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Are click-evoked BAEPs useful in case of neonate hyperbilirubinemia?
International Elsevier
Journal of Pediatric Otorhinolatyngology,
231
17 (1989) 231-237
PEDOT 00586
Are click-evoked BAEPs useful in case of neonate hyperbilirubinemia? Isabelle
Soares Bernard
‘, Lionel
Collet
‘, Chantal
Salle 2 and Alain Morgon
Delorme
I,
’
’ Pavilion U, Laboratoire d’Explorations Fonctionnelies Neurosensorielles, and ’ Pavillon J, Service de N.Gonatalogie, HGpital Edouard Herriot, Lyon (France)
Key work
Brainstem auditory evoked potential; Hyperbilirubinemia; Neonate; Premature
Abstract There is still controversy about the usefulness of click-evoked brainstem auditory evoked potentials (BAEPs) for the investigation of neonatal hyperbilirubinemia. The present work concerns the study of click-evoked BAEP responses in a population of 72 hyperbilirubinemic children (conceptional age between 33 and 42 weeks). Their bilirubinemia rates were between 219 and 600 pmol/l. The waves I, III and V were always present, and click BAEP thresholds were normal in all subjects. Latency anomalies were found only for 8 of the 72 subjects. The comparison of subjects having the higher (> 307 pmol/l) bilirubin levels with the group having the lower ones failed to show any significant differences for the I-III and I-V intervals. The influence of prematurity in BAEP alteration has not been demonstrated in this study. These data show, on the one hand, normal click-BAEP thresholds but, on the other hand, alterations of central conduction time in some hyperbilirubinemic newborns. It seems that other factors than hyperbilirubinemia might be operating.
Introduction Does neonatal hyperbilirubinemia alter BAEPs? Hyperbilirubinemia is one of the major problems in neonatology. The neurological sequels, notably the consequences of kemicterus, are well-known. There is still
Correspondence: I. Soares, Pavillon U, Laboratoire d’Exp1oration.s Fonctionnelles Neurosensorielles, 3 place cl’Arsonvr& 69003 Lyon, France.
0165-5876/89/$03.50
0 1989 Elsevier Science Publishers B.V
232
controversy about the usefulness of click-evoked BAEPs in the investigation of neonatal hyperbilirubinemia: it is still hard to specify whether BAEP changes could influence the indication of exchange transfusion, or not [l]. The results of the studies mentioned below are to be seen in the context of current findings concerning BAEP generators. Wave I generators are situated at the auditory nerve, near the cochlea. The wave III generators have been shown to be the bulbar cochlear nuclei, and for wave V, the termination of the lemniscus lateralis
[121*
Most hyperbihrubinemia studies use click-evoked BAEPs and concern either premature or full-term neonates. Findings are fairly varied: - A study of full-term neonates (bilirubinemia > 255 pmol/l) showed alterations along the auditory pathway, the cochlea being preserved. (IV-V peak loss statistically significant and few missing wave I and III). These changes proved to be reversible alterations with remission of jaundice [16]. - Persistence of co&ear responses in a majority of hyperbilirubinemic children has been observed [2]. This persistence of cochlear response accompanied latency lengthening for waves III and V in 10 of the subjects [ll]. Such lengthening might indicate early impregnation of the central nervous system by bilirubin, well before onset of hearing-loss. - An increase in the I-V interval, and also in some cases absence of wave I has been found, perhaps indicating an effect of hyperbilirubinemia on the cochlea/auditory nerve complex. In 25% of a population of 39 children weighing less than 1500 g, sensorineural hearing loss associated with a high bilirubin level ( > 240 pmol/l) was found [7,8]. Measures of click-evoked BAEPs in neonates before and after exchange transfusion, have shown interpeak interval lengthening (I-V, III-V, I-III) with improvement following exchange transfusion [14,18,19]. - Another study [13] showed prolonged peak latencies of wave I and wave V and abnormal interpeak latency between I-V interpeak. Exchange-transfusion improved latencies and amplitude. The authors think the I-V interpeak modification is linked to an auditory nerve alteration. Moreover, abnormal click-evoked BAEP responses were more closely correlated with unbound bilirubin levels than with total bilirubin levels (however, subjects with unbound bilirubin represent less than 10% of the population). In a study of 30 neonates and premature babies between 27 and 41 weeks, latency lengthenings were obvious only in those 4 subjects having a bilirubin level higher than 306 pmol/l [lo]. As we can see, a review of the literature shows considerable controversy conceming the existence of an audiological and neurological alteration, detectable by click-evoked BAEPs, which can be linked to hyperbilirubinemia. Our present study sought to answer the following questions: (1) Is there any alteration of click-evoked BAEPs, concerning click-BAEP auditory thresholds, or latencies of the waves I, III and V, and the length of the interpeaks? (2) Are such possible alterations linked to prematurity, or to bilirubin levels, when comparing the group of infants with higher bilirubin levels to the group of infants with lower ones?
