluate treatment outcomes in tinnitus patients: a systematic review.

OBJECTIVE: To identify all disease-specific health-related quality-of-life (HR-QoL) instruments used to assess tinnitus in clinical trials and detail their psychometric properties. DATA SOURCES: A literature search was performed in the bibliographical databases of PubMed and Embase to identify all articles using specific HR-QoL instruments in tinnitus trials. REVIEW METHODS: The HR-QoL instruments used in these articles were investigated in more detail, focusing on characteristics and psychometric values by two independent reviewers. RESULTS: Seventeen studies were identified by the systematic search. The most used HR-QoL questionnaire was the Tinnitus Questionnaire, followed by the Tinnitus Handicap Inventory, the Tinnitus Reaction Questionnaire, and the Tinnitus Handicap Questionnaire. Internal consistency (Cronbach's alpha > 0.9) and reproducibility (> 0.8) were high for all questionnaires, and there was heterogeneity in responses between patients, endorsing the use of these questionnaires for discriminative purposes. However, the responsiveness, i.e., the usefulness of these questionnaires in evaluating treatment effects, is not known yet. CONCLUSION: The HR-QoL instruments used in tinnitus trials appear not to be validated to measure effectiveness of interventions. Using tests or instruments that are valid and reliable is a crucial component of research quality, and both should therefore be studied before final conclusions can be drawn from the questionnaires in upcoming clinical trials.

Is hearing loss a feature of Joubert syndrome, a ciliopathy?

OBJECTIVE: To assess if hearing loss is a feature of Joubert syndrome (JBS), one of the ciliopathies and therefore possibly associated with hearing loss. DESIGN: Retrospective case series. SETTING: University Children's Hospital. PATIENTS: Dutch patients with JBS. MAIN OUTCOME MEASURES: Audiological data. RESULTS: Data from 22 Dutch Joubert syndrome (JBS) cases (17 males, 5 females) aged 3-40 years were available. Audiological tests were successfully performed in 14 cases. Three cases (aged 17-26 years) showed very mild sensorineural hearing loss (SNHL) at different frequencies. Conductive hearing loss due to middle ear infections occurred frequently in young JBS children (6 out of 22 cases). In three cases (aged 3-13 years) the parents reported the child was hypersensitive to sound. CONCLUSION: We found no evidence for significant hearing loss in Joubert syndrome patients. However, given the compromised speech development in JBS, conductive hearing loss due to middle ear infections should be treated vigorously. SNHL at a later age cannot be excluded on the basis of our data, given the sample size. Three of the older cases showed discretely increased hearing thresholds. Analogous to the ciliopathy Bardet-Biedl syndrome, where hearing thresholds were reported to be subclinically increased in a group of adolescents patients, we recommend follow-up of JBS patients in view of the possibility of progressive, late-onset SNHL.

ATP8B1 is essential for maintaining normal hearing.

ATP8B1 deficiency is caused by autosomal recessive mutations in ATP8B1, which encodes the putative phospatidylserine flippase ATP8B1 (formerly called FIC1). ATP8B1 deficiency is primarily characterized by cholestasis, but extrahepatic symptoms are also found. Because patients sometimes report reduced hearing capability, we investigated the role of ATP8B1 in auditory function. Here we show that ATP8B1/Atp8b1 deficiency, both in patients and in Atp8b1(G308V/G308V) mutant mice, causes hearing loss, associated with progressive degeneration of cochlear hair cells. Atp8b1 is specifically localized in the stereocilia of these hair cells. This indicates that the mechanosensory function and integrity of the cochlear hair cells is critically dependent on ATP8B1 activity, possibly through maintaining lipid asymmetry in the cellular membranes of stereocilia.

Combined sensory impairment (deaf-blindness) in five percent of adults with intellectual disabilities.

Our purpose in this cross-sectional study with 1,598 adult clients who had intellectual disabilities was to obtain valid prevalences of sensory impairments and to identify associations. The diagnoses were made through ophthalmologic and audiometric assessments, applying WHO/IASSID definitions. Re-weighted prevalences were 5.0% (95% CI 3.9- 6.2%) for the total adult population; 2.9% (1.9-4.1), less than 50 years; and 11.0% (7.9- 14.7), 50 years and over. Apart from being 50 years of age and over, p = .000, risk factors were more severe intellectual disability, p = .0001, and Down syndrome, p = .001. Results show that the risk of combined sensory impairment in this population is considerably increased compared with the general population. Part of the underlying conditions are treatable or can be rehabilitated. However, the complete diagnosis had been identified in only 12%.

Audiological performance after cochlear implantation: a 2-year follow-up in children with inner ear malformations.

