The estimated prevalence of congenital profound bilateral hearing loss is 1 in 1000 newborns.2 Another 1 to 2 in 1000 newborns have mild-to-moderate bilateral hearing loss or unilateral hearing loss of any degree of severity.15 The most common causes of congenital sensory hearing loss are infections (syphilis, toxoplasmosis, rubella, and CMV), inner ear malformations (30% to 40%), and genetic causes (50%).16 Rubella was once the most common viral cause of congenital sensory hearing loss, but vaccination has made it rare today.17 Congenital syphilis, which had declined for decades and remains uncommon, is on the rise, with an incidence of 23.3 per 100,000 live births in 2017.18 Nearly 50% of children with congenital hearing loss do not have a specific diagnosis.

The Zika virus is transmitted by the Aedes aegypti mosquito and can cross the placental barrier and infect the developing fetus. Congenital Zika Syndrome (CZS) may cause microcephaly, reduced brain parenchyma, and visual and hearing impairment. Approximately 7% of infants with CZS have sensorineural hearing loss.19 Although the main concern with Zika virus infections is CZS, children infected with Zika virus after the neonatal period are at risk for Guillain-Barré syndrome and transient sensorineural hearing loss.

The incidence of congenital hearing loss is higher in premature children and becomes lower with increasing gestational age and birth weight (1.2% to 7.5% born at 24‒31 weeks and 1.4% to 4.8% with birth weight 750 to 1500 g). Hearing loss affects 1.2% to 7.5% of infants in neonatal ICUs.20 Interventions such as assisted ventilation, prolonged hospital stays (≥12 days), central venous access, and antibiotic use in the neonatal ICU increase the likelihood of hearing loss.

GJB2, the first gene to be implicated in nonsyndromic human deafness, was discovered in 1997. It is the gene most related to hearing loss. Since then, more than 130 genes and nearly 8000 gene variations have been identified and are associated with severe-to-profound nonsyndromic sensorineural hearing loss. These variations differ significantly based on the ethnic population examined. There are also over 600 clinical syndromes that include deafness. In many of them, deafness is the first clinical feature to manifest.21 According to estimates, there are over 1000 genes that can cause hearing impairment.22

Some syndromes such as coloboma, heart disease, choanal atresia, retarded growth and development, genital hypoplasia, ear anomalies/deafness (CHARGE), associated with genetic causes, may also cause hearing loss due to middle or inner ear malformations.23

Some children may develop deafness after the neonatal period, and this will not be detected by current UNHS. Importantly, a significant number of children who develop prelingual deafness after the neonatal period go undetected by currently implemented UNHS. Dedhia et al.24 estimated that nearly 25% of all children with sensorineural hearing loss are not identified by UNHS and that two-thirds of them had severe-to-profound deafness. Some syndromes can only be identified over time.

Pendred syndrome is associated with recessive variants in the SLC26A4 gene. It is the most common syndromic form of hereditary sensory hearing loss and is associated with thyroid dysfunction, goiter, Enlarged Vestibular Aqueduct (EVA), and cochlear incomplete partition type II (Mondini deformity).25

Usher syndrome is also autosomal recessive and has 3 clinical types, associated with at least 9 genes that are differentiated by the severity of hearing loss, vestibular dysfunction, and age at onset of vision loss.26 Alport syndrome is an X-linked (80%) or recessive (depending on the gene) disorder resulting in kidney failure, eye abnormalities (lenticonus, subcapsular cataract, retinopathy), and progressive sensory hearing loss usually detected in late childhood.27

Delayed-onset hearing loss may also occur after congenital infections. Historically, prenatal exposure to STORCH agents was a common cause of congenital hearing loss. However, the epidemiology of these agents has changed, and congenital CMV (cCMV) currently is a major cause of delayed-onset hearing loss in many countries. The prevalence of cCMV infection is 0.4% to 2.3% of all newborns. Of infants with confirmed congenital loss, 6% to 7% have cCMV.28 However, up to 43% of infants with cCMV initially undergo UNHS but will later experience sensory hearing loss.28

Hearing loss in children may have multiple etiologies over time, such as temporal bone fractures, infections, exposure to ototoxic drugs, autoimmune diseases, and noise exposure. The estimated prevalence of hearing loss in children up to 18 years of age is 18%.29

Trauma may cause conductive, mixed, or sensorineural hearing loss, depending on the location and type of temporal bone injury. Up to 82% of children with temporal bone fractures will have hearing loss at presentation; of these cases, 56% will be conductive, 17% will be sensorineural, and 10% will be mixed.30 Conductive hearing loss may result from tympanic membrane perforation or ossicular chain injury. Temporal bone fractures may damage the cochlea and the cochlear nerve, or cause a labyrinthine fistula, which often leads to severe-to-profound sensorineural hearing loss.31 Temporal bone concussions without fracture may also result in temporary or permanent sensory hearing loss.32

Infectious causes of sensory hearing loss include measles, mumps, varicella-zoster virus, Lyme disease, bacterial meningitis, and, rarely, otitis media. Measles and mumps with subsequent hearing loss are more common in unvaccinated children.33 Meningitis in children is the most common postnatal cause of acquired bilateral hearing loss. Meningogenic labyrinthitis (with or without new bone formation) is most often due to bacterial meningitis and is usually bilateral. The offending pathogens are believed to invade the membranous labyrinth through the cochlear aqueducts or the lamina cribrosa of the vestibule, resulting in suppurative labyrinthitis. Three radiologic stages are described in labyrinthitis: acute stage, fibrous stage, and labyrinthitis ossificans, shown by both Computed Tomography (CT) and Magnetic Resonance Imaging (MRI).30

Hearing loss resulting from bacterial meningitis may be progressive and is more common after Streptococcus pneumoniae infections that can cause ossification of the labyrinth. Cochlear implantation is indicated as soon as possible.34 Acute and chronic otitis media may also cause hearing loss. They are usually conductive and can be resolved with antibiotic therapy or surgery.

