Adaptation of distortion product otoacoustic emission in humans.

Previous studies of animals observed a phenomenon of adaptation of distortion product otoacoustic emission (DPOAE) and found that the phenomenon was mediated to a large extent by the medial olivocochlear (MOC) reflex. The present study investigated DPOAE adaptation in humans. The following stimuli were used: f2/f1 = 1.2; f2 = 2, 4, or 5.65 kHz; L2 = 50-65 dB SPL re 20 microPa rms, L1 - L2 = 0-15 dB, where L1 and L2 represent levels of the f1 and f2 tones, respectively; duration of two-tone burst = 5.5 s; interburst gap = 20 or 30 s; number of repetitions = 40 or 64. We analyzed the 2f1 - f2 DPOAE as a function of time using a method of heterodyne envelope detection. The subjects were 20 humans aged from 15 to 54 years (median = 21 years) with normal hearing. We observed that (1) humans exhibited DPOAE adaptation phenomenon; (2) the time course of DPOAE level was characterized by a 2-exponential function; (3) distributions of the fast and slow time constants were well separated with their median values being 69 ms and 1.51 s, respectively; (4) distributions of the magnitudes of the fast and slow adaptation components were largely overlapped with their median values being 0.65 and 0.40 dB, respectively; and (5) the combined magnitude of the adaptation ranged from 0.4 to 3.0 dB with a median of 1.10 dB. To our knowledge, the present study is the first published article to describe adaptation of DPOAE in humans. These results should help advance the basic knowledge of human cochlear mechanics operating under the control of the MOC feedback system and contribute to the development of practical applications such as identifying people at high risk of acoustical injury and a clinical test of the functional status of the MOC system.

Sources of distortion product otoacoustic emissions revealed by suppression experiments and inverse fast Fourier transforms in normal ears.

Primary and secondary sources combine to produce the 2f1-f2 distortion product otoacoustic emission (DPOAE) measured in the ear canals of humans. DPOAEs were obtained in nine normal-hearing subjects using a fixed-f2 paradigm in which f1 was varied. The f2 was 2 or 4 kHz, and absolute and relative primary levels were varied. Data were obtained with and without a third tone (f3) placed 15.6 Hz below 2f1-f2. The level of f3 was varied in order to suppress the stimulus frequency otoacoustic emission (SFOAE) coming from the 2f1-f2 place. These data were converted from the complex frequency domain into an equivalent time representation using an inverse fast Fourier transform (IFFT). IFFTs of unsuppressed DPOAE data were characterized by two or more peaks. Relative amplitudes of these peaks depended on overall primary level and on primary-level differences. The suppressor eliminated later peaks, but early peaks remained relatively unaltered. Results are interpreted to mean that the DPOAE measured in humans includes components from the f2 place (intermodulation distortion) and DP place (in the form of a SFOAE). These findings build on previous work by providing evidence that multiple peaks in the IFFT are due to a secondary source at the DP place.

Some issues relevant to establishing a universal newborn hearing screening program.

This article describes some of the factors relevant to the establishment of a universal newborn hearing screening (UNHS) program. First, the difficulty in providing precise estimates of test sensitivity and specificity are reviewed. This section is followed by hypothetical estimates of overall programmatic costs, first for a fixed number of babies to be screened and then as a function of the number of babies to be screened in a year. Included in these estimates are the costs for equipment, disposables, personnel, and follow-up testing. These estimates are provided for three different screening protocols: auditory brainstem response (ABR) alone, otoacoustic emission (OAE) alone, and OAE followed by ABR only for those babies who failed the OAE screening. If follow-up costs are not included, it is less expensive to screen newborns with OAEs compared with the other two protocols. However, once follow-up testing is included as part of the program costs and there are at least 400 births per year, procedures in which OAEs are performed first, followed by an ABR on those infants who do not pass the OAE test, result in the lowest costs. Hospitals with as few as 400 births per year should expect per-baby costs not exceeding $30, regardless of which protocol is used. For all three protocols, the unit costs decrease as the number of babies screened increases. The final section describes data from a local UNHS program in which all infants are screened first with an OAE test, followed by an ABR test on infants not passing the OAE screening. Idiosyncratic features to this program are described, including the fact that all screening tests are performed by audiologists, who are paid on a part-time basis, adding cost to the program. Even under these circumstances, the unit cost is under $30. These data lead us to conclude that all infants can be screened in a cost-effective manner.

Distortion product otoacoustic emission input/output functions in normal-hearing and hearing-impaired human ears.

DPOAE input/output (I/O) functions were measured at 7f2 frequencies (1 to 8 kHz; f2/f1 = 1.22) over a range of levels (-5 to 95 dB SPL) in normal-hearing and hearing-impaired human ears. L1-L2 was level dependent in order to produce the largest 2f1-f2 responses in normal ears. System distortion was determined by collecting DP data in six different acoustic cavities. These data were used to derive a multiple linear regression model to predict system distortion levels. The model was tested on cochlear-implant users and used to estimate system distortion in all other ears. At most but not all f2's, measurements in cochlear implant ears were consistent with model predictions. At all f2 frequencies, the ears with normal auditory thresholds produced I/O functions characterized by compressive nonlinear regions at moderate levels, with more rapid growth at low and high stimulus levels. As auditory threshold increased, DPOAE threshold increased, accompanied by DPOAE amplitude reductions, notably over the range of levels where normal ears showed compression. The slope of the I/O function was steeper in impaired ears. The data from normal-hearing ears resembled direct measurements of basilar membrane displacement in lower animals. Data from ears with hearing loss showed that the compressive region was affected by cochlear damage; however, responses at high levels of stimulation resembled those observed in normal ears.

