Half of all adult cochlear implant recipients had residual hearing at lower frequencies prior to surgery.Only a minority of CI recipients retain their residual hearing after cochlear implantation.Lateral wall electrode arrays are preferred for hearing preservation.Speech perception with CI not improved in CI recipients with preserved residual hearing.Surgical experience had no influence on hearing preservation outcomes.1The success of cochlear implants (CI) has led to a more diverse population of CI recipients. Originally, only patients with near‐total hearing loss were eligible for a CI. Nowadays, however, more and more CI recipients have considerable residual hearing at lower frequencies prior to implantation. This development has led to a renewed focus on achieving hearing preservation (HP) in the CI field.HP might be important for three main reasons. (1) CI recipients might benefit from their residual hearing as it can be used for electric‐acoustic stimulation (EAS).Although there is no lack of studies investigating HP, no consensus exists on how to achieve HP.22.1low) of the 125, 250 and 500 Hz frequencies <80 dB HL (decibels hearing level) were eligible for inclusion. The following exclusion criteria were used:revision surgeryimplantation at age <18 yearshistory of otologic surgery in the implanted earsigns of acute or chronic middle ear infections and/or mastoiditis during surgeryincomplete electrode insertioninner ear malformations or otosclerosisA retrospective cohort study was performed of adult patients who underwent cochlear implantation in a single tertiary referral centre (UMC Utrecht) from 01 January 2015 to 23 October 2020. The patients were identified using the CI registration list. Patients with a preoperative pure‐tone average threshold . Strobe reporting guideline was used for this manuscript.All CI recipients receive at least one year after surgery rehabilitation services. In the first three months, at least 4 sessions are planned with audiologists and speech therapists. Evaluation sessions are held at 3 and 12 months postoperative.2.2low outcomes of the implanted and contralateral ear, and consonant/vowel/consonant (CVC)‐word test outcomes.The following data were collected from the electronic medical records: age at implantation, cause of deafness, side of implantation, date of implantation, name of surgeon, electrode‐array type, the use of perioperative corticosteroids , the use of hyaluronic acid, pre‐ and postoperative PTA2.3The pure‐tone audiogram outcomes were subtracted from medical records with SAS Enterprise Guide. The HP scores of 125, 250 and 500 Hz were separately calculated by adapting the equation of Skarzynski et al. 2013:HP = hearing preservation in %; thresholds in decibels hearing level (dB HL); outputmax = maximal detectable hearing level of the audiological setup at the tested frequency .The HP scores were categorised, also according to consensus paper of Skarzynski et al. 2013, as follows: complete HP (>75%), partial HP (>25%–75%), minimal HP (0%–25%) and complete loss of hearing (no measurable hearing). These HP scores were also checked manually. In cases with a difference between the pre‐ and postoperative hearing level at the same frequency of 5 dB, which is equal to the margin of error of the audiometry, HP on this frequency was considered as complete HP.The CVC‐word test outcomes were extracted preoperatively (approximately 6 months prior to surgery), and postoperatively at 3 and 12 months. The preoperative CVC scores were obtained with hearing aids in both ears. Postoperative CVC scores were obtained with activated CI and hearing aid contralaterally to adequately determine the speech perception shifts. These CVC scores were obtained in a situation without background noise. Patients with one‐sided hearing impairment were included in the analyses for HP, but excluded for CVC‐score analyses.The pure‐tone audiometry outcomes were extracted of the contralateral non‐implanted ear in 45 patients to evaluate deterioration of hearing levels irrespective of surgery. The electrode‐array type was categorised as perimodiolar or lateral wall. The mid‐scala electrode array of Advanced Bionics was classified as perimodiolar electrode array, because it is precurved.3n = 101, 73%). See Table A total of 470 patients underwent cochlear implant surgery. Of this group, 307 patients were adult and underwent primary cochlear implantation. In total, 140 patients were eligible for inclusion . See Figure 3.1low outcomes were extracted of the contralateral non‐implanted ear for 45 patients, showing no difference between pre‐ and postoperative outcomes (p > 0.05). Average time between cochlear implantation and postoperative tone audiogram was 88 days for all patients .Descriptive data are shown in Table 3.2H‐test (3) = 8.01, p = 0.046). However, there was a very weak correlation between age and HP as continuous measure (r = −0.21). Gender (χ2 (3) = 4.41, p > 0.05) and side of implantation (χ2 (3) = 3.49, p > 0.05) were not different between HP groups. Weak correlation was observed between preoperative PTAlow and HP as a continuous measure (r = −0.19). Taken together, no baseline differences between HP groups were identified.The mean age of all patients was 61 years. This was only significantly lower when comparing complete HP group with minimal HP group (3.32 (3) = 9.87, p = 0.019).Looking at electrode array, PM arrays were used in 66 patients (47%), of which 4 had complete HP (6%) and 31 complete hearing loss (47%). A LW array was used in 74 patients. Ten patients had complete HP (14%), and 17 patients had no preservation of their hearing (23%). Patients with LW arrays had better HP than patients with PM arrays (χ2 (3) = 7.48, p > 0.05). Local corticosteroids were administered in eight patients, of which three had complete HP and five had partial HP. The use of local corticosteroids seems to be associated with better HP , although all 8 patients also received a LW array. Hyaluronic acid was received by 105 patients (75%), with no differences between HP groups (χ2 (3) = 1.72, p > 0.05).Forty‐eight patients (34%) received intravenous corticosteroids during surgery. Total dose ranged between 4 and 24 mg, in 1–3 administrations. The use of intravenous corticosteroids was not associated with HP (χ3.4n = 102), and these HP outcomes were analysed. Before 2015, this surgeon performed around 40 implantations. There was no correlation between experience in days and HP . The remainder of the patients (n = 38) was implanted by one of five surgeons, and sample sizes were too low (range 2–19) to show a meaningful distribution of HP.The majority of the included implantations were done by one surgeon (3.5p > 0.05).A total of 110 CI recipients had CVC scores available at 3 months after surgery, see Figure 4This retrospective cohort study provides a complete overview of a general adult CI population of the last 5 years. Almost half of the adult patients (46%) who underwent primary cochlear implantation had residual hearing at lower frequencies. Complete HP was achieved in 10% of these patients, partial HP in 26%, minimal HP in 30% and complete loss of residual hearing was seen in 34%. LW arrays in general, and intraoperative local corticosteroids usage in small sample set of 8 patients, were associated with better HP. Speech perception of patients with preserved residual hearing was not better than patients without residual hearing after surgery. Lastly, surgical experience had no effect on HP outcomes.4.1Several different classifications are used to indicate HP at lower frequencies after CI surgery.4.2In our study, patients with LW arrays had more often complete HP than patients with PM arrays (14% vs. 6%). Scalar translocation is regarded as severe insertion trauma, occurring more often with PM arrays, and negatively influences residual hearing of CI recipients.4.3Preserved residual hearing can improve speech perception in patients with EAS.5Approximately half of all adult CI recipients had residual hearing at lower frequencies before surgery. The majority of these patients lost their residual hearing after cochlear implantation. In current medical practice, only electrode choice seems to have a clear effect on hearing preservation rates. Much improvement is needed to preserve the residual hearing of CI recipients in the future.SJ and HT designed the work. ED and SJ acquired and analysed data. All the authors drafted, revised, approved the manuscript and agreed to be accountable for all aspects of the work.


