



* Department of Communication Studies/Communication Sciences and Disorders, Dyson College of Arts and Sciences, Pace University, New York, New York
Audiology and Speech Pathology Division, Department of Otolaryngology/Head and Neck Surgery
Department of Pediatrics
|| Irving Center for Clinical Research, Columbia University Medical Center, New York, New York
| ABSTRACT |
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Method. Analysis of electrophysiologic measures and medical record reviews of the first 22 months of the universal newborn hearingscreening program was conducted. Association of the AN/AD profile was evaluated with the following factors: gender, gestational age, ototoxic drug regimen, low birth weight, hyperbilirubinemia, hydrocephalus, low Apgar score, anoxia, respiratory distress syndrome, pulmonary hypertension, intraventricular hemorrhage, multiple birth, seizure activity, and family history.
Results. One hundred fifteen (24.1%) of the 477 infants failed the ABR in 1 or both ears and passed OAEs bilaterally. Comparisons of infants fitting the AN/AD profile with those not fitting the AN/AD profile were negative with 3 exceptions: those with hyperbilirubinemia and those who were administered vancomycin or furosemide. A logistic-regression analysis model failed to predict which infants would be at risk for the AN/AD profile either unilaterally or bilaterally.
Conclusions. Screening of NICU infants should be conducted with ABR first, followed by OAE after failure on ABR. Because the incidence of the AN/AD profile was found to be 24% in this at-risk population, additional study is warranted.
Key Words: auditory neuropathy/dyssynchrony newborn hearing screening infants hyperbilirubinemia ototoxicity auditory brainstem response otoacoustic emissions neonatal intensive care prematurity
Abbreviations: ABR, auditory brainstem response OAE, otoacoustic emission CM, cochlear microphonics AN, auditory neuropathy AD, auditory dyssynchrony GA, gestational age CUMC, Columbia University Medical Center DPOAE, distortion-product otoacoustic emission
Techniques currently used in newborn hearing screening can discriminate peripheral (ie, cochlear) from central (ie, brainstem) auditory function. Two-phase screening using 2 different electrophysiologic measures, otoacoustic emissions (OAEs) and auditory brainstem response (ABR), allows detection of various failure patterns and provides more complete information about auditory function. State-mandated newborn hearing screening was introduced in New York State in 2001; however, as in many states, no specific electrophysiologic screening tool was prescribed.
A specific failure pattern is the presence of OAEs and/or cochlear microphonics (CM) with the absence of ABR. Auditory neuropathy/auditory dyssynchrony (AN/AD) disorder is manifested by normal outer hair cell function and abnormal, absent, or dyssynchronous neural function at the level of the VIIIth nerve.1, 2 Acoustic reflexes are absent and pure-tone audiometric findings range from near normal to severe-profound thresholds.3, 4 In addition, children with AN/AD often have speech perceptual difficulties, particularly in noise, which may make them functionally deaf.47 Table 1 reviews current literature and etiologic contributions to AN/AD in children.2, 4, 710
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The purpose of this study was to report the outcome of 2 electrophysiologic measures in a cohort of infants admitted to a neonatal intensive care unit (NICU). In view of findings in the literature, which demonstrated that the AN/AD profile could only be discovered with a combined method of ABR and OAE, 2-phase screening was introduced at the end of 2002 and was aimed specifically at this high-risk cohort. The literature suggested an association of the AN/AD profile with multiple etiologic factors. In this study, the following 3 questions were asked: (1) What is the incidence of absent ABRs and present OAEs in the NICU population? (2) Can the AN/AD profile be predicted from the following variables: gender, gestational age (GA), ototoxic drug regimen, low birth weight, hyperbilirubinemia (bilirubin level of >12 mg/dL in term infants or >0.5/kg in preterm infants), hydrocephalus, low Apgar scores, anoxia, respiratory distress syndrome, pulmonary hypertension, intraventricular hemorrhage, multiple birth, seizure activity, or family history? (3) What is the relative proportion of unilateral and/or bilateral auditory findings?
| METHODS |
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Risk factors were extracted from medical records of the entire NICU cohort. Auditory failure patterns were recorded. One individual coded data, which were verified/reviewed by the 3 senior authors. Nonparametric and a logistic-regression analyses were used to determine if risk factors were predictive of the AN/AD profile.
