Maturation of the auditory brainstem in low risk preterm infants: a comparison with age-matched full term infants up to 6 years

Maturation of the auditory lxkmtem in low r&k pmtem infF@ts: a comparisoa witi full term infants up to 6 years Ze Dong Jiangavb p&mrtment of Child Health, Children’s Hmpital, Sk&d A&died U&ersity, S-i, P. A!.C. bLuboratory of Physioogy, University of Oxfmd, Parks Romd. &ford OXI 3PT. UK Reeeived 17 November 1994; revision received 13 February i995; aaxpted 28 February I995

Whether preterm birth has a significant effect on the umturation of tBe huu~@ by& reme~aaequivQcalis8ue.S dt#tctia, it is cmceivabie that extra the I3m&mtion of the developing human brain. The present study CXMQMW t&e posHem mt@atim of the cm&al compmmts of brainstem auditory evoked mpms@ @AlS) in low tiak~ptmmn infants with that of age-matched full term infants up detnonstrated .Gmihu maturationaI profiIes to those of the tervaIsandaalpIitude-. No systematic, statisticalfy Mwaanthcpretmnandtefmi&m.siaanyoftbeBASRvam tended to be slightIy shortened in the prematurely born in&Us. pmtem birth or eadier exposure to sound envirorment extra Nero iwwliWy to W.to: s&ificant neurophysiological consequence in the dew&ping auditory brainstem of bw risk infants. Ke~~dr: Neurodevelspment; Auditory maturation: Premature infants; Child neuroiogy; Auditory evoked responses 1. -

The survhd rate of high risk preterzn infants has baen inrproved sig&fit& by advances in perinatal care. Nevertheless, pretextn labour remains one of the niajor * Comsponding

author, Tel.: +44 865 272513; Fax: +44 1 865 272469.

Ekovier !ScienccIreland Ltd. SSDI 0378-3782(95)01639-K

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uncontrolled elements in perinatal medicine. Neurological outcome and functional development of prematurely born infants are major concerns. Histopathological studies have revealed that neuronal development proceeds in a normal fashion in most preterm infants, but shows abnormalities, including developmental delay or arrest, in the remaining infants [l]. Neurobehavioural studies have demonstrated that infants born prematurely tend to have lower scores in mental and psychomotor tests compared with term infants [2-51. Many of the surviving high risk preterm infants demonstrate long-term neurological disorders or behaviour problems such as minimal brain damage and learning disabilities. The incidence and severity of neurodevelopmental abnormalities are found to correlate inversely with gestational age and birthweight [6]. Whether preterm birth affects brain maturation in low risk infants remains a question to be answered. Since experience plays a crucial role in the development of the human brain, it could be hypothesized that experience in utero and extra utero exerts different impacts on the maturation of the developing human brain. Infants born prematurely would be an excellent model for testing this hypothesis by comparison of maturational profiles in infants with the same conceptional age (CA) but a different gestational age. The development of the central auditory pathway includes increasing synaptic efficiency, dendritic growth and axonal myelination. Numerous data have suggested that sound experience plays an important role in the formation of auditory system cytology, neuron morphology and in sound localization. Acoustic experience can affect the formation or consolidation of connections in the auditory brainstem. Abnormal development of neuronal responses in the auditory pathways may occur following exposure to abnormal acoustic environments or interference with the ear. It is presumable, therefore, that preterm or earlier exposure to sound environment extra utero could exert some potential effects on the maturation of the auditory pathways. Recent advances in technology have allowed non-invasive, precise and quantitative assessment of the structural and functional development of the human brain. For example, magnetic resonance imaging (MRI) and brainstem auditory evoked response (BAER) have being increasingly used to observe maturational profiles of the brain. Some MRI studies demonstrated delayed myelination in preterm infants compared with term infants [7,8]. Others did not find any differences in the stages of myelination and the size of some brain structures between preterm and term infants at 37-44 weeks CA [9]. The BAER is composed of a series of peaks that originate at different levels of the auditory pathways along the brainstem. Maturational changes in the BAER reflect the neurophysiological maturation of the brainstem auditory pathways, including peripherally the maturation of the cochlea and centrally the increase in synaptic efficiency, dendritic growth and axonal myelination of the auditory pathways. The maturation of the BAER depends on both inborn and environmental factors. Study of the BAER during maturation could provide pertinent information relating to the functional development of both peripheral and central auditory structures. This technique may detect neuronal damage in the brainstem which cannot be identified using conventional neurophysiological techniques. One of its applications is to evaluate the maturational profiles early in life, particularly