The following drugs are known to be ototoxic and cause permanent hearing loss: aminoglycosides, chemotherapy drugs (especially cisplatin), and loop diuretics. Radiotherapy involving the temporal bones, associated with cisplatin, increases the risk of sensorineural hearing loss, which may manifest a few years after the end of treatment.35 Although aminoglycoside-induced ototoxicity is strongly related to serum drug level and cumulative dosage, genetic susceptibility to ototoxicity is well described (including mitochondrial gene mutations, especially RNA 1555A>G and 1494C>T in mitochondrial 12S ribosomal RNA), with hearing loss occurring after even a single dose in some patients who have these mutations.36 Other drugs such as salicylates and macrolides may cause hearing loss that is usually reversible.37 Close monitoring of serum drug doses and levels can decrease the chance of inner ear injury.

Autoimmune hearing loss is due to either primary autoimmune dysfunctions in the inner ear or systemic autoimmune diseases such as Cogan syndrome (interstitial keratitis, progressive hearing loss, and vestibular dysfunction).38 Hearing loss is often rapidly progressive and sometimes responds to immunosuppressants.

According to the WHO, 1.1 billion young people are at risk of hearing loss due to prolonged and excessive exposure to loud sounds.39 Children and adolescents are at higher risk of developing hearing loss because of frequent exposure to loud music during leisure activities, on transport services, and while playing sports.40,41 Headphones improve the listening experience but also increase the risk of noise-induced hearing loss. The use of portable music players such as MP3 players, iPods, smartphones, and similar devices has increased worldwide over the past few decades.42

In the 2019 JCIH statement recommendations,9 there is a major concern with starting rehabilitation as early as possible. Screening is suggested to be done up to 1 month of age, diagnosis of hearing loss to be made up to 2 months of age, and rehabilitation to be started up to 3 months of age. This new goal has been established mainly for programs that already meet the 2007 recommendations6 of screening up to 1 month, diagnosis up to 3 months, and start of rehabilitation up to 6 months. This concern is based on the knowledge that early intervention is critical for successful rehabilitation outcomes. Delays have a negative impact not only on language development and communication but also on children’s well-being and cognition.

In Brazil, the reality is still far from ideal, despite a 2010 law5 defining the mandatory nature of UNHS. In a study on UNHS coverage in public maternity hospitals in the country, a 34.4% coverage was identified by 2018. There were large regional differences, with almost 70% coverage in the South region and only 21.9% in the North region in the same period.48

Newborns at high risk for hearing loss

In newborns at high risk for hearing loss, as previously described, sensorineural deafness accounts for 2.5% to 10% and conductive hearing loss for 25% to 35%.14,53,54 The main causes are congenital or perinatal. Thus, UNHS is extremely important in this population.

Hearing screening of newborns with risk factors (Fig. 1) should consist of both OAE and AABR testing. AABR in this population is essential for identifying auditory neuropathy, which is very common in patients with hyperbilirubinemia, extreme prematurity, and hydrocephalus.6 Newborns who pass should be followed up every 6 months for language development at primary health care units. When they fail screening, the test must be repeated up to 15 days and, if they fail again, they should be referred to appropriate centers for diagnosis of the severity and type of hearing loss between 1 month and 3 months of life.

Figure 1.

Universal newborn hearing screening flowchart in newborns with risk factors.

(0.36MB).

For diagnosis, ABR, automated steady-state response, and distortion-product OAE should be performed. When otitis media with effusion is unclear, 1000 Hz impedance meters should be used in children aged 9 months or older.6

If these newborns are hard of hearing, they should be referred for appropriate rehabilitation, which should be started as soon as possible. This can be done through a Hearing Aid (HA) or Cochlear Implant (CI) so that they experience appropriate hearing and speech development.

All children with suspected progressive hearing loss, as in the case of CMV or genetic disorders, require hearing monitoring up to 4 years of age (Fig. 1).

Newborns who are on mechanical ventilation for more than 5 days receive antibiotic therapy for secondary infection prevention, account for 10% to 15% of all live births, and deserve special attention in neonatal hearing screening.55 Gentamicin (an ototoxic drug) is used in most cases,55 supporting the hypothesis of sensorineural hearing loss in this population. Incubators are potentially noisy and may cause hearing loss.

In the pediatric ICU, newborns have several comorbidities such as malformations, severe infections, and low birth weight. Because they are in a noisy environment (incubators), it is difficult to perform the OAE and AABR tests, which delays hearing screening. The diagnosis is frequently delayed or not made.

Another important factor for not performing the tests in newborns with risk factors is that neonatal ICU speech therapists often do not specialize in audiology. Furthermore, hospitals rarely have audiologists available on holidays or weekends, which may leave these children unattended in case of hospital discharge. A suggestion to solve this problem is to provide training for intensive care nursing staff or to prepare an on-call schedule for audiologists in maternity hospitals.