CONCLUSIONS: Open-set speech perception in children with an inner ear malformation is equal to that of other congenitally deaf children after an average of 2 years follow-up. OBJECTIVE: To analyze audiological performance after cochlear implantation in a sample of children with radiographically detectable malformations of the inner ear compared to performance in prelingually deafened children at large. MATERIALS AND METHODS: Nine children with osseous inner ear malformations were compared to 22 congenitally deaf children, all of whom underwent cochlear implantation. All subjects were tested on their electrical evoked compound action potential. Speech perception tests were performed using the monosyllabic trochee polysyllabic test without visual support and the open-set monosyllabic wordlist. RESULTS: In all, 20% of the congenitally deaf children in our center study have inner ear abnormalities. Inner ear malformations were limited to incomplete partition of the cochlea; none of the subjects had common cavity malformations. Electrical compound action potentials were successfully recorded in both groups intraoperatively. Speech perception tests on open-set speech yielded an average of 48.8% (SD 21.2%) in the group of children with inner ear malformations vs 54.5% (SD 21.1%) in congenitally deaf children. In four of nine cases with an inner ear malformation we encountered a minor CSF leak.

Prevalence of hearing loss in 1598 adults with an intellectual disability: cross-sectional population based study.

A cross-sectional epidemiological study on prevalence of hearing loss was carried out in an age- and Down's syndrome- stratified random sample of 1598 persons drawn from a base population of 9012 persons, representative of the Dutch adult population of intellectual disability (ID) service users. The re-weighted population prevalence is 30.3% (95% confidence interval [CI]: 27.7-33.0%). Subgroup prevalences range from 7.5% (95% confidence interval [CI]: 3.6-13.3) in the subgroup aged 18-30 years with ID by other causes than Down's syndrome, up to 100% (95% CI: 79.4-100%) in adults over 60 years of age with Down's syndrome. Down's syndrome (OR 5.18, 95% CI 3.80-7.07) and age were confirmed to be risk factors. Age-related increase in prevalence in persons with Down's syndrome appears to occur approximately three decades earlier, and in persons with ID by other causes approximately one decade earlier than in the general population.

Characteristics of hearing loss in HDR (hypoparathyroidism, sensorineural deafness, renal dysplasia) syndrome.

Haploinsufficiency of the zinc finger transcription factor GATA3 causes the triad of hypoparathyroidism, deafness and renal dysplasia, known by its acronym HDR syndrome. The purpose of the current study was to describe in detail the auditory phenotype in human HDR patients and compare these to audiometrical and histological data previously described in a mouse model of this disease. Pure tone audiometry, speech audiometry, speech in noise, auditory brainstem responses and transiently evoked otoacoustic emissions were measured in 2 patients affected by HDR syndrome. Both patients were affected by a moderate-to-severe sensorineural hearing loss. Speech reception thresholds were shifted and speech recognition in noise was disturbed. No otoacoustic emissions could be generated in either patient. Auditory brainstem response interpeak intervals were normal. The human and murine audiological phenotypes seem to correspond well. Hearing loss in HDR syndrome is moderate to severe, seems to be slightly worse at the higher end of the frequency spectrum and may be progressive with age. The absence of otoacoustic emissions and the loss of frequency selectivity suggest an important role for outer hair cells in causing the hearing loss.

Impact of conventional anesthesia on auditory brainstem responses in mice.

Anesthesia is known to affect the auditory brainstem response (ABR) in animals often used in hearing research. This study describes the differences in ABRs between awake and anesthetized FVB/N mice. Intracranial electrodes connected to a head fixation pedestal were used for click-evoked ABR recordings. This pedestal served to immobilize mice, either awake or under anesthesia, in a 'free' sound field. The presence of myogenic noise in the awake condition obviously increases recording time. However it is demonstrated that recording times can be significantly reduced by increasing the stimulus repetition rate from 23 up to 80 impulses per second. This causes only a small but significant increase in absolute peak latencies in the awake condition, but has no significant effect on the overall ABR-waveform, nor on the ABR-threshold, nor on the ABR interpeak latencies, nor on the absolute peak latencies in the anesthetized condition. Anesthesia with ketamine/xylazine caused a significant prolongation of ABR-peak latencies and interpeak latencies as well as a significant upward shift (8.0+/-1.8 dB) of ABR-thresholds as compared to the awake condition. Under anesthesia the measurement accuracy of peak latencies, interpeak latencies and thresholds decreases. In conclusion, the awake condition is preferable for more accurate measurements of ABR characteristics, in spite of the myogenic noise concomitant with this condition.

Hearing loss in infantile Pompe's disease and determination of underlying pathology in the knockout mouse.

