J Am Acad Audiol 4: 13-17 (1993) Early ABRs in Infants Undergoing Assisted Ventilation L. Clarke Cox* Richard J. Martint Waldemar A. Carlot Maureen Hack t Abstract ABR was performed on 42 preterm infants undergoing assisted ventilation with conventional or high-frequency oscillatory ventilation (HFOV) . ABRs from these very young neonates were evaluated to further detail the emerging response and to determine if type of ventilation or other perinatal factors had effects on the ABR . While responses were present down to 26 weeks gestational age, the only factors which appeared related to absent ABRs were birthweight and gestational age . Key Words: Auditory brainstem response (ABR), gestational age (GA), high-frequency oscillatory ventilation (HFOV), maturation, neonatal intensive care unit (NICU) ypical ABRtesting in the neonatal intensive care unit (NICU) occurs when inT fants are older, stable, and ready for discharge. While this protocol is prudent because it reduces the number of infants who fail the ABR, it has produced a paucity of data on the emerging human ABR. While limited, there are studies reporting ABR data on infants whose gestational age (GA) was less than 30 weeks (Starr et al, 1977 ; Hecox and Burkard, 1982 ; Krumholz et al, 1985). Recently in a study involving assisted ventilation of preterm infants, there occurred an opportunity to test very young infants with ABR thereby providing additional information on the emerging response . While assisted ventilation has improved the survival rate of preterm infants with respiratory distress syndrome (RDS), there exists a high incidence of neonatal lung injury associated with barotrauma (Avery et al, 1987). Efforts to reduce lung injury have employed various forms of high-frequency ventilation, such as *Department of Otolaryngology, Boston University Medical Center, Boston, Massachusetts ; and t Department of Pediatrics, Rainbow Babies & Childrens Hospital, Cleveland, Ohio Reprint requests : L . Clarke Cox, Department of Otolaryngology, 720 Harrison Ave ., Suite 601, Boston, MA 02118 high-frequency oscillatory ventilation (HFOV), as an alternative to conventional mechanical ventilation (Marchak et al, 1981). In a large multicenter study (HIFI Study Group, 1989), HFOV was found to offer no advantage over conventional ventilation, although some authors continue to report that HFOV may reduce the incidence of chronic lung disease in neonates with RDS (Clark et al, 1990). The impact of HFOV on other organ systems is relatively unknown, even though HFOV produces considerable body vibration that may affect neural or auditory system structures . The auditory brainstem response (ABR) test has been documented as an effective measure of neural and auditory function . Studies have repeatedly shown that the ABR can be used to assess auditory and neural structures in the preterm infant (Cox, 1984). There were two purposes of the present study. The first was to determine if HFOV, when compared to conventional ventilation, produced differential effects on the auditory or neural system as determined by ABR. The second was to gather additional data on the emerging ABR response . METHOD he study population that comprises this T report was enrolled in the multicenter 13 Journal of the American Academy of Audiology/Volume 4, Number 1, January 1993 HIFI trial that evaluated the efficiency of HFOV versus conventional ventilation (HIFI Study Group, 1989). Forty-two preterm infants (gestational age 24-32 weeks, birthweight 7601600 g) randomized to conventional ventilation (n = 25) or HFOV (n = 17) were tested with ABR. Initial testing was accomplished approximately 48 hours after intubation and again just prior to hospital discharge. Test protocol consisted of attaching silver chloride electrodes to the forehead (noninverting), ipsilateral mastoid (inverting) and shoulder (ground) . Click stimuli (0 .1 msec) presented at 22 per second were delivered to a monaural earphone (THD49), which was held over the pinna. Two thousand sweeps were amplified (10^) and averaged (Cadwell 5200 or Teledyne TA 1000) with each run being replicated twice . Response presence was determined by a repeatable wave V. The infants were kept in their isolette housed in the NICU with all support and monitoring equip- Table 1 Factors Influencing the Initial ABR Assessment Passed (n = 23) Factor Birthweight in g (Mean and SD) a/AOZ/Paw Sex t p 1092+222 964+ 157 2.06 045* 29+2 27+ 2 203 048* 3.8 ± 2.3 6.8+ 1 .4 3.2 ± 1 .6 6 .4 ± 2.1 87 76 388 451 033 ± .02 51 613 . 