These children frequently have multiple comorbidities that will be treated after discharge. However, they are often not taken to the office for out-of-hospital hearing screening testing, which causes enormous damage to this population, as they are diagnosed too late, when appropriate auditory rehabilitation is no longer possible.

Creating a UNHS protocol has multiple benefits, including: Identifying newborns at risk of deafness who could benefit from early intervention but are missed by current screening programs; Providing etiologic information as part of screening; Possibly decreasing the number of children who are lost to follow-up; Potentially saving costs by reducing the frequency of later testing.21

Any screening test must weigh false negatives versus false positives to best serve the screened population. “False positive” may refer to the actual screening device used, but here it refers to the overall result given to parents ‒ “pass” or “refer” ‒ versus the subsequent diagnostic confirmatory physiologic testing, which serves as the “gold standard”. The Positive Predictive Value (PPV) is the probability that individuals who screen positive actually have the disease. An ideal screening test would have a high PPV and a high sensitivity. Although negative predictive value and specificity are also considered in the design of screening tests, a confirmatory or diagnostic test should aim for a high negative predictive value and a high specificity as false negatives are reduced.

Once the diagnosis of hearing loss is established, the search for an underlying etiologic diagnosis is recommended. Available guidelines include screening for congenital infections, imaging, and genetic testing.56,57 Ophthalmologist consultation has been shown to have a high yield for visual anomalies in children with sensorineural hearing loss.58 The investigation may be complemented by a renal ultrasound to check for congenital malformations, an electrocardiogram to rule out long QT syndrome (as seen in Jervell and Lange-Nielsen syndrome), and other tests based on clinical findings. In unilateral hearing loss, the etiologic investigation may be limited to a thorough clinical examination for a syndromic cause of hearing loss, investigation of possible congenital infections, and imaging of the inner ear.59

A series of diagnostic laboratory tests that can help determine the cause are shown in Table 6. Since the diagnostic yield of these tests is low (ranging from 0% to 2%),60 they should only be ordered if indicated by medical or family history.

The diagnosis of cCMV is based on the identification of viral particles in saliva and urine using a PCR technique in the short window period up to the third week of life,68 as sensitivity decreases over time. In intrauterine life, after 20 weeks’ gestation, identification can be done through the amniotic fluid. This procedure is indicated in very specific situations.

Although described years ago, this method has not reached consensus. For health funding reasons, testing is most often performed in patients considered a target for the disease, such as symptomatic patients with a suggestive clinical status. If screening for cCMV is performed only in this population, the consensus statements point to a significant proportion of asymptomatic patients and patients with cCMV who would miss the chance of being diagnosed early.68,69

According to these consensus statements, in addition to apparent cases, children who fail the UNHS or who present with sensorineural hearing loss of unapparent cause should be tested for cCMV regardless of age.68,69 The same applies to neonates born to mothers with a documented seroconversion during pregnancy. According to Cannon et al.,70 for cases of cCMV-induced sensorineural hearing loss, there is good evidence that routine newborn screening has a positive impact on communication-related outcomes and should be considered for all children.

Prenatally, a PCR test for CMV in amniotic fluid can confirm cCMV infection (PPV is close to 100%).66 After birth, urine, saliva, or throat swabs should be collected and analyzed. Samples must be collected within 3 weeks of birth, as viral shedding after this period may reflect an infection acquired in the postnatal period and thus noncongenital. In children undergoing etiologic evaluation of sensorineural hearing loss over 3 weeks of age, cCMV infection can only be confirmed retrospectively, using stored newborn blood as a model source for PCR-based diagnosis.

In many high-income countries, a blood sample is routinely collected during the first week of life to screen for metabolic, endocrine, and other disorders. If cCMV infection is suspected, in addition to laboratory testing, brain imaging (cranial ultrasound or MRI), visual function assessment, and hearing assessment are required. However, cCMV infection is virtually asymptomatic in 90%of newborns. These children generally have fewer neurodevelopmental problems than those who are symptomatic at birth, but 10% will develop substantial sensorineural hearing loss at some point during childhood.65

Because of the cost of implementing universal screening, low- and middle-income countries do not routinely test newborns. In an SBO discussion forum, medical participants from all Brazilian regions consensually encouraged the practice of universal screening for cCMV. If this is not possible, neonates suspected of having this condition should be tested before discharge.

The phenotypes of hearing loss may vary. The most severe forms, characterized as profound bilateral sensorineural hearing loss, seem to occur more often in patients with primary infection, in cases of symptomatic neonates.64,71 However, intermediate forms of hearing loss are recognized in long-term follow-up studies.64,71 Sensorineural hearing loss in cCMV has been described as unilateral or bilateral, asymmetric, progressive, and fluctuating. Several protocols for longitudinal follow-up of children with cCMV have been described. To propose an evidence-based audiologic clinical follow-up closer to the Brazilian reality, the Ribeirão Preto cohort study53 can serve as a basis with small adjustments for each Brazilian region. According to the authors, neonates undergo UNHS at birth, consisting of OAE and AABR testing, to minimize false positives and negatives and to detect sensorineural hearing loss at specific frequencies as well as cases of auditory neuropathy.