233
Materials and methods Subjects 72 neonates (38 male, 34 female) participated in this study. Their conceptional age was between 33 and 42 weeks (mean = 38.2; S.D. = 2.70). 32 were preterm neonates born between 30 and 37 weeks, 40 were full-term neonates, born between 38 and 42 weeks. All of them suffered from jaundice, with bilirubin levels between 219 and 600 pmol/l (mean = 308.3 pmol/l; S.D. = 54.3, median = 307). All birthweights were average for gestational age (age of birth in weeks); Apgar over 7 at 5 min; absence of family or personal history of deafness; absence of mother’s disease during pregnancy. Conceptional ages (age of birth (weeks) + extra-uterine life duration (weeks) were calculated from the mother’s last period; in case of doubt, they were also calculated using the Dubowitz Neonate Maturity Scale [9]. These criteria allow us to exclude dysmature subjects, BAEP changes having been described in dysmaturity [18]. Click-evoked BAEP recordings The BAEPs of neonates were recorded in the Neonatal Intensive Care Unit (Edouard Herriot Hospital, Lyon) without removing the baby from its bassinet or incubator, and without the use of sedatives. The clicks were generated by passing 100 ps pulses through the right earphone. The right ear and unfiltered clicks were chosen arbitrarily. The sound came through a 2-cm diameter earphone (RACIA) held in contact with the external auditory canal; the click rate was 20 Hz. The intensity studied was 80 dB nHL. The intensities used to determine the auditory threshold were arbitrarily included between 80 and 30 dB (30 dB was the lowest level tested in consideration of the noise inside the Neonatal Intensive Care Unit). Records were made with disc electrodes on forehead and ipsilateral mastoid, the other mastoid electrode serving as the subject ground. Latencies were measured with a cursor from a screen. Responses were amplified by a MEDELEC AA6 MK3 (filter setting being 140-1600 Hz with 6 and 12 dB/octave), and averaged by a MEDELEC D.A.V.6 (1024 points). The analysis period was 20 ms and 2500 responses were averaged. Bilirubin levels were measured within the 12 hours preceding BAEP recording. Bilirubin dosage Total bilirubin levels were measured by Hijmans-Van den Berg reaction [16], during the 12 hours preceding BAEPs. Phototherapy was administered to all jaundiced infants. Measures were in pmol/l (20 mg/dl = 332 pmol/l).
Measurements
and statistics
Latencies were measured for waves I, III and V at 80 dB HL and checked by an independent researcher. The analysis concerned these latencies and the I-III, III-V and I-V intervals.
234
Results were analyzed in 3 stages: (1) The presence of waves I, III and V at 80 dB HL, and the click BAEP auditory thresholds were examined. (2) Latencies and interpeak intervals at 80 dB were, for each subject, compared to normal values established in our laboratory with 154 healthy premature and full-term neonates (mean + 2 S.D.) according to conceptional age. (3) Comparisons were made between full-term and preterm infants and between the higher and the lower bilirubin level groups concerning latency and interpeak values, using Student t-test and SNEDECOR F-test.