038+ .04 (24-26 weeks) Female 3 (27-29 weeks) Female Male Female Male 6 (75%) 6 (55%) 5 (100°%) 5 (83%) (30-32 weeks) Male ABR Failed (n = 19) Gestational age in weeks (Mean and SD) Apgar 1 min 5 mins ment operational. Ambient acoustic noise levels in the test area were in the 65 to 75 dBA range. While it was recognized that the NICU represents a hostile recording environment, the authors made a conscious decision to test in this environment because it was not feasible to move the infant to a more favorable test location . Every effort was made to reduce electric and acoustic noise . If acoustic levels became elevated, or if extraneous electric activity was noted in the ongoing EEG, averaging was stopped until desired levels were seen . ABR failures on initial testing were designated by absent responses at 90 dB nHL (120 peSPL) . It was our intent at the outset of the study to use serial ABRs to evaluate individual ear response differences and generate data at different intensity levels to tease out possible subtle effects. We soon discovered, however, that if 24- to 26-week-old infants responded, they did so only at high intensities and that 1 (60%) (14%) X, p 2 (40%) 6 (86%) 2.74 102 41 530 0 93 315 2 (25%) 5 (45%) 1 (17%) IV bleed Grade III or IV Hemorrhage 3 No Hemorrhage 20 (43%) (60%) 15 (40%) 4 (57%) 57 326 Mortality Lived pied 22 1 (56%) (33%) 17 (44%) 2 (67%) 66 345 Pneumothorax Yes No 1 22 (20%) (59%) 15 (41%) 4 (80%) 2 .94 071 Respirator type HFOV Conventional 11 12 (64%) (48%) 6 (36%) 13 (52%) 90 251 *p < .05 . 14 FI til c l`~I alto Ill l~ll~lllllll i Early ABRs/Cox et al Baby A Baby B 90 dB 90 dB 27 Weeks GA 26 Weeks GA 0 d8 0dB 10 msec 43 Weeks GA 30 dB 10 cosec 44 Weeks GA 30 dB 10 cosec Figure l infant . Example of repeatable ABR in a 26-week GA there were no unilateral asymmetries; i.e ., ifthe response was present in one ear it was present in the other, and if absent in one ear it was also absent on the opposite side . Repeat ABR testing was effected just prior to hospital discharge . Test protocol was similar to initial testing but differed in several areas. The infants were tested in an open crib located in a quiet room . Electrode position was similar except for the ground that was attached to the contralateral mastoid . High and low click intensities (70 and 30 dB nHL) were used and ABR failure was determined by absence of repeatable responses at 30 dB nHL in either ear . Data acquisition was accomplished with either a Cadwell 5200 or a Nicolet CA 1000 . Statistic comparison of the two types of ventilators was effected with the Chi-square test . In addition, other factors that may have been related to the ABR outcome were also analyzed with Chi-square or t-test measures . These included sex, birthweight, gestational age, Apgar scores, respiratory insufficiency index (a/AOZ/Paw, expressed as mm Hg per centimeter of H20, which is the arterial/alveolar oxygen ratio divided by mean airway pressure), grade III or IV intraventricular hemorrhage, pneumothorax, and mortality. Analysis of the sex data was completed in a stratified manner to account for the sizeable difference in gestational age between the male and female Figure 2 Example of ABR responses initially absent, but present at discharge in a 27-week GA infant . subjects (X GA = 27 .5 vs 29 .3 weeks for males and females, respectively) . Gestational age was determined from the maternal history and confirmed by a combined physical/neurologic assessment of each infant . The former was used for gestational assessment unless there was a discrepancy of at least 2 weeks between maternal dates and the infant evaluation, in which case the latter was employed . Baby C 9.8 90 dB 31 Weeks GA O dB 42 Weeks GA t uv . 30 dB 6 Figure 3 Example of responses present initially, but absent at discharge in a 31-week GA infant . Journal of the American Academy of Audiology/Volume 4, Number 1, January 1993 Table 2 Distribution of Infants with ABRs by Age and Mean Wave V Latency GA n Number with ABR 24 1 0 7 4 25 26 3 8 28 29 30 7 5 4 27 31 32 4 4 0 4 3 4 3 4 4 X Wave V Latency (MS) Range 0 0 50 57 43 10 .42 10 .34 10 .26 8 .94-11 .24 9 .20-11 .00 9 .70-10 .91 75 100 9 .98 9 .43 8 .86-11 .83 8 .65-10 .17 80 100 RESULTS ineteen (45%) of 42 infants failed the iniN tial ABR test . Results shown in Table 1 suggest that while ventilator type had no significant effect on passing or failing the ABR, birthweight and gestational age did. Of the 39 surviving infants, only three (7 .5%) failed (no response at 30 dB nHL) the ABR just prior to hospital discharge. These three failures were later attributed to transient middle ear disorder based on subsequent otoscopic examinations and acoustic immittance testing in concert with a complete ABR evaluation . These data confirmed a mild conductive hearing loss with cochlear, eighth nerve and brainstem integrity. Figures 1 to 3 illustrate typical responses observed in the study population . Figure 1 shows a 26-week GA, 860 g infant with an ABR. While waveform morphology is poor, the response was repeatable . It appears that waves I and III are present. Figure 2 illustrates a 27-week-old infant whose ABR was initially absent but did appear just prior to discharge . Figure 3 shows results in a 31-week-old infant whose responses were present at birth but absent just prior to discharge. We found that ABR waves could be elicited earlier than previously reported . Table 2 illustrates that four of eight infants at 26 weeks GA and four of seven at 27 weeks GA exhibited responses . We also found that as the infants matured, they were more likely to have a response . We also discovered that females were more likely to have responses at 26 weeks GA, but at 30 to 32 weeks GA males and females were equivalent . Table 2 also provides mean data for wave V latency. It is important to realize that these data represent small Ns and that precise peak latency determination was challenging given waveform morphology. 