Children with cCMV and those who failed the second test, in the case of retesting at 30 days, are referred to specialized centers for diagnostic hearing evaluation until the sixth year of life; assessments are performed every 6 months until the third year, and annually thereafter. The diagnostic evaluation consists of audiometry suitable for the child’s neuropsychomotor development. In the case of free-field audiometry, an OAE test is combined so as not to miss patients with unilateral sensorineural hearing loss. In the presence of any abnormality, immittance testing is performed to rule out the conductive causes of hearing loss so common in children. If a diagnosis is made, children are evaluated by click and tone-burst ABR at specific frequencies to reach a conclusion or classification of sensorineural hearing loss.

It is important that otolaryngologists and pediatricians are aware of some approaches based on current evidence and consensus statements68,69 when conducting a general clinical evaluation in children with cCMV. Patients should undergo imaging assessment of the Central Nervous System (CNS), where transcranial ultrasound is considered the initial test of choice and can be complemented and/or replaced by cranial MRI. As these patients are children, cranial CT should be avoided to prevent high exposure to radiation.69

Common findings suggestive of cCMV include CNS malformations, ventriculomegaly, microcephaly, and cortical and periventricular calcifications. Because these changes are present in 80% of patients with sensorineural hearing loss and symptomatic cCMV,64 they are relevant for the otolaryngologist providing auditory rehabilitation for these patients. Those with only limited changes have demonstrated the best rehabilitation outcomes.

Other key assessments are hematology, liver enzyme, bilirubin, and renal function tests, especially when pharmacologic therapy is indicated. These children also require a complete ophthalmologic examination for the diagnosis of congenital cataract and chorioretinitis.

Despite the high prevalence and high degree of morbidity, a gold-standard diagnostic test and a definitive treatment for cCMV have not yet been established.72 For symptomatic patients, 6-week treatment with valganciclovir has been approved and is associated with improved audiologic levels.73

In cases of moderate-to-severe symptomatic cCMV, relevant consensus statements68,69 recommend antiviral treatment in the neonatal period for 6 weeks to 6 months. The available drugs are oral and intravenous ganciclovir and valganciclovir. Antivirals as well as hyperimmune gamma globulin, initially suggested as a possible fetal protective measure in mothers with confirmed seroconversion, are not recommended for routine use. The controversy in the literature refers to asymptomatic patients or those with mild forms of cCMV presenting with early or delayed hearing loss.

The recommendations of the European consensus statement68 are based on the understanding that these children exhibit an evolutionary situation supposedly linked to the development of the disease in the CNS. Although the real action of the virus in the inner ear remains unclear, the agent is believed to have a possible direct cytopathic effect on the inner ear cells. Conversely, the immune reaction also seems to play a role in the pathogenesis of cCMV-related sensorineural hearing loss.69

Although not unanimously, pharmacologic intervention was recommended by most European consensus members for patients with asymptomatic or mild forms of cCMV with sensorineural hearing loss at birth or developing later. However, at a subsequent meeting, the experts did not support this approach because there were few studies showing scientific evidence and most of them were not randomized clinical trials. In the absence of evidence, during the SBO discussion forum, we supported the possibility of pharmacologic intervention with the provision of clear information on the uncertain prognosis and potential harm to the child’s health.

Since different phenotypes are possible, the choice of auditory rehabilitation method should be individualized and shared with the family of the child with sensorineural hearing loss and cCMV. Most often, a multidisciplinary team is required because different impairments may affect the child’s global development. All forms of auditory rehabilitation can be indicated, and the same patient may need more than one method at different times. Regardless of the method indicated, longitudinal follow-up of the infant with cCMV is important, as it is common for sensorineural hearing loss to progress on the same side or on the opposite side.74

Several efforts have been made to establish the prognosis of hearing loss progression in patients with cCMV. The belief that only primary gestational infections generate neonates with symptomatic forms and would be responsible for worse hearing outcomes has not been supported in the scientific literature.75

For clinical practice guidance, the following elements are indicative of worse outcomes of sensorineural hearing loss in cCMV and delayed-onset hearing loss76: Symptomatic forms of Ccmv; Prolonged period of transmission as detected by urinary viral shedding; Higher viral loads.

Two studies evaluated some predictors of good auditory rehabilitation outcomes for patients with CIs.77,78 More advanced white matter lesions on MRI correlated with worse outcomes. However, despite having poorer auditory outcomes in auditory rehabilitation, patients with cCMV, according to these authors, had results that justify the need for the procedure. These variables, considered predictors of auditory rehabilitation outcomes, can be used during the preoperative period in the management of family expectations and counseling.

A more detailed analysis of the methodology of these studies shows that the most important covariate possibly affected is the patient’s intellectual quotient, often associated with the amount of CNS imaging abnormalities, which will certainly exert greater influence on patient outcomes during auditory rehabilitation. Conversely, the anatomic site of the lesions and the presence of changes in the temporal and parietal lobes, sites related to the auditory and motor cortical areas of speech, seem to lead to worse outcomes in the follow-up of children with cCMV undergoing auditory rehabilitation with CIs.

To date, no vaccines have been approved for marketing in Brazil, but 2 are being tested in the United States in phase II, placebo-controlled, randomized clinical trials. These trials have shown seroconversion in 50% of pregnant women receiving the glycoprotein B vaccine.79 In a previous investigation, an important association of seroconversion was reported for 30% of the pregnant women whose children attended day care centers.80

The consensus statements recommend that pregnant women and mother-and-child health professionals be clearly informed of the forms of transmission and prevention. The measures aim to protect pregnant women from secretions from children under 2 years of age, especially those attending day care centers as they have a prolonged period of transmission and are subject to constant reinfections. Washing hands after diaper changes, avoiding kissing, and not sharing food and cutlery are measures that have been shown to reduce seroconversion in pregnant women.

