Early ABRs in Infants Undergoing Assisted Ventilation

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.
REFERENCES
Avery ME, Tooley WH, Keller JB, Hurd SS, Bryan MH,
Cotton RB, Fitzhardinge PM . (1987) . Is chronic lung
disease in low birthweight infants preventable? Asurvey
of eight centers. Pediatrics 79 :26-31 .
Clark RH, Gertsman DR, Null DM Jr . (1990) . Highfrequency oscillatory ventilation reduces the incidence of
severe chronic lung disease in respiratory distress syndrome. Am Rev Respir Dis 141:686 (Abstr).
Cox LC . (1984). The current status of auditory brainstem
response testing in neonatal populations. Pediatr Res
18 :780-783 .
Cox LC, Hack M, Metz DA. (1984) . Auditory brainstem
response abnormalities in the very low birthweight infant : incidence and risk factors. Ear Hear 5:47-51 .
Eggermont JJ, Salamy A. (1988) . Development of ABR
parameters in preterm and term born population . Ear
Hear 9:283-291 .
Fria TJ, Doyle WJ . (1984) . Maturation of the auditory
brainstem response (ABR): additional perspectives . Ear
Hear 5 :361-365 .
Hecox K. (1975) . Electrophysiological correlates of human auditory development. In : Cohen L, Salapateck P,
eds. Infant Perception . Vol 2. NewYork : Academic Press,
151-191.
Hecox K, Burkard R. (1982) . Developmental dependencies of the human brainstem auditory evoked response.
Ann N YAcad Sci 308 :539-556 .
HIFI Study Group. (1989) . High-frequency oscillatory
ventilation compared with conventional mechanical ventilation in the treatment of respiratory distress syndrome . NEngl JMed 320 :88-93 .
Krumholz A, Felix JK, Goldstein PJ, McKenzie E. (1985).
Maturation of the brainstem auditory evoked potential
in premature infants . Electroencephalogr Clin
Neurophysiol 62 :124-134 .
Marchak BE, Thompson WK, Duffty P, Miyak T, Bryan
MH, Bryan AC, Froese AB . (1981) . Treatment of RDS by
high-frequency oscillatory ventilation : a preliminary report . J Pediatr 99 :287-292 .
Starr A, Amlie RN, Martin WH, Saunders S. (1977) .
Development of auditory function in newborn infants as
revealed by auditory brainstem potentials . Pediatrics
60 :831-839.