Identification of neonatal hearing impairment: a multicenter investigation.

OBJECTIVES: This article describes the design of a multicenter study sponsored by the National Institutes of Health. The purpose of this study was to determine the accuracy of three measures of peripheral auditory system status (transient evoked otoacoustic emissions, distortion product otoacoustic emissions, and auditory brain stem responses) applied in the perinatal period for predicting behavioral hearing status at 8 to 12 mo corrected age. The influences of the infant's medical status, the test environment, and test and response parameters on test performance were examined. DESIGN: Seven institutions participated in this study. There were 7179 infants evaluated in the perinatal period. All graduates of the neonatal intensive care unit (4478) and well babies with one or more risk factor for hearing loss (353) were targeted for follow-up testing using visual reinforcement audiometry (VRA) at 8 to 12 mo corrected age. Well babies without any risk indicators (N = 2348) were not targeted for follow-up VRA testing. However, 80 of these well babies did not pass the screening protocol and thus were targeted for follow-up VRA testing as well. Perinatal test performance was evaluated using the VRA data as the "gold standard." RESULTS: The results of this study are described in a series of 11 articles following this introductory article. CONCLUSIONS: The evaluation of newborn hearing tests required a longitudinal study in which newborn test results were compared with a gold standard based on behavioral audiometric assessment. Such an evaluation was possible because all newborns, passes as well as refers, were followed up long enough to permit reliable behavioral measurements. In addition, prenatal, perinatal, and maternal history information, test environment, and test parameter information were collected to provide data that led to a complete description of factors affecting test outcomes. All of these data were obtained in a sample of sufficient ethnic, medical, and geographic diversity in efforts to increase the generalizability of the results. Finally, the data were combined in a relational data base to examine the factors that influence test performance. Specific information related to these issues is presented in the articles that follow.

Identification of neonatal hearing impairment: experimental protocol and database management.

OBJECTIVE: The purposes of this article are to describe the overall protocol for the Identification of Neonatal Hearing Impairment (INHI) project and to describe the management of the data collected as part of this project. A well-defined protocol and database management techniques were needed to ensure that data were 1) collected accurately and in the same way across sites; 2) maintained in a database that could be used to provide feedback to individual sites regarding enrollment and the extent to which the protocol was complete on individual subjects; and 3) available to answer project questions. This article describes techniques that were used to meet these needs. DESIGN: This study was a prospective, randomized study that was designed to evaluate auditory brain stem responses, transient evoked otoacoustic emissions, and distortion product otoacoustic emissions as hearing-screening tools, and to relate neonatal test findings to hearing status, defined by visual reinforcement audiometry at 8 to 12 mo of age. Measures of middle-ear function also were obtained at some sites as part of the neonatal test battery. In addition, other clinical and demographic data were gathered to determine the extent to which factors, other than auditory status, influenced test behavior. Three groups were evaluated: neonatal intensive care unit (NICU) infants (those who spent 3 or more days in a NICU), well babies with risk factors for hearing loss, and well babies without risk factors. Six centers participated in the trial. The testers for the project included audiologists, technicians, audiology graduate students, and medical research staff. The same computerized neonatal test program was applied at each center. This program generated the neonatal test database automatically. Clinical and demographic data were collected by means of concise data collection forms and were entered into a database at each site. After the neonatal test, subjects from the NICU and at-risk well babies were evaluated with visual reinforcement audiometry starting at 8 to 12 mo of age. All data were electronically transmitted to the core site where they were merged into one overall database. This database was exercised to provide feedback and to identify discrepancies throughout the course of the study. In its final form, it served as the database on which all analyses were performed. RESULTS AND CONCLUSION: The protocol was a departure from typical hearing screening procedures in terms of 1) its regimented application of three screening measures; 2) the detailed information that was obtained regarding subject clinical and demographic factors; and 3) its application of the same procedures across six centers having diverse geographic location and subject demographics. A learning curve for successfully executing the study protocols was observed. Throughout the study, monthly reports were generated to monitor subject enrollment, check for data completeness, and to perform data integrity checks. In combination with monthly data reports and checks that occurred throughout the progression of the study, miscellaneous data audits were performed to check accuracy of neonatal testing programs and to cross-check information entered in the clinical and demographic database. The data management techniques used in this project helped to ensure the quality of the data collection process and also allowed for detailed analyses once data were collected. This was particularly important because it enabled us to evaluate not only the performance of individual measures as screening tools, but also permitted an evaluation of the influence of other variables on screening test results.

Identification of neonatal hearing impairment: distortion product otoacoustic emissions during the perinatal period.