Colorectal polyps are the most common precursors of colorectal cancer (CRC). The close relationship has been observed between colorectal polyps and gut microbiota. However, gut microbiota signatures among sampling sites in patients with colorectal polyps and healthy adults remain elusive.To learn about gut microbiota signatures in tissues of the colorectal polyp and normal colorectal mucosa, and faeces.We performed 16S rRNA gene sequencing and bioinformatic analysis for the microbiota in the normal colorectal mucosa, the colorectal polyps and faeces of adults with colorectal polyps (n = 24) and in faeces and normal mucosa of healthy adults (n = 16) in this preliminary trial.P < 0.05). The composition of microbiota based on PCoA and ANOSIM analysis showed the significant differences only between faeces and tissues of the normal mucosa and polyp (P < 0.05). Based on the LEfSe analysis, the abundances of Bacteroides, Prevotella-2 and Agathobacter were higher, whereas the abundances of Haemophilus, Escherichia_Shigella, Fusobacterium and Streptococcus were lower in faeces both in patients with colorectal polyp and healthy individuals, compared with those in the normal mucosa in two groups or polyp tissues. In healthy individuals, the abundance of Fusobacterium was significantly higher in the normal colorectal mucosa than in faeces. Moreover, there was no significant difference in the abundance of Fusobacterium between the normal colorectal mucosa and polyps in patients with colorectal polyps, but it was significantly higher in the mucosa and polyps than in faeces. Remarkably, the abundance of Fusobacterium in the normal colorectal mucosa was significantly higher in healthy individuals than in the polyp group.The Ace and Chao indexes were higher in the normal colorectal mucosa and polyp tissues compared to faecal samples (Fusobacterium may be a normal colonizer in colonic mucosa, and an abnormal increase of Fusobacterium detected in faeces may be related with the injury of the colorectal mucosa. The difference of the faecal microbiota and mucosal microbiota should be carefully considered in studies on gut microbiota in patients with colorectal lesions.The microbial structure in faeces differs from that in tissues of polyp and normal mucusa. Additionally,  Colorectal polyps are protrusions on the surface of the colorectum, which are the most common precursors of colorectal cancer (CRC) . ColorecFusobacterium was significantly higher in mucosa than in faeces , and this preliminary trial was registered at the Chinese Clinical Trial Registry (ChiCTR2200063806). All participants were 18–80 years old and were voluntarily enrolled prior to presenting for colonoscopy. Twenty-four patients with colorectal polyps were classified as the polyps group, while 16 healthy individuals were classified as the control group. The inclusion criteria including patients: 1. were diagnosed with proliferative polyps, inflammatory polyps and adenomatous polyps by colonoscopy and pathological results; Those patients: 1. with history of colonic cancer, colonic polyps or diabetes; 2. with use of antibiotics or probiotics in the past three months; 3. with symptoms of infection within 1 week; 4. with other intestinal diseases were excluded.Faecal samples were self-collected by participants after enrollment and before bowel preparation. Colorectal polyps and normal mucosal biopsies were collected by the sterile biopsy forceps with colonoscopy following a bowel preparation. These tissues together with the mucus were collected, but the mucus was washed away with saline before DNA extraction. All specimens were labeled and immediately archived at -80°C (within 1 hour) until further processing. These specimens were labeled as the normal colorectal mucosal tissues (NC_), colorectal polyp tissues (CP_) and faecal sample (FS_) in the colorectal polyps group (_P) and the healthy control group (_C).® Soil DNA Kit  instructions from manufacturer. 1% agarose gel electrophoresis was used to check the DNA integrity. The NanoDrop ND-1000 spectrophotometer  was used to measure the DNA concentration and purity.DNA extraction was performed according to E.Z.N.A.® 9,700 polymerase chain reaction thermocycler  using the following primer pair: 338F, 5’- ACTCCtacGGGagGCAGcagCAG-3’ and 806R, 5 ‘- GGACTACHVGGGTWTCTAAT - 3 ‘. Purified amplicons were pooled in equimolar and paired-end sequenced on the Illumina MiSeq PE300 platform  according to the standard protocols by HonSunBio Technology Co. Ltd . The 16S rRNA sequencing was performed using a MiSeq Reagent Kit v3 . The OTU clustering of sequences based on 97% similarity was performed using UPARSE software (version 8.1) (The variable region V3-V4 was amplified by an ABI Gene Ampion 8.1) , and indAfter sequencing, the raw 16S rRNA gene sequencing reads were quality-fifiltered by fastp (version 0.21.0)  and merghttps://www.R-project.org) and QIIME (version 1.9.1) , and categorical variables were expressed as frequency and percentage. All statistical analyses were performed by one-way ANOVA or t-test using GraphPad Prism software (version 9.0.0), and P < 0.05 represented statistically significant difference. Besides, “*” was marked in the corresponding plot for P < 0.05, and “**” was marked in the corresponding plot for P < 0.01.Both the R software (version 4.1.2) (n 1.9.1)  were empP < 0.01). However, there was no significant difference in the Ace and Chao indexes between their normal colorectal mucosa and polyp tissues. In healthy individuals, the Ace and Chao indexes in the normal colorectal mucosa were higher than that in faeces (P < 0.05). Besides, the Shannon and Simpson index suggested that there was no difference in the community diversity among sampling sites both in patients with colorectal polyps and healthy individuals (P > 0.05).As shown in The overall composition of faecal microbial communities appeared similar at the levels of phylum and genus in patients with colorectal polyps and healthy individuals, and so did the normal mucosal microbial communities. In patients with colorectal polyps, the composition of the microbial communities in colorectal polyps tissue appeared similar with that in the normal mucosa at the levels of phylum and genus. Nevertheless, microbial communities in faeces appeared different from that in tissues of the normal colorectal mucosa and polyp Figure 2As shown in Escherichia_Shigella, Haemophilus, Streptococcus, Fusobacterium and Granulicatella were the dominant genera, while the abundance of Bacteroides, Agathobacter, Phascolarctobacterium and Prevotella-2 were lower  for the differential bacterial taxa in normal colorectal mucosa, polyp tissue and faecal samples were screened out using the LEfSe analysis. Compared with the faecal sample, in the polyp tissues, Bacteroides, Prevotella-2 and Agathobacter were enriched in faeces, whereas Haemophilus, Escherichia_Shigella, Fusobacterium and Streptococcus were enriched in normal mucosa and polyps . The trial has been registered at the Chinese Clinical Trial Registry (ChiCTR2200063806). Written and verbal informed consent was obtained from all subjects.YW, JX and FZ designed the trial. YW, JX and XZ conducted the study. XZ and FZ analyzed and interpreted the data. XW, FZ and HC were responsible for project administration and supervision. XZ wrote the first draft of the manuscript and had primary responsibility for the manuscript’s final content. All authors critically revised the manuscript. All authors contributed to the article and approved the submitted version.


They were also randomly divided into three subgroups depending on the steroid administration regime: (1) intravenous dexamethasone (0.1 mg/kg body weight twice a day for three days); (2) combined intravenous and oral steroids (dexamethasone 0.1 mg/kg body weight twice a day plus prednisone 1 mg/kg weight once a day); and (3) no steroids (control group). The results were measured by pure tone audiometry (PTA) at three time points: (i) before implantation, (ii) at processor activation, and (iii) 12 months after activation. A hearing preservation (HP) figure was also calculated by comparing the preoperative results and the results after 12 months. Further measures collected were electrode impedance and hearing threshold in the non-operated ear. The highest HP measures  were obtained in the subgroups who were given steroids. Of the 102 patients given steroids, HP was partial or complete in 63 of them (62%). In comparison, partial or complete HP was achieved in only 15 patients out of 45 (33%) who were not given steroids. There were differences between the three cochlear implant groups, with the Med-El and Advanced Bionics groups performing better than the Oticon group . Hearing thresholds in the non-operated ear were stable over 12 months. Generally, impedance was slightly lower in the 12 month follow-up in comparison with the activation period, with the exception of the Oticon group. (4) Conclusions: Pharmacological treatment with steroids in patients undergoing cochlear implantation helps to preserve residual hearing.The main aim of this study was to assess the clinical effect of steroids (dexamethasone and prednisone) on hearing preservation in patients who underwent cochlear implantation with different cochlear implant systems (Oticon According to the current clinical indications for cochlear implantation (CI), which have been progressively expanded, candidates for the procedure are those with partial deafness , children with congenital profound hearing loss, single-sided deafness patients, and those over 65 years of age, as well as those with acquired bilateral sensory hearing loss ,2,3. SomInformation from two of the world’s foremost agencies responsible for drug authorization—the Food and Drug Administration (FDA) and the European Medical Agency (EMA)—indicate that there is no drug or medical device approved for delivery direct to the inner ear. There are some options for delivering drugs intracochlearly , although these are largely restricted to animal studies and prototypes ,9. There®, Advanced Bionics®, and Med-El®). The primary endpoint was the degree of hearing preservation calculated using the hearing preservation equation , which basically measures the change in average hearing threshold after a CI relative to the preoperative period. We wanted to investigate how average rates of preservation varied depending on the type of implant used and the pharmacological treatment employed. A second endpoint was the stability of hearing in both the operated and non-operated ears. A third endpoint was the mean impedance of the electrodes, again as a function of type of implant and treatment regime. Each endpoint was analysed in comparison with a control group, one for each main group, where steroids were not administered.The main aim of the study was to assess the clinical effect of steroids (dexamethasone and prednisone) on hearing preservation in patients who underwent implantation with three different CI systems (OticonU-test). A chi-square test was used to assess the relationship between treatment regime and hearing preservation. Statistical significance was set at p < 0.05. The analysis was performed using IBM SPSS Statistics, v. 24.Sex and age differences between the subgroups were assessed with the chi-square test and the Kruskal-Wallis test. A Wilcoxon test was used to compare preoperative hearing thresholds with those obtained 12 months after CI activation. Additionally, within each implant type group, comparisons of hearing thresholds obtained 12 months after CI activation were made between the intravenous, oral + intravenous, and control groups  changed significantly regardless of which group the patients belonged to. The average change was from 5 dB HL to 16.4 dB HL.i.v. group  or in the oral + i.v. group .In the Advanced Bionics group, hearing thresholds obtained 12 months after