Seminars in Fetal & Neonatal Medicine (2006) 11, 444e451

a v a i l a b l e a t w w w. s c i e n c e d i r e c t . c o m

j o u r n a l h o m e p a g e : w w w. e l s e v i e r. c o m / l o c a t e / s i n y

Brainstem auditory evoked response in neonatal neurology

Andrew R. Wilkinson*, Ze D. Jiang
Neonatal Unit, Department of Paediatrics, University of Oxford, John Radcliffe Hospital, Headington, Oxford OX3 9DU, UK

KEYWORDS
Brainstem auditory evoked response; Evoked potentials; Neonatal hearing; Auditory impairment; Neural development; Brainstem

Summary Over the last three decades, the brainstem auditory evoked response (BAER) has been used to assess functional integrity and development of the auditory system and the brain in conditions that affect the brainstem auditory pathway. As a non-invasive objective test, BAER is particularly suitable in very young or sick infants. It is the major tool to detect hearing impairment in high-risk infants, and a component in universal hearing screening. BAER is also a valuable adjunct to detect neurological impairment in many developmental disorders and functional abnormalities in a range of neurological diseases. The maximum length sequence (MLS) technique has recently been incorporated into neonatal BAER study. Recent results indicate that the MLS has the potential to improve the diagnostic value of BAER in some clinical situations, although the wider utility of this relative new technique remains to be further explored. 2006 Elsevier Ltd. All rights reserved.

Introduction
The brainstem auditory evoked response (BAER) or potential (BAEP) reects electrophysiological activity of a large number of neurons in the brainstem auditory pathway following acoustic stimulation. The BAER is the far-eld reection of sequentially activated neurons at successively higher levels of this pathway. The responses are very small compared with the electroencephalographic background activity, and it is necessary to average more than 1000 individual stimulations to improve the signal-to-noise amplitude ratio.

* Corresponding author. Tel.: 44 1865 221355; fax: 44 1865 221366. E-mail address: andrew.wilkinson@paediatrics.ox.ac.uk (A.R. Wilkinson).

After averaging several thousand times, the waveforms of BAER can be distinguished by signal averaging linked to the stimuli. The submicrovolt deections in BAER occur in the rst 10 ms after the stimuli and are identied as waves IeVII after Jewett and Williston in 1971. In the last three decades, non-invasive electrophysiological examination of the functional integrity of the brainstem and the auditory system in the neonate has focused on BAER. Technically BAER is easier to record than visual or somatosensory evoked potentials. The BAER can be used to assess peripheral auditory function e and also the functional integrity and development of the brain in general e in conditions that affect the brainstem auditory pathway. BAER is a non-invasive objective test that is unaffected by sedatives, general anaesthetics, or anticonvulsants, and so is particularly suitable in very young or sick patients. In neonatology, BAER has been widely used to

1744-165X/$ - see front matter 2006 Elsevier Ltd. All rights reserved. doi:10.1016/j.siny.2006.07.005

BAER in neonatal neurology study hearing and central neural function in various conditions such as perinatal asphyxia, fetal growth restriction, meningitis, hyperbilirubinaemia, and intraventricular haemorrhage (IVH). In this article, we review some recent advances in the use of BAER in neonatal neurology.

445 maturational changes up to term, and then more slowly in infancy. The most reproducible and easily denable components are waves I, III, and V. Waves II, VI, and VII are often too variable to allow systematic study and wave IV is sometimes fused with wave V. The latencies of the most prominent three BAER components (I, III, and V) decrease as a function of gestation, with a maximal shift occurring in the weeks prior to 34 weeks gestation. The maturational changes continue after term, although more slowly, up to approximately 2e4 years of age. The maturational phases of BAER parallel the critical period of brainstem myelination, axonal sprouting, increase in axonal diameter, development of central dendritic properties, formation of central synaptic connections, and improvement of synaptic efciency, summation, synchronization, and phase-locking capabilities of the auditory system. The decrease in the latency of wave I and BAER threshold with maturation indicates improvement in peripheral processing of the auditory stimulus, which is related to improvement of middle-ear conduction, the cochlear receptors, or the transduction of cochlear receptor potentials into VIIIth nerve activity (i.e. wave I). The maturational changes in BAER later waves e i.e. a decrease in wave latencies, interpeak intervals and threshold, and an increase in wave amplitudes with the increase in age e reect the change in myelination, axon diameter, and synaptic efcacy in the brainstem auditory pathways. Study of maturation of BAER can gain insight into the development of the auditory brainstem.