OBJECTIVES: 1) To describe distortion product otoacoustic emission (DPOAE) levels, noise levels and signal to noise ratios (SNRs) for a wide range of frequencies and two stimulus levels in neonates and infants. 2) To describe the relations between these DPOAE measurements and age, test environment, baby state, and test time. DESIGN: DPOAEs were measured in 2348 well babies without risk indicators, 353 well babies with at least one risk indicator, and 4478 graduates of neonatal intensive care units (NICUs). DPOAE and noise levels were measured at f2 frequencies of 1.0, 1.5, 2.0, 3.0, and 4.0 kHz, and for primary levels (L1/L2) of 65/50 dB SPL and 75/75 dB SPL. Measurement-based stopping rules were used such that a test did not terminate unless the response was at least 3 dB above the mean noise floor + 2 SDs (SNR) for at least four of five test frequencies. The test would terminate, however, if these criteria were not met after 360 sec. Baby state, test environment, and other test factors were captured at the time of each test. RESULTS: DPOAE levels, noise levels and SNRs were similar for well babies without risk indicators, well babies with risk indicators, and NICU graduates. There was a tendency for larger responses at f2 frequencies of 1.5 and 2.0 Hz, compared with 3.0 and 4.0 kHz; however, the noise levels systematically decreased as frequency increased, resulting in the most favorable SNRs at 3.0 and 4.0 kHz. Response levels were least and noise levels highest for an f2 frequency of 1.0 kHz. In addition, test time to achieve automatic stopping criteria was greatest for 1.0 kHz. With the exception of "active/alert" and "crying" babies, baby state had little influence on DPOAE measurements. Additionally, test environment had little impact on these measurements, at least for the environments in which babies were tested in this study. However, the lowest SNRs were observed for infants who were tested in functioning isolettes. Finally, there were some subtle age affects on DPOAE levels, with the infants born most prematurely producing the smallest responses, regardless of age at the time of test. CONCLUSIONS: DPOAE measurements in neonates and infants result in robust responses in the vast majority of ears for f2 frequencies of at least 2.0, 3.0 and 4.0 kHz. SNRs decrease as frequency decreases, making the measurements less reliable at 1.0 kHz. When considered along with test time, there may be little justification for including an f2 frequency at 1.0 kHz in newborn screening programs. It would appear that DPOAEs result in reliable measurements when tests are conducted in the environments in which babies typically are found. Finally, these data suggest that babies can be tested in those states of arousal that are most commonly encountered in the perinatal period.

Identification of neonatal hearing impairment: characteristics of infants in the neonatal intensive care unit and well-baby nursery.

OBJECTIVE: The objective of this study was to describe the demographic data, medical status, and incidence of risk factors for hearing impairment in the neonatal intensive care unit (NICU) and well-baby populations in a multicenter prospective study designed to assess neonatal hearing impairment and to evaluate factors that might affect neonatal hearing test performance. DESIGN: This was a prospective multicenter study funded by the National Institutes of Health-National Institute on Deafness and Other Communication Disorders to evaluate the effectiveness of auditory brain stem response, transient evoked otoacoustic emissions, and distortion product otoacoustic emissions for newborn hearing screening. Research staff at each site obtained informed consent and detailed demographic and medical data, including information on established risk factors for hearing loss on 4478 high-risk infants cared for in the NICU, 2348 infants from the well-baby nurseries with no risk factor, and 353 infants from the well-baby nurseries with risk factors. For follow-up purposes the sample was divided further to include a subgroup called selects. Selects were either infants from the well-baby nursery who had an established risk factor for hearing impairment (N = 353) or did not pass the neonatal hearing screen protocol (N = 80). In this study, we focus on the distribution of infants by nursery and risk factors only. Particular effort was made to enroll infants with risk factors for hearing loss in both the NICU and well-baby nurseries. Descriptive analyses are used to describe characteristics of this sample. RESULTS: All 10 of the risk factors established by the Joint Committee on Infant Hearing in 1994 were identified in the NICU population. The four most common were ototoxic medications (44.4%), very low birth weight (17.8%), assisted ventilation > 5 days (16.4%), and low Apgar scores at 1 or 5 min (13.9%). In contrast, only six risk factors were present in the well-baby nurseries: family history (6.6%), craniofacial abnormalities (3.4%), low Apgar scores (2.8%), syndromes (0.5%), ototoxic medications (0.2%), and congenital infection (0.1%). CONCLUSION: These descriptive risk factor data reflect both the newborn populations at the study sites and the bias for enrolling infants at risk for hearing loss. The high-risk NICU sample reflects the characteristics typically found in graduates of the NICU. The data summarized in this study will be used to assess the relationships between risk factor and hearing test outcome.

Identification of neonatal hearing impairment: transient evoked otoacoustic emissions during the perinatal period.

OBJECTIVES: 1) To describe transient evoked otoacoustic emission (TEOAE) levels, noise levels and signal to noise ratios (SNRs) for a range of frequency bands in three groups of neonates who were tested as a part of the Identification of Neonatal Hearing Impairment multi-center consortium project. 2) To describe the relations between these TEOAE measurements and age, test environment, baby state, and test time. DESIGN: TEOAEs were measured in 4478 graduates of neonatal intensive care units (NICUs), 353 well babies with at least one risk indicator, and 2348 well babies without risk factors. TEOAE and noise levels were measured for frequency bands centered at 1.0, 1.5, 2.0, 3.0, and 4.0 kHz for a click stimulus level of 80 dB SPL. For those ears not meeting "passing" stopping criteria at 80 dB pSPL, a level of 86 dB pSPL was included. Measurement-based stopping rules were used such that a test did not terminate unless the response revealed a criterion SNR in four out of five frequency bands or no response occurred after a preset number of averages. Baby state, test environment, and other test factors were captured at the time of test. RESULTS: TEOAE levels, noise levels and SNRs were similar for NICU graduates, well babies with risk factors and well babies without risk factors. There were no consistent differences in response quality as a function of test environment, i.e., private room, unit, open crib, nonworking isolette, or working isolette. Noise level varied little across risk group, test environment, or infant state other than crying, suggesting that the primary source of noise in TEOAE measurements is infant noise. The most significant effect on response quality was center frequency. Responses were difficult to measure in the half-octave band centered at 1.0 kHz, compared with higher frequencies. Reliable responses were measured routinely at frequencies of 1.5 kHz and higher. CONCLUSIONS: TEOAEs are easily measured in both NICU graduates and well babies with and without risk factors for hearing loss in a wide variety of test environments. Given the difficulties encountered in making reliable measurements for a frequency band centered at 1.0 kHz, its inclusion in a screening program may not be justified.