CI activation were similar in both steroid groups. However, hearing thresholds in the control group were significantly worse than those in the i.v. group than in the oral + i.v. group; U = 82.0; p = 0.012). Hearing thresholds in the control group did not differ significantly from those obtained in the two steroid groups.In the Oticon group, hearing thresholds obtained 12 months after CI activation were different in each of the steroid groups  or in the oral + i.v. group .In the Med-El group, hearing thresholds obtained 12 months after CI activation were similar in both steroid groups. But hearing thresholds in the control group were significantly worse than in the The above results relate to average hearing thresholds. Hearing outcomes in terms of degrees of hearing preservation are shown in χ2 = 16.12; p = 0.013) as well as in the Med-El group , but not in the AB group . In the Oticon group, most cases of no measurable hearing were found in the i.v. (81%) and control group (60%), while the widest range in hearing status was observed in the oral + i.v. group. In the Med-El group, most cases of partial or complete HP were found in the oral + i.v. group (52.4% and 33.3% respectively) and in the i.v. group (54.5 and 22.8%), while in the control group most patients had no measurable hearing. The results in the AB group were fairly similar to those in the Med-El group, but overall the relationship was not statistically significant.A statistically significant relationship between treatment regime and hearing preservation was found in the Oticon group (i.v. group implanted with Advanced Bionics) to 3.6 dB HL (in the control group implanted with Oticon). However, only in one of the subgroups—the control group implanted with Advanced Bionics —was the change between pre- and post-op hearing thresholds statistically significant . However, in this case the mean deterioration was only 2.6 dB, i.e., less than the audiometer resolution. Mean hearing thresholds  in the non-operated ear are shown in Hearing thresholds in the non-operated ear were stable over 12 months. Mean changes between pre- and post-op ranged from 0.1 dB HL (in the Electrode impedance was averaged within each group and is shown in According to the introduction and the data from Food and Drug Administration (FDA) and European Medical Agency (EMA), as of now there is no approved drug or medical device with constant relieve of drug for wide-using for delivering directly to the inner ear. There are some possibilities to deliver the drug locally intracochlearly via the oval window or round window by injections, catheter/micropumps, stapes surgery or cochlear implants, but this is not a widely used way of administering of drugs  ,15,16,17The preservation of residual hearing after CI surgery is an important issue for patients. The aim of this study was to investigate the optimum type of steroid, dose, and duration of treatment in comparison with the control group (without steroid administration). The benefit of extended preoperative systemic steroids on hearing after cochlear implantation surgery has already been shown , but wheDexamethasone has high anti-inflammatory and immune-modulative properties ,25,26,27All patients who were enrolled in this study had severe or profound hearing loss according to the Skarzynski’s classification of partial deafness treatment (PDT). Nevertheless, the HP results, as shown in It is clear from Similar comparisons were made when the results of changes in the hearing threshold over two different periods were examined: preoperatively and in the 12-month follow-up period. The hearing thresholds in both steroid groups  were better than in the control groups, regardless of the type of CI system . Hearing thresholds in the non-operated ears were stable over 12 months.The measurement of impedance is routinely done after the cochlear implantation. The results of impedance monitoring check if electrodes work correctly and additionally to monitor the implant functioning during the fitting of the speech processor. As a rule, impedance was slightly lower in the 12 month-follow up in comparison to the activation period, with the exception of the Oticon group of patients. However, the comparison between different brands of cochlear implants should be done with caution. The current method of testing allows the determination of only the overall electrode impedance with the different contribution of its components: access resistance and polarization impedance. It was demonstrated that access resistance increased slowly over time, whereas polarization impedance decreased after the commencement of electrical stimulation after the activation of the CI system. The increase of access resistance is caused by the formation of a layer of fibrous tissue around the electrode within the cochlear canal, The decrease of polarization impedance is due to the fact that electrical stimulation appears to disperse the surface layer of protein which is formed on the surface of the electrode in the early phase after implantation. We can speculate that the method of testing applied in AB and Med-El is more sensitive to the decrease of polarization impedance and the method of testing used in Oticon facilitates the monitoring of an increase in access resistance. However, our results indicate that there is no difference in overall impedances tested with the current method at activation and 12 months post activation between the steroid and control groups.This work adds to our knowledge of hearing preservation in cochlear implantation and supports the pharmacological use of steroids. The 12 months of observation strengthen the validity of the findings, as does the high number of patients enrolled . This study has compared different types of cochlear implants (three types of cochlear implants) and different steroid administration, which is pioneering. The discrepancy between the number of participants in each groups may be a limitation, but appropriate statistical methods were applied for unequal groups in order to gain reliable results.n = 40; Slim J electrode), Oticon , and Med-El . Each of the three groups was subdivided into two subgroups with different strategies for steroid administration , as well as a separate third control group. Characteristics of the patients in terms of sex, age, and operated ear are presented in This study involved 147 patients who were implanted with three different systems: Advanced Bionics . The same was true for the Oticon group  and the Med-el group .In each of the three groups , it was checked whether there were sex and age differences in each subgroup. In the Advanced Bionics group there were no statistically significant differences in terms of sex  and the Med-el group .In the Advanced Bionics group, some differences in terms of age were apparent; the patients in the intravenous group were slightly younger than other patients, The criteria for inclusion were as follows: (1) age above 18 years and qualified for cochlear implantation; (2) severe or profound hearing loss according to Skarzynski’s classification of partial deafness treatment (PDT) such that the patient received either: (a) PDT electrical-acoustic stimulation (PDT-EAS) or (b) PDT electrical stimulation (PDT-ES) as illustrated in i.v.) at a dose of 0.1 mg per kg body weight 30 min before the insertion of the electrode to the inner ear and subsequently twice a day (every 12 h) for the next three days  was administered intravenously (ree days . The sini.v.) combined with orally administered (p.o.) prednisone. The administration regime was as follows. Three days prior to cochlear implantation, prednisone at a dose of 1 mg per kg body weight (p.o.) was administered. Then, 30 min before insertion of the electrode into the inner ear, and for the next three days, dexamethasone was administered i.v. every 12 h (twice a day). For the next three days, prednisone was also administered p.o. (1 mg of prednisone per kg body weight). After this time, the dose was reduced, as shown in ®; the same applied for prednisone (Encorton®).In subgroup 2, steroid therapy consisted of dexamethasone (DEX) administered intravenously  0–25%; partial hearing preservation  26–75%; and complete hearing preservation (complete HP) > 75%.Steroid administration in patients who undergo cochlear implantation is beneficial in preserving residual hearing. Of the 102 patients given steroids, HP was partial or complete in 63 of them (62%). In comparison, partial or complete HP was achieved only in 15 patients out of 45 (33%) who were not given steroids. The type of electrode also appears to play a part: the best results were obtained using the Med-El and Advanced Bionics devices, although here age may have been a confounding factor, and atraumatic insertion of the electrode is always important. The most beneficial regime for HP is intravenous dexamethasone at a dose of 0.1 mg per kg body weight, although in some cases a combination of prednisolone and dexamethasone may provide even better results.


To evaluate the follow-up of children diagnosed with deafness in neonatal hearing screening and risk factors for hearing loss. Quantitative, cross-sectional, and retrospective study to evaluate factors associated with hearing loss and the follow-up of cases of children diagnosed with audiological dysfunction, by analyzing electronic medical records of 5,305 children referred to a Specialized Center in Type I Rehabilitation, from January/2016 to February/2020, in the city of Manaus, Amazonas. The statistical study used Pearson’s chi-square test and binary logistic regression in which odds ratio scans were obtained with reliability intervals of 95%. Of the 5,305 children referred for the otoacoustic emission retest, 366 (6.9%) failed the retest. Children diagnosed with sensorineural hearing loss continued in the study, totaling 265 (72.4%). Only 58 (21.9%) children continued in the study to its end, of these 39 had received hearing aids at that point; and 16 (41%) had surgical indication for cochlear implants, of which only 3 (18.7%) had undergone surgery. Among the risk factors for hearing loss, we found 2.6 times more chance of failure in the otoacoustic emissions retest in those children who had a family history of hearing loss and ICU stay. Although the screening flow reaches a large part of live births, the dropout rates during the process are high, therefore, the socioeconomic and geographic characteristics of regions such as the Amazon should be considered as relevant factors to the evasion of rehabilitation programs of these children. Hospitalization in the neonatal ICU and family history of hearing loss in the investigations could be identified as the main and most important factors for alteration of the otoacoustic emissions retests. Hearing impairments may hinder or prevent speech, language, cognition, and socioemotional development from occurring, thus impairing the general cognitive development3. Early diagnosis is fundamental to minimize these damages.Child deafness has a great impact on the community, whether from an economic or psychosocial point of view. It is the most frequent sensory deficit in humans, with an incidence ranging from 1:300 to 1:1,000 children. According to the World Health Organization (WHO), hearing loss affects about 10% of the world’s population. The frequency of deafness in Brazil is estimated at 4:1,000 birthsNeonatal hearing screening (NHS) is an important instrument in implementing hearing conservation programs and detecting hearing disorders early. This procedure is recommended by Brazilian health policies as the first stage of a neonatal hearing health program, which should preferably be performed in the first days of life (24–48 hours), still in maternity and, at most, during the 1st month of life, to minimize the damage caused by this pathology so common in our country.4.In the prevention