Abstract
The goal of this study was to investigate the probable difference in auditory perception and speech intelligibility performance amongst cochlear implanted children who experienced hyperbilirubinemia or auditory neuropathy in comparison to the cochlear implanted children with unknown etiology for hearing loss. This case–control study was carried out on 106 cochlear implanted children with mean age of 32.36 ± 11.98 months who were purposively selected and allocated into four groups. Out of the total, 30 had no specific etiology for hearing loss, while the others had experienced auditory neuropathy or hyperbilirubinemia with/without blood exchange. The auditory perception and speech intelligibility performance of all the participants who had received auditory verbal therapy were assessed after 6 and 12 months of rehabilitation. Then, the data was analyzed, using the Statistical Package for Social Sciences-version 21(SPSS-21). Results indicated poor auditory perception and speech intelligibility performance of the cochlear implanted children with hyperbilirubinemia and blood exchange (P ≤ 0.05), while the participants in the control group with no specific etiology for hearing loss, the children with hyperbilirubinemia with no blood exchange, and those who suffered from auditory neuropathy performed better, respectively. Also, a significant correlation between auditory neuropathy and hyperbilirubinemia was observed. Despite lower improvement of auditory perception and speech intelligibility of the hearing impaired children who were experiencing moderate to severe degrees of hyperbilirubinemia or auditory neuropathy, cochlear implantation is highly recommended not only for children with unknown etiology for severe hearing loss but also for this group of hearing impaired children.
Keywords: Cochlear implantation, Hyperbilirubinemia, Auditory neuropathy, Auditory perception, Speech intelligibility
Introduction
Amongst factors affecting the sense of hearing, neonatal hyperbilirubinemia is one of the known acquired etiologies of hearing loss and various degrees of motor disorder that might interfere with the normal process of auditory perception and speech intelligibility in children who have experienced it.
The prevalence of hyperbilirubinemia in full-term and premature newborns can be as high as 60% and 80% respectively during the first week of life [1]. Thus, it can be considered as one of the main reasons for infants bedridden, especially in the case of liver involvement, failure of the red blood cells or metabolic disorders [2, 3].
The negative effect of hyperbilirubinemia on auditory system and motor movement abilities of the affected children can be reduced through blue-light phototherapy, albumin transfusion and blood exchange [3]. In case of neonatal hyperbilirubinemia, the auditory system might be affected by high concentrations of unbound bilirubin (UB). This can lead to complex functional changes such as apoptosis, auditory nerves damage or necrosis in the nerve cells which ultimately might cause hearing loss [1, 3–5]. Also, it is observed that severe hyperbilirubinemia might result in infants and young children auditory neuropathy spectrum disorder (ANSD) in which the sound cannot be transmitted from the inner ear to the auditory processing centers of the brain left hemisphere. In case of ANSD, the electrophysiological test of otoacoustic emission (OAE) is normal, while various degrees of abnormalities might be seen in auditory brainstem response (ABR) [6, 7]. As a result, the children will suffer from severe to profound sensory neural hearing loss.
In spite of the negative confirmed effect of hyperbilirubinemia on children's auditory system, some of this group have been excluded from the implantation candidacy in the early years of cochlear implantation with the assumption of uncertain prognosis in auditory perception and speech intelligibility. So, the limited number of cochlear implanted children who have experienced hyperbilirobinemia, auditory neuropathy or both has lead to few studies in this context. Due to these days expansion of cochlear implantation selection criteria, the present study was carried out to find whether hyperbilirubinemia or auditory neuropathy may encounter the cochlear implanted children with various problems in different aspects of auditory perception and speech intelligibility.
Method and Materials
In total, 106 cochlear implanted children from three different cochlear implant centers with mean implantation age of 32.36 ± 11.98 months old were purposively selected and analyzed. There were 61 males and 45 females who were assigned to 4 groups of 30 cochlear implanted children with no specific etiology for hearing impairment; 26 cochlear implanted children who encountered severe neonatal hyperbilirubinemia and 1 or 2 times blood exchange; 24 patients with mild hyperbilirubinemia who only had received Blue-light phototherapy, and 26 children with auditory neuropathy accompanied with neonatal hyperbilirubinemia or not.
It is worth stating that all of the selected children had participated in auditory verbal rehabilitation classes. Also, the children had no severe motor disorder or any other accompanied problems, such as brain injury, infection history, inner ear anomaly or serious irritation of external or middle ear.