Prevention of fetal infection will only be indicated in cases of contamination confirmed by testing via amniotic fluid between 20 and 21 weeks.74 Hyperimmune immunoglobulin is indicated for patients admitted to authorized clinical trials. Prevention of vertical transmission will supposedly have an important impact on the occurrence of permanent sequelae, the most frequent being hearing loss.

Identifying the cause is important for the prognosis of hearing loss and language development, as well as for the choice of treatment. Genetic testing should be considered in children with hearing loss of unknown cause. It has a high yield, identifying the condition in 44% of patients with bilateral sensorineural hearing loss.81 Genetic causes are 2.5 times more common in bilateral sensorineural hearing loss than in unilateral sensorineural hearing loss. The diagnostic yields of genetic testing are 22% and 1% in children with asymmetric or unilateral sensorineural hearing loss, respectively.81 Approximately 70% of genetic causes are nonsyndromic.

Genetic deafness can be classified by the type of genetic inheritance: Autosomal recessive inheritance is the most common and has the following profile: sensorineural, severe to profound, prelingual. Classified as DFNB; Autosomal dominant inheritance is most commonly characterized as progressive, post lingual, moderate hearing loss. Classified as DFNA; Mitochondrial inheritance is when a man or woman inherits maternal mitochondrial DNA; X-linked inheritance is when a woman, the carrier of the mutation, transmits the gene that manifests only in male family members.

To date, 124 genes linked to nonsyndromic hearing loss have been identified, 78 of which are autosomal recessive, 51 are autosomal dominant, and 5 are X-linked.82 Among these, GJB2 (connexin 26) is the most common. The GJB2 (connexin 26) and GJB6 (connexin 30) genes, both at the DFNB1 locus, are most commonly associated with bilateral sensorineural hearing loss, accounting for up to 31% of genetic cases confirmed in a recent study.

First described in the literature by Pendred in 1896, this syndrome is characterized by sensorineural hearing loss, inner ear malformations (incomplete partition type II and EVA), and thyroid dysfunction.95 Pendred syndrome is inherited in an autosomal recessive manner and results from biallelic mutations in the PDS/SLC26A4 gene.103 EVA can be observed in nonsyndromic hearing loss if there is homozygosity for wild-type SLC26A4 or only one mutated allele.104 Overall, Pendred syndrome has been estimated to account for up to 10% of hereditary hearing loss, with an incidence of 7.5 to 10 in 100,000.98

Audiologic phenotypes may vary, with mild-to-profound, congenital or late-onset hearing loss. Most patients present with severe-to-profound progressive congenital hearing loss, which can be aggravated by traumatic brain injury or barotrauma.105 Especially in children, the only clue to the diagnosis of Pendred syndrome may be the detection of radiologic abnormalities – EVA and incomplete partition type II. These diagnoses have important implications for management, as children with EVA may present with sudden and significant hearing loss after mild traumatic brain injury.106

Goiter is characteristically multinodular, with onset in the second decade of life. It develops during puberty in 40% of cases and in adulthood in 60%.98 Thyroid hormones can be at normal (in most cases) or low levels. Delayed thyroid iodine organification results in a positive perchlorate discharge test.27

Two other genes have been described to cause Pendred syndrome, accounting for less than 2% of affected individuals: FOXI1 encoding Forkhead box protein I1 and KCNJ10 encoding the adenosine triphosphate-sensitive potassium channel.27 Individuals with Pendred syndrome or DFNB4 should undergo annual hearing tests due to the possibility of hearing loss progression. In addition, thyroid function should also be monitored in children with Pendred syndrome, as there is a risk of developing goiter during puberty.105

Imaging is extremely important for the diagnostic evaluation of pediatric patients. It plays a role in determining the etiology, identifying abnormalities related to hearing loss progression, and surgical planning.111,112 Imaging allows the evaluation of the anatomy of the structures of the cochlea, labyrinth, cranial nerves, and central auditory pathways. In addition, several malformations can interfere with decisions about which hearing rehabilitation methods to use and, in some cases, contraindicate interventions.113

The diagnostic yield of imaging studies in the evaluation of children with profound bilateral sensorineural hearing loss ranges from 7% to 74%, with high specificity and high PPV.114 The choice of imaging modality should take into account radiation exposure, diagnostic accuracy, duration, need for sedation, and cost.115

The imaging modalities of choice for the assessment of pediatric sensorineural hearing loss are high-resolution CT and MRI. CT provides better visualization of bone structures, lower costs, and faster imaging, which makes it easier to use in pediatric patients. However, CT scans expose children to ionizing radiation, and longitudinal studies have shown an increased lifetime risk of developing certain types of cancer.116 MRI provides better quality images of soft tissues and neural structures, but it is associated with higher cost and longer acquisition time, often requiring sedation to be accomplished.117,118 If there is no suspicion of neoplastic, infectious, or inflammatory processes, intravenous contrast may not be necessary.