program, at the time of hospital discharge after birth, universal neonatal hearing screening (UNHS) is performed by transient otoacoustic emissions (TOAE) and cochlear-palpebral reflex (CPR) research. If a newborn passes the test, that is, presents a response to TOAE in both ears in the hearing screening test, and has no risk for progressive or retrocochlear loss, an orientation is made on the development of hearing and language and they are discharged. Otherwise, if a newborn fails (when they show no response in one or both ears) the 30-day retest and follow-up by a multidisciplinary team is oriented, aiming at diagnosing this deficiency, to perform periodic evaluations and appropriate interventions for them and their families during the first two years of life5, for example, cochlear implant surgery, which is an effective device for children with severe and/or profound prelingual hearing loss, since it considerably improves the acquisition of oral language via the auditory pathway, which can positively impact other areas of development9.The NHS is part of a set of actions that should be carried out for comprehensive attention to hearing health in childhood: screening, monitoring and follow-up of auditory and language progression, diagnosis, and rehabilitation. Thus, the NHS should be integrated into the network of care for people with disabilities and maternal and child follow-up actions. Articulation, training, and integration with primary care is also extremely important to ensure monitoring and follow-up of the hearing and language development, and for adhesion to referrals to specialized services12: parents’ concern about hearing and speech development; family history of permanent childhood hearing loss; neonatal ICU for more than five days; intrauterine infections such as Cytomegalovirus (CMV), herpes, rubella, syphilis, toxoplasmosis, and more recently Zika; craniofacial malformations; syndromes associated with hearing loss; neurodegenerative disorders; positive cultures in postnatal infections; head trauma; and chemotherapy12. The maternal age group equal to or older than 35 years, considered a risk factor for numerous negative outcomes to newborns, has a higher frequency of adverse perinatal outcomes when compared with women aged between 20 and 34 years, with emphasis on prematurity, low birth weight, and low Apgar index, which are risk factors for hearing loss15.The 2019 Joint Committee on Infant Hearing (JCIH) establishes as a risk indicator for hearing loss (RIHL)16.In 2012, the Ministry of Health instituted the guidelines for the universal neonatal hearing screening care in the country, in which the rates of performance of the UNHS should be higher than 95% of live births19. This makes the medical and speech therapy intervention in the critical period of maturation and functional plasticity of the central nervous system, between six months and two years of age of the child, impossible20.However, factors such as lack of family adhesion and the peculiarities of the diagnosis slowed the processes down, preventing most children from reaching the recommended indicatorsPolítica Nacional de Atenção à Saúde Auditiva , promoting wide coverage in the care of patients with hearing impairment in Brazil23. Despite the advances in the PNASA implementation process, difficulties persist with the early diagnosis, the agility of hearing aids acquisition, the rehabilitation, and the guarantee of access to user monitoring by the Unified Health System (SUS).To minimize the damage of hearing loss in the population, the Ministry of Health, via Ordinance no. 2,073, of September 28, 2004, instituted the Given the above statement and the reality of the SUS, this study the primarily aimed to describe the follow-up of neonates who showed alterations in the NHS test, and the fraction of neonates who are reevaluated, diagnosed with hearing loss, treated, and followed by a multidisciplinary team.24, to perform the retest, totaling 5,305 medical records analyzed. The 366 cases with retest failure were evaluated according to the ENT diagnosis of hearing loss , according to Ordinance no. 1,303, from June 28, 2013ing loss . The preParametric statistical association methods between qualitative variables (chi-square test and binary logistic regression model) were used. The results were interpreted in terms of the statistical significance of the association  and odds ratios (OR) between the associated factors.The research followed the recommendations on ethics in studies with human beings and was approved by the Research Ethics Committee of the School of Health Sciences of the Universidade do Estado do Amazonas (CEP/ESA/UEA) under the opinion number 3,827,675 of February 7, 2020.25. Of these, 5,305 (3.56%) were referred for diagnostic confirmation of hearing loss in a Specialized Center in Type I Rehabilitation (CER I) in the same city, they comprised 2,989 (56.34%) males and 2,316 (43.66%) females.In the study period, from January 2016 to February 2020, 148,991 children underwent the otoacoustic emissions test in maternity hospitals in the municipality of Manaus, according to TabNet-DatasusOf the 5,305 children submitted to retest in CER I, 4,939 (93.10%) passed and were discharged from the investigative follow-up with proper guidance, whereas 366 (6.9%) failed and proceeded to diagnostic complementation , imaging tests (computed tomography scan – CT scan and/or magnetic resonance imaging – MRI of the ear) and therapy (hearing aids and/or CI – cochlear implants). The study followed up the children diagnosed with sensorineural hearing loss, totaling 265 (72.4%). Only 58 (21.9%) children continued in the study to its end; 39 had received hearing aids at that point; and 16 (41%) had surgical indication for cochlear implants, of which only 3 (18.7%) had undergone surgery. A total of 207 (78.1%) children dropped out. At the end, 19 (32.7%) were awaiting release of the hearing aid and 13 (81.3%) were waiting in line for cochlear implant surgery .Among the RIHL, 26. These authors identified a total of 1,821 newborns. Of those, 81% passed the initial test; 423 (23.22%) were referred for failing the first test and followed up after 2 weeks. Among these babies, 24 (7.03%) failed the retest, of whom, 9 (37.50%) were confirmed with bilateral hearing loss. The incidence of hearing loss in the aforementioned study was 4.94:1,000 and confirmed hearing loss was statistically higher in boys than in girls. Note the importance of exploring a two-stage NHS model to reduce false-positive responses, considering a possible “maturation” of the auditory pathway. The literature already showed suggestions of a delay in the auditory pathway maturation in premature babies compared with full-term newborns. A possible delay in the NHS retest could be considered, in selected cases, significantly saving economic resources and the anxiety of parents, according to the study by Ciorba et al. (2019)27 who concluded the BAEP response  went through a possible “maturation” in 1.3% of the infants.In this study we identified a retest failure of 366 (6.9%) children and a higher prevalence in males, corroborating the studies by Ayas and Yassen (2021)12 this risk factor is well known and studied mainly when the ICU stay is longer than five days and involves the need for artificial respiration. And this relationship is established due to diseases, metabolic disorders, and iatrogenesis during the period of intensive care. The specific length of stay in the ICU was not detailed in the cases studied.Of the total number of patients referred for the retest, 3,123 (58.9%) showed some risk indicator for hearing loss (RIHL), and some children manifested more than one associated risk factor. Of these evaluated RIHL, 426 children had ICU admission, and 62 (14.5%) failed the retest, with statistical significance (p = 0.0001) . Accordi28 demonstrated an OR of 1.20 with 787 neonates and infants, whereas the study by Barboza et al. (2013)29 revealed an OR of 1.14. In this study, the family history of hearing loss was present in 180 children; of these 26 (14.4%) failed the otoacoustic emission retest, with a significant association between the variables family history and retest failure, with p = 0.0001 = 0.0001 .30 found that 15% of patients with hearing test alteration had hyperbilirubinemia, whereas this proportion was 0.2% in the group without hearing impairment. Rechia et al. (2016)31 also found a significant association between hyperbilirubinemia in children hospitalized in neonatal ICU and failure in the retest. Neonatal jaundice and retest failure showed no statistical significance in this study (p = 0.534) = 0.534) .29, Onoda et al. (2011)32, Escobar-Ipuz et al. (2019)33, and Marinho et al. (2020)6 show that prematurity is the main RIHL in the studied population, on the other hand, the study by Oliveira et al. (2015)34 did not observe this association. Our study reported prematurity in 745 (14%) of the children; 68 (9.1%) failed the retest, corroborating, alongside the cited studies, this evidence of association between the variables prematurity and failure in the retest (p = 0.01).Prematurity is an important risk factor for congenital hearing loss, especially in neonates with less than 1,500 g at birth. Barboza et al. (2013)28. In this study, most of the infectious events during pregnancy were urinary tract infections.Infections during pregnancy are well-established risk factors in the literature for hearing loss, especially when they are one of the STORCH infections . Urinary tract infection is common in young women and represents the most frequent clinical complication during pregnancy. Thus, newborns and infants of mothers who had urinary infections can be considered at risk for hearing loss, not by the infection itself, but in case the treatment used ototoxic medicationPrenatal follow-up, an important preventive care strategy in pregnant women and children, can guide the promotion of health and well-being, besides opportunities to treat problems that can affect mothers and their children during this period. Neonatal infections and changes in maternal blood pressure also showed statistically significant, with p = 0.0001, association with failing the retest .This study also observed that children with indicators of family history of hearing loss and ICU stay were 2.6 times more likely to fail the retest . Since nIn fact, the noticeably high prevalence throughout the series of dropouts during the follow-up of these children after confirmation of the diagnosis of sensorineural hearing loss stands out. Although this study did not measure the number of absences in the retest, considering the initial number of referrals is unknow, we observed problems in the clinical conduction in which 207 (78.1%) children who failed the retest and performed diagnostic confirmation dropped out during the follow-up.35, regardless of the management model , low scores were found in response to the Primary Care Assessment Tool (PCATool) child version questionnaire – which assesses the quality of health services, measuring aspects of structure, process, and result, relating the users’ experiences with the professionals and the health service, measuring their satisfaction. Parents evaluated some points as unsatisfactory, such as accessibility, comprehensiveness, and family orientation. This performance can negatively affect the quality and integrality of care to the at-risk baby. In this research, the factors reported in the medical records about the discontinuity of follow-up were social issues, such as a chemically dependent mother, a change of home residence, a dissatisfaction with the quality of primary health care services, the geographic characteristics of our region, and the financial difficulties to abide by the follow-up.According to Samelli et al. (2019)37, since some mothers claim not to have enough money for bus