Identification of neonatal hearing impairment: auditory brain stem responses in the perinatal period.

OBJECTIVES: 1) To describe the auditory brain stem response (ABR) measurement system and optimized methods used for study of newborn hearing screening. 2) To determine how recording and infant factors related to the screening, using well-defined, specific ABR outcome measures. DESIGN: Seven thousand one hundred seventy-nine infants, 4478 from the neonatal intensive care unit (NICU) and the remaining from the well-baby nursery, were evaluated with an automated ABR protocol in each ear. Two channel recordings were obtained (vertex to mastoid or channel A and vertex to nape of neck or channel B) in response to click stimuli of 30 and 69 dB nHL in all infants as well as 50 dB nHL in infants who did not meet criteria for response at 30 dB. Criteria for response included F(SP) > or =3.1 and a tester-judgment of response. Criteria could be met in the first or repeat test with a maximum of 6144 accepted sweeps per test. RESULTS: More than 99% of infants could complete the ABR protocol. More than 90% of NICU and well-baby nursery infants "passed" given the strict criteria for response, whereas 86% of those with high risk factors met criterion for ABR response detection. The number of infants who did not meet ABR response criteria in one or both ears was systematically related to stimulus level with the largest group not meeting criteria at 30 dB followed by 50 and 69 dB nHL. Meeting criteria on the ABR was positively correlated with the amplitude of wave V, with low noise and low electrode impedance. Factors that predicted how many sweeps would be needed to reach criterion F(SP) included noise level of the test site, state of the baby (for example, quiet sleep versus crying), recording noise, electrode impedance and response latency. Channel A (vertex to mastoid) reached criterion more often than channel B (vertex to nape of neck) due to higher noise in channel B. Average total test time for 30 dB nHL screening in both ears was under 8 minutes. Well babies with risk factors took slightly longer to evaluate than other groups with this automated ABR procedure and have higher noise levels. CONCLUSIONS: ABR implemented with an automated detection algorithm using a 30 dB nHL click stimulus is reliable technique for rapid assessment of auditory status in newborns. Factors other than hearing loss that influenced the test result include infant state, electrode location and impedance, testing site, and infant risk status. Even so, ABRs were reliably recorded in the vast majority of babies under circumstances in which most babies are found in the perinatal period.

Identification of neonatal hearing impairment: ear-canal measurements of acoustic admittance and reflectance in neonates.

OBJECTIVES: 1) To describe broad bandwidth measurements of acoustic admittance (Y) and energy reflectance (R) in the ear canals of neonates. 2) To describe a means for evaluating when a YR response is valid. 3) To describe the relations between these YR measurements and age, gender, left/right ear, and selected risk factors. DESIGN: YR responses were obtained at four test sites in well babies without risk indicators, well babies with at least one risk indicator, and graduates of neonatal intensive care units. YR responses were measured using a chirp stimulus at moderate levels over a frequency range from 250 to 8000 Hz. The system was calibrated based on measurements in a set of cylindrical tubes. The probe assembly was inserted in the ear canal of the neonate, and customized software was used for data acquisition. RESULTS: YR responses were measured in over 4000 ears, and half of the responses were used in exploratory data analyses. The particular YR variables chosen for analysis were energy reflectance, equivalent volume and acoustic conductance. Based on the view that unduly large negative equivalent volumes at low frequencies were physically impossible, it was concluded that approximately 13% of the YR responses showed evidence of improper probe seal in the ear canal. To test how these outliers influenced the overall pattern of YR responses, analyses were conducted both on the full data set (N = 2081) and the data set excluding outliers (N = 1825). The YR responses averaged over frequency varied with conceptional age (conception to date of test), gender, left/right ear, and selected risk factors; in all cases, significant effects were observed more frequently in the data set excluding outliers. After excluding outliers and controlling for conceptional age effects, the dichotomous risk factors accounting for the greatest variance in the YR responses were, in rank order, cleft lip and palate, aminoglycoside therapy, low birth weight, history of ventilation, and low APGAR scores. In separate analyses, YR responses varied in the first few days after birth. An analysis showed that the use of a YR test criterion to assess the quality of probe seal may help control the false-positive rate in evoked otoacoustic emission testing. CONCLUSIONS: This is the first report of wideband YR responses in neonates. Data were acquired in a few seconds, but the responses are highly sensitive to whether the probe is fully sealed in the ear canal. A real-time acoustic test of probe fit is proposed to better address the probe seal problem. The YR responses provide information on middle-ear status that varies over the neonatal age range and that is sensitive to the presence or absence of risk factors, ear, and gender differences. Thus, a YR test may have potential for use in neonatal screening tests for hearing loss.