Results Click BAEP auditory thresholtis Waves I, III and V were identified without any problem in every infant’s recording at 80 dB. Wave V could always be followed as far as 30 dB or less. Latencies and interpeaks Abnormalities were found only in 8 subjects. (Table I) (i.e. latencies and interpeaks were more than 2 S.D. greater than mean norm waves). The latency of wave III was increased in 2 neonates and that of wave V for 4 others (these
TABLE I Characteristics Sub- G.A. ject No.
of infants with abnormal click-evoked
C.A.
S.B. I level (80 dB)
1
32
34
324
2 3
34 36
34 37
256 380
4 5
39 39
39 39
325 336
6
40
40
320
7
40
41
306
8
40
41
423
III (80 dB)
BAEP responses
V (80 dB)
I-III
I-V
1.84 5.10 7.90 3.26 * 6.06 * (2.09 +0.62) (4.91+ 0.80) (7.28 + 0.72) (2.82 + 0.88) (5.18 kO.64) 1.97 5.44 7.91 3.47 * 5.94 * 2.06 5.79 * 7.55 3.73 * 5.49 (2.04 f 0.46) (4.84+ 0.70) (7.12 kO.62) (2.79 f 0.63) (5.07 f 0.58) 2.14 5.08 7.63 * 2.94 5.46 1.85 4.87 7.60 * 3.02 5.75 * (2.09* 0.55) (4.77 xbO.72) (7.13 kO.68) (2.68 k 0.80) (5.04 f 0.73) 2.00 5.15 7.64 * 3.15 * 5.64 (1.98 + 0.40) (4.69 ztzO.50) (6.96 kO.54) (2.70* 0.42) (4.98 k 0.51) 2.03 5.21 * 7.48 31.8 * 5.45 (1.98 kO.40) (4.69 f 0.50) (6.96 + 0.54) (2.70 + 0.42) (4.98 + 0.51) 2.08 4.79 8.47 * 2.71 6.33 * (1.98 1tO.40) (4.69 + 0.50) (6.96 + 0.54) (2.70 kO.42) (4.98 * 0.51)
III-V
2.80 (2.6 * 0.63) 2.47 1.76 (2.28 +0.56) 2.55 2.73 (2.36 f 0.60) 2.49 (2.27 kO.47) 2.27 (2.27 * 0.47) 3.62 * (2.27 kO.47)
values with sign * differ significantly from the normative values; values between brackets correspond to our normative vahtes (+,2 S.D.) for a given age group at 80 dB HL; G.A., gestational age; C.A., conceptional age; S.B. level: serum bilirubin level. (332 gmol/R = 20 mg/dl); normative values are identical for 40 and 41 weeks.
235 TABLE II Measures of laiencies and interpeaks according IO bilirubin level Bilirubin level
I
III
V
I-III
I-V
2.05 (0.25) 2.00 (0.18) 1.00 NS
4.90 (0.26) 4.83 (0.26) 1.0 NS
7.16 (0.41) 7.14 (0.45) 0.15 NS
2.85 (0.30) 2.84 (0.26) 0.05 NS
(0.40) 5.14 (0.50) 0.4 NS
III-V
(lJmol/U c 307 n = 33 2 307 n = 39 1 P
5.11
2.26 (0.27) 2.3 (0.35) 0.6 NS
NS = non-significant.
anomalies causing several lengthenings of the I-III, III-V, I-V intervals). Subject No. 1 has a precocious latency for wave I. 6 of the 8 neonates showing pathological BAEPs had bilirubinemia in the > 307 pmol/l range. Three of these children were premature neonates. Intergroup comparison The population was divided into 2 groups (Table II): Group 1: bilirubin level x 307 pmol/l (33 subjects) (mean = 270.2 pmol/l; S.D. = 24.9). Group 2: bilirubin > 307 pmol/l (39 subjects) (mean = 34.04 pmol/l; S.D. = 51.7). Groups were matched for conceptional ages: Group 1: mean = 37.8 weeks; S.D. = 3. Group 2: mean = 38.4 weeks, S.D. = 2.4. t = 1.07 (NS); degree of freedom = 70. Latencies and inter-peaks between the 2 groups were compared, using Student t-test. No significant differences were found for waves I, III and V and interpeaks I-III, I-V and III-V. No difference in latencies and interpeak intervals was found either in the preterm or in the full-term group.