tickets. The author identified 20% of absence in the retest in the neonatal unit of the University Hospital of the municipality of Maringá, state of Paraná, a similar situation to the one in the work of Berni et al. (2010)38 when studying the NHS in a public hospital, located in the municipality of Campinas, state of São Paulo, absences to retest was 24.8%.Among the factors that lead to dropout are: low schooling level of mothers, who are unaware of the importance of hearing screening and low socioeconomic status12.About half of the children with alterations in the initial otoacoustic emissions test lacked an adequate follow-up to confirm their diagnosisAmong those who maintained the follow-up and confirmed the sensorineural deafness diagnosis, with indication of the hearing aid device, 19 (32.7%) were not yet in use, since they were waiting for the prosthesis to be authorized. Of the 39 children using hearing aids, 16 (41%) had surgical indication of cochlear implant (CI) but only 3 (18.75%) could undergo the surgery until the end of data collection (performed outside the state of Amazonas), the other 13 (81.25%) were still in the waiting list of the regulation system (SISREG) waiting for authorization to perform preoperative imaging and diagnostic examinations .Tratamento Fora de Domicílio (TFD – Out-of-Home District Treatment) of the state of Amazonas Department of Health.Part of the justification for the slow progression to surgery seems to be related to the extensive imaging investigation protocol (tomographies and resonances under sedation) and the administrative process for approving tickets, lodging, and scheduling consultations/surgical evaluation to be performed, mainly in the State of São Paulo, via the public service in the SUS program Regarding the follow-up for CI surgery, we cite as an example some cases that may explain the social reasons for non-progression in therapy: the first, one of the children who came from the municipality of São Gabriel da Cachoeira, state of Amazonas (852 km away from Manaus), and belonged to an indigenous ethnic group. Born premature, with late diagnosis of hearing loss at 2 years of age already in irregular use of hearing aids, with indication for CI surgery, the case reported the difficulties of access to speech therapy even with the hearing aid. The second child was from the rural area of Itacoatiara, state of Amazonas (270 km away from Manaus), whose family lived on subsistence agriculture. The child also presented social and financial difficulties to attend consultations and speech therapy, which is why she did not go to surgery. Two other children came from the outskirts of the city of Manaus and, despite living in the capital, both had a social context of risk, ranging from involvement of parents with illicit activities to reports of theft of the hearing aids.Within this context, the Amazon sociogeographic situation is an important issue for consideration when planning the promotion and implementation of public policies of auditory health, especially in the child population. In cases where the enormous distances are the obstacle, we have other barriers such as situations of crime and social vulnerability that hinder access to rehabilitation treatment.39, when studying the follow-up of children with hearing loss regarding the implantation of hearing aids, noticed that only 26% sought the service spontaneously. When social services requested the follow-up, this number reached 44%. These findings reinforce the importance of the parents’ adhesion to the hearing screening program and subsequent follow-up, besides revealing the need for a neonatal hearing screening program including a work front with social workers who can accompany these mothers to reduce the program’s dropout rate.Lanzetta (2008)Note that the Northern region of Brazil has a single cochlear implant center of the SUS, at the Bettina Ferro de Souza University Hospital, in the municipality of Belém, state of Pará, and that, despite being in the same region, due to the continental Brazilian dimensions, to the internal demand of the state of Pará, and to the TFD policy adopted in the state of Amazonas, displacement remains a major obstacle to these cases.Although we observed a broad coverage of neonatal hearing screening, the follow-up difficulties, especially for CI surgery, should be reevaluated with public policies designed specifically for the region, considering social, economic, and geographic challenges.In conclusion, although the screening flow reaches a large part of live births, the dropout rates during the process are high, therefore, the socioeconomic and geographic characteristics of regions such as the Amazon should be considered as relevant factors to these children dropping out of rehabilitation programs. Hospitalization in the neonatal ICU and family history of hearing loss in the investigations could be identified as the main and most important factors for alteration of the otoacoustic emissions retests. 1. Deficiências auditivas podem dificultar ou impedir que o desenvolvimento da fala, linguagem, cognição e desenvolvimento socioemocional ocorra, prejudicando, assim, o desenvolvimento cognitivo geral3. A importância de um diagnóstico precoce é fundamental para minimizar esses danos.A surdez infantil exerce um grande impacto sobre a comunidade, seja do ponto de vista econômico ou psicossocial. É o déficit sensorial mais frequente em humanos, com incidência que varia de 1:300 a 1:1.000 crianças. Segundo a Organização Mundial da Saúde (OMS), a perda auditiva atinge cerca de 10% da população mundial. A frequência da surdez no Brasil é estimada em 4:1.000 nascimentosA triagem auditiva neonatal (TAN) é um importante instrumento na implantação de programas de conservação da audição e na detecção precoce das alterações auditivas. Esse procedimento é recomendado pelas políticas de saúde brasileiras como a primeira etapa de um programa de saúde auditiva neonatal, que, preferencialmente, deve ser realizado nos primeiros dias de vida (24–48 horas), ainda na maternidade e, no máximo, durante o 1º mês de vida, para que possamos minimizar os prejuízos causados por esta patologia tão comum em nosso meio.4.No programa de prevenção, por ocasião da alta hospitalar após o nascimento, é realizada a triagem auditiva neonatal universal (TANU) por meio de emissões otoacústicas transientes (EOAT) e pesquisa do reflexo cócleo palpebral (RCP). Se o neonato passa, ou seja, apresenta resposta às EOAT em ambas as orelhas no teste da triagem auditiva, e não tem riscos para perda progressiva ou retrococlear, é feita uma orientação sobre o desenvolvimento da audição e da linguagem e ele recebe alta. Caso contrário, se há falha (quando não apresenta resposta em uma ou ambas as orelhas) é orientado o reteste com 30 dias e acompanhamento por uma equipe multidisciplinar, com o objetivo de encaminhá-los para diagnóstico desta deficiência, para realizar avaliações periódicas e intervenções adequadas a eles e seus familiares, durante os dois primeiros anos de vida5, por exemplo, a cirurgia de implante coclear, o qual é um dispositivo eficaz para crianças com perda auditiva pré-lingual severa e/ou profunda, pois proporciona considerável melhora na aquisição da linguagem oral por meio da via auditiva, o que pode ter um impacto positivo em outras áreas do desenvolvimento9.A TAN faz parte de um conjunto de ações que devem ser realizadas para a atenção integral à saúde auditiva na infância: triagem, monitoramento e acompanhamento da progressão auditiva e da linguagem, diagnóstico e reabilitação. Desta forma, a TAN deve estar integrada à rede de cuidados à pessoa com deficiência e às ações de acompanhamento materno-infantil. Também é de extrema importância a articulação, capacitação e integração com a atenção básica para garantir o monitoramento e acompanhar o desenvolvimento da audição e da linguagem, e para a adesão aos encaminhamentos para serviços especializadosJoint Committee on Infant Hearing (JCIH) de 2019 estabelece como indicador de risco para deficiência auditiva (IRDA)12: preocupação dos pais com relação ao desenvolvimento da audição e fala; histórico familiar de perda auditiva infantil permanente; UTI neonatal por mais de cinco dias; infecções intrauterinas, como Citomegalovírus (CMV), herpes, rubéola, sífilis, toxoplasmose e mais recentemente o Zika; malformações craniofaciais; síndromes associadas à perda auditiva; desordens neurodegenerativas; culturas positivas em infecções pós-natal; trauma cranioencefálico e quimioterapia12. A faixa etária materna igual ou superior a 35 anos, considerada fator de risco para inúmeros desfechos negativos relacionados aos recém-nascidos, têm maior frequência de resultados perinatais adversos quando comparada às mulheres com idade entre 20 e 34 anos, com destaque para prematuridade, baixo peso ao nascer e baixo índice de Apgar, sendo fatores de risco para perda auditiva15.O 16.Em 2012, o Ministério da Saúde instaurou as diretrizes de atenção da triagem auditiva neonatal universal no país, em que os índices de realização da TANU devem ser superiores a 95% dos nascidos vivos19. O que impossibilita a intervenção médica e fonoaudiológica no período crítico de maturação e plasticidade funcional do sistema nervoso central, entre os seis meses e dois anos de idade da criança20.Contudo, fatores como a não adesão da família e as peculiaridades do diagnóstico retardaram os processos, impedindo que os indicadores preconizados fossem alcançados, na maior parte das crianças23. Apesar dos avanços no processo de implementação da PNASA, persistem dificuldades com diagnóstico precoce, a agilidade da aquisição das próteses auditivas, a reabilitação e da garantia do acesso ao acompanhamento do usuário pelo Sistema Único de Saúde.Com vistas a minimizar o dano da deficiência auditiva na população, o Ministério da Saúde, por meio da Portaria n. 2.073, de 28 de setembro de 2004, instituiu a Política Nacional de Atenção à Saúde Auditiva (PNASA), promovendo a ampla cobertura no atendimento aos pacientes portadores de deficiência auditiva no BrasilMediante a afirmativa acima e da realidade do SUS, o objetivo primário desse estudo foi descrever o seguimento dos neonatos que apresentaram alteração no teste de TAN, bem como a fração de neonatos que são reavaliados, diagnosticados com perda auditiva, tratados e acompanhados por uma equipe multidisciplinar.24, para realização do reteste, totalizando 5.305 prontuários analisados. Os 366 casos com falha no reteste foram avaliados segundo o diagnóstico otorrinolaringológico de perda auditiva , segundo a Portaria n. 1.303, de 28 de junho de 2013auditiva .Consider(odds ratio) entre os fatores associados.Foram utilizados métodos estatísticos paramétricos de associação entre as variáveis qualitativas (teste qui-quadrado e modelo de regressão logística binária). Os resultados foram interpretados em termos da significância estatística da associação  e das razões de chances A pesquisa seguiu as recomendações sobre ética em estudos com seres humanos, sendo aprovado pelo Comitê de Ética em Pesquisa da Escola Superior de Ciências da Saúde da Universidade do Estado do Amazonas (CEP/ESA/UEA) sob o número de parecer 3.827.675 de 07 de fevereiro de 2020.25. Dessas, 5.305  foram encaminhadas para confirmação diagnóstica de perda auditiva em um Centro Especializado em Reabilitação Tipo I (CER I) na mesma cidade, sendo 2.989  do sexo masculino e 2.316  do sexo feminino.No período do estudo, de janeiro de 2016 a fevereiro de 2020, 148.991 crianças realizaram o teste da orelhinha nas maternidades da cidade de Manaus, segundo TabNet-DatasusDas 5.305 crianças submetidas ao reteste no CER I, 4.939  passaram e receberam alta do seguimento investigativo com as devidas orientações, enquanto 366  não passaram e seguiram para complementação diagnóstica , exames de imagens (tomografia computadorizada – TC e/ou ressonância magnética – RM de ouvido) e terapia . Para o interesse do estudo permaneceram as crianças com diagnóstico de perda auditiva neurossensorial que totalizaram 265 . Destas, prosseguiram no estudo apenas 58  crianças; 39 tinham recebido aparelho auditivo até o presente estudo; e 16 (41%) já tinham indicação cirúrgica para implante coclear, sendo que apenas três  haviam realizado a cirurgia. Ocorreu evasão em 207  das crianças. 