Neural origin and development during the neonatal period

The BAER consists of a sequence of seven positive waves occurring in the rst 10 ms after the stimuli. These represent neural activity at different levels of the brainstem auditory pathway (Fig. 1). There is evidence to suggest that BAER waves I and II are generated in the extracranial and intracranial portions of the VIIIth nerve, respectively. Subsequent waves IIIeVII are generated in auditory centres at gradually higher levels of the pathway, with partially overlapping contributions to individual waves. Wave III is derived from the cochlear nucleus; wave IV is generated in the superior olivary complex; and wave V e together with the negative potential that follows it e is generated in the region of the lateral lemniscus and possibly inferior colliculus. Waves VI and VII are likely to originate from the inferior colliculus, although the exact origins remain to be determined. The human brainstem auditory pathway is anatomically formed at about 26 weeks of gestational age (GA) and develops rapidly thereafter. The BAER can be rst recorded as early as 26 weeks GA, and can be more reliably recorded by 28 weeks GA. From that time on, BAER shows dramatic

Neonatal hearing screening

Normal language and social and learning skills are dependent on hearing. Therefore, early identication of infants with hearing impairment is important. Moreover, the relatively high incidence of impairment in survivors of neonatal intensive care identies a well-dened population for screening. Recently, universal screening of all neonates has been recommended.1e10 The risk factors for hearing impairment e and for which BAER screening was recommended by the Joint Committee on Infant Hearing in 1994 e include a family history of hearing loss, in utero infections, craniofacial anomalies, birth weight <1500 g, severe hyperbilirubinaemia, ototoxic medications, bacterial meningitis, perinatal asphyxia, mechanical ventilation >5 days, and stigmata suggestive of a syndrome associated with hearing loss. The most commonly recommended screening procedure for preterm infants consists of BAER testing of the infant just prior to hospital discharge, or at least as close to 40 weeks post-conception as possible when he or she is medically stable, and preferably in a room separate from the neonatal unit.1,2,5,6,9 The combination using otoacoustic emissions and BAER provides much more information than either alone, and both are needed for a comprehensive hearing screening program.1e3,7,10 The initial screening procedure consisted of automated auditory evoked response, or transient evoked otoacoustic emissions, which measures sounds in the ear canal that are generated and emitted by the outer hair cells of the cochlea in response to acoustic stimulation. This technique is quicker and less expensive than BAER but misses

Figure 1 Neural origin of the brainstem auditory evoked response (BAER). VIII N, auditory nerve; E, extracranial; I, intracranial; DCN, dorsal cochlear nucleus; VCN, ventral cochlear nucleus; NTB, trapezoid body; SOC, superior olivary complex; LL, lateral lemniscus; IC, inferior colliculus; MGN, medial geniculate nucleus; and AC, auditory cortex.

446 retrocochlear abnormalities (e.g. auditory neural disease). Consequently, BAER screening is more suitable. Infants who fail otoacoustic emissions are re-tested by BAER. The incidence of failure of either screening test at the time of hospital discharge is relatively high. Re-testing after failure is best carried out at approximately 2e6 weeks of age when the large majority will have normal responses,5,6 suggesting that the initial failures were transient, reversible disturbances or false-positive results. The fact that hearing deficits develop in the rst months of life, after normal results in the neonatal period, emphasizes the importance of re-test after the neonatal period or after discharge from hospital. Increased evidence indicates that the universal hearing screening of neonates with and without audiological risk factors is feasible and effective.1,2,9

A.R. Wilkinson, Z.D. Jiang rate-dependent change decreased signicantly in IeIII interval, but increased signicantly in IIIeV interval and IIIeV/Ie III interval ratio. The IeIII interval decreased signicantly at higher click rates while the IIIeV interval and IIIeV/IeIII interval ratio increased signicantly at 21/s, 51/s, and particularly at 91/s. These results suggest that very-preterm infants have an advanced peripheral development of the brainstem auditory pathway, which is probably related to the earlier exposure to a sound environment ex utero, but a delayed central development, which may be related to the associated perinatal conditions.