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to the in preterm infants. A number of authors have 1. The possibleeffect of preterm birth on the develo results,however, are somewhatequivocal. Fmre, almost all oftMe pmvious studieswere rest&W to a population of the very young tit& a rat&r short time spanof extra-uterine life, from a few daysto weeks.Limited inf&mation is avail&& concerning whether there is any long-term effect of preterm birth on the developing auditory brainstem. In this study the BAER was compared between low risk preterm infants and full term infants at the sameCA up to 6 years. The major goal is to explore whether preterm birth leads to signilicant neurophysiological consequencein the developing brain, the auditory brainstem in particular. Special attention was devoted to the maturational profiles of the central components of the BAER. Although interpeak intervals of the BAER are generally not signilicantly afFectedby peripheral hearing disorders, such as cochlear hearing loss (h&i&e’s disease,n&e damage) [J&4,251, to avoid any possibleinlluence of peripheral hearing losson the central components of the BAER [26,27J, we excluded those infants who showed any evidence of peripheral hearing loss.

2.1. Subjects The subjectsincluded in this study were a cohort of 82 low risk prematurely born infants. The gestationalageranged between30 and 35(32.4 f 1.7) weeks.BachgesMona1 week had 12-16 subjects.The gestational agewas by the maternal data (n = 64) or, in those whose obstetric data were inadequate (n = 18), by Dubowitz Newborn Maturation Scalesf28] wbizh were carried out within 2 days after birth. The maturational change in the BAER was oW at five developmental stagespost-term (correctedfor gestationalage): 1month, correqonding to 42-46 weeksCA (gestational age plus chronoIogica1 age), 6 moMha &r&l 1,2-3 and 4-6 years.Eachagegroup consistedof 1% 18infants. All snbj&ts were selectedrandomly when they receivedregular health checks.To avoid any factors which would affect the maturation of the brain, other than preterm b&b, we choosesubjectswho were judged to be stable in the nursery and had no major per&&al complications such as asphyxia, periventricular haemorrhage and ne had congenital abnormalities of the central nervous sys suchas congenital infections, chromosomal disorders, congenital mal&umations, inborn errors of metabolism and hydrocephalus, and any other documented postnatal disorders which would affect the development of the auditory systemor the central nervous system.Infants with a history of administration of ototoxic drugs or a po&ive family history for hearing loss were excluded. The BAER threshold, deFtnedas the minimum intensity of clicks that evoked visible and reproducible wave V, was < 20 dB normal hearing level (nHL) in all cases.The 0 nHL was referred to the average BAER threshold, tested in the sameenvironment using the sameinst~n~tion and experimental procedures as those for the infants, in young adults with normal hearing. In order to avoid any possibleinfluence of intrauterine growth retardation

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on the BAER [10,23,29], the birthweight was appropriate for the gestation in all cases. None of the subjects exhibited major neurological or audiological problems or abnormalities in psycho-motor development, based on developmental screening tests (Denver Developmental Screening Test or Peabody Picture Vocabulary Test). Normal controls comprised 145 age-matched, healthy full term infants, selected

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1ii z I1 11 11 11 11 I 0 2 4 6 8 10 TfME (ms) Fig. 1. Sample BARR raxwdings at ditbmt agles.Duplicate solid traces are recorded from prematurely born infants and dashed traces from term born infants at the click of 70 dB nHL and 10/s.