19  aguardavam liberação do aparelho auditivo e 13  seguiam na fila de espera para realização da cirurgia de implante coclear .Na Dentre os indicadores de risco para deficiência auditiva (IRDA) encontramos 2,6 vezes mais chance de falha no reteste da orelhinha naquelas crianças que tinham história familiar de perda auditiva  e internação em UTI , conforme 26 (2021). Esses autores identificaram um total de 1.821 recém-nascidos. Foram aprovados no teste inicial 81% dos bebês; 423  foram encaminhados por falharem ao primeiro teste e acompanhados após 2 semanas. Entre esses bebês, 24  falharam no reteste. Nove  dos 24 bebês foram confirmados com perda auditiva bilateral. A incidência de perda auditiva no estudo supracitado foi de 4,94:1.000 e a perda auditiva confirmada foi estatisticamente maior em meninos do que em meninas. Vale ressaltar a importância de explorar um modelo de TAN de dois estágios para reduzir as respostas falso-positivas, levando em consideração uma possível “maturação” da via auditiva. Já foi sugerido na literatura um atraso na maturação da via auditiva em bebês prematuros em comparação com recém-nascidos a termo. Um possível atraso no reteste da TAN poderia ser considerado, em casos selecionados, com economia significativa de recursos econômicos e ansiedade dos pais, conforme o estudo de Ciorba et al. (2019)27 que concluíram uma possível “maturação” da resposta do PEATE  em 1,3% dos lactentes.Neste estudo identificamos uma falha no reteste de 366  crianças e uma prevalência maior no sexo masculino, corroborando os estudos de Ayas e Yassen12(2019) este fator de risco é bem conhecido e estudado principalmente quando a permanência é superior a cinco dias na UTI e envolve a necessidade de respiração artificial. E essa relação se estabelece devido a doenças, distúrbios metabólicos e iatrogenias durante o período de cuidados intensivos. Não houve detalhamento do tempo específico de permanência na UTI dos casos estudados.Do total de pacientes encaminhados para realização do reteste da orelhinha, 3.123  apresentavam algum indicador de risco para deficiência auditiva (IRDA), e algumas crianças manifestavam mais de um fator de risco associado. Destes IRDA avaliados, a internação em UTI foi observada em 426 crianças, sendo que 62  falharam no reteste, com significância estatística  . Segundo28 com 787 neonatos e lactentes, demonstrou uma OR de 1,20 enquanto o estudo de Barboza et al. (2013)29 revelou uma OR de 1,14. Neste trabalho, a história familiar de perda auditiva esteve presente em 180 crianças; destas 26  tiveram falha no reteste da orelhinha havendo associação significativa entre as variáveis histórico familiar e falha no reteste, com p = 0,0001 = 0,0001 .30 encontrou que 15% dos pacientes com alteração no teste auditivo tinham hiperbilirrubinemia, enquanto no grupo sem alteração auditiva essa proporção foi de 0,2%. Rechia et al. (2016)31 também encontrou associação significativa entre hiperbilirrubinemia em crianças internadas em UTI neonatal e falha no reteste da orelhinha. Não houve significância estatística entre icterícia neonatal e falha no reteste, nesta pesquisa  = 0,534) .29, assim como em Onoda et al. (2011)32, Escobar-Ipuz et al. (2019)33 e Marinho et al. (2020)6 demonstram ser a prematuridade a principal IRDA na população estudada, em contrapartida essa associação não foi observada no estudo de Oliveira et al. (2015)34. Neste estudo a prematuridade foi relatada em 745 (14%) das crianças; 68  apresentaram falha no reteste, corroborando com os estudos citados, essa evidência de associação entre as variáveis prematuridade e falha no reteste .Sobre a prematuridade trata-se de importante fator de risco para perda auditiva congênita, notadamente em neonatos com menos de 1.500g ao nascer. Barboza et al. (2013)28. Neste estudo, grande parte dos eventos infecciosos durante a gestação foram infecções do trato urinário.Infecções durante a gestação são fatores de risco bem estabelecidos na literatura para perda auditiva, principalmente quando são uma das STORCH . A infecção do trato urinário é comum em mulheres jovens e representa a complicação clínica mais frequente no período gestacional. Isso faz com que os neonatos e lactentes das mães que tiveram infecções urinárias possam ser considerados de risco para perda auditiva, não pela própria infecção, mas no caso de ter havido tratamento por medicação ototóxicaO acompanhamento pré-natal, estratégia importante de cuidados preventivos em gestantes e crianças, é capaz de orientar a promoção da saúde e do bem-estar, além de oportunizar o tratamento de problemas que podem afetar as mães e seus filhos nesse período. Infecções neonatais e alteração na pressão arterial materna também teve significância estatística, com p = 0,0001, associados à falha no reteste da orelhinha .Neste trabalho foi observado, ainda, que as crianças com indicadores de história familiar de perda auditiva e internação em UTI apresentavam 2,6 vezes mais chances de falha no reteste da orelhinha . Como a De fato, chama a atenção, em toda a casuística, a alta prevalência de evasão durante o seguimento dessas crianças após confirmação do diagnóstico de perda auditiva neurossensorial. Embora este trabalho não tenha aferido o número de faltas ao reteste, tendo em vista desconhecermos o quantitativo inicial de encaminhamentos, notou-se problemas na adesão à condução clínica em que 207  crianças que falharam no reteste e realizaram a confirmação diagnóstica evadiram durante o seguimento.35, independente do modelo de gestão , verificou-se baixos escores, em resposta ao questionário PCATool versão criança – o qual avalia a qualidade dos serviços de saúde, mensurando aspectos de estrutura, processo e resultado, relacionando as experiências do usuário com os profissionais e com o serviço de saúde, medindo sua satisfação. Os pais avaliaram como insatisfatórios alguns pontos, como acessibilidade, integralidade e orientação familiar. Esse desempenho pode trazer consequências negativas para a qualidade e integralidade do cuidado ao bebê de risco. Nesta pesquisa, os fatores relatados nos prontuários sobre a descontinuidade do seguimento foram questões sociais, como mãe dependente química, mudança de residência domiciliar, insatisfação com a qualidade dos serviços de atenção primária à saúde, características geográficas da nossa região e dificuldades financeiras em seguir o acompanhamento.Segundo Samelli et al. (2019)37, visto que algumas mães alegam não ter dinheiro suficiente para passagens de ônibus. O autor identificou 20% de falta ao reteste na unidade neonatal do Hospital Universitário da cidade de Maringá, PR, situação semelhante encontrada no trabalho de Berni et al (2010)38 ao estudar a TAN em um hospital da rede pública, situado na cidade de Campinas, SP, encontrou 24,8% de faltas ao reteste.Entre os fatores que levam à evasão estão: baixo grau escolar das mães, que não se conscientizam da importância da triagem auditiva e o baixo nível socioeconômico12.Cerca de metade das crianças que apresentam alteração no teste inicial da orelhinha não têm um adequado seguimento para confirmação de seu diagnósticoJá, entre aquelas que mantiveram o seguimento e confirmaram o diagnóstico de surdez neurossensorial, com indicação do uso do aparelho de amplificação sonora individual (AASI), 19  ainda não estavam em uso, pois aguardavam liberação da prótese. Das 39 crianças usuárias de AASI, 16 (41%) tiveram indicação cirúrgica de implante coclear (IC), porém, apenas 3  conseguiram realizar a cirurgia até o final da coleta de dados , as outras 13  seguiam na fila de espera do sistema de regulação (SISREG) aguardando autorização para realizar exames de imagem pré-operatórios e diagnóstico .Parte da justificativa para a morosidade na progressão para a cirurgia parece estar relacionada ao extenso protocolo de investigação imagenológica (tomografias e ressonâncias sob sedação) e o processo administrativo para liberação de passagens, hospedagem e agendamento de consultas/avaliação cirúrgica a serem realizadas, principalmente no Estado de São Paulo, via serviço público no programa SUS da Secretaria Estadual de Saúde do Amazonas de Tratamento Fora de Domicílio (TFD).Sobre o seguimento para a cirurgia do IC, citamos como exemplo alguns casos que podem explicar as razões sociais da não progressão na terapia: a primeira, uma das crianças que era proveniente do município de São Gabriel da Cachoeira, AM (852 km até Manaus), e pertencia a uma etnia indígena. Nascida de parto prematuro, com diagnóstico tardio de perda auditiva aos 2 anos de idade já em uso irregular do AASI, com indicação para cirurgia de IC, relatava as dificuldades de acesso ao acompanhamento fonoterápico mesmo com o AASI. A segunda criança era da zona rural de Itacoatiara, AM (270 km até Manaus), cuja família vivia de agricultura de subsistência. Ela também apresentava dificuldades sociais e financeiras para comparecimento às consultas e à fonoterapia, razão pela qual não seguiu para a cirurgia. Ainda, outras duas eram oriundas da periferia da cidade de Manaus e, apesar de habitarem na capital, o contexto social de ambas era de risco, havendo desde envolvimento dos pais com atividades ilícitas até relato de furto do AASI.Dentro desse contexto, a situação sociogeográfica amazônica é uma questão importante a ser considerada ao se planejar a promoção e execução de políticas públicas de saúde auditiva, em especial na população infantil. Nos casos em que as enormes distâncias são o obstáculo, temos outras barreiras como situações de criminalidade e vulnerabilidade social que dificultam o acesso ao tratamento de reabilitação.39 (2008) ao estudar o acompanhamento de crianças com perda auditiva quanto à implantação de AASI, percebeu que apenas 26% procuraram o serviço espontaneamente. Quando o serviço social solicitava o retorno, este número chegava a 44%. Estes achados reforçam a importância da adesão dos pais ao programa de triagem auditiva e posterior acompanhamento, além de revelar a necessidade de um programa de triagem auditiva neonatal incluindo uma frente de trabalho com assistentes sociais que possam acompanhar essas mães com o objetivo de diminuir o índice de evasão do programa.LanzettaÉ válido destacar que a região Norte do Brasil possui um único centro de implante coclear do SUS, localizado no Hospital Universitário Bettina Ferro de Souza, em Belém do Pará, e que embora seja na mesma região, pelas dimensões continentais brasileiras, pela própria demanda interna do estado do Pará e pela política de TFD adotada no estado do Amazonas, o deslocamento continua sendo grande empecilho para estes casos.Apesar de observarmos uma cobertura ampla para a realização da triagem auditiva neonatal, as dificuldades do seguimento, em especial para a cirurgia do IC, deverão ser repensadas por meio de políticas públicas desenhadas especificamente para a região, considerando os desafios sociais, econômicos e geográficos.Conclui-se que, embora o fluxo de triagem alcance boa parte dos nascidos vivos, as taxas de evasão durante o processo são altas, portanto, as características socioeconômicas e geográficas de regiões como a Amazônica, devem ser consideradas como fatores relevantes à evasão dos programas de reabilitação dessas crianças. Foi possível identificar que a internação em UTI neonatal e o histórico familiar de perda auditiva presentes nas investigações, compõem os principais e mais importantes fatores para alteração de retestes da orelhinha.