All participants' parent or guardian signed a general informed written consent form to permit using the data of their medical records with consideration of their privacy. Also, the routine rehabilitation program (Auditory verbal therapy), was performed for all the children. In addition, study protocol was reviewed and approved by the Ethics Committee of our university.
By the end of 6 and 12 months of the intervention, the participant's auditory perception performance and speech intelligibility were assessed, using the Categories of Auditory Performance (CAP) and Speech Intelligibility Rating tests (SIR), respectively.
The CAP was used to measure the ability of cochlear implanted children in auditory perception. This scale has a hierarchical structure ranging from 0 that displays no awareness of the environmental sounds, to 7 which means that the child can talk on the telephone with a friend or family members(8). It is necessary to mention that the inter-user reliability of this scale was previously evaluated [8].
In order to perform the SIR test, two expert speech therapists were asked to listen and score the cochlear implanted children's short passage of connected speech, using an equal-appearing interval scale from 0 to 10, which refers to a domain from unintelligible speech to intelligible to all listeners. It is worth mentioning that the SIR test reliability was confirmed through a study that was performed in 1998 [9].
After gathering the data on performing the two above mentioned tests in six and twelve months after implantation, the statistical analysis was carried out using Statistical Package for Social Sciences-version 21(SPSS-21). Based on the Kolmogorove-Smirnov test result, the distribution of CAP and SIR scores were not normal (P < 0.05). Consequently, the Kruskal–Wallis test was conducted to compare the 4 groups.
Gender distribution was assessed through Pearson Chi-square test. Also, the Spearman correlation coefficient was carried out to assess the probable correlation between hyperbilirubinemia and 1 or 2 times blood exchange with auditory neuropathy.
Results
In the present study 106 cochlear implanted children with mean age of 32.36 ± 11.98 months were assigned to the four mentioned groups.
Table 1 shows no significant difference between the 4 groups with respect to age distribution (P ≥ 0.05).
Table 1.
Age distribution of the children in the intervention and control groups
| Groups | N | Minimum | Maximum | Mean ± Sd | P value |
|---|---|---|---|---|---|
| Controla | 30 | 16 | 55 | 34.4 ± 11.93 | 0.4 |
| Hyper bilirubin & blood exchange | 26 | 13 | 48 | 29.07 ± 8.97 | |
| Hyper bilirubin with no blood exchange | 24 | 19 | 69 | 32.91 ± 12.64 | |
| Auditory neuropathy | 26 | 14 | 65 | 32.80 ± 13.9 | |
| Total | 106 | 13 | 69 | 32.36 ± 11.98 |
aCochlear implanted children with no specific etiology for hearing impairment
Also, Pearson Chi square test indicated no significant difference between the groups in terms of gender distribution (P ≥ 0.05).
Based on the data shown in Table 2, the mean auditory perception performance and speech intelligibility test scores in the control group were always higher than the other three groups.
Table 2.
The distribution of mean auditory perception performance and speech intelligibility test scores
| Groups | Vriable | Mean ± Sd | Minimum | Maximum |
|---|---|---|---|---|
| Control | Cap 1 | 4.9 ± 0.99 | 3 | 6 |
| Cap 2 | 6.5 ± 0.62 | 5 | 7 | |
| Sir 1 | 1.6 ± 0.49 | 1 | 2 | |
| Sir 2 | 2.5 ± 0.90 | 1 | 5 | |
| Hyperbilirubin & blood exchange | Cap 1 | 2.88 ± 1.17 | 1 | 5 |
| Cap 2 | 4.61 ± 1.32 | 2 | 7 | |
| Sir 1 | 1.26 ± 0.45 | 1 | 2 | |
| Sir 2 | 1.92 ± 0.56 | 1 | 3 | |
| Hyperbilirubin with no blood exchange | Cap 1 | 4.08 ± 0.88 | 2 | 6 |
| Cap 2 | 5.29 ± 0.95 | 4 | 7 | |
| Sir 1 | 1.41 ± 0.58 | 1 | 3 | |
| Sir 2 | 2.25 ± 0.60 | 1 | 3 | |
| Auditory neuropathy | Cap 1 | 3.92 ± 0.74 | 2 | 5 |
| Cap 2 | 5.15 ± 0.96 | 3 | 7 | |
| Sir 1 | 1.57 ± 0.75 | 1 | 4 | |
| Sir 2 | 2.46 ± 0.86 | 1 | 5 | |
| Total | Cap 1 | 3.98 ± 1.21 | 1 | 6 |
| Cap 2 | 5.44 ± 1.21 | 2 | 7 | |
| Sir 1 | 1.47 ± 0.58 | 1 | 4 |
Cap 1: Category of auditory perception performance after 6 months of rehabilitation
Cap 2: Category of auditory perception performance after 12 months of rehabilitation
Sir 1: Speech intelligibility rating after 6 months of rehabilitation
Sir 2: Speech intelligibility rating after 12 months of rehabilitation
Before analyzing the probable significant mean difference of the auditory perception performance and speech intelligibility rating test scores, the Kolmogorove-Smirnov test was carried out to evaluate the normality distribution of the dependent variables (Auditory perception performance and speech intelligibility rating test scores). According to the abnormal distribution of variables (P = 0.001), the groups' test scores after 6 and 12 months of rehabilitation were compared by Kruskal–Wallis non-parametric statistical analysis.
