Congenital Nonprofound Bilateral Sensorineural Hearing Loss in Children: Comprehensive Characterization of Auditory Function and Hearing Aid Benefit
Round 1
Reviewer 1 Report (New Reviewer)
The conclusion is too diffuse, making it difficult for the reader to grasp the main points.
Please reorganize and streamline the conclusion.
Suggest detail revision before publication.
Author Response
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Author Response File: 
Author Response.pdf
Reviewer 2 Report (New Reviewer)
Thank you for this interesting article. The issues are very timely. The topic is about sensorineural hearing loss and the use of hearing aids. The whole work corresponds to the title, in my opinion it is worth adding in the title that the work is about children.
It is useful to divide the abstract into specific parts and and mark them separately : introduction, material and methods, results and conclusions, it is more readable and clear for readers. In Keywords: „cochlear hearing loss”- I would change it to „sensorineural hearing loss”
The overall structure of the paper is good however the discussion paragraph is missing
Introduction
In my opinion, the introduction should be about the topic, providing general information about the problem being addressed and its characteristics. The information that the author gives, the research group, the methods should not be in this part. In this part, the author should clearly state the purpose without details of the course, this is described in another part of the work.
Materials and Methods
In my opinion, the final number of patients and their demographics should be presented in a table.
In the methods, the author states that the study was conducted in aided and unaided conditions. The author does not provide information before that children use hearing aids. What kind of devices are they, how set up ...- this information should be given in the inclusion criteria.
The methods are described in detail, the results well presented.
Author Response
Please, see attached file.
Author Response File: Author Response.pdf
This manuscript is a resubmission of an earlier submission. The following is a list of the peer review reports and author responses from that submission.
Round 1
Reviewer 1 Report
Thank you for the opportunity to review the article: “Congenital nonprofound bilateral sensorineural hearing loss. Comprehensive characterization of auditory function and hearing aid benefit.” The aim of the authors was to explore the auditory function and mechanisms of bilateral nonprofound congenital SNHL. The main goals for this study, and why this particular population was chosen, is not clear. It is also unclear how these patients were included. Why not just evaluate a cohort of children with nonprofound hearing loss, what is the relationship with their newborn hearing screen? Also, if the goal was to simply characterize the auditory function tests of patients with moderate to severe hearing loss, this should be stated more clearly.
Introduction
The introduction is long, and the goals of the study are not clear at all. The details about the individual auditory tests can be placed in the methods section.
Methods:
“All subjects underwent recordings in left and right ears, but most recording only were performed in the better ear”. Why is this? This sentence contradicts itself
Please explain what “low ambient sound levels” mean? Is this a soundproof booth?
It is not clear how these patients were recruited. There is no reported link between the original newborn hearing screen and how they were finally evaluated at a mean age of 11.
Results
“Quite symmetrical hearing threshold at large were reflected by high correlation between worse and better ear PTAs”, what is the clinical significance of this finding? Is a correlation needed, or are you just trying to show that the hearing loss tends to be symmetric in this small group of patients?
Overall the results are very lengthy, especially considering that only 11 children were evaluated, and the statistical analyses used are very difficult to put within a clinical context.
For example, it is very difficult to comprehend the statistical analysis performed on the questionnaires, we have no metric of reference, and need to scroll back several pages to understand the uncommon acronyms (EC, BN, RV etc).
Discussion
You bring up a comparison to young normal hearing adults in the first paragraph, but there was never a mention in the methods of assessing a control population, it only appears for the first time in the results section.
The discussion is long and does not highlight salient features. I believe that saying that MRI may not add diagnostic value is likely an overstatement, especially considering that less that 11 patients were imaged. There are several pathologies (EVA for example) that are not syndrome-related, where having the information on imaging can help predict outcomes.
Author Response
Please see the attached file
Author Response File: Author Response.pdf
Reviewer 2 Report
Congenital nonprofound bilateral sensorineural hearing loss. Comprehensive characterization of auditory function and hearing aid benefit
The manuscript describes a cases-series of 11 subjects with nonprofound alleged nonsyndromic SNHL. At the age of 11 years, an audiology test battery was performed. The primary outcomes are:
Congenital SNHL leads to
- Recruitment
- Upward spread of masking
- PTA-dependent DPOAE amplitudes
- PTA-dependent ABR amplitude
- Deterioration of the ability to understand speech in noise
Subjects show:
- No MRI abnormalities
- Hearing-aid benefit
The primary outcome of the manuscript is a detailed summary of an (average) auditory profile in selected (young) participants.