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from thosewho have beendetailed elsewhere(30,31J. In brief, t&8e f&d4W i&ants :fas)lt 37 were testedwhen they received rcguiar ha chscks.T%c to 42 weeks(39.2 3t 0.8 weeks)and the birthweight was h&w- the M&hand percentile of the local population. The BAER tkreshoid was ~20 dB nHL in ail cases. 2.2. BAER recording and malysis

Info& consent was obtained from the parents of the ir&Ms. Th%BA#S was recorded in a quiet room that was sound-isolated& e&etrie&y a&4&4. The str$jectslay supine on a soft bed. Auditory evok ly betweenhigh forehead in the midline (Fz, the surfaceAg-AgCl discelectrodes.The earlobe contrtiai to the alumni was used as ground. The skin was gently and 1 was applied to the electrode disc to ensure tha tained b&w 5 k0. The acoustic stimuli consi&ed of cikks of rx+rt&cti @a&y, which were generated by rectanguiar pulses tith a duration of 100 # aaadwere delivered monaurally through TDH 39earphones.White noise wasused to mask the contralateral ear. The clickswere presentedat a repetition rate of IO/sand the inten-

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sities from 90 or 80 to 0 dB nHL by 5-10 dB steps. Following high-gain amplification ( x 105), recording signals were filtered between 100 and 2000 Hz (6 dB/octave), averaged and stored on disk. A PC/XT computer was used for data processing. Sweep time was 20 ms. An automatic artifact rejection was used to reduce the inclusion of high-amplitude muscular activity in the averaged responses. The ongoing filtered EEG and the running averaged BAER were monitored while averaging. Sampling was discontinued when muscle artifacts were visible on the monitoring oscilloscope. Responses to 1024 clicks were averaged to complete each run, To ensure reproducible waveforms, at least two trials were obtained for each recording condition and the averaged data were used for analysis. Right and left ears were tested separately for each subject and the mean values of the latency and amplitude data from the two ears were obtained. Detailed analysis of the recorded BAER waveform was conducted off-line. The main BAER measures assessed were interpeak intervals of I-V, I-III and III-V, and amplitudes of waves I and V, obtained at the click intensity of 70 dB nHL. The amplitude was measured by means of peak-to-following trough 1311.The relative interval ratio of the III-V and I-III intervals, or the III-V/I-III interval ratio, and relative amplitude of waves V and I, or the V/I amplitude ratio, were also calculated.

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In accordance with previous reports, maturation in the BAER for both the preterm and full term infants varied systematicallywith age. The tioml changeswere most prominent in early infancy and becameslower with an increase in age. No obvious difference in BAER waveforms was observed between the preterm and full term groups. Fig. 1 shows sample recordings at different ages. 3.1. BAER interpeak intervals

All interpeak intervals of the BAEB shortened as a function of age. Figs- 2 and 3 show a comparison of the maturational c in the I-V, I-III and III-V intervals of the preterm infants and the age-matchedterm controls. These~mterv&rtended to be slightly shorter in the preterm infants with the i&ll term counterparts for most periods of the time studied, in at 6 and Iknonths post-term. The meanI-V interval in the preterm infants ws that in the term infants at the youngest age, i.e. 1 month a&r term eqniva&t date. Subsequently,this interval in the preterm infants becameslightly shorter compared with that of their term counterparts. All these differences, however, did not reach

a o.s0 F: s 0.8 -= If. 5 2

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Fig. 4. Age-&ted change in the means and standard deviations of the III-V/I-III preterm and full term infants.

interval ratio in the

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statisticalsignificance(Student’s t-test, all P > 0.05). There were also no significant differences in both the I-III and III-V intervals betweenthe two groups of infants at all ages. Maturational change in the III-V/I-III interval ratio of the preterm infants and the full term peersis shown in Fig. 4. Similar to that in the term infants, the interval ratio in the preterm infants demonstrated a tendency towards increasing with age. No statisticallysignificant differenceswere found betweenthe data from the preterm and full term infants at all comparable ages (all P > 0.05). 3.2. BAER wave amplitude measures