According to P value, a significant difference between the groups in term of auditory perception performance scores was observed. Also, the mean ranks indicated a better performance of the control group in comparison with the others. This pattern was also observed after 12 months of rehabilitation (P = 0.001, Mean rank = 81.30).
The results of speech intelligibility rating test are illustrated in Table 4.
Table 4.
Test of between-subjects effects for speech intelligibility rating performance after 6 months of rehabilitation
| Groups | N | Mean rank | Chi-square | df | Sig. |
|---|---|---|---|---|---|
| Control | 30 | 61.40 | 6.18 | 3 | 0.1 |
| Hyper bilirubin & blood exchange | 26 | 44.37 | |||
| Hyper bilirubin with no blood exchange | 24 | 50.75 | |||
| Auditory neuropathy | 26 | 56.06 | |||
| Total | 106 |
Although the mentioned data in Table 4 represents no significant difference amongst the groups' speech intelligibility rating performance after 6 months of rehabilitation, the mean rank of control group is higher than the others. Therefore, the groups' speech intelligibility rating performance was compared after 12 months of rehabilitation too.
Once again, significant better performance of the control group in speech intelligibility rating was observed (P ≤ 0.05).
All in all, the Tables 3, 4, 5 data are based on the poor auditory perception and speech intelligibility rating performance of the cochlear implanted children with hyperbilirubin and one or two times blood exchange while the control group with no specific etiology for hearing loss, the children with hyperbilirubinemia with no blood exchange, and the last group who suffered from auditory neuropathy performed better, respectively (Fig. 1). This finding is also shown in the two bellow figures, but there is only one exception that is stated in Fig. 2 (lines 1& 4), concerning the approximate equal performance of the control group and children with auditory neuropathy in speech intelligibility rating.
Table 3.
Test of between-subjects effects for auditory perception performance after 6 months of rehabilitation
| Groups | N | Mean rank | Chi-square | df | Sig. |
|---|---|---|---|---|---|
| Control | 30 | 76.12 | 36.65 | 3 | 0.001 |
| Hyper bilirubin & blood exchange | 26 | 28.56 | |||
| Hyper bilirubin with no blood exchange | 24 | 55.27 | |||
| Auditory neuropathy | 26 | 50.71 | |||
| Total | 106 |
Table 5.
Test of between-subjects effects for speech intelligibility rating performance after 12 months of rehabilitation
| Groups | N | Mean rank | Chi-square | df | Sig. |
|---|---|---|---|---|---|
| Control | 30 | 61.47 | 9.78 | 3 | 0.02 |
| Hyper bilirubin & blood exchange | 26 | 39.60 | |||
| Hyper bilirubin with no blood exchange | 24 | 53.00 | |||
| Auditory neuropathy | 26 | 58.67 | |||
| Total | 106 |
Fig. 1.
The transformation trend of auditory perception scores among the groups
Fig. 2.
The transformation trend of speech intelligibility rating among the groups
Finally, the Spearman correlation coefficient indicated a significant correlation between auditory neuropathy and hyperbilirubinemia (Table 6).
Table 6.