Our findings disclose click-evoked BAEP alteration for only 8 (out of the 72) neonates by comparison with our norm values. The comparison was by age-group, allowing for latency and interpeak alterations linked with maturation [3-61. The finding that there is no wave I latency change is compatible with relatively unimpaired cochlear functioning and consistent with the data from the literature [15]. Thus alterations basically concern the I-III and I-V intervals, according to the findings of several authors [3,4,11,13]. The presence of an auditory response at 30 dB may appear to be in contradiction with the findings of some authors [7,8] who have noticed a sensorineural hearing-loss. But the presence of BAEP at 30 dB cannot exclude some high frequency sensorineural hearing loss.
236
The part played by prematurity in click-evoked BAEP changes failed to be demonstrated in this study: of the 8 subjects showing anomalies, 3 were preterm (out of 32 preterm subjects tested), and 5 full-term (out of 40). No clear causal relation between bilirubin concentration and click-evoked BAEP alteration could be established, as no difference was found between the lower and the higher bilirubinemia group. Hyperbilirubinemia alone cannot explain the BAEP alterations found in this study. Taken as a whole, our findings do not allow any firm conclusion concerning the usefulness of click-evoked BAEPs in oto-neurological testing for hyperbilirubinemia.
Acknowledgements The authors wish to thank Pr. Jouvenceaux and the Blood Transfusion Center of Lyon for their help in the carrying out of this study, and also Mrs A. Vidal for typing this manuscript.
References 1 Ahlfors, C.E., Changes in the auditory brainstem response associated with unconjugated hyperbilirubinemia in the newborn. J. Perinatol., VI (1986) 193-196. 2 Chisin, R., Perlman, M. and Sohmer, M., Cochlear and brainstem responses in hearing loss following neonatal hyperbilirubinemia, Ann. Oto-Rhino. Laryngol., 89 (1979) 352. 3 Collet, L., Delorme, C., Chanal, J.M., Dubreuil, C., Morgon, A. and Salle, B., Effect of stimulus intensity variation on brainstem auditory evoked potentials: comparison between neonates and adults, Electroencephalogr. Clin. Neurophysiol., 68 (1987) 231-233. 4 Collet, L., Soares, I., Delorme, C., Morgon, A. and Salle, B. Effect of stimulus-intensity variation on brainstem auditory evoked potentials: maturational changes, Dev. Neurosci., 10 (1988) 57-64. 5 Collet, L., Morgon, A., Soares, I., Disant, F. and Salle, B., Maturational changes in the intensity-latency relation of the brainstem auditory evoked potentials in humans, Acta Otolaryngol., 105 (1988) 473-476. 6 Despland, P.A., Maturation changes in the auditory system as reflected in human brainstem evoked responses, Dev. Neurosci., 7 (1985) 73-80. 7 De Vries, L.S., Lary, S. and Dubowitz, L.M.S., Relationship of serum bilirubin levels to ototoxicity and deafness in high risk low-birth-weight infants, Pediatrics, 76 (1985) 351-354. 8 De Vries, L.S., Lary, S., Whitelaw, A.G. and Dubowitz, L.M.S., Relationship of serum bilirubin levels and hearing impairment in newborn infants, Early Hum. Dev., 15 (1987) 269-277. 9 Dubowitz, L.M.S., Dubowitz, V. and Goldberg, C., Clinical assessment of gestational age in the newborn infant, J. Pediatr., 77 (1970) l-10. 10 Kuriyama, M., Konishi, Y. and Mirawa, H., The effect of neonatal hyperbihrubinemia on the auditory brainstem responses, Brain Dev., 8 (1986) 240-245. 11 Lenhardt, M.L., McArtor, R. and Bryant, B., Effects of neonatal hyperbilirubinemia on the brainstem electric responses, J. Pediatr., 104 (1984) 281-284. 12 Moller, A.R., Jannetta, P.J. and Moller, M.B., Neural generators of the brainstem evoked responses. Results from human intracranial recordings. Ann. Otol. Rhino. Laryngol., 90 (1981) 591-596. 13 Nakamura, H., Takada, S., Shimabuku, R., Matsuo, M., Matsuo, T. and Negishi, H., Auditory nerve and brainstem responses in newborn infants with hyperbilirubinemia, Pediatrics, 75 (1985) 703-708.