Main comments:
The rationale for testing at age 11 seems unclear; it is mentioned that it is because of the ability to participate in the advanced testing (l. 47-49). While I understand this for pure tone audiometry and speech-in-noise testing, it is hardly the case for physiological testing (i.e., DPOAE, ABR). Why is chosen for this timepoint as the screening is already performed in the first weeks after birth
Based on a sample of 30.000 screened newborns, 11 subjects were studied. It is unclear whether this is the total number of newborns that failed the screening (based on other sources with point-prevalence of 1/1000 – 3/1000 [1,2], I would expect between 30 and 90 newborns) or a small fraction from the total based on the type of hearing loss (I see mentioned nonprofound SNHL) or the loss from follow-up, or other reasons. An incidence of 11/30.000 or 1/3000 seems to be an underestimation of the total number of newborns with SNHL.
The hearing loss is alleged nonsyndromic SNHL; yet, apart from imaging, no genetic testing was performed or offered. This is important because there are many forms of syndromic hearing loss where the phenotype is either not clear or where complaints (part of the syndromic phenotype) only manifest at a later age. Examples are Pendred [3] and Usher [4] syndrome, where in the age range tested, the syndromic phenotype has not yet come apparent (i.e., affected thyroid, balance problems with Pendred, and vision loss due to RP in their teens). Also, the link with the site-of-lesion (l. 86) should be elucidated using Whole Exome Testing as many forms of HL may have overlapping sites-of-lesions while the mechanism of HL may be very different. This is problematic since it is possible that there is no single cause and thus a varying phenotype in the study population, limiting the conclusions and implications. In line 744, the authors even highlight another cause of HL, CMV, as an example of etiology affecting the stria, which, in turn, may benefit from a more linear setting.
All in all, I think the idea of obtaining a hearing profile is essential for hearing aid fitting and evaluation of future therapy. Yet, in its current form, the manuscript lacks vital ingredients. First, the exact etiology remains unknown, and assumptions are not tested. Furthermore, the data is pooled (on only 11 pre-selected subjects) and used to hypothesize the relation of the site-of-lesion, the underlying etiology, and potential consequences on the auditory profile, which, in turn, may guide rehabilitation. I’m left with the idea that we should do advanced testing. Yet, the ingredients of the auditory profile remain rather vague. How does the auditory profile relate to the hypothesized site-of-lesion, and what knowledge do we gain from studying the (individual!) auditory profile?
Other comments:
Exclusion criteria are vague; it is stated that, e.g., profound bilateral SNHL is excluded from the study based on:
- No response in psychoacoustic tests […]
- CI
The first criterion is not clear: no ABR response (peak jV?) at 90 dBnHL? ASSR > 90 dBnHL, no OAEs present? I would expect more detailed information re the exact exclusion criteria. Also, section 2.1.4 (l 114-119) gives more information on the eligible subjects (n=18); it is unclear how many of the newborns referred did not meet the inclusion criteria.
PTT; why is presented as a single median PTT curve (and UCL) (figure 1); giving the considerable variation (CI of PTA of 24.8-77.5 dB (better ear)), this would correspond to PTA ranging from mild to severe/profound. I prefer to assess the single-subject data (when symmetrical, as shown in Fig 2, even AD/AS averaged; although I noticed that the data was shown with the function fit; on average, there is a 6.0 dB difference between best/worse. Is this conditional on the order of testing?
UCL
Even in adult subjects, testing UCL is highly dependent on the exact instructions but also very dependent on the expectation of the participants. How is this exactly tackled in the young kids? What is the test-retest of the UCLs found?
OAE SNR vs. PTA
Figure 3 shows the OAE SNR vs. PTA and a decrease in both TEOAE and DPOAE SNR with increasing PTA. While this is not disputed, it makes more sense to look at the overall level of the OAE (like fig 4) and have an exclusion criterion based on either or both an overall level of the noise (e.g., < -10 dB SPL) or the signal > -10 dB in combination with SNR > 6 dB. In other words, while the patterns would probably not likely change, it would explain the very high SNR measurements and the interpretation of the active mechanotransduction of OHCs up to 60 dB. With very low noise levels, the SNR could be artificially elevated to the point of physiological not meaningful. The OAE level, however, would be meaningful. A more critical issue is the bias in the selection of participants. This is limited to nonprofound SNHL, which will affect the data and its interpretation. In addition, the rationale for the frequency-specific analysis is not made clear in the manuscript.