Spearman correlation coefficient between auditory neuropathy and hyperbilirubinemia
| Hyperbilirobin | Auditory neuropathy | |
|---|---|---|
| Spearman's rho | ||
| Hyperbilirobin | ||
| Correlation coefficient | 1 | |
| Sig. | ||
| N | 106 | |
| Auditory neuropathy | ||
| Correlation coefficient | 0.364** | 1 |
| Sig. | 0.001 | |
| N | 106 | |
| Sig. | 106 | |
| N |
**Correlation is significant at the 0.01 level (2-tailed)
Discussion
Hyperbilirubinemia which predominantly lead to blood exchange, auditory neuropathy or motor delay is one of the acquired etiologies of hearing loss. Nowadays, it is confirmed that along with the importance and necessity of cochlear implantation and its post-op rehabilitation program in severe to profound sensory neural hearing impaired children with unknown etiology for hearing loss, other groups of hearing impaired children who have experienced moderate to severe degrees of hyperbilirubinemia, auditory neuropathy or motor delay can benefit from cochlear implantation. Based on this study result and in spite of lower improvement of cochlear implanted children who had experienced hyperbilirubinemia with/without blood exchange, auditory neuropathy or motor delay in comparison with the control group, they exhibited various degrees of improvement in auditory perception performance and speech intelligibility. Another important finding of this study, which is in line with Jie Xu et al. 2019, concerns the positive correlation between auditory neuropathy occurrence and hyperbilirubinemia with/without exchange transfusion. According to the aforementioned study, the incidence of ANSD was 11.57% and 11.97% in the exchange transfusion group and phototherapy with no blood exchange group. So, severe hyperbilirubinemia was assumed to be a positive predictor of ANSD [10].
This pattern was observed in a study by Chung-Ku Rhee et al. 2009, in which eleven neonates with severe hyperbilirubinemia who had experienced blood exchange were examined through ABR and OAE. Four of the samples showed abnormal or no response and the rest had normal response in ABR. Based on TEOAEs results, the entire participant's cochlea performance were normal. However, two neonates showed significant improvement in auditory perception performance during the 3rd or 6th month follow‐up tests [11].
Alongside ANSD as the most characterized auditory manifestation of hyperbilirubinemia, various degrees of speech and language disorder have also been reported. It is expected that children with ANSD will suffer from language difficulties which is mostly due to auditory deprivation during the golden time remaining for language acquisition [11, 12]. As a result, language will not be acquired normally and the process of speech perception and production skills might negatively be affected too [13, 14].
Despite this, early detection of hearing impairments might result in a significant reduction in the eventual damage to language acquisition. In addition, follow up of children who have experienced hyperbilirubinemia, with periodic audiometry tests for several years, permits early diagnosis and suitable intervention [15–17]. Consequently, early intervention in hearing impaired children, especially the ones who suffer from negative effects of hyperbilirubinemia will significantly decline the difficulties in auditory perception performance and speech intelligibility.
Finally, in spite of the positive findings in the present study, it is necessary to state some of its limitations; including the small sample size and no assessment and comparison of communication abilities of the participants. Therefore, utilizing different communication measures, especially on a large number of cochlear implanted children with the inclusion criteria is highly suggested.
Acknowledgements
The authors would like to thank all the cochlear implant centers who collaborated in data collection. The authors wish to thank Mr. H. Argasi at the Research Consultation Center (RCC) of Shiraz University of Medical Sciences for his invaluable assistance in editing this manuscript too.
Author's contribution
HSB and ML proposed the main concept and idea of the research, performed the research, interoperated the data and wrote the paper and made critical contribution to the concept and design of the research; RM did the statistical analysis and revision related to content of the manuscript. HF, RM, DA, FM, EH, contributed equally in the concept and design of the study and data collection, interpretation of data for the work, investigating and resolving the questions related to the work.
Funding
No funding was received for conducting this study.
Declarations
Conflict of interest
The authors declare no conflict of interest.
Ethical approval and Consent
All procedures performed in the present study were in accordance with the ethical standards of Shiraz University of Medical Sciences research committee and with the 1964 Helsinki declaration and its later amendments. The study protocol was reviewed and approved by the Ethics Committee of Shiraz University of Medical Sciences, Shiraz, Iran. (Ethic code: IR.SUMS.MED.REC.1399.043).