237 14 Nwaesei, C.G., Van Aerde, J., Boyden, M., and Perlman, M., Changes in auditory brainstem responses in bilirubinemic infants before and after exchange transfusion, Pediatrics, 74 (1987) 800-803. 15 Perhnan, M., Feimnesser, P., Sohmer, H., Tamari, H., Wax, Y. and Pevsmer, B., Auditory nerve brainstem evoked responses in hyperbihrubinemic neonates, Pediatrics, 72 (1983) 658-664. 16 Rodier, J. and MaIlein, R., Manuel de Biochimie Pratique, MaIoine, 1968, 310 pp. 17 Soares, I., Collet, L., Morgon, A., and Salle, B., Effect of brainstem auditory evoked potentials stimulus intensity variations in neonates of small for gestational age, Brain Dev. 10 (1988) 174-177. 18 Streletz, L.J., Graziani, L.J., Branca, P.A., Desai, H.J., Travis, S.F. and Mikaetian, D.O., Brainstem auditory evoked potentials in fullterm and preterm newborns with hyperbilirubinemia and hypoxemia, Neuropediatrics, 17 (1986) 66-71. 19 Wennberg, R.P., Ahlfors, C.E., Bickers, R., McMurtry, C.A. and Shetter, J.L., Abnormal auditory brainstem responses in a newborn infant with hyperbilirubinemia; improvement with exchange transfusion, J. Pediatr., 100 (1982) 62%626.
Journal of Pediatric Otorhinolatyngology,
231
17 (1989) 231-237
PEDOT 00586
Are click-evoked BAEPs useful in case of neonate hyperbilirubinemia? Isabelle
Soares Bernard
‘, Lionel
Collet
‘, Chantal
Salle 2 and Alain Morgon
Delorme
I,
’
’ Pavilion U, Laboratoire d’Explorations Fonctionnelies Neurosensorielles, and ’ Pavillon J, Service de N.Gonatalogie, HGpital Edouard Herriot, Lyon (France)
Key work
Brainstem auditory evoked potential; Hyperbilirubinemia; Neonate; Premature
Abstract There is still controversy about the usefulness of click-evoked brainstem auditory evoked potentials (BAEPs) for the investigation of neonatal hyperbilirubinemia. The present work concerns the study of click-evoked BAEP responses in a population of 72 hyperbilirubinemic children (conceptional age between 33 and 42 weeks). Their bilirubinemia rates were between 219 and 600 pmol/l. The waves I, III and V were always present, and click BAEP thresholds were normal in all subjects. Latency anomalies were found only for 8 of the 72 subjects. The comparison of subjects having the higher (> 307 pmol/l) bilirubin levels with the group having the lower ones failed to show any significant differences for the I-III and I-V intervals. The influence of prematurity in BAEP alteration has not been demonstrated in this study. These data show, on the one hand, normal click-BAEP thresholds but, on the other hand, alterations of central conduction time in some hyperbilirubinemic newborns. It seems that other factors than hyperbilirubinemia might be operating.
Introduction Does neonatal hyperbilirubinemia alter BAEPs? Hyperbilirubinemia is one of the major problems in neonatology. The neurological sequels, notably the consequences of kemicterus, are well-known. There is still
Correspondence: I. Soares, Pavillon U, Laboratoire d’Exp1oration.s Fonctionnelles Neurosensorielles, 3 place cl’Arsonvr& 69003 Lyon, France.