All BAER wave amplitudes increasedwith advancing agein both the preterm and term infants. Figs. 5 and 6 present graphically age-relatedchangesin the meansand standard deviations for wave V amplitude and the V/I amplitude ratio, respectively. Both the wave V amplitude and the V/I amplitude ratio in the preterm infants demonstrated similar maturational changesto those in the full term counterparts. t differences in either the Statistical analysis revealed that them were no wave V amplitude or the VA amplitude ratio betweenthe two populations at all ages (Wilcoxon’s rank sum test, all P > 0.05).

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4. Dixm%h 4.1. Hypotheses concerning the possible effect of preterm birth on the developing auditory brainHem Whether preterm birth affects the deveioping BAER in early infancy has been tddresd by a number of authors [I I-21 1. Three hypotheses are suggested by these reports. Null hypothei.r. Extra-uterine preterm exposure to environmentaI acoustk stimuli does not have any signiftcant effect on the maturational profiles of both the periphd and central auditory systems. This hypotksis relies on the fact that no sign&ant difference in the BAER was found between preterm infants and their term countmparts in early infancy. Lary et al. 1141 reportad that thae was no apparmt dWereDce in the BAER threshold at term equivalent date weether maturation occurs inside or outside the uterus. Starr et al. Ill], DespIand and G&unbos 112) and Fawer and Dubowitz [13] did not find any dif%ercmces ia BAER Lateades and interped intervals between pnterm and tenu infants at the same CA. Rottevee~ et al. [MJ reported that at term and 3 months post-term the degree of prematurity did not

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influence the development of the BAER. Paludetti et al. [17] investigated the influences of birthweight on BAER maturation. No significant differences in the BAER were observed between preterm and full term newborns with a birthweight appropriate for CA, although abnormal BAER was observed in the newborns with a birthweight small for CA at birth and tended to normalize during the follow-up tests. Consistent with these BAER findings, Schulte et al. [32] reported that the maturation of auditory cortical evoked response (ACR) in preterm infants was not influenced by exposure to the extra-uterine acoustic environment and that a few weeks of exposure to continuous incubator noise did not affect the auditory evoked responses. A recent MRI study has demonstrated that the maturation in stages of myelination and the size of some brain structures are normal in the preterm infants

t91. Extra-uterine preterm exposure to environmental acoustic stimuli causes a delayed maturation of the auditory pathways. This alternative hypothesis is based on the finding of prolonged wave latencies and interpeak intervals and reduced wave amplitudes in the BAER of preterm infants. Pasman et al. [20] compared the maturation of auditory evoked potentials, including the BAER, middle latency auditory evoked response (MLR) and ACR, between preterm and term infants at term (40 weeks CA) and 3 months after term (52 weeks CA) [20]. The BAER in the prematurely born infants demonstrated a consistent trend towards longer latencies and interpeak intervals. These infants also exhibited a longer latency for the early component PO in MLR and were remarkably different from the term infants with regard to the latencies of ACR components Na and P2. The authors explained that mild conductive hearing loss (middle ear effusions) in combination with retarded myelination of the central auditory pathway may be responsible for these differences between the preterm and term infants. The delayed myelination in preterm infants is also suggested by some MRI studies [7,8]. Acceleration. Extra-uterine preterm exposure might lead to accelerated maturation of the central auditory pathway. This is reflected in the BAER by shorter interpeak intervals and higher wave amplitudes. Delorme et al. [15] and Collet et al. [19] reported that the latencies of waves III and V and the interpeak intervals of I-III and I-V in infants with an extra-uterine life longer than 2 weeks were significantly shorter compared with infants at the same CA but with an extra-uterine life c2 weeks CA. It seems that longer extra-uterine life may enhance the maturation of the brainstem auditory pathway. However, since head size in the group with a greater extra-uterine life duration was smaller, the authors attributed the BAER findings to anatomical factors rather than an accelerated maturation of the auditory system. Eggermont and Salamy [ 181 reported that prematurely born infants had longer latency for waves I, III and V, but their I-III, III-V and I-V interpeak intervals did not differ from those in term infants. These results may be produced by three possible mechanisms: mild conductive hearing loss (otitis media), high frequency hearing loss (damage to the basal part of the cochlea) and the presence of masking noise, such as in the neonatal intensive care unit. The authors concluded that the likely mechanism for their findings was the higher incidence of otitis media in the Retardation.