Footnotes
Publisher's Note
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References
- 1.Boo NY, Rohani AJ, Asma A. Detection of sensorineural hearing loss using automated auditory brainstem-evoked response and transient-evoked otoacoustic emission in term neonates with severe hyperbilirubinaemia. Singap Med J. 2008;49(3):209–214. [PubMed] [Google Scholar]
- 2.Akinpelu OV, Waissbluth S, Daniel SJ. Auditory risk of hyperbilirubinemia in term newborns: a systematic review. Int J Pediatr Otorhinolaryngol. 2013;77(6):898–905. doi: 10.1016/j.ijporl.2013.03.029. [DOI] [PubMed] [Google Scholar]
- 3.Amin SB, Wang H. Unbound unconjugated hyperbilirubinemia is associated with central apnea in premature infants. J Pediatr. 2015;166(3):571–575. doi: 10.1016/j.jpeds.2014.12.003. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 4.Soorani-Lunsing I, Woltil HA, Hadders-Algra M. Are moderate degrees of hyperbilirubinemia in healthy term neonates really safe for the brain? Pediatr Res. 2001;50(6):701–705. doi: 10.1203/00006450-200112000-00012. [DOI] [PubMed] [Google Scholar]
- 5.Saluja S, Agarwal A, Kler N, Amin S. Auditory neuropathy spectrum disorder in late preterm and term infants with severe jaundice. Int J Pediatr Otorhinolaryngol. 2010;74(11):1292–1297. doi: 10.1016/j.ijporl.2010.08.007. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 6.Rhee CK, Park HM, Jang YJ. Audiologic evaluation of neonates with severe hyperbilirubinemia using transiently evoked otoacoustic emissions and auditory brainstem responses. Laryngoscope. 1999;109(12):2005–2008. doi: 10.1097/00005537-199912000-00021. [DOI] [PubMed] [Google Scholar]
- 7.Starr A, Picton TW, Sininger Y, Hood LJ, Berlin CI. Auditory neuropathy. Brain. 1996;119(Pt 3):741–753. doi: 10.1093/brain/119.3.741. [DOI] [PubMed] [Google Scholar]
- 8.Archbold S, Lutman ME, Nikolopoulos T. Categories of auditory performance: inter-user reliability. Br J Audiol. 1998;32(1):7–12. doi: 10.3109/03005364000000045. [DOI] [PubMed] [Google Scholar]
- 9.Allen MC, Nikolopoulos TP, O'Donoghue GM. Speech intelligibility in children after cochlear implantation. Am J Otol. 1998;19(6):742–6. [PubMed] [Google Scholar]
- 10.Xu J, Weng M, Li N, Wu X, Gao L, Yao H, et al. Relationship research between auditory neuropathy spectrum disorder and exchange transfusion in neonates with severe hyperbilirubinemia. Int J Pediatr Otorhinolaryngol. 2019;123:146–150. doi: 10.1016/j.ijporl.2019.04.044. [DOI] [PubMed] [Google Scholar]
- 11.Rhee CK, Park HM, Jang YJ. Audiologic evaluation of neonates with severe hyperbilirubinemia using transiently evoked otoacoustic emissions and auditory brainstem responses. Laryngoscope. 2009;109(12):2005–8. doi: 10.1097/00005537-199912000-00021. [DOI] [PubMed] [Google Scholar]
- 12.Olds C, Oghalai JS. Audiologic impairment associated with bilirubin-induced neurologic damage. Semin Fetal Neonatal Med. 2015;20(1):42–46. doi: 10.1016/j.siny.2014.12.006. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 13.Paul R. Language disorders from infancy through adolescence. USA: Mosby; 2007. [Google Scholar]
- 14.Fagan MK, Pisoni DB. Hearing experience and receptive vocabulary development in deaf children with cochlear implants. J Deaf Stud Deaf Educ. 2010;15(2):149–161. doi: 10.1093/deafed/enq001. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 15.Shapiro SM, Nakamura H. Bilirubin and the auditory system. J Perinatol. 2001;21:S52–S55. doi: 10.1038/sj.jp.7210635. [DOI] [PubMed] [Google Scholar]
- 16.Matkin ND, Carhart R. Auditory profiles associated with Rh incompatibility. Arch Otolaryngol (Chicago III: 1960) 1966;84(5):502–13. doi: 10.1001/archotol.1966.00760030504008. [DOI] [PubMed] [Google Scholar]
- 17.Amin SB, Ahlfors C, Orlando MS, Dalzell LE, Merle KS, Guillet R. Bilirubin and serial auditory brainstem responses in premature infants. Pediatrics. 2001;107(4):664–670. doi: 10.1542/peds.107.4.664. [DOI] [PubMed] [Google Scholar]