0165-5876/89/$03.50
0 1989 Elsevier Science Publishers B.V
232
controversy about the usefulness of click-evoked BAEPs in the investigation of neonatal hyperbilirubinemia: it is still hard to specify whether BAEP changes could influence the indication of exchange transfusion, or not [l]. The results of the studies mentioned below are to be seen in the context of current findings concerning BAEP generators. Wave I generators are situated at the auditory nerve, near the cochlea. The wave III generators have been shown to be the bulbar cochlear nuclei, and for wave V, the termination of the lemniscus lateralis
[121*
Most hyperbihrubinemia studies use click-evoked BAEPs and concern either premature or full-term neonates. Findings are fairly varied: - A study of full-term neonates (bilirubinemia > 255 pmol/l) showed alterations along the auditory pathway, the cochlea being preserved. (IV-V peak loss statistically significant and few missing wave I and III). These changes proved to be reversible alterations with remission of jaundice [16]. - Persistence of co&ear responses in a majority of hyperbilirubinemic children has been observed [2]. This persistence of cochlear response accompanied latency lengthening for waves III and V in 10 of the subjects [ll]. Such lengthening might indicate early impregnation of the central nervous system by bilirubin, well before onset of hearing-loss. - An increase in the I-V interval, and also in some cases absence of wave I has been found, perhaps indicating an effect of hyperbilirubinemia on the cochlea/auditory nerve complex. In 25% of a population of 39 children weighing less than 1500 g, sensorineural hearing loss associated with a high bilirubin level ( > 240 pmol/l) was found [7,8]. Measures of click-evoked BAEPs in neonates before and after exchange transfusion, have shown interpeak interval lengthening (I-V, III-V, I-III) with improvement following exchange transfusion [14,18,19]. - Another study [13] showed prolonged peak latencies of wave I and wave V and abnormal interpeak latency between I-V interpeak. Exchange-transfusion improved latencies and amplitude. The authors think the I-V interpeak modification is linked to an auditory nerve alteration. Moreover, abnormal click-evoked BAEP responses were more closely correlated with unbound bilirubin levels than with total bilirubin levels (however, subjects with unbound bilirubin represent less than 10% of the population). In a study of 30 neonates and premature babies between 27 and 41 weeks, latency lengthenings were obvious only in those 4 subjects having a bilirubin level higher than 306 pmol/l [lo]. As we can see, a review of the literature shows considerable controversy conceming the existence of an audiological and neurological alteration, detectable by click-evoked BAEPs, which can be linked to hyperbilirubinemia. Our present study sought to answer the following questions: (1) Is there any alteration of click-evoked BAEPs, concerning click-BAEP auditory thresholds, or latencies of the waves I, III and V, and the length of the interpeaks? (2) Are such possible alterations linked to prematurity, or to bilirubin levels, when comparing the group of infants with higher bilirubin levels to the group of infants with lower ones?