Detecting neurological abnormalities

The brainstem auditory pathway is anatomically close to many other pontomedullary structures. The BAER has been well documented to change with neurological maturation and to vary with functional integrity of the brainstem. As the BAER assesses integrity of the ascending auditory neuraxis projecting through the brainstem, abnormalities may reect more diffuse injury to the structures along the auditory pathway. Following the introduction of BAER for the assessment of hearing, it has been extended to assessing neural integrity in the brainstem and the brain in a range of clinical conditions that affect the brainstem auditory pathway. Abnormalities in BAER have been found in a range of neonatal diseases, particularly during acute disturbances of neurological function. In BAER, the IeV interpeak interval is widely regarded as reecting the functional status of the auditory brainstem and central auditory conduction time. An increased IeV interval is the most frequent abnormal nding in neurological diseases. Recently, in a detailed analysis of IeIII and IIIe V intervals, Jiang et al. found that the two components of the IeV interval provide additional information regarding functional integrity at different parts of the auditory brainstem, i.e. the more peripheral or caudal (IeIII interval) and more central or rostral parts (IIIeV interval).13,14 The two intervals showed some differential changes in certain clinical conditions, e.g. very-preterm birth and chronic lung disease.13,14 In addition to these interpeak intervals, the absence of waves e particularly later components such as wave V e has been seen in brainstem tumour, a reduction in wave V amplitude and V/I amplitude ratio in perinatal asphyxia,15 and in infants born to mothers known to have abused alcohol during pregnancy.

Assessing neural development

BAER enables quantitative assessment of functional maturation of the auditory pathway and the central nervous system in general. This has typically been shown in studies of the effect of preterm birth and intrauterine growth restriction (IUGR) on development of the central nervous system. Since the mid-1980s, BAER has been used as an objective tool to study neural development in infants following IUGR.11,12 However, the results were varied. Most investigators found a shortened IeV interval, reecting a faster neural conduction in the auditory brainstem, suggesting accelerated or precocial neural maturation. Others found an increased IeV interval, suggesting delayed neural maturation. The remaining found no BAER abnormalities. Nevertheless, it is generally agreed that IUGR can adversely affect neural function and development of the brain. Jiang et al. studied BAER with different repetition rates of click stimuli in 30 small-for-gestational age (SGA) preterm infants when they reached term age.11 Compared to the BAER in 36 appropriate-for-gestational age (AGA) term infants, the preterm SGA infants did not show any apparent abnormalities at the conventionally used click rate of 21/s. At a much higher rate e 91/s e IeIII interval shortened whereas the IIIeV interval and IIIeV/IeIII interval ratio increased (all P < 0.05). Thus, there are no major abnormalities in BAER up to 91/s clicks at term in these SGA infants. The slight increase in IIIeV interval at high-rate stimulation suggests a subtle degree of central neural dysfunction or developmental delay. Whether preterm birth affects neural development has attracted the interest of many researchers. Most investigators studying BAER found no signicant abnormalities in preterm infants, although some reported a slightly shortened or increased IeV interval. This is comparable with the nding by some studies using magnetic resonance that there was no signicant difference in myelination stage between verypreterm and term infants at term. Others found an increase in BAER wave latencies and intervals in preterm infants when they reached term, suggesting that myelination of the central auditory pathway is delayed in preterm infants. Jiang et al. reported that in low-risk very-preterm infants, as the repetition rate of clicks was increased from 21/s to 51/ s and 91/s, IeV interpeak interval increased similarly to normal term neonates.13 Further analysis showed that the

Perinatal asphyxia
The BAER is very sensitive to arterial blood oxygen tension.16 After perinatal asphyxia infants are often found to have BAER abnormalities, including an elevated response threshold, increased wave latencies and interpeak intervals, reduced wave amplitudes, and decreased V/I amplitude ratio.15,17,18 Amplitude reduction in wave V is the main abnormality in children who survive perinatal asphyxia.17 The changes in BAER after asphyxia are basically similar in preterm and term infants. When preterm infants after asphyxia reached term age their BAER had only slight abnormalities, mainly increased IIIeV interval, suggesting minor impairment in central auditory function.