Given the several factors mentioned above, there is considerable variation between clinical practice and institutional protocols in diagnostic methods used.60,119 Several consensus statements have been published to provide a standardized approach to the assessment of congenital sensorineural hearing loss, but they have not been universally adopted. A systematic review indicates that imaging should play a crucial role in the diagnosis of sensorineural hearing loss in children, with results influenced by both the severity of hearing loss and the results of genetic testing.120

Several studies have demonstrated a correlation between diagnostic yield and hearing loss severity, with an increase of almost 20% in diagnostic yield in severe-to-profound hearing loss compared with mild-to-moderate hearing loss. The diagnostic yield is lower in patients who test positive for mutations in the GJB2 gene, which is the most common cause of nonsyndromic hearing loss.121

It remains unclear which imaging modality should be ordered, but several studies have reported a higher diagnostic yield with the use of CT than MRI.122 It is common to order CT or MRI separately, but several groups have also reported the concomitant use of both methods. Two systematic reviews indicate that CT appears to have a higher diagnostic yield than MRI to diagnose EVA and cochlear abnormalities, whereas MRI can detect more cochlear nerve abnormalities.123,124

The diagnostic yield of CT is estimated at approximately 30% based on systematic reviews. This estimate corresponds to a number needed to image of 4, that is, 4 pediatric patients with congenital bilateral sensorineural hearing need to undergo CT to find a morphologic abnormality. In this same systematic review, CT was able to identify 8.7% more findings than MRI.123

In a multicenter study evaluating the diagnostic yield of CT versus MRI in children with profound bilateral hearing loss, the concordance rate between CT and MRI was 92%, with the diagnostic yield of CT being 7% higher than that of MRI (p = 0.0001).125 In another study with a similar design comparing diagnostic yield between CT and MRI, the concordance rate between them was 86%, with MRI having a 14% higher yield for detecting diagnostic findings in children with profound bilateral sensorineural hearing loss.126

In cases of auditory neuropathy, MRI proved to be highly effective at detecting cochlear nerve hypoplasia, a common finding in these cases.127 Between 12% and 18% of children with congenital sensorineural hearing loss have hypoplasia or aplasia of the eighth cranial nerve (Fig. 2). MRI has the highest diagnostic yield in these cases.128 The internal auditory canal may also be hypoplastic in these cases, which can be detected on CT.

Figure 2.

Magnetic resonance imaging (T2-weighted image). Axial plane. Patient with bilateral sensorineural hearing loss. Evidence of eighth nerve aplasia in the right ear.

(0.18MB).

The facial nerve has an abnormal course in 16% of children with inner ear malformations, representing increased difficulty in CI surgery, especially when it runs across the promontory or makes the facial recess narrower. In some children, the facial nerve may be split, and a second nerve may be located anteriorly, in addition to a branch located in the normal position of the facial recess.129 In these cases, a detailed study with MRI and CT is recommended.

The most common inner ear malformation is EVA, which can be detected by CT or MRI. The modern radiologic definition of EVA has been established as a mean diameter greater than 1.5 mm (Fig. 3).129 Mutations in the SLC26A4 gene are a common cause of EVA. It often accompanies other inner ear anomalies, such as incomplete partition type II (Fig. 4). CT is the best imaging modality to assess the vestibular aqueduct. MRI offers complementary visualization of the endolymphatic sac and duct that are usually also enlarged.96

Figure 3.

Computed tomography scan of the mastoid. Axial plane. Right ear. Patient with sensorineural hearing loss. Enlarged vestibular aqueduct.

(0.16MB).

Figure 4.

Computed tomography scan of the mastoid. Axial plane. Right ear. Patient with sensorineural hearing loss. Enlarged vestibular aqueduct and incomplete partition type II.

(0.12MB).

Hearing loss after meningitis is the most common cause of acquired bilateral sensorineural hearing loss in the pediatric population. During the acute stage, the CT scan may be normal, but MRI reveals intense cochlear enhancement.130 In later stages, fibrosis is shown by loss of fluid signal in the cochlea. Cochlear ossification can be seen on both CT and MRI. MRI is essential to assess the extent of injury and feasibility of CI surgery in these cases (Figs. 5 and 6).

Figure 5.

Magnetic resonance imaging (T2-weighted image). Axial plane. Patient with meningitis. Ossification of the cochlea on the right side.

(0.16MB).

Figure 6.

Magnetic resonance imaging (T2-weighted image). Coronal plane. Patient with meningitis. Bilateral ossification of the membranous labyrinth.

(0.19MB).

Traumatic brain injury can lead to drastic conditions, such as facial paralysis and profound sensorineural hearing loss with involvement of the otic capsule (Fig. 7).

Figure 7.

Computed tomography scan of the mastoid. Axial plane. Right ear. Patient with sensorineural hearing loss and peripheral facial paralysis. Presence of transverse fracture with injury to the labyrinth and basal turn that extends to the tympanic portion of the facial nerve.

(0.16MB).

Although rare in children, vestibular schwannomas can occur bilaterally (NF2) (Fig. 8). MRI is the most suitable imaging technique in these cases.

Figure 8.

Magnetic resonance imaging (contrast-enhanced T1-weighted image). Axial plane. Presence of bilateral vestibular schwannoma (neurofibromatosis type 2).

(0.25MB).