The electrical stimulation generated by the Cochlear Implant (CI) may improve the neural synchrony and hence contribute to the development of auditory skills in patients with Auditory Neuropathy / Auditory Dyssynchrony (AN/AD).Prospective cohort cross-sectional study to evaluate the auditory performance and the characteristics of the electrically evoked compound action potential (ECAP) in 18 children with AN/AD and cochlear implants.The auditory perception was evaluated by sound field thresholds and speech perception tests. To evaluate ECAP's characteristics, the threshold and amplitude of neural response were evaluated at 80Hz and 35Hz.No significant statistical difference was found concerning the development of auditory skills. The ECAP's characteristics differences at 80 and 35Hz stimulation rate were also not statistically significant.Clinical Trials: NCT01023932The CI was seen as an efficient resource to develop auditory skills in 94% of the AN/ AD patients studied. The auditory perception benefits and the possibility to measure ECAP showed that the electrical stimulation could compensate for the neural dyssynchrony caused by the AN/AD. However, a unique clinical procedure cannot be proposed at this point. Therefore, a careful and complete evaluation of each AN/AD patient before recommending a Cochlear Implant is advised.  The approach for habilitating and rehabilitating patients with auditory neuropathy/auditory dys-synchrony (AN/AD) has raised diverging questions and opinions, because these individuals continue to be placed in the special cases group for cochlear implants. The term auditory neuropathy has been used generically to name discrepancies between the cochlear and neural functions of the auditory system.AN/AD has been described in the literature as a change in neural synchronism whereby the function of outer hair cells is preserved while afferent neural transmission is compromised. However, to this date the exact injury site has not been demonstrated by current methods in clinical practice.AN/AD can significantly affect speech understanding and production. Thus, adequate habilitation and rehabilitation is needed especially in children, who go through critical hearing and language development periods.Individual hearing aids have shown poor results; amplification may improve the detection of sounds but does not provide any benefit for the development of speech discrimination, recognition, and understanding.3Other communication strategies - communication by gestures, lip reading, and frequency modulated (FM) systems - have been suggested for habilitation and rehabilitation in this group of patientsAbout one third of AN/AD patients present severe to profound hearing loss, and are thus candidates for cochlear implantsCochlear implants are indicated in this group because this electronic device can partially replace the function of auditory sensory cells. These devices stimulate the auditory nerve directly, thereby improving neural synchrony and supporting language and hearing developmentAt the same time, the compound action potential of the electrically evoked auditory nerve (ECAP) or neural response in cochlear implant users can objectively demonstrate changes in hearing following electrical stimulation of the auditory system in AN/AD patients.Because the electrical stimulation of cochlear implants may improve neural synchrony and support auditory ability development, the purpose of this study was to assess hearing performance and ECAP features in a group of AN/AD children with cochlear implants.A cross-sectional cohort study was undertaken of 18 AN/AD children with cochlear implants for at least six months that participated in two different cochlear implant programs in São Paulo state.The institutional ethics review board for research in human being approved this study (no. 316/2005 UEP-CEP).Parents and caretakers of participants were informed about the procedures, and signed a free informed consent form.Regarding the inclusion criteria, the surgical indication for cochlear implants in children with prelingual hearing loss is made in both centers according to international criteria, namely: age around 1 year; cochlear permeability for inserting the electrodes surgically; bilateral severe to profound and/or profound sensorineural hearing loss; auditory threshold with normal amplification over 60 dB at 500, 1,000, and 2,000 Hz after intense and effective auditory habilitation; limited benefit for auditory abilities with the use of hearing aids; absence of intellectual or emotional deficits; motivated family for using cochlear implants and to develop favorable communication attitudes in the children; adequate family expectation about the results of cochlear implants; participation of children in auditory habilitation and rehabilitation programs in their city of origin.Preoperative imaging exams  were normal in all subjects.Other clinical peculiarities not mentioned above were analyzed in each patient and defined as special cases.Cochlear implants are not indicated in prelingual hearing impaired children also according to international criteria in both cochlear implant programs from which data were gathered, as follows: severe neurological conditions associated with hearing loss; medical or psychological conditions that contraindicate surgery; hearing loss due to cochlear or auditory nerve agenesis, or central injuries; active middle ear infection; unreal family expectations about the benefits, results, and limits of cochlear implants.The audiological and electrophysiological features of AN/AD in the study sample were as follows: normally functioning OHCs identified by otoacoustic emissions (OAE) and/or cochlear microphonism; neural alterations in which brainstem auditory evoked potentials were markedly altered or absent; altered audiometric thresholds; limited results with conventional amplification in hearing and language development.The age at which surgery was done in the study sample ranged from 1 year and 8 months to 6 years and 11 months (mean - 3 years and 8 months). The duration of cochlear implant use ranged from 10 months to 3 years and 5 months.The cochlear implant brand and model in the study subjects were not taken into account in the inclusion/ exclusion criteria. Nevertheless, all subjects used the Nucleus 24 cochlear implant (Cochlear Corporation) and the electrodes were completely inserted.Based on Davis and Silverman's (1970)Data were taken from files of prenatal, perinatal, and postnatal registries, the etiology of hearing loss, audiologic and electrophysiologic tests , and the cochlear implant surgery.Behavioral assessment of hearing  and speech perception assessment  were used to test hearing perception.The following procedures were used for testing speech perception: procedure to assess children with profound hearing lossThe nature of hearing ability tasks in study subjects was classified according to the observed hearing abilities in the speech perception assessment procedures.The category “detection of sounds” was used in children with results showing limited speech perception that were able to carry out only Test 1 of the GASP.The closed set category was done in children that were able to carry out Test 5 of the GASP, in which children are presented with alternative answersChildren that were able to carry out Test 6 of the GASP - and therefore the list of disyllables - were classified in the open set category. In this test, children had no choice of answers, and required more complex hearing abilitiesImpedance telemetry or reverse telemetry or bidirectional telemetry was done in all stimulation modes present in the Nucleus 24 cochlear implant system to assess the neural response; the aim was to analyze the integrity of the intracochlear electrodes.The impedance values of intracochlear electrodes 20, 15, 10, and 5 were evaluated.Electrodes with altered impedance values - indicating a short circuit or open circuit - were excluded from the evaluation. The adjacent apical electrode  was then used in the research protocol.Four out of 72 electrodes had altered impedance values; therefore, adjacent apical electrodes were used.The ECAP was carried out with electrodes 20, 15, 10 and 5, which were in the surgically inserted electrodes.The parameters that were applied in recording the neural response were taken from published recommendationsECAP threshold measurements were taken at the 80 and 35Hz stimulation frequencies to assess possible changes in the characteristics of the neural response as the stimulation frequency is reduced. The same neural response recording parameters were used for the two tested stimulation frequencies. ECAP responses were classified according to the following parameters: presence of N1 (measurable peak); presence of P1/P2 (measurable peak); response morphology; response reproducibility; and consecutive valid recordings.Neural response amplitude and threshold value criteria were applied to assess the recordings qualitatively and quantitatively.Two-way analysis of variance was applied to evaluate correlations between age at surgery, duration of cochlear implant use, and speech perception results.Fisher's exact test was applied to check the relation between TOAE results and hearing abilities.Repeated measures analysis of variance was applied to study the relationship between mean speech frequency auditory thresholds , and open and closed set speech recognition results in each subject. Free field auditory threshold means at each frequency were marked with triangles at different tested frequency ranges.Repeated measures analysis of variances was also applied to analyze neural response amplitude and thresholds at 35 and 80 Hz.The causes of hearing loss in the study sample were as follows: association of multiple indicators of hearing loss at birth  in 50% of subjects; unknown or idiopathic in 44% of subjects; and congenital rubella in 6% of subjects.Speech perception results  were distributed in the study population as follows: closed set speech recognition - 61% of subjects; open set speech recognition - 33% of subjects; and detection of sounds only in 6% of subjects.There were no statistically significant differences among the mean ages at surgery, the duration of use of cochlear implants, and speech recognition auditory abilities.p=0.304) and left ear (p=0.620).There was no statistically significant relationship in speech perception performance for open and closed set speech