BAER in neonatal neurology To examine whether high presentation rates of clicks while recording BAER improves the detection of central auditory impairment, Jiang et al. analysed BAER at different repetition rates of clicks in infants after perinatal asphyxia.15,18 At the routinely used 21/s clicks, all BAER wave latencies increased signicantly. After excluding the neonates who had a signicantly elevated BAER threshold, only wave V latency increased slightly. The intervals of IeV and IIIeV also increased slightly. Similar results were found at 51/s clicks. When clicks were increased to 91/s, the IIIeV interval increased more significantly and, in particular, wave V amplitude reduced signicantly compared with normal controls (Fig. 2). The authors concluded that although a moderate increase in the click rate (e.g. 51/s) does not improve detection of hypoxiceischaemic brainstem impairment, an increase to 91/s does, mainly manifesting as an abnormal reduction of wave V amplitude. In experimental animals, BAER has also been used to study neural response of the brain to certain interventions such as hypothermia.16 Recent studies in newborn animals with experimental hypoxiaeischaemia have shown that BAER correlated with the severity of hypoxiaeischaemia, and that BAER is useful in assessing the neuroprotective effects of hypothermia.16,19,20

447

Neonatal chronic lung disease (CLD)

Infants with neonatal CLD often have poorer growth and are more likely to have developmental decits, including severe visual impairment, cerebral palsy, abnormal muscle tone, mental retardation, and learning disabilities. However, it is not known whether these infants are also at risk of auditory e particularly central auditory e decits. Recently, Jiang et al. studied BAER in infants with neonatal CLD but no other major perinatal problems, and found that BAER components which mainly reect central auditory function increased signicantly.14 Wave V latency and IeV and IIIeV interpeak intervals increased in the CLD infants. The increase in wave V latency and IeV interval was mainly produced by the increase in IIIeV interval, the more central component of the IeV interval. These results suggest that neural conduction in the more central portion of the brainstem auditory pathway is delayed, reecting impairment of myelination of the central nervous system.14 On the other hand, information transmission along the more peripheral or caudal part of the brainstem is relatively intact.

Brain haemorrhages and hydrocephalus

Whether there are any signicant changes in BAER in infants with IVH remains a subject of debate. Some have found abnormal waveforms, increased latencies, and decreased V/I amplitude ratio, while others did not nd any signicant abnormalities in preterm infants with severe IVH. Patients with hydrocephalus due to congenital anomaly, meningitis, or intracranial haemorrhage often show BAER abnormalities, including a decreased V/I amplitude ratio, increased IeV interval, and abnormal morphology of waves III and V.

Sensorineural hearing loss

The BAER continues to play a major role in the detection of sensorineural hearing loss (SNHL) in the newborn. Both prospective and retrospective studies, including BAER studies, show that perinatal asphyxia is one of the major perinatal risks of acquired SNHL in infants and children.17,21e24 Recent BAER studies provide further evidence that infants with hyperbilirubinaemia are at high risk of SNHL.23,25e29 The combination of BAER and otoacoustic emission tests can provide more auditory information about neonates with hyperbilirubinaemia. Studies with BAER show that congenital cytomegalovirus (CMV) infection is a leading cause of SNHL, in addition to an important cause of severe neurological handicap.30,31 There is a concern regarding the sequelae of extracorporeal membrane oxygenation (ECMO), including neurological impairment and SNHL. Abnormal BAER was found in 16e75% of infants treated with ECMO, and was associated with SNHL and/or developmental delay.32 The commonest ototoxic drugs used in the neonatal period are aminoglycosides and diuretics.33e36 Along with otoacoustic emissions and electrocochleography,37 BAER has the potential for monitoring ototoxicity. Although it may be reversible, SNHL is the most common single sequela following meningitis. The BAER has been used as a major tool to diagnose hearing loss after meningitis.38,39

Figure 2 Brainstem auditory evoked response (BAER) recordings at different repetition rates of clicks on days after birth in term infants. (A) Normal infant. (B) Infant after perinatal asphyxia. Although there were no apparent differences in BAER between the two infants at 21/s and 51/s clicks, all wave latencies and IeV and, in particular, IIIeV intervals increased at 91/s in the infant after asphyxia, compared with those in the normal infant. From Jiang et al. (2004, Clin Neurophysiol 115:1605e15) with permission.