Identification of neonatal hearing impairment: recruitment and follow-up.

OBJECTIVE: The purpose of this study is to describe the recruitment and retention strategies as well as the sample demographics for families with infants completing the neonatal examination and returning for follow-up. These data are compared to those infants inactivated from the study. DESIGN: This study was a prospective, randomized clinical study. All infants who were confined to the neonatal intensive care unit (NICU) and well babies with at least one risk indicator were targeted for behavioral audiometric follow-up testing. In addition, infants without risk factors from the well-baby nursery, but who failed a newborn test, were also followed. Several variables were evaluated to determine those factors, if any, that might predict which families returned for follow-up testing. RESULTS: Recruitment was achieved as per study design with 4911 high-risk infants and 2348 well-baby nursery infants (without risk indicators for hearing) enrolled. Of the 4911 high-risk infants enrolled, 64% were successfully recruited into the follow-up portion of the study. This was less than the projected rate of 80%. Factors predicting noncompliance with the study protocol for follow-up were predominantly sociodemographic and included nonwhite race, no insurance, substance abuse, young maternal age, more than two children at home, and late onset of prenatal care. CONCLUSIONS: Factors related to low socioeconomic status and increased social risk were the strongest predictors of poor study protocol compliance. Despite retention challenges, 64% of the targeted, high-risk infants subsequently returned for the 8-to 12-mo behavioral hearing assessment protocols for validation purposes.

Identification of neonatal hearing impairment: hearing status at 8 to 12 months corrected age using a visual reinforcement audiometry protocol.

OBJECTIVES: 1) To describe the hearing status of the at-risk infants in the National Institutes of Health-Identification of Neonatal Hearing Impairment study sample at 8 to 12 mo corrected age (chronologic age adjusted for prematurity). 2) To describe the visual reinforcement audiometry (VRA) protocol that was used to obtain monaural behavioral data for the sample. DESIGN: All neonatal intensive care unit infants and well babies with risk factors (including well babies who failed neonatal tests) were targeted for follow-up behavioral evaluation once they had reached 8 mo corrected age. Three thousand one hundred and thirty-four (64.4%) of the 4868 surviving infants returned for at least one behavioral hearing evaluation, which employed a well-defined VRA protocol. VRA thresholds or minimum response levels (MRLs) were determined for speech and pure tones of 1.0, 2.0, and 4.0 kHz for each ear using insert earphones. RESULTS: More than 95% of the infants were reliably tested with the VRA protocol; 90% provided complete tests (four MRLs for both ears). Ninety-four percent of the at-risk infants were found to have normal hearing sensitivity (MRLs of 20 dB HL) at 1.0, 2.0, and 4.0 kHz in both ears. Of the infants, 2.2% had bilateral hearing impairment, and 3.4% had impairment in one ear only. More than 80% of the impaired ears had losses of mild-to-moderate degree. CONCLUSIONS: This may be the largest study to attempt to follow all at-risk infants with behavioral audiometric testing, regardless of screening outcome, in an effort to validate the results of auditory brain stem response, distortion product otoacoustic emission, and transient evoked otoacoustic emission testing in the newborn period. It is one of only a few studies to report hearing status of infants at 1 yr of age, using VRA on a clinical population. Successful testing of more than 95% of the infants who returned for the VRA follow-up documents the feasibility of obtaining monaural behavioral data in this population.

Identification of neonatal hearing impairment: infants with hearing loss.

OBJECTIVE: This article describes the audiologic findings and medical status of infants who were found to have hearing loss, detected as part of the Identification of Neonatal Hearing Impairment (INHI) project. In addition, the neonatal and maternal health variables for the group of infants who could not be tested with visual reinforcement audiometry (VRA) due to developmental and visual disability are presented. DESIGN: The overall goal of the INHI project was to evaluate the test performance of auditory brain stem response and evoked otoacoustic emission (OAE) tests given in the newborn period. These tools were evaluated on the basis of the infants' hearing when tested behaviorally with VRA at 8 to 12 mo corrected age. The neonatal test results, VRA results, medical history information and a record of intercurrent events occurring between the neonatal period and the time of VRA were collated and reviewed. The purpose of this article is to review the characteristics of those infants who were found to have hearing loss. RESULTS: Of 2995 infants who had VRA tests judged to be of good or fair reliability, 168 had a finding of hearing loss for at least one ear, an incidence of 5.6%. Sixty-six infants had bilateral losses, an incidence of 2%, and 22 infants had bilateral hearing losses in the moderate to profound range, an incidence 0.7%. The prevalence of middle ear problems was greater than 50% among these infants with hearing loss. From the larger group of 168 infants with hearing loss, a group of 56 infants (86 ears) was chosen as those with a low probability that the hearing loss was due to transient middle ear pathology and was more likely hearing loss of a permanent nature. These were the infants used for the analyses of neonatal test performance (Norton et al., 2000). In this selected group there were 30 infants with bilateral impairment of at least mild degree, which is an incidence of 1%. There were approximately equal numbers of ears in the mild, moderate, severe and profound range of hearing loss. Risk factors associated with hearing loss were reviewed for the total sample of infants tested with VRA and for those infants with hearing loss. A history of treatment with aminoglycosides was the risk factor most often reported in the entire sample; however, there was no difference in prevalence of this risk factor for the normal-hearing and hearing-impaired groups. The risk factor associated with the highest incidence of hearing loss was stigmata of syndromes associated with sensorineural hearing loss and other neurosensory disorders. Sixty-seven infants who returned for follow-up could not be tested with VRA due to severe developmental delay or visual disability. Many of these infants had medical histories indicating the sequelae of extreme prematurity and/or very low birthweight. CONCLUSIONS: Most of the hearing losses found in this study were mild and, based on clinical history and tympanometry tests, many of the mild and some of the moderate impairments may have been acquired in early infancy due to middle ear effusion. In the group of infants used for determination of neonatal test performance there were approximately equal numbers of mild, moderate, severe and profound losses. Only a small percentage of infants with a conventional risk indicator for hearing loss actually had a hearing loss, and there were a significant number of infants with hearing loss who did not have a risk indicator. These findings support the need for an early identification program based on universal neonatal hearing screening rather than by targeted testing of those with risk indicators.