recognition and the presence of OAE before surgery in the right ear (p=0.485).There were no statistically significant differences among the means of pure tone thresholds at speech frequencies or in open and closed set speech recognition abilities  at both 35 Hz and 80 Hz stimulus frequencies.A difference was found in the threshold means of four electrodes (p=0.566).Specific analysis per electrode revealed no differences in visual threshold means at 35 and 80 Hz stimulus frequencies (p=0.000). The visual mean of electrode 15 was lower than that of electrode 10. A comparison of the visual threshold means in electrodes 10 and 5 yielded a marginal p value (p=0.051).The results of comparing electrodes revealed that the visual threshold mean was lower in electrode 20 compared to the other electrodes  in all tested electrodes.There were no statistically significant differences among the neural response amplitude means at stimulus frequencies of 35 and 80 Hz (p=0.096) at stimulus frequencies of 35Hz and 80Hz (p=0.527).A comparison of neural response amplitudes among electrodes revealed no statistically significant differences among the neural response amplitude means in electrodes 20,15, 10, and 5 . This condition, therefore, did not appear to be a determining factor for ECAP recordings.Our analysis was based on existing studies on ECAP in cochlear implant users in general because of the similarity between ECAP findings in our study sample and in the clinical population of cochlear implants users, and because there have been few studies describing specifically the neural response characteristics in AN/AD patients.Neural responses were present in over 80% of our recordings. Similar possibilities in ECAP recordings have been described elsewhereCharasse et al. (2004)Using lower stimulus frequencies in AN/AD cases could presumably generate more robust neural responses; thus, altered neural synchrony could be the cause of speech perception difficulties.The hypothesis that the hearing system responds more slowly in AN/AD patients because of altered auditory nerve neuron triggering, and that the resulting lower stimulus presentation rate generates more evident neural responses, motivated us to measure the neural response characteristics at stimulus frequencies of 35 and 80 Hz.However, no statistically significant differences between visual neural response thresholds were found when comparing the two stimulus frequencies. These findings corroborate previous papersSimilarly, there were no statistically significant differences in neural response amplitudes as the stimulus frequency was reduced to 35 Hz. However, the mean neural response amplitude values were higher at 35 Hz in all electrodes, indicating better neural response measurements at this stimulus frequency. Other authors have also reported that neural response amplitudes tended to increase at lower stimulus frequenciesSimilarities in neural response characteristic at stimulus frequencies of 35 and 80 Hz suggests that the auditory system in the study population retrieved the temporal properties in coded information, following electrical stimulation, irrespective of the stimulus frequency. Significant differences in the quality of neural responses have been described in the literature only for recordings obtained at stimulus frequencies over 150 HzIn the present study, the benefits for hearing perception seen in AN/AD children that use cochlear implants - and the possibility of recording ECAP - have shown that electric stimulation from cochlear implants compensated for the altered neural synchrony caused by AN/AD.Except for one study subject in our series, cochlear implant use in AN/AD children resulted in comparable development of hearing abilities to children without AN/ AD that also used cochlear implants. Intrinsic variables that are inherent to the pathophysiology of AN/AD did not appear to affect the development of hearing abilities in AN/AD patients following electric stimulation. AN/AD children do not require specific adjustments of programming parameters for the speech processor.It should be noted that the results of cochlear implant use in AN/AD patients were closely related with the site of the alteration. However, it is sill not possible to define exactly the injury site to specify which AN/AD cases could benefit most from cochlear implants. Encouraging results in our study sample related to the development of hearing abilities in AN/AD patients using cochlear implants suggest that neural function is preserved. Altered neural synchrony in these cases was possibly due to altered outer hair cells and/or the synapses of these cells with the auditory nerve.A longitudinal study of AN/AD patients that use cochlear implants may clarify specific nuances in the rehabilitation process of this group as these patients use cochlear implants. At the same time, a test protocol that includes an assessment of hearing abilities in the presence of competing noise, of language abilities, and of speech production, may help establish the specific clinical features of AN/AD patients that use cochlear implants.In this study, cochlear implants are effective measures for developing auditory abilities in 94% of AN/AD subjects. Use of a reduced stimulation frequency (35 Hz) did not result in statistically significant changes in neural response amplitudes and thresholds.However, a common approach cannot yet be defined and adopted, given the heterogeneous nature of our clinical group of cases.


Despite much attention on the history of goat evolution, information on origin, demographic history, and expansion route remains controversial. To address these questions, we collected 4,189 published goat DNA sequences including 1,228 sequences from 57 breeds in China and 2,961 sequences including 193 goat breeds from 71 other countries and carried out an integrated analysis. We found goat breeds from South China had the highest genetic diversity of lineage B, and subclades B2 only were found in Southwest China, suggesting that lineage B  probably originated from Southwest China and its surrounding areas. In addition, in this study, we found that lineage A from South China also presented higher genetic diversity and earlier expansion time , even earlier than breeds from the Middle East. Hence, we speculated that South China and surrounding areas were the origin of lineage B and also the transportation hub for lineage A spreading to North China and Southwest Asia. Furthermore, according to the analysis of correlation between genetic differentiation value λ1 and λ2 and geographical distance, we further confirmed two phases of migration in goat breeds of North China. These results will contribute to a better understanding of the origin and migration history of domestic goat. Capra hircus) was an important globally distributed farm animal that provided indispensable animal products such as meat, milk, hides, and fiber for humans and also played important roles in agriculture and culture for human civilizations , C. ibex nubiana (AJ317871), C. sibirica (AJ317874), C. caucasica (AJ317875), C. falconeri (AB044305), and C. aegagrus blythi (AB110590), sequences (FST) values were calculated using Arlequin v.3.5  were obtained from GenBank, including 1,228 sequences from 57 breeds of China and 2,961 sequences including 193 breeds from 71 other countries (Table S1 and Table S5). In addition, six wild goat, equences  and 22 requences . All seqequences . Neighboequences , with a in v.3.5 . The obtin v.3.5 . To visuin v.3.5 . The invin v.3.5 . We carrA total of 217 polymorphic sites defining 1,427 haplotypes were detected among 4,189 sequences, and the total haplotype diversity (Hd) and nucleotide diversity (Nd) were 0.9904 and 0.0210, respectively. Phylogenetic analysis constructed based on 1,427 haplotypes and six wild goat sequences in this study presented the six previously defined lineages  . Among tp < 0.05; p values >0.05  according to the observed values . Howeveres >0.05 . Furtheres >0.05 . Lineagees >0.05 . SouthweMultidimensional scaling (MDS) plot dimension revealed that breeds from Southern China were separated from other breeds and clustered with several individuals from Southwest Asia and Africa, whereas breeds from Northern China and Qinghai–Tibet regions clustered with the Middle East, Southwest Asia, and Europe goat breeds . In addi. Six mtDNA lineages described previously in domestic goat were detected according to the results of NJ tree (Capra species captured recently and hybridized with domestic goats (ST distances also confirmed the mixture in goat breeds of seven regions (In this study, we analyzed the mt DNA 4189 sequence variation covering Asia, Africa, and Europe to investigate their maternal origins, population structure, and demographic history . Six mt NJ tree  (Figure  NJ tree . Lineage NJ tree , in agre NJ tree , indicat NJ tree , meaning NJ tree . The oth NJ tree  (Figure  NJ tree . Further NJ tree , the ori NJ tree . Lineage NJ tree  (Figure  NJ tree . Interes NJ tree  and the  NJ tree . Meanwhi NJ tree . Additio NJ tree . Lineage NJ tree  (Figure  NJ tree . It was ic goats . In addiic goats . Additioic goats , which wic goats . Moreoveic goats . This phic goats . Further regions . However regions , being s regions . Moreove regions . Combine regions , we spec regions . Therefo regions . However regions .Moreover, according to findings from this and previous studies, goats from north China arrived from two possible domestication centers through ancient human migration or commercial trade routes . It implIn summary, the current study provided a comprehensive insight into genetic diversity, distribution pattern, and origin of domestic goats based on world-scale mitochondrial DNA data. Our study detected a relatively high mtDNA diversity in goat breeds from Southwest China, which may be the area of origin for lineage B and also probably was an important goat propagation route to Southeast Asia. In addition, we speculated that two independent domestication centers may have contributed to the formation of goat populations in North China. The results of this study significantly improved our understanding of goat domestication, particularly the dispersal to and from the East Asia region. However, the information based on mtDNA reflected only the female-mediated gene flow. In recent years, with the rapid development of next-generation sequencing technology, nuclear genome research is increasing . For exa