448

A.R. Wilkinson, Z.D. Jiang the potential to improve the sensitivity of BAER in the detection of neuropathology. The major advantage of this technique is that it can present acoustic stimuli up to 1000/s or even higher.42e46 This stimulus stress has the potential to improve detection of some neuropathology, particularly a subtle or early one, which may not be detected by presenting less stressful stimuli (i.e. low-rate stimulation) using conventional averaging techniques. In the last decade, Jiang et al. have used the MLS BAER to study functional integrity and maturation of the brainstem and central auditory system in neonates and to evaluate the value of MLS BAER in the detection of neurological abnormalities.42e46 By studying dynamic changes in the MLS BAER during the rst month after birth, Jiang et al. showed a time course of brainstem pathophysiology after perinatal asphyxia.43,44 On day 1, wave III and V latencies and all interpeak intervals increased signicantly at all rates of clicks used (91e910/s), especially the higher rates. On day 3, all these latencies and intervals increased further and differed more signicantly from the normal controls. Thereafter, the latencies and intervals decreased progressively. On day 7, wave V latency and all intervals still differed signicantly from the controls. These dynamic changes were more signicant at higher rates of clicks than at lower rates. On days 10 and 15, all intervals decreased signicantly. On day 30, all wave latencies decreased to the values in the normal controls on the same day. The intervals also approached normal values, although IIIeV and IeV intervals still increased slightly. These MLS BAER changes have been further conrmed in our recent larger samples (Fig. 3). These results indicate that hypoxiceischaemic brain damage persists during the rst week, with a peak on day 3, and recovers progressively thereafter. By 1 month, this has largely returned to normal. This correlates with other evidence that the rst week, particularly the rst 3 days, is a critical period of hypoxiceischaemic brain damage. This time course could be used as a reference to monitor cerebral function and might help to judge the value of neuroprotective and/or therapeutic interventions. In addition, these authors found that MLS BAER results correlated well with the stage of hypoxiceischaemic encephalopathy during the rst week. More recently, Jiang et al. studied functional integrity of the auditory brainstem in preterm infants using the MLS BAER.45,46 When preterm infants reached term age, those who had perinatal complications (high-risk infants) showed a tendency to an increase in wave V latency and IeV and IIIe V intervals at all 91e910/s clicks, with statistical signicance at higher rates. Wave V latency and IeV interval increased signicantly at 455/s and 910/s, but not at lower rates (Fig. 4A, B). IIIeV interval increased at all click rates, which was more signicant at higher rates (Fig. 4C). The IIIeV/IeIII interval ratio increased at most rates. Waves III and V amplitudes reduced signicantly mainly at 455/s and 910/s. In preterm infants who had no perinatal complications (low-risk infants), there were no major MLS BAER abnormalities except an increase in IIIeV interval at 91e910/s (Fig. 4AeC). Compared to these low-risk infants, the preterm infants with perinatal complications had a signicant increase in wave V latency, IeV and IIIeV intervals, and IIIeV/IeIII interval ratio at 455/s and 910/s clicks (Fig. 4AeC). On the other

Developmental disorders
BAER abnormalities found in infants with Downs syndrome include no response, decreased latencies of waves I and V and IeV interpeak interval, or increased latencies of waves I and V. These results indicate a high incidence of hearing loss at middle and inner ear levels, and some anomaly in the brainstem. In infantile spasms, BAER abnormalities include partial disappearance of latter waves, increase in IeV interpeak interval, and no responses. These abnormalities are compatible with the nding on MRI of brainstem atrophy in babies with infantile spasms. In Cornelia de Lange syndrome BAER manifests no response, mild wave V threshold elevation, and markedly increased wave V, suggesting a high prevalence of peripheral SNHL. BAER may predict the severity of clinical brainstem symptoms in myelomeningocoele as the brainstem is distorted and elongated due to the downward dislocation of the pons, medulla oblongata, and fourth ventricle. In nocturnal enuresis, BAER manifests increased IeIII and IeV intervals, suggesting functional delay in brainstem maturation.40 Patients with congenital hypothyroidism or transient hypothyroidism often have increased wave latencies and interpeak intervals in BAER.41 In addition, the BAER has been widely used to diagnose, localize, and monitor intracranial pathology in many myelin or degenerative diseases that involve the brainstem, such as Leigh disease, metachromatic leukodystrophies, maple syrup urine disease, and phenylketonuria. The abnormalities are mainly increased wave latencies and interpeak intervals.