In humans, the regulation of the body balance occurs through the integration of multiple systems and organs that send information to the CNS (classically, the brainstem and cerebellum), process this information, and send signals and reflexes to control our posture and gait. Among the different sensory systems that contribute to maintaining balance, the following stand out: vision, vestibular system, and proprioception (a bundle of nerves, muscles, and joints).131

The vestibular system consists of 3 semicircular canals (anterior, posterior, and lateral) and 2 otolith organs (saccule and utricle). Each of these 5 structures has sensory receptors consisting of highly specialized hair cells, with the ampullary cristae located in the ampullae of the semicircular canals, and the utricular and saccular maculae located in the corresponding otolith organs.132 The ampullary cristae are responsible for detecting angular accelerations, such as moving the head in different directions, whereas the maculae are responsible for detecting linear accelerations and head tilt, both in the vertical plane (saccular macula) and in the horizontal plane and in inclination (utricular macula).133

The vestibular system has a close anatomic relationship with the cochlea, sharing the same bone scaffold and membranous ducts, having similar sensory hair cells, and sharing the same embryonic origin. Thus, disturbances in one system can affect the other system and vice versa.134 Several studies have demonstrated a close relationship and high prevalence of vestibular disorders in children with congenital sensorineural hearing loss, ranging from 20% to 70%. Some studies even suggest a relationship between the etiology and severity of hearing loss and vestibular disorders. Children with severe-to-profound bilateral hearing loss would be more likely to have vestibular dysfunction, and some etiologies, such as cCMV infection and GJB2 gene mutations, would also be more closely related to vestibular deficits.135

Unlike hearing disorders, which are more easily diagnosed using different methods, vestibular dysfunction is rarely confirmed in early childhood, and, in most cases, it is not even considered by the physicians who first assess the child, such as pediatricians and otolaryngologists. Perhaps the main reason for this is a lack of knowledge of the importance and function of the vestibular system and/or the unavailability of diagnostic methods for pediatric vestibular assessment.134,135

It is important to note that vestibular dysfunction in childhood presents as a delay in some motor development milestones, such as neck control, sitting, crawling, and walking. This makes some children more susceptible to falls and deficits in fine motor skills, thus leading them to avoid, often unconsciously, exposure to more challenging situations involving body balance, such as walking on unstable surfaces (e.g., soft sand). Clear signs, such as the presence of spontaneous nystagmus, are not so common because most patients have bilateral vestibular dysfunction.134–136

There is no doubt that major challenges of vestibular assessment in children with hearing impairment include the methods available for assessing labyrinthine function, their limitations, parameters, and particularities to be performed in this pediatric population.

Auditory Neuropathy Spectrum Disorder (ANSD) is a common cause of hearing loss, affecting 1.2% to 8.4% of those with hearing loss depending on the population.145,146 Auditory neuropathy is a term used to describe individuals who have hearing loss with normal function of cochlear hair cells. Hearing loss is characterized by OAEs and/or presence of cochlear microphonics, indicating normal cochlear function, and by altered ABRs measured by AABR testing, indicating abnormal transmission of the synaptic signal to the CNS.146–148

ANSD often encompasses auditory dyssynchrony and auditory neuropathy, which, in some cases, cannot be distinguished from each other. The site of the injury that causes auditory neuropathy may involve: (1) Presynaptic region, where glutamate is released by hair cells; (2) Synapse, involving postsynaptic excitatory neurotransmitters; (3) Region of onset of postsynaptic excitation (Excitatory Postsynaptic Potential [EPSP]) on the terminal dendrite; (4) Region along the spiral ganglion that affects neural signal transmission from the auditory nerve to the brainstem.

In cases of auditory neuropathy, inner and outer hair cells, regardless of neural signal transmission, have injuries that result in auditory dyssynchrony. Therefore, individuals typically have deficits in temporal processing of sound that result in impaired speech perception and sound localization.

ANSD is caused by both genetic and environmental factors. There are 13 known genes. Environmental causes primarily affect newborns and include hyperbilirubinemia, thiamine deficiency, and hypoxia. ANSD can also be noise-induced or age-related. Spiral ganglion neurons are bipolar and have a cell body located in the cochlear modiolus, peripheral axons distributed along the spiral limbus toward the row of cochlear inner hair cells, and proximal axons that synapse in the midbrain. These neurons are tonotopically organized with the cochlea.149

Multiple spiral ganglion neuron fibers synapse with each inner hair cell. Their axons are myelinated and project to the brainstem. In response to glutamatergic stimulation at the synapse, EPSPs in the peripheral axon lead to gradual Na+ influx via a large number of channels, which allows temporal encoding of acoustic stimuli.149,150

Genetic lesions that affect the transmission of the auditory signal to the brain lead to a loss of temporal precision and dyssynchrony, with a degraded potential and altered perception and/or difficulty understanding sound, thus leading to deafness due to auditory neuropathy.

The reported incidence of Autism Spectrum Disorder (ASD) has increased dramatically over the past 2 decades, and these trends have led to an increase in the number of referrals to the otolaryngologist for evaluation of individuals with ASD.