Identification of neonatal hearing impairment: summary and recommendations.

OBJECTIVES: This article summarizes the results of a multi-center study, "Identification of Neonatal Hearing Impairment," sponsored by the National Institutes of Health. The purpose of this study was to determine the performance characteristics of three measures of peripheral auditory system status, transient evoked otoacoustic emissions (TEOAEs), distortion product otoacoustic emissions (DPOAEs), and auditory brain stem responses (ABR), applied in the neonatal period in predicting hearing status at 8 to 12 mo corrected age. DESIGN: The design and implementation of this study are described in the first two articles in this series. Seven institutions participated in this study; 7179 infants were evaluated. Graduates of the neonatal intensive care unit and well babies with one or more risk factors for hearing loss were targeted for follow-up testing using visual reinforcement audiometry (VRA) at 8 to 12 mo corrected age. Neonatal test performance was evaluated using the VRA data as the "gold standard." RESULTS: The major results of the study are described in the nine articles preceding this summary article. TEOAEs in response to an 80 dB pSPL click, DPOAEs in response to L1 = 65 and L2 = 50 dB SPL and ABR in response to a 30 dB nHL click performed well as predictors of permanent hearing loss of 30 dB or greater at 8 to 12 mo corrected age. All measures were robust with respect to infant state, test environment and infant medical status. No test performed perfectly. CONCLUSIONS: Based on the data from this study, the 1993 National Institutes of Health Consensus Conference-recommended protocol-an OAE test followed by an ABR test for those infants failing the OAE test-would result in low referral rate (96 to 98%). TEOAEs for 80 dB pSPL, ABR for 30 dB nHL and DPOAEs for L1 = 65 dB SPL and L2 = 50 dB SPL perform well in predicting hearing status based on the area under the relative operating characteristic curve. Accuracy for the OAE measurements are best when the speech awareness threshold or the pure-tone average for 2.0 kHz and 4 kHz are used as the gold standard. ABR accuracy varies little as a function of the frequencies included in the gold standard. In addition, 96% of those infants returning for VRA at 8 to 12 mo corrected age were able to provide reliable ear-specific behavioral thresholds using insert earphones and a rigorous psychophysical VRA protocol.

Identification of neonatal hearing impairment: evaluation of transient evoked otoacoustic emission, distortion product otoacoustic emission, and auditory brain stem response test performance.

OBJECTIVES: The purpose of this study was to compare the performance of transient evoked otoacoustic emissions (TEOAEs), distortion product otoacoustic emissions (DPOAEs), and auditory brain stem responses (ABRs) as tools for identification of neonatal hearing impairment. DESIGN: A total of 4911 infants including 4478 graduates of neonatal intensive care units, 353 well babies with one or more risk factors for hearing loss (Joint Committee on Infant Hearing, 1994) and 80 well babies without risk factor who did not pass one or more neonatal test were targeted as the potential subject pool on which test performance would be assessed. During the neonatal period, they were evaluated using TEOAEs in response to an 80 dB pSPL click, DPOAE responses to two stimulus conditions (L1 = L2 = 75 dB SPL and L1 = 65 dB SPL L2 = 50 dB SPL), and ABR elicited by a 30 dB nHL click. In an effort to describe test performance, these "at-risk" infants were asked to return for behavioral audiologic assessments, using visual reinforcement audiometry (VRA) at 8 to 12 mo corrected age, regardless of neonatal test results. Sixty-four percent of these subjects returned and reliable VRA data were obtained on 95.6% of these returnees. This approach is in contrast to previous studies in which, by necessity, efforts were made to follow only those infants who "failed" the neonatal screening tests. The accuracy of the neonatal measures in predicting hearing status at 8 to 12 mo corrected age was determined. Only those infants who provided reliable, monaural VRA test results were included in the analysis. Separate analyses were performed without regard to intercurrent events (i.e., events between the neonatal and VRA tests that could cause their results to disagree), and then after accounting for the possible influence of intercurrent events such as otitis media and late-onset or progressive hearing loss. RESULTS: Low refer rates were achieved for the stopping criteria used in the present study, especially when a protocol similar to the one recommended in the National Institutes of Health (1993) Consensus Conference Report was followed. These analyses, however, do not completely describe test performance because they did not compare neonatal screening test results with a gold standard test of hearing. Test performance, as measured by the area under a relative operating characteristic curve, were similar for all three neonatal tests when neonatal test results were compared with VRA data obtained at 8 to 12 mo corrected age. However, ABRs were more successful at determining auditory status at 1 kHz, compared with the otoacoustic emission (OAE) tests. Performance was more similar across all three tests when they were used to identify hearing loss at 2 and 4 kHz. No test performed perfectly. Using either the two- or three-frequency pure-tone average (PTA), with a fixed false alarm rate of 20%, hit rates for the neonatal tests, in general, exceeded 80% when hearing impairment was defined as behavioral thresholds > or =30 dB HL. All three tests performed similarly when a two-frequency (2 and 4 kHz) PTA was used as the gold standard; OAE test performance decreased when a three-frequency PTA (adding 1 kHz) was used as the gold standard definition. For both PTA and all three neonatal screening measures, however, hit rate increased as the magnitude of hearing loss increased. CONCLUSIONS: Singly, all three neonatal hearing screening tests resulted in low refer rates, especially if referrals for follow-up were made only for the cases in which stopping criteria were not met in both ears. Following a protocol similar to that recommended in the National Institutes of Health (1993) Consensus Conference report resulted in refer rates that were less than 4%. TEOAEs at 80 dB pSPL, DPOAE at L1 = 65, L2 = 50 dB SPL and ABR at 30 dB nHL measured during the neonatal period, and as implemented in the current study, performed similarly at predicting behavioral hearing status at 8 to 12