Maximum length sequence BAER e a technique to improve detection of neurological disorders

An increasing repetition rate of click stimuli can improve the detection of neurological abnormalities in some clinical situations. However, BAER waveform morphology tends to deteriorate at very high rates (e.g. higher than 51/s). This can make it difcult to measure BAER accurately and reliably. In particular, there will be a loss of the latter part of wave V due to the overlapping of the following stimulus artefacts. This is often seen in very young or very sick infants with a signicant increase in wave V latency and IeV and IIIeV intervals at higher rates (e.g. 91/s). Furthermore, the conventional averaging technique can increase the repetition rate up to only about 100/s. This limits the ability of increasing rate to improve detection of neuropathology in conventional BAER. Eysholdt and Schreiner in 1982 developed the maximum length sequence (MLS) to record and analyse the evoked potentials. However, this technique was not used to study neonatal neurology until recently.42e46 The MLS technique uses patterned stimulus presentation rather than the uniformly spaced stimuli of conventional BAER. It permits the overlap of responses to successive stimuli, and thus allows presentation of stimuli at much higher rates. Since the higher rates provide a much stronger physiological challenge to auditory neurons and permit a more exhaustive sampling of physiological recovery or fatigue than is possible using conventional stimulation, this technique has

BAER in neonatal neurology

Wave V latency (ms)
10.0 10.0

449

A
Wave V latency (ms)

9.3

9.3

8.6
Term

8.6

7.9

7.9

Preterm low-risk

7.2
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7.2 6.5 6.5 21 91 227 455 910 7.0 21 91 227 455 910

Click Rate (/sec)

Click Rate (/sec) I-V interval (ms)

7.5

B
I-V interval (ms)

6.5

6.8

6.0
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6.1

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5.0
Preterm high-risk

4.7

4.5

21

91

227

455

910

4.0

Click Rate (/sec)

21 91 227 455 910

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3.5

Figure 3 Means and standard errors of wave V latency (A) and IeV interval (B) in conventional brainstem auditory evoked response (BAER) (21/s) and maximum length sequence (MLS) BAER (91e910/s) at 40 dB above the BAER threshold during the rst month after birth in term infants after perinatal asphyxia. The symbols in sequence represent the data of normal controls on days 1e3, asphyxiated infants on days 1, 3, 5, 7, 10, 15, and 30, and the controls on day 30. During the period studied, the abnormality (i.e. signicant increase in wave V latency and IeV interval) increases with the increase in click rate. The dynamic change and abnormalities are more signicant at higher click rates than at lower rates during the rst week.

3.2

III-V interval (ms)

2.9
Term

2.6

Preterm low-risk

2.3
Preterm high-risk

2.0

21

91

227

455

910

Click Rate (/sec)

hand, both low- and high-risk preterm infants had no major abnormalities in the IeIII interval that reect functional integrity of the more peripheral portion of the brainstem auditory pathway. Instead, the interval tended to decrease, which is probably due to the preterm birth that exposes the infants to a sound environment ex utero earlier than term infants, leading to accelerated maturation or myelination in the peripheral neural pathway of the auditory system. Fig. 5 shows sample MLS BAER recordings in a normal term infant (A), a preterm low-risk infant (B), and a preterm high-risk infant (C) recorded at term. These results suggest that, at term, although there are no major abnormalities in brainstem auditory function in preterm infants without perinatal complications, the auditory brainstem e mainly the more central part e in

Figure 4 Means and standard errors of wave V latency (A) and IeV (B) and IIIeV (C) intervals in conventional brainstem auditory evoked response (BAER) (21/s) and maximum length sequence (MLS) BAER (91e910/s) at 40 dB above the BAER threshold in preterm infants, recorded at term, and normal term controls. Compared to term controls, preterm high-risk infants show a signicant increase in wave V latency and IeV interval at 455/s and 910/s (P < 0.05e0.001). The IIIeV interval increases signicantly at all click rates (P < 0.05e0.001). These increases are more signicant at higher rates. Preterm low-risk infants do not have any major MLS BAER abnormalities except an increase in IIIeV interval at 91e910/s (P < 0.05e0.01). Compared to these low-risk infants, wave V latency and IeV and IIIeV intervals in preterm high-risk infants increase signicantly at 455/s and 910/s clicks (P < 0.05e0.001). From Jiang et al. (2005, Pediatr Res 58:1164e9) with permission.