233
Materials and methods Subjects 72 neonates (38 male, 34 female) participated in this study. Their conceptional age was between 33 and 42 weeks (mean = 38.2; S.D. = 2.70). 32 were preterm neonates born between 30 and 37 weeks, 40 were full-term neonates, born between 38 and 42 weeks. All of them suffered from jaundice, with bilirubin levels between 219 and 600 pmol/l (mean = 308.3 pmol/l; S.D. = 54.3, median = 307). All birthweights were average for gestational age (age of birth in weeks); Apgar over 7 at 5 min; absence of family or personal history of deafness; absence of mother’s disease during pregnancy. Conceptional ages (age of birth (weeks) + extra-uterine life duration (weeks) were calculated from the mother’s last period; in case of doubt, they were also calculated using the Dubowitz Neonate Maturity Scale [9]. These criteria allow us to exclude dysmature subjects, BAEP changes having been described in dysmaturity [18]. Click-evoked BAEP recordings The BAEPs of neonates were recorded in the Neonatal Intensive Care Unit (Edouard Herriot Hospital, Lyon) without removing the baby from its bassinet or incubator, and without the use of sedatives. The clicks were generated by passing 100 ps pulses through the right earphone. The right ear and unfiltered clicks were chosen arbitrarily. The sound came through a 2-cm diameter earphone (RACIA) held in contact with the external auditory canal; the click rate was 20 Hz. The intensity studied was 80 dB nHL. The intensities used to determine the auditory threshold were arbitrarily included between 80 and 30 dB (30 dB was the lowest level tested in consideration of the noise inside the Neonatal Intensive Care Unit). Records were made with disc electrodes on forehead and ipsilateral mastoid, the other mastoid electrode serving as the subject ground. Latencies were measured with a cursor from a screen. Responses were amplified by a MEDELEC AA6 MK3 (filter setting being 140-1600 Hz with 6 and 12 dB/octave), and averaged by a MEDELEC D.A.V.6 (1024 points). The analysis period was 20 ms and 2500 responses were averaged. Bilirubin levels were measured within the 12 hours preceding BAEP recording. Bilirubin dosage Total bilirubin levels were measured by Hijmans-Van den Berg reaction [16], during the 12 hours preceding BAEPs. Phototherapy was administered to all jaundiced infants. Measures were in pmol/l (20 mg/dl = 332 pmol/l).
Measurements
and statistics
Latencies were measured for waves I, III and V at 80 dB HL and checked by an independent researcher. The analysis concerned these latencies and the I-III, III-V and I-V intervals.
234
Results were analyzed in 3 stages: (1) The presence of waves I, III and V at 80 dB HL, and the click BAEP auditory thresholds were examined. (2) Latencies and interpeak intervals at 80 dB were, for each subject, compared to normal values established in our laboratory with 154 healthy premature and full-term neonates (mean + 2 S.D.) according to conceptional age. (3) Comparisons were made between full-term and preterm infants and between the higher and the lower bilirubin level groups concerning latency and interpeak values, using Student t-test and SNEDECOR F-test.
Results Click BAEP auditory thresholtis Waves I, III and V were identified without any problem in every infant’s recording at 80 dB. Wave V could always be followed as far as 30 dB or less. Latencies and interpeaks Abnormalities were found only in 8 subjects. (Table I) (i.e. latencies and interpeaks were more than 2 S.D. greater than mean norm waves). The latency of wave III was increased in 2 neonates and that of wave V for 4 others (these
TABLE I Characteristics Sub- G.A. ject No.
of infants with abnormal click-evoked
C.A.
S.B. I level (80 dB)
1
32
34
324
2 3
34 36
34 37
256 380
4 5
39 39
39 39
325 336
6
40
40
320
7
40
41
306
8
40
41
423
III (80 dB)
BAEP responses
V (80 dB)
I-III
I-V
1.84 5.10 7.90 3.26 * 6.06 * (2.09 +0.62) (4.91+ 0.80) (7.28 + 0.72) (2.82 + 0.88) (5.18 kO.64) 1.97 5.44 7.91 3.47 * 5.94 * 2.06 5.79 * 7.55 3.73 * 5.49 (2.04 f 0.46) (4.84+ 0.70) (7.12 kO.62) (2.79 f 0.63) (5.07 f 0.58) 2.14 5.08 7.63 * 2.94 5.46 1.85 4.87 7.60 * 3.02 5.75 * (2.09* 0.55) (4.77 xbO.72) (7.13 kO.68) (2.68 k 0.80) (5.04 f 0.73) 2.00 5.15 7.64 * 3.15 * 5.64 (1.98 + 0.40) (4.69 ztzO.50) (6.96 kO.54) (2.70* 0.42) (4.98 k 0.51) 2.03 5.21 * 7.48 31.8 * 5.45 (1.98 kO.40) (4.69 f 0.50) (6.96 + 0.54) (2.70 + 0.42) (4.98 + 0.51) 2.08 4.79 8.47 * 2.71 6.33 * (1.98 1tO.40) (4.69 + 0.50) (6.96 + 0.54) (2.70 kO.42) (4.98 * 0.51)
III-V
2.80 (2.6 * 0.63) 2.47 1.76 (2.28 +0.56) 2.55 2.73 (2.36 f 0.60) 2.49 (2.27 kO.47) 2.27 (2.27 * 0.47) 3.62 * (2.27 kO.47)
values with sign * differ significantly from the normative values; values between brackets correspond to our normative vahtes (+,2 S.D.) for a given age group at 80 dB HL; G.A., gestational age; C.A., conceptional age; S.B. level: serum bilirubin level. (332 gmol/R = 20 mg/dl); normative values are identical for 40 and 41 weeks.