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preterm infants. A recent study of the 3 n6oaateti From 29 we&s to 43 weeks praem birth on the developing BAER enviwt is associat6d w conduelpion cotnpad with and central auditory pathways may not auditory experience may exert differential impacts on the two portions of the auditory pathways. These previous studies were concentrated on the posaibIe s&t-term e&W of pteterm birth on the BAER. The present work was devoted to the posa#$e effect during maturation. This would provide pertinent i~~un whether preterm birth leads to significant ne~~y~~~1 consequence in the devtloping auditory brainstem. 4.2. A#&uration of the auditory bra&stem in prematurely born infants reveed by the present study As mentioned above, retarded maturation, particularly myelination, of the central auditory pathway is expected to induce prolonged interpeak intervals, reduced wave amplitudes and poorer waveforms in the BAER. Baca~~ of the cmtri@aI Won of the myehnation process, delayed myelination afkcts the late BAER anapoacnts earlier and more significantly than the early BAER components, producing, for exampk, a prolonged III-V interval, an increased III-V/I-III interval ratio and a reduced amplitude of wave V. Conversely, aaderad maturation is refbcbd in the BAER by shorter interpeak intervals and higher wave amplitudes. In this study, we did not find any systematic, significant alterations in either interpeak inter&s or wave amplitude measures of the BAER in the prematuseiy born infants during postterm d6vebpment. These observations suggc8t neither retarded nor ace&rated maturation and, instead, support the null hypo&sis that preterm birth is uniikdy to cause significant neurophysiological consequence in the developing auditory brainstem. Nevertheless, we cannot rule out a possibility that preterm birth or earlier extrauterine auditory experience might have some subtk long-term effect on the develop ing auditory brainstem. Age-related changes in interpeak intervals with dev-t have been attributed to maturational changes in nave conduction velocity aasociated with axonal diameter, myehnation and synaptic etticacy. The shgbtly shortened I-V interval in the pretenn infants might reflect a subtk degree of accelerated aeurophysiological maturation. It is known that unusual conditions in early life may induce certain organ systems to mature at an accelerated rate. There is evident suggesting that preterm infants may be more resistant to some unfavourabk factors. For exampk, respiratory distress syndrome is rarely seen in premature newborns of heroin addicted mothers 1331. There are some other possible explanations for the slightly shortened I-V interval in the preterm infants relative to the term peers. In gpacral, interpeak intervals of the BAER are not significantly affected by peripheral hearing disorders, such as cochlear hearing loss (MbnitWs disease, noise damage) and conductive hearing loss.

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However, high-frequency hearing loss could produce a slightly shortened I-V interval by way of prolonging the latencies of the earlier BAER waves (I-IV) to a greater extent than that of wave V. This is especially evident at lower stimulus intensities and there was very little difference from normal hearing at higher intensities [26,27]. In this study the interpeak intervals were determined at a high intensity (70 dB nHL). In addition, despite the fact that premature infants may have as much as 20% incidence of significant hearing loss 1341, the age at which the I-V interval became slightly shorter in our prematurely born infants was 6 months post-term when a high incidence for significant hearing loss is very unlikely. Furthermore, we excluded those infants who showed any evidence of peripheral hearing loss. Thus, the slightly shortened I-V interval in the preterm infants is unlikely due to high-frequency hearing loss. In Down’s syndrome infants, we also found a slightly shortened I-V interval, which may be related to anatomical abnormality of the brain in Down’s syndrome [35]. In the preterm infants, however, it is very unlikely to be any prominent anatomical abnormality of the brain which could account for the slightly shortened I-V interval. 4.3. Why ispreterm birth unlikely to lead to significant neurophysiological in the developing auditory brainstem?