Study Subjects
Subjects were drawn from NICU discharges from March 2002 to December 2003 at the CUMC Morgan Stanley Children's Hospital of New York-Presbyterian in New York City, New York. Criteria for admission to the NICU included premature infants at <36 weeks' gestation and/or with a birth weight of <1800 g; term infants with suspected or established sepsis; infants with congenital anomalies; infants with elevated bilirubin levels requiring exchange transfusion (term infants: 20 mg/dL; preterm infants: variable and dependent on weight and etiology) and/or phototherapy (term infants: at 2/3 exchange level; preterm infants: at exchange level); metabolic illness; infants requiring surgical correction of anomalies; infants of mothers with insulin-dependent diabetes; or infants requiring closer monitoring or evaluation than could be provided in the well-infant nursery.
Of the 1736 admissions in this time period, 477 infants were screened with ABR first and OAEs second if they failed the ABR. The remaining 1259 infants were transferred back to referring hospital and were not required to have a hearing screen at this site (378 infants); expired (96 infants); received only 1 electrophysiologic measure (628 infants); had a positive ("referred") finding on both the ABR and OAE (89 infants); or were missed and therefore not screened (68 infants).
Study Procedures
The newborn hearingscreening program at CUMC began in March 2002. Infants admitted to the NICU were screened initially by using OAE technology. In late 2002, based on literature review, screening protocols were modified. All NICU infants were screened initially with ABR and underwent OAE screening when they failed ("referred") on ABR. The medical records were examined for the following factors: gender, GA, birth weight, presence or absence of respiratory distress, presence of hyperbilirubinemia, administration of ototoxic medications, multiple births, seizures, and family history. Potentially ototoxic medications (gentamicin, vancomycin, and furosemide) were coded to indicate that they were not given, given at subclinical or nontoxic levels versus potentially injurious levels, or determined by blood samples when therapy lasted >48 hours.
Infants were tested by using the ABaer system (Bio-logic Corp, Mundelein, IL) with the following preset OAE and ABR screening parameters. Infants were screened by using distortion-product OAEs (DPOAEs), set at a 2- to 5-kHz screen with 3 of 4 frequency bands required present for a pass. Intensity was calibrated at a 65-dB sound pressure level for band 1 and 55-dB sound pressure level for band 2. Parameters for the ABR included a 100-microsecond click stimulus, alternating polarity, a click rate of 37.1 clicks per second, and an intensity of 35-dB nHL. The low-pass filter was set at 1500 Hz, and the high pass filter was set to 100 Hz; a minimum of 1536 sweeps up to a maximum of 2 trials of 6144 sweeps were obtained. A patented signal-detection algorithm, point-optimized variance ratio, determined the presence of an ABR and assigned a pass or refer result. A point-optimized variance ratio score of 3.50 was necessary for a pass. The specificity of the screening ABR test is in excess of 98.5%. The verified theoretical sensitivity for the bilateral ABR test is >99.96% (G. Raviv, PhD, Bio-logic Corp, written communication, 2005).
| RESULTS |
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2 results were significant (P < .01) in all comparisons for hyperbilirubinemia (df = 1,N = 477; P = .0001), vancomycin (df = 1,N = 475; P = .007), and furosemide (df = 1,N = 475; P = .005).
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Laterality and Bilaterality
Of the 115 infants who fit the AN/AD profile, ABRs were absent in 35 (30.4%) with right ear stimulation, 53 (46%) with left ear stimulation, and 27 (23.5%) for both ears. That is, 88 (76.5%) were affected unilaterally, and 23.5% were affected bilaterally.
| DISCUSSION |
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AN/AD can occur in the absence of any other apparent medical condition6; however, a perinatal history of hyperbilirubinemia, anoxia, or infectious diseases (one or more of these) are all factors.8, 23, 24 Familial patterns of inheritance,10, 25 syndromic and nonsyndromic recessive inheritance,26, 27 have been described also. It is interesting to note that in this cohort, no family history of hearing dysfunction was reported (see Table 2). Thus, etiologic factors associated with AN/AD remain unclear. Reports of AN/AD, from single case studies27, 28 to small samples,4, 9, 29 have provided limited insight. Sininger30 reviewed the incidence of the AN/AD profile in NICU infants and found a range in the literature extending from 5.3% to 14.8% (mean: 10.8%).