450

A.R. Wilkinson, Z.D. Jiang ndings indicate that the MLS technique has the potential to improve the diagnostic value of BAER. Compared to conventional BAER, MLS BAER is a better method to detect early brain damage and central auditory impairment in some clinical situations, e.g. perinatal asphyxia. However, further studies are needed to describe the wider utility of this relative new technique.

Practice points
 BAER is an important objective tool to detect auditory impairment and neurological abnormalities in a range of neonatal diseases.  Recent studies with BAER suggest that neural conduction in the central nervous system is delayed in neonatal CLD, reecting impairment of myelination.  MLS BAER can detect early brain damage and central auditory abnormalities that affect the brainstem auditory pathway.  The MLS technique has the potential to improve the diagnostic value of BAER in some clinical situations.

References
1. Berg AL, Spitzer JB, Towers HM, Bartosiewicz C, Diamond BE. Newborn hearing screening in the NICU: prole of failed auditory brainstem response/passed otoacoustic emission. Pediatrics 2005;116:933e8. 2. Johnson JL, White KR, Widen JE, Gravel JS, James M, Kennalley T, et al. A multicenter evaluation of how many infants with permanent hearing loss pass a two-stage otoacoustic emissions/automated auditory brainstem response newborn hearing screening protocol. Pediatrics 2005;116:663e72. 3. Joint Committee On Infant Hearing. Year 2000 position statement: principles and guidelines for early hearing detection and intervention programs. Pediatrics 2001;106:798e817. 4. Meyer C, Witte J, Hildmann A, Hennecke K-H, Schunck K-U, Maul K, et al. Neonatal screening for hearing disorders in infants at risk incidence, risk factors, and follow-up. Pediatrics 1999;104:900e4. 5. Task Force on Newborn and Infant Hearing. Newborn and infant hearing loss, detection and intervention. Pediatrics 1999;103: 527e30. 6. Hayes D. State programs for universal newborn hearing screening. Pediatr Clin North Am 1999;46:89e94. 7. Thornton AR, Kimm L, Kennedy CR. Methodological factors involved in neonatal screening using transient-evoked otoacoustic emissions and automated auditory brainstem response testing. Hear Res 2003;182:65e76. 8. Thompson DC, McPhillips H, Davis RL, Lieu TL, Homer CJ, Helfand M. Universal newborn hearing screening: summary of evidence. JAMA 2001;286:2000e10. 9. Pastorino G, Sergi P, Mastrangelo M, Ravazzani P, Tognola G, Parazzini M, et al. The Milan Project: a newborn hearing screening programme. Acta Paediatr 2005;94:458e63. 10. Hall 3rd JW, Smith SD, Popelka GR. Newborn hearing screening with combined otoacoustic emissions and auditory brainstem responses. J Am Acad Audiol 2004;15:414e25.

Figure 5 Maximum length sequence brainstem auditory evoked response (MLS BAER) recordings in a normal term infant (A), a preterm low-risk infant (B), and a preterm high-risk infant (C) recorded at term. Compared to the infants in (A) and (B), the infant in (C) shows a signicant increase in wave V latency, IeV and particularly IIIeV intervals, and a signicant reduction in wave V amplitude at 455/s and 910/s clicks, but not at lower rates. From Jiang et al. (2005, Pediatr Res 58:1164e9) with permission.

preterm infants with perinatal complications is impaired, which becomes more apparent at very high stimulus rates. Thus, preterm infants with perinatal complications are at high risk of central auditory impairment. These studies show evidence that MLS BAER abnormalities are better detected with the increase in the rate of clicks, particularly at the very high rates 455/s and 910/s, which cannot be achieved in conventional BAER. These

BAER in neonatal neurology

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