Recognition of speech in spatially separate competing speech (section 3.11)
Since there are substantial differences between subjects, the aided threshold is expected to vary significantly (as indicated by the SD for each frequency [min/max = 3.6-32.0 dB]). This will have a profound effect on the available (aided) speech and thus speech understanding. In other words, how is the effect of audibility/attenuation separated from the effects of, e.g., distortion (see ref 5)? This is an important distinction as separate sites-of-lesions may differently affect the D-factor (see 6). Also, we know that speech understanding is partly explained by top-down processes and age. How is corrected for (both) factors? [7]
The same also applies to more complex psychophysical testing e.g., the PTCs – how is this affected by age?
Section 4.4
The section should be the focus of the paper; here, all findings should be integrated and linked to sites of lesions. The main problem now is that the results are based on the group data where a highly heterogeneous phenotype of hearing loss (substantial differences in PTT) and where no clear etiology is found (or simply assumed). The overall picture is that there is slight dysfunction of the IHCs or the synapse or the tectorial membrane or the stria vascularis (and endocochlaer potential). There is no way to differentiate between the various potential causes. And later in section 4.7 the exact cause (or the specific case where OHCs are affected) may be important for HA fitting. Yet, a general approach for HA fitting has been taken using DSL (i.e., considering the threshold and an estimated or measured UCL).
In other words, what change can we apply to hearing aid fitting, and how does it relate to the auditory profile obtained.
refs
[1] Erenberg A, Lemons J, Sia C, Trunkel D, Ziring P. Newborn and infant hearing loss: detection and intervention. American Academy of Pediatrics. Task Force on Newborn and Infant Hearing, 1998–1999. Pediatrics 1999; 103:527–30.
[2]. Mehl AL, Thomson V. Newborn hearing screening: the great omission. Pediatrics 1998;101: E4.
[3] Smith RJH, Iwasa Y, Schaefer AM. Pendred Syndrome/Nonsyndromic Enlarged Vestibular Aqueduct. 1998 Sep 28 [updated 2020 Jun 18]. In: Adam MP, Mirzaa GM, Pagon RA, Wallace SE, Bean LJH, Gripp KW, Amemiya A, editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993–2022. PMID: 20301640.
[4] Castiglione A, Möller C. Usher Syndrome. Audiol Res. 2022 Jan 11;12(1):42-65. doi: 10.3390/audiolres12010005. PMID: 35076463; PMCID: PMC8788290.
[5] Plomp R. Auditory handicap of hearing impairment and the limited benefit of hearing aids. J Acoust Soc Am. 1978 Feb;63(2):533-49. doi: 10.1121/1.381753. PMID: 670550.
[6] Lanting, Cris P., Ad Snik, Joop Leijendeckers, Arjan Bosman, and Ronald Pennings. 2020. “Genetic Hearing Impairment Affects Cochlear Processing and, Consequently, Speech Recognition in Noise.” MedRxiv, January, 2020.01.03.19015826. https://doi.org/10.1101/2020.01.03.19015826.
[7] Koopmans, Wiepke J. A., S. Theo Goverts, and Cas Smits. 2018. “Speech Recognition Abilities in Normal-Hearing Children 4 to 12 Years of Age in Stationary and Interrupted Noise.” Ear and Hearing 39 (6): 1091–1103. https://doi.org/10.1097/AUD.0000000000000569.
Author Response
PLease, see attched file
Author Response File: Author Response.pdf
Round 2
Reviewer 1 Report
Thank you for the changes brought to the manuscript and for addressing the comment appropriately.
Author Response
Please, see attachment
Author Response File: Author Response.pdf
Reviewer 2 Report
After receiving the revised manuscript I still think the quality of the manuscript could be improved. First of all, the etiology in 11 children is not known ( alleged nonsyndromic). Even if it is not syndromic, the variance between congenital hearing loss and its phenotype is high - a general description of this cohort is therefore not enough and a thorough description of the etiology is needed. It could very well be that various subgroups exist within the group. Secondly, alhtough the idea of precision medicine in rehabilitation is what is really needed, the manuscript only speculates on this without real evidence or experimental data relating the specific causes (not known) to the specific auditory profiles (very generic). The impact of the manuscript is therefore limited in my opinion and the main points are not properly adressed.
Author Response
PLease, see attachment
Author Response File: Author Response.pdf