consequence

During the second trimester, the human fetal brain enters a period of rapid growth that is characterized by a tremendous increase in dendritic complexity and synaptic connectivity. These maturational changes may continue up to the 3rd or 4th postnatal year (36,371. Unlike the cat and rat, in which auditory sensitivity develops postnatally, the human auditory sensitivity develops prenatally. The cochlea becomes functional at -20 weeks CA. At this time other portions of the auditory pathways are capable of signalling its function. The peripheral portion of the auditory pathways is nearly mature during the third trimester of pregnancy and reaches its full morpho-functional growth during the 1st weeks of post-term life. The human fetus hears and appears to develop memories of in utero sound such as its mother’s voice and her heartbeats [38,39]. Intense noises may have potentially harmful effects on the peripheral auditory system of the human fetus during the last 3 months of gestation and on the newborn shortly after birth [40-431. Due to the attenuation of maternal tissue and fluid to external sound, the fetus grows in an environment devoid of sound external to the mother. In the central auditory pathway, there is considerable synaptogenesis in the prenatal and postnatal period and a tremendous growth of dendrites after term (44,451. The neurophysiological maturation of the auditory system proceeds from the periphery to the cortex, i.e. in the centripetal direction. Myelination occurs during the second growth spurt of the brain, which takes place in the second half of gestation and lasts well into the 2nd postnatal year or later (36,461. Compared with other fibre systems at the level of the brainstem, the brainstem auditory pathway myelinates early and rapidly before term (44,471. At term this pathway is myelinated in 95% of infants. The central and peripheral auditory systems exert reciprocal control over each other [48]. Early in embryonic life the major inducer for the inner ear is the developing rhombencephalon. With the maturation of the inner ear, its input is necessary

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for the developmental organization of at least part of the central auditory nervous system. As the organism develops further to a state at whioh the ~~~ au&tory system is functional, input from this system appears to be nv for the control of maturation and innervation of portions of the central auditory system. Sensory input, or acoustic stimuli, could affect the anatomical configuration of the centrai auditory system. Audition depends on the development of a normal anatomic transformer (middle ear) and transducer (inner ear); a central nervous system and its auditory afferent and efferent connections; and exposure to appropriate auditory stimuli that is an essential component of the normal development of audition. The of the auditory system is modified by environmental sound. Abnormal a raduced by at least three types of development error of exposure to sound, i.e. the q&&y, the q+utntity and the timing of the sound to which the ed [48]. As far as preterm birth is concerned, all the three ty 1 errors are involved, i.e. earlier exposure to sound environment extra U&TO which differs from that in utero in both quality and quantity. In addition, due to variona canditions the preterm infants are often placed in the newborn intensive care unit, where there is relatively high noise levels, for periods of time. From the developmental point of view, sensory input from lower levels may affect the development at higher levels and hence the process of neural maturation of the central auditory pathway depends on auditory experience. Abnormal acoustic input from the environment may impact the development of the central auditory pathway. It is likely that the BAER in prematurely born infants may demonstrate a maturation profk which differs somewhat from that in term infants at the same CA. Nevertheless, the present study did not reveal any sign&ant neurophysiological consequence in the developing auditory brainstem. The most likely mechanism underlying this finding is that the developing auditory system of the prematurely born infants has adjusted to adapt to preterm exposure to sound environment extra utero. Animal experiments have shown that conductive hearing loss in the hatching chicken does not result in obvious degenerative changes in the cochlear nucleus [49]. In ferrets reared with a unilateral ear plug, the reduction in the level of sound reaching the ear does not lead to a reduction in the volume of the cochlear nucleus on the affected side or to a reduction in either the size or number of individual neurons in the cochlear nucleus [50]. The auditory neurons in the superior colIiculus (SC) of the plug-reared ferrets can adjust to compensate for the altered binaural cues experienced and the map of auditory space in the nucleus is preserved. The presentation of auditory space in the SC adjusts to distorted cues to maintain a correct topographic relation both to the surface of the nucleus and to the representation of visual space across that surface [51]. In adult ferrets we found that the brachium of the inferior colliculus (BIC), the major auditory input to the SC, projects to the SC in a topographical manner along the rostrocaudal axis of the SC [52]. This provides a possible anatomical basis for the representation of sound azimuth within the SC. In the neonatal ferrets, despite some differences, the overall topographical organization of the BIC-SC projection is essentially the same as that in the adults 153). However, the SC neurons in young ferrets are very broadly tuned for sound location,