16 9.82 9.49 8.76-11 .22 8.77-10 .24 DISCUSSION T he present study was undertaken to gather additional data on the emerging ABR and to see if body vibration associated with the administration of HFOV affected auditory or neural structures as determined by ABR. The absence of significant differences suggests that HFOV does not produce ABR-detected undesirable auditory or neural side effects. While more HFOV infants passed the ABR than did not, failure to reach levels of significance precludes support for improvement of ABR with HFOV. Analysis of additional factors suggests that those infants who failed the ABR were of lower birthweight and gestational age. While there is a paucity of ABR data on preterm infants less than 30 weeks of age, published results are consistent with our findings . Starr et al (1977) reported that although auditory cortical responses were present, brainstem responses were absent in infants less than 28 weeks gestational age. Hecox and Burkard (1982) reported that the earliest age ABR could be elicited was between 28 and 30 weeks. Krumholz et al (1985) tested three infants 25 to 27 weeks conceptional age and found that consistent responses were absent . Between 27 and 29 weeks, however, three of five infants exhibited reproducible responses . The mean gestational age for the 42 infants studied was 28 weeks, the age at which the ABR reportedly begins to emerge. The mean age of infants who exhibited an ABR was 29 weeks, which is older than the expected age for the appearance of the ABR response . In contrast, the mean gestational age of infants with an absent ABR was 27 weeks, which is at the expected age of ABR appearance . At birth the auditory peripheral system (cochlea and eighth cranial nerve) and caudal brainstem are anatomically mature in the term infant (Hecox, 1975). Functional maturation of Early ABRs/Cox et al these structures, however, continues for the next 36 months (Fria and Doyle, 1984). During this time the ABR exhibits predictable changes in response waveform latency, amplitude, and appearance . Infants born preterm exhibit immature ABR responses characteristic of their age that mature on the same schedule as their term counterparts (Eggermont and Salamy, 1988). The absence of identifiable responses below 28 weeks presumably is due to the immaturity of the auditory brainstem. Based on this assumption, gestational age could account for the ABR failures seen in this study since the mean age of the failure group fell below the age of expected ABR response . The significant differences associated with birthweight could also be attributed to gestational age since the younger infants who failed the ABR would logically also weigh less . Based on these data it would seem possible that gestational age may have been the contributing factor to all the significant differences seen . We conclude from our study that the ABR can be elicited in 26-week GA infants. While waves I, III, and V are present, wave V appears to be the most robust . Responses below 26 weeks GA are not present or are difficult to detect. While we detected ABRs at a younger age than previously reported, these unique data must be tempered along with all other reported studies due to the error inherent in determining age at birth . We also conclude that ventilator type, respirator insufficiency, hemorrhage, etc. do not affect the ABR, while GA and birthweight do . We would issue a caveat with respect to effecting very early ABR testing. While the above data suggest that responses can be obtained in infants down to 26 weeks GA, it would be unwise to expect that ABR testing could be routinely carried out on such young infants. The fact that responses can only be elicited at high levels and are absent in many infants would negate this practice . Furthermore, these infants are typically sick with complications of premature birth, i.e ., RDS, acidosis, apnea, etc., which collectively can compromise the ABR (Cox et al, 1984). For routine ABR screening it is well to wait until the infant is stable and older. On the other hand, if possible, early testing with serial ABRs should be considered to further our knowledge about the emerging and maturing ABR. 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