Distortion product otoacoustic emission test performance when both 2f1-f2 and 2f2-f1 are used to predict auditory status.

The objective of this study was to determine whether distortion product otoacoustic emission (DPOAE) test performance, defined as its ability to distinguish normal-hearing ears from those with hearing loss, can be improved by examining response and noise amplitudes at 2 f1-f2 and 2f2-f1 simultaneously. In addition, there was interest in knowing whether measurements at both DPs and for several primary frequency pairs can be used in a multivariate analysis to further optimize test performance. DPOAE and noise amplitudes were measured at 2f1-f2 and 2 f2-f1 for 12 primary levels (L2 from 10 to 65 dB SPL in 5-dB steps) and 9 pairs of primary frequencies (0.5 to 8 kHz in 1/2-octave steps). All data were collected in a sound-treated room from 70 subjects with normal hearing and 80 subjects with hearing loss. Subjects had normal middle-ear function at the time of the DPOAE test, based on standard tympanometric measurements. Measurement-based stopping rules were used such that the test terminated when the noise floor around the 2 f1-f2 DP was < or = -30 dB SPL or after 32 s of artifact-free averaging, whichever occurred first. Data were analyzed using clinical decision theory in which relative operating characteristics (ROC) curves were constructed and areas under the ROC curves were estimated. In addition, test performance was assessed by selecting the criterion value that resulted in a sensitivity of 90% and determining the specificity at that criterion value. Data were analyzed using traditional univariate comparisons, in which predictions about auditory status were based only on data obtained when f2 = audiometric frequency. In addition, multivariate analysis techniques were used to determine whether test performance can be optimized by using many variables to predict auditory status. As expected, DPOAEs were larger for 2f1-f2 compared to 2 f2-f1 in subjects with normal hearing. However, noise amplitudes were smaller for 2f2-f1, but this effect was restricted to the lowest f2 frequencies. A comparison of signal-to-noise ratios (SNR) within normal-hearing ears showed that the 2f1-f2 DP was more frequently characterized by larger SNRs compared to 2f2-f1. However, there were several subjects in whom 2f2-f1 produced a larger SNR. ROC curve areas and specificities for a fixed sensitivity increased only slightly when data from both DPs were used to predict auditory status. Multivariate analyses, in which the inputs included both DPs for several primary frequency pairs surrounding each audiometric frequency, produced the highest areas and specificities. Thus, DPOAE test performance was improved slightly by examining data at two DP frequencies simultaneously. This improvement was achieved at no additional cost in terms of test time. When measurements at both DPs were combined with data obtained for several primary frequency pairs and then analyzed in a multivariate context, the best test performance was achieved. Excellent test performance (ROC) curve areas >0.95% and specificities >92% at all frequencies, including 500 Hz, were achieved for these conditions. Although the results described should be validated on an independent set of data, they suggest that the accuracy with which DPOAE measurements identify auditory status can be improved with multivariate analyses and measurements at multiple DPs.

Cochlear generation of intermodulation distortion revealed by DPOAE frequency functions in normal and impaired ears.

Distortion product otoacoustic emission (DPOAE) frequency functions were measured in normal-hearing and hearing-impaired ears. A fixed-f2/swept-f1 paradigm was used with f2 fixed at half-octave intervals from 1 to 8 kHz. L1 was always 10 dB greater than L2, and L2 was varied from 65 to 10 dB SPL in 5-dB steps. The responses were quantified by the frequency and amplitude of the peak response. Peak responses were closer to f2 in higher frequency regions and for lower intensity stimulation. Results from hearing-impaired subjects suggest that audiometric thresholds at the distortion product frequency, fdp, in addition to hearing status at f2, can affect DPOAE results. Results are discussed in terms of several manifestations of a second resonance model, as well as a dual source model for the generation of DPOAEs as measured in the ear canal of humans. It appears that a dual source model accounts for the data better than second filter models.

Distortion product otoacoustic emission test performance for a priori criteria and for multifrequency audiometric standards.