The present study found an incidence estimate of 24.1% of the AN/AD profile in the NICU, a higher rate than has been reported previously. It is possible that this cohort reflects a more at-risk population because it is a regional perinatal center site. Of course, neurologic immaturity may have been a factor here, and additional follow-up will confirm the AN/AD diagnosis. Regarding incidence, Rance et al8 found in a retrospective study that 20 (0.38%) of the 5199 children assessed between 1991 and 1996 had absent ABRs and present CM. Of the 5199 infants, 109 (2.09%) had some type of permanent hearing deficit. Of the 109 infants identified with some type of hearing loss, 11% (1 in 9) were subsequently diagnosed with AN/AD, and 97 (89%) were subsequently diagnosed with a sensory-type hearing loss.
Hall et al31 concluded that the combined ABR/OAE screening was the only means to avoid missing infants with the AN/AD profile. They suggested 2 feasible approaches: (1) use the combined ABR/OAE-screening method on those infants with neurologic risk factors or (2) use the combined ABR/OAE-screening method on all infants who are admitted to the NICU. In our sample, the risk factors did not prove sensitive enough to identify the bulk of infants who fit the AN/AD profile; thus, the second approach (ie, 2-phase screening using both ABRs and OAEs of all NICU discharges) is recommended. Programs implementing only OAEs in their NICU test protocol will miss this profile. It should be noted that an all-ABR protocol would also refer appropriate infants into a diagnostic setting, although the administration of the OAE heightens the alert and is easily administered.
A recent study by de Hoog et al32 found that serum concentrations above the therapeutic range of vancomycin, tobramycin, or furosemide were not related to failure on automated ABR in at-risk neonates. Of all risk factors analyzed in the present study, only 3 (hyperbilirubinemia and administration of vancomycin and furosemide) had any discriminating power. However, when using the powerful logistic-regression tool, no factors or combinations were effective in predicting the AN/AD profile. There are possible explanations for this result: (1) insufficient statistical power; (2) this NICU population is so diverse that 1 profile could not be developed to distinguish between the 2 groups; or (3) there may be other factors that are presently unknown. Starr21 reports that etiology is unknown in 40% of individuals with AN/AD. Our data echo this finding.
Approximately one third (33.9%) of infants with the AN/AD profile had a GA of
38 weeks. This finding suggests that, for all intents and purposes, these children were admitted to the NICU for reasons other than prematurity and may well have been missed had they been admitted to the well-infant nursery, in which an OAE-screening technique is typically used. Of the 20 infants that Rance et al8 examined and ultimately diagnosed with AN/AD, 13 (65%) had a GA of
38 weeks, also supported by our findings.
Consistent with Starr,21 there seems to be no gender preference in our sample. In contrast to his findings of 96% of cases having bilateral AN/AD results, our sample reflected a large proportion (88 [76%]) of unilateral findings of the AN/AD profile, supporting the concept that diagnostic evaluation is critical to confirm AN/AD.
Clearly, the next step is longitudinal evaluation of these children. A study is under way to clarify how many cases with the AN/AD profile represent auditory immaturity, transient neurologic abnormality,33, 34 or AN/AD. Care must be taken not to diagnose AN/AD without sufficient evidence. All of the following assessments should be included for an infant AN/AD work-up: ABR using separate trials of condensation and rarefaction clicks; OAEs; acoustic reflex threshold testing or middle-ear muscle testing; and behavioral audiometry using visual reinforcement audiometry.5, 34 Consideration should be given to the use of slower than typically administered ABR click rates (ie, 11.1 per second for enhancement of waveform morphology). Now that universal newborn hearing screening is mandated in 38 states and the District of Columbia (as of 2004), the ability to detect the AN/AD configuration of findings is something that we must be prepared to recognize and address.
| ACKNOWLEDGMENTS |
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| FOOTNOTES |
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Address correspondence to Abbey L. Berg, PhD, Department of Communication Studies/Communication Sciences and Disorders, Pace University, 1 Pace Plaza, New York, NY 10038. E-mail: aberg{at}pace.edu and alb35{at}columbia.edu
No conflict of interest declared.
| REFERENCES |
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