235 TABLE II Measures of laiencies and interpeaks according IO bilirubin level Bilirubin level
I
III
V
I-III
I-V
2.05 (0.25) 2.00 (0.18) 1.00 NS
4.90 (0.26) 4.83 (0.26) 1.0 NS
7.16 (0.41) 7.14 (0.45) 0.15 NS
2.85 (0.30) 2.84 (0.26) 0.05 NS
(0.40) 5.14 (0.50) 0.4 NS
III-V
(lJmol/U c 307 n = 33 2 307 n = 39 1 P
5.11
2.26 (0.27) 2.3 (0.35) 0.6 NS
NS = non-significant.
anomalies causing several lengthenings of the I-III, III-V, I-V intervals). Subject No. 1 has a precocious latency for wave I. 6 of the 8 neonates showing pathological BAEPs had bilirubinemia in the > 307 pmol/l range. Three of these children were premature neonates. Intergroup comparison The population was divided into 2 groups (Table II): Group 1: bilirubin level x 307 pmol/l (33 subjects) (mean = 270.2 pmol/l; S.D. = 24.9). Group 2: bilirubin > 307 pmol/l (39 subjects) (mean = 34.04 pmol/l; S.D. = 51.7). Groups were matched for conceptional ages: Group 1: mean = 37.8 weeks; S.D. = 3. Group 2: mean = 38.4 weeks, S.D. = 2.4. t = 1.07 (NS); degree of freedom = 70. Latencies and inter-peaks between the 2 groups were compared, using Student t-test. No significant differences were found for waves I, III and V and interpeaks I-III, I-V and III-V. No difference in latencies and interpeak intervals was found either in the preterm or in the full-term group.
Our findings disclose click-evoked BAEP alteration for only 8 (out of the 72) neonates by comparison with our norm values. The comparison was by age-group, allowing for latency and interpeak alterations linked with maturation [3-61. The finding that there is no wave I latency change is compatible with relatively unimpaired cochlear functioning and consistent with the data from the literature [15]. Thus alterations basically concern the I-III and I-V intervals, according to the findings of several authors [3,4,11,13]. The presence of an auditory response at 30 dB may appear to be in contradiction with the findings of some authors [7,8] who have noticed a sensorineural hearing-loss. But the presence of BAEP at 30 dB cannot exclude some high frequency sensorineural hearing loss.
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The part played by prematurity in click-evoked BAEP changes failed to be demonstrated in this study: of the 8 subjects showing anomalies, 3 were preterm (out of 32 preterm subjects tested), and 5 full-term (out of 40). No clear causal relation between bilirubin concentration and click-evoked BAEP alteration could be established, as no difference was found between the lower and the higher bilirubinemia group. Hyperbilirubinemia alone cannot explain the BAEP alterations found in this study. Taken as a whole, our findings do not allow any firm conclusion concerning the usefulness of click-evoked BAEPs in oto-neurological testing for hyperbilirubinemia.
Acknowledgements The authors wish to thank Pr. Jouvenceaux and the Blood Transfusion Center of Lyon for their help in the carrying out of this study, and also Mrs A. Vidal for typing this manuscript.
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