Hearing deficit occurs in several lysosomal storage disorders but has so far not been recognized as a symptom of Pompe's disease (glycogen storage disease type II). We discovered quite unexpectedly 30-90 dB hearing loss in four infants with Pompe's disease, who participated in a study on the safety and efficacy of enzyme replacement therapy. Three other patients with juvenile Pompe's disease did not have this symptom. The ABR (auditory brainstem response) thresholds but not the interpeak latency times were increased. This pointed to middle or inner ear pathology rather than to involvement of the central auditory nervous system. The possible occurrence of cochlear pathology was supported by the absence of oto-acoustic emissions. We investigated this hypothesis in a knockout mouse model of Pompe's disease and found glycogen storage in the inner and outer hair cells of the cochlea, the supporting cells, the stria vascularis, and the spiral ganglion cells. We conclude that cochlear pathology is the most likely cause of hearing loss in infantile Pompe's disease and possibly a characteristic feature of this clinical subtype.

Hearing loss following Gata3 haploinsufficiency is caused by cochlear disorder.

Patients with HDR syndrome suffer from hypoparathyroidism, deafness, and renal dysplasia due to a heterozygous deletion of the transcription factor GATA3. Since GATA3 is prominently expressed in both the inner ear and different parts of the auditory nervous system, it is not clear whether the deafness in HDR patients is caused by peripheral and/or central deficits. Therefore, we have created and examined heterozygous Gata3 knockout mice. Auditory brainstem response (ABR) thresholds of alert heterozygous Gata3 mice, analyzed from 1 to 19 months of age, showed a hearing loss of 30 dB compared to wild-type littermates. Neither physiological nor morphological abnormalities were found in the brainstem, cerebral cortex, the outer or the middle ear. In contrast, cochleae of heterozygous Gata3 mice showed significant progressive morphological degeneration starting with the outer hair cells (OHCs) at the apex and ultimately affecting all hair cells and supporting cells in the entire cochlea. Together, these findings indicate that hearing loss following Gata3 haploinsufficiency is peripheral in origin and that this defect is detectable from early postnatal development and maintains through adulthood.

Newborn hearing screening: tobramycin and vancomycin are not risk factors for hearing loss.

OBJECTIVE: To investigate the chance of detecting hearing loss with neonatal hearing screening in relation to exposure to tobramycin and vancomycin. STUDY DESIGN: Automated auditory brainstem response (A-ABR) hearing screening was performed in all neonates with at least one risk factor. Data on drug administration were abstracted from patient files. Exposure to these drugs was related to the result of hearing screening. In patients failing hearing screening, exposure to ototoxic medication was assessed in the light of other risk factors for hearing loss. RESULTS: Six hundred twenty-five patients were analyzed; 45 neonates failed hearing screening. Tobramycin, vancomycin, and furosemide were used in 508, 130, and 174 patients, respectively. Exposure to vancomycin, tobramycin, or furosemide or a combination, defined in terms of treatment duration, total dose, or serum concentrations of antibiotics, was not related to failure to pass A-ABR screening. Ototoxic medication was not the most probable risk factor in any of the patients with serum concentrations outside the therapeutic range. CONCLUSIONS: Routine therapeutic drug monitoring of vancomycin and tobramycin in neonates for ototoxicity reasons is not helpful in detecting patients at risk for clinically important hearing loss in the 2- to 4-kHz range. A longer period of audiometric follow-up is needed to determine any long-term effects.

Clinical consequences of feedback on ear surgery: the continuous recording of adverse events and complications with regard to reducing the number of surgeons who perform otosclerosis surgery.

Electronically stored data may be used to generate feedback overviews. This paper describes a method for establishing a picture of ear surgery complications. In this prospective study, the working definition of adverse events and complications is "incidents that are not intrinsic to the surgical procedure and that have a potential or actual negative effect on surgical outcome or postoperative morbidity". A simple method is used to categorise otologic adverse events and complications. This scale varies from adverse events (grade A) to death (grade D). All adverse events and complications in ear surgery that met this definition were documented electronically as part of continuous follow-up between 1 July 1992 and 30 June 1999. In the first 3 years, 1,009 ear operations were performed, and in 51 (5%) of them, adverse events or complications were noted during or after surgery. There were 30 (3%) grade A (adverse events), 18 (2%) grade B (minor complications), 3 (0.3%) grade C (major complications) and no grade D complications. Otosclerosis surgery was evaluated additionally, because halfway through a 7-year period, the number of surgeons was changed. Only three experienced, senior members of staff were involved, and inexperienced residents no longer were allowed to perform this kind of surgery. The reduction of surgeon numbers did indeed improve the outcome of the stapes surgery. Our results were comparable to the literature. This monitoring of outcome-results in relation to changes in care can be seen as a study of care quality. A review of this kind links daily clinical practice to the literature and induces an improvement in quality.