OBJECTIVES: 1) To describe distortion product otoacoustic emission (DPOAE) test performance when a priori response criteria are applied to a large set of DPOAE data. 2) To describe DPOAE test performance when multifrequency definitions of auditory function are used. 3) To determine DPOAE test performance when a single decision regarding auditory status is made for an ear, based on DPOAE data from several frequencies. 4) To compare univariate and multivariate test performance when multifrequency gold standard definitions and response criteria are applied to DPOAE data. DESIGN: DPOAE and audiometric data were analyzed from 1267 ears of 806 subjects. These data were evaluated for three different frequency combinations (2, 3, 4 kHz; 2, 3, 4, 6 kHz; 1.5, 2, 3, 4, 6 kHz). DPOAE data were collected for each of the f2 frequencies listed above, using primary levels (L1/L2) of 65/55 dB SPL and a primary ratio (f2/f1) of 1.22. Sensitivity and specificity were evaluated for signal to noise ratios (SNRs) of 3, 6, and 9 dB, which are in common clinical use. In addition, test performance was evaluated using clinical decision theory, following the convention we have used in previous reports on otoacoustic emission test performance. Both univariate and multivariate analyses techniques were applied to the data. In addition to evaluating DPOAE test performance for the case when audiometric and f2 frequency were equal, multifrequency gold standards and multifrequency criterion responses were evaluated. Three new gold standards were used to assess test performance: average pure-tone thresholds, extrema thresholds that took into account both the magnitude of the loss and the number of frequencies at which hearing loss existed, and a combination of the two. These new gold standards were applied to each of the three frequency groups described above. RESULTS: As expected, SNR criteria of 3, 6, and 9 dB never resulted in perfect DPOAE test performance. Even the most stringent of these criteria (9 dB SNR) did not result in a sensitivity of 100%. This result suggests that caution should be exercised in the interpretation of DPOAE test results when these a priori criteria are used clinically. Excellent test performance was achieved when auditory status was classified on the basis of the new gold standards and when either SNR or the output of multivariate logistic regressions (LRs) were used as criterion measures. Invariably, the LR resulted in superior test performance compared with what was achieved by the SNR. For SNR criteria of 3, 6, and 9 dB and (by definition) for the LR, specificity, in general, exceeded 80% and often was greater than 90%. Sensitivity, however, depended on the magnitude of hearing loss. Diagnostic errors, when they occurred, were more common for patients with mild hearing losses (21 to 40 dB HL); sensitivity approached 100% once the hearing loss exceeded 40 dB HL. The largest differences between test performance based on SNR or LR occurred for the ears with mild hearing loss, where the LR resulted in more accurate diagnoses. CONCLUSIONS: It should not be assumed that the use of a priori response criteria, such as SNRs of 3, 6, or 9 dB, will identify all ears with hearing loss. Test performance when multifrequency gold standards are used to define an ear as normal or impaired and when data from multiple f2 frequencies are used to make a diagnosis, resulted in excellent test performance, especially when the LR was used. When predicting auditory status with multifrequency gold standards, the LR resulted in relative operating characteristic curve areas of 0.95 or 0.96. An output from the LR can be selected that results in a specificity of 90% or better. When the loss exceeded 40 dB HL, the same output from the LR resulted in test sensitivity of nearly 100%. These were the best test results that were achieved. (ABSTRACT TRUNCATED)

Predicting audiometric status from distortion product otoacoustic emissions using multivariate analyses.

OBJECTIVES: 1) To determine whether multivariate statistical approaches improve the classification of normal and impaired ears based on distortion product otoacoustic emission (DPOAE) measurements, in comparison with the results obtained with more traditional single-variable applications of clinical decision theory. 2) To determine how well the multivariate predictors, derived from analysis on a training group, generalized to a validation group. 3) To provide a way to apply the multivariate approaches clinically. DESIGN: Areas under the relative operating characteristic (ROC) curve and cumulative distributions derived from DPOAE, DPOAE/Noise, discriminant function (DF) scores and logit function (LF) scores were used to compare univariate and multivariate predictors of audiometric status. DPOAE and Noise amplitudes for 8 f2 frequencies were input to a discriminant analysis and to a logistic regression. These analyses generated a DF and LF, respectively, composed of a linear combination of selected variables. The DF and LF scores were the input variables to the decision theory analyses. For comparison purposes, DPOAE test performance was also evaluated using only one variable (DPOAE or DPOAE/Noise when f2 = audiometric frequency). Analyses were based on data from over 1200 ears of 806 subjects, ranging in age from 1.3 to 96 yr, with thresholds ranging from -5 to >120 dB HL. For statistical purposes, normal hearing was defined as thresholds of 20 dB HL or better. For the multivariate analyses, the database was randomly divided into two groups of equal size. One group served as the "training" set, which was used to generate the DFs and LFs. The other group served as a "validation" set to determine the robustness of the DF and LF solutions. RESULTS: For all test frequencies, multivariate analyses yielded greater areas under the ROC curve than univariate analyses, and greater specificities at fixed sensitivities. Within the multivariate techniques, discriminant analysis and logistic regression yielded similar results and both yielded robust solutions that generalized well to the validation groups. The improvement in test performance with multivariate analyses was greatest for conditions in which the single predictor variable resulted in the poorest performance. CONCLUSIONS: A more accurate determination of auditory status at a specific frequency can be obtained by combining multiple predictor variables. Although the DF and LF multivariate approaches resulted in the greatest separation between normal and impaired distributions, overlap still exists, which suggests that there would be value in continued efforts to improve DPOAE test performance.