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which differs significantly from that in the adults. It seemsthat the immature representationof auditory spacein the young ferrets is unlikely due to the immaturity of the innervation pattern from the BIC. It is more likely that the lack of topography in the neural responsesreflects immaturity in the functional properties of those neurons. The map of sound azimuth in the SC gradually emergesduring early postnatal life. This is most likely under the influence of postnatal sound experience.It is evident that the developing auditory systemcan be moditied by variations of acoustic stimuli, i.e. sound experience [48]. In conclusion, the present study showedthat preterm birth or earlier exposure to sound environment extra utero is unlikely to lead to significant neurophysiological consequencein the developing auditory brainstem. This may be explained by neuronal plasticityof the brain, i.e. the auditory brainstem adjuststo the preterm exposure to sound environment extra utero through some adaptive mechanisms or developmental changes.In a more general sense,our results may indicate that the brain can adjust to the input by the environment in which the infant lives. The maturational data of the BAER from low risk preterm infants could be used to describenormal maturational profiles of the human BAER. Nevertheless,we cannot rule out a possibility that there might be some subtle degree of neuronal deviation or functional alteration in the developing auditory brainstem, such as aberrant binaural hearing that can not be divulged by the conventional BAER testing. If this is so, the understanding is of great importance for us to formulate and implement strategiesfor modifying the preterm auditory experience.It has been suggestedthat early auditory experienceaffects the development of binaural processingin the brain [54]. Binaural hearing is more susceptibleto alterations in experiencethan other types of hearing. The period of normal development and susceptibility to altered experienceis more protracted for binaural processingthan for other aspectsof auditory perception. To explore whether preterm exposure affects the development of binaural processing,examination of binaural interaction components in the BAER is one neurophysiological approach that may be used. Acknowledgments

I would like to thank Professor Xianyun Liu, AssociateProfessor Linyin Fen and Dr. Yungya Wu for their substantial assistancein BAER recording and data analysis.Dr. Travis S. Tiemey from the Laboratory of Physiology,University of Oxford, is gratefully acknowledged for his critical review of the manuscript.

[l]

Takashima, S., Laurence, E.B. and Chart, F. (1982): Retardation of neuronal maturation in premature infants compared with term infants of the same post CA. Pediatrics, 69, 33-39. [2] Drillien, CM. (1972): Aetiology and outcome in low-birthweight infants. Dev. Med. Child Neural., 14, 563-574. [3] Saint-Anne Dargassies, S. (1977): Long-term neurological follow-up study of 286 truly premature infants. I: neurological sequelae. Dev. Med. Child Neurol., 19, 462-478. 14) Forslund, M. and Bjerre, I. (1983): Neurological assessment of preterm infants at term CA in corn+ parison with normal full-term infants. Early Hum. Dev., 8, 195208.

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