According to the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5), ASD is characterized as a neurodevelopmental disorder marked by impairment in social interaction, communication, and repetitive/restrictive behaviors.157 Moreover, individuals with ASD may present with cognitive disorders of attention and memory, lack of eye contact, affection and reciprocal interaction, in addition to impaired language development.157

Autism remains a complex diagnosis because of its phenotypic heterogeneity, and its etiology is still debated. Some studies have shown a series of factors involved in the etiology that include genetic, immunological,158,159 and environmental aspects, such as prematurity, viral infections, and exposure to agrochemicals,160 which may also be present in combination.158,159

The pioneering study on the epidemiology of autism was conducted by Lotter, who reported an incidence of 4.5 diagnosed children per 10,000 in England.161 In the United States, the Centers for Disease Control and Prevention (CDC) have implemented a surveillance system to estimate the incidence of ASDs in 11 US states, with the first report published in 2000 resulting in 1 in every 150 children being autistic.162 In the most recent report, the results point to an incidence of 1 in every 44 children diagnosed with ASD.163

In Brazil, there is a lack of studies addressing the epidemiology of ASD nationwide. A study in the state of Santa Catarina found a prevalence of autism of 1.31 per 10,000 population.164 In a study conducted in southern Brazil, the prevalence of autism was 3.85 per 10,000 population.165 Another Brazilian study, conducted in the Federal District, reported a substantial increase in the rate of schoolchildren diagnosed with ASD and pervasive developmental disorder compared with other disabilities and disorders between 2012 and 2017.166

The increase in the diagnosis of children with ASD, as reported in the literature,163,167 may be explained by greater dissemination of knowledge, modification and broadening of diagnostic criteria, increased availability of services, and the actual increase in children born with the disorder.168,169

Some warning signs to identify children with ASD are also common to children with hearing loss, such as not looking when called and language impairment. Therefore, since hearing loss may be the cause of language impairment, or it may even co-occur with the diagnosis of ASD,170 audiologic assessment should be part of the test battery for children with speech delay and under investigation for ASD. It is important that this assessment be performed as soon as possible, since early diagnosis favors both ASD intervention and auditory development, providing multidisciplinary support.171

In the literature, there is evidence of abnormal otolaryngologic and audiologic findings in objective and subjective172 tests in individuals with ASD, even in the absence of hearing loss, including changes in ABR absolute and interpeak latencies,173–175 reduced amplitude in cognitive auditory event-related potential (P300),176 changes in central auditory processing,177 behaviors interfering with the measurement of auditory thresholds in pure tone assessment,172 and auditory hyper-responsiveness.170

Assessing the presence of hearing loss or impairment in individuals with ASD can be an even greater challenge in young children. In this age group, the otolaryngologic and audiologic evaluation involves a battery of physical examination and behavioral, electroacoustic, and electrophysiologic assessments guided by the crosscheck principle, in which possible differential diagnoses are analyzed before the audiologic diagnosis is accepted.178

OAE, immittance, and ABR testing, which are objective tests commonly recommended and used in clinical otolaryngologic practice, require the child to remain motionless, to wear headphones and have a probe inserted into the external auditory canal, and to have electrodes placed in the head and ears, which often makes assessment difficult in children with ASD.170

Therefore, objective assessments should be performed during natural sleep, and it is often necessary to schedule one or more visits to complete them; in some cases, they need to be performed with sedation in the operating room. Additionally, in subjective assessments, the child may have interfering behaviors, such as not conditioning to the test, not cooperating with the examiner, paying poor attention to the task, engaging in excessive activity, not tolerating headphones, and being combative toward the examiner.

Therefore, otolaryngologic and audiologic assessments in these children may be a difficult task for health professionals and families. It is important to investigate these difficulties in order to propose solutions, guidelines, and improvements in the environment, procedure, and evaluation protocol, minimizing assessment time and the number of sessions and favoring a timely diagnosis. Moreover, identifying the adversities of audiologic assessment in ASD allows the health professional to interpret the test findings critically, thus helping to rule out or confirm a diagnosis of hearing loss, in addition to making it possible to recognize ASD diagnostic biomarkers.179

To identify factors that can complicate otolaryngologic assessment in ASD.

To identify the main hearing tests and evaluation protocols used in this population.

To identify the main child behaviors that can interfere with assessment.

To characterize the group of children with suspected and/or confirmed ASD who have undergone hearing assessment.

Protocol for otolaryngologic evaluation of patients with a presumptive diagnosis of autism spectrum disorder (address all steps)

Call center/reception: Proper training of call center staff or care team.

Call center/reception: Guidance on conducting the assessments.

Child must be asleep during some of the audiologic tests (sleep in the center).

Test should be scheduled following the child’s usual bedtime routine.

Sleep deprivation; bring the child tired (playing or other activities).

Does the child tolerate headphones? (Assess need for desensitization).

Is the child afraid of physicians in white coats?

Family – Special support from family and friends.

Otolaryngologists – Acknowledge the need for different approaches to patients and their families.

Audiologists – Acknowledge the need for different approaches to patients and their families.

Child must be asleep during electrophysiologic and electroacoustic assessments.

Crosscheck principle.

Outpatient: Perform meatoscopy; explain the need for a complete hearing assessment and suggest a previous assessment with an otolaryngologist; record behaviors identified during audiometry.

Selected genetic syndromes that are known etiologies of ASD: 22q11.2 deletion syndrome, including velo-cardio-facial syndrome (Shprintzen); Angelman syndrome; CHARGE syndrome; Cornelia de Lange syndrome; Fragile X syndrome; Mutations in MED12 (Lujan-Fryns syndrome); Prader-Willi syndrome; Mutations in PTEN ‒ Phosphatase and Tensin (Cowden syndrome and Bannayan-Riley-Ruvalcaba syndrome); Rett syndrome; Smith-Lemli-Opitz syndrome; Smith-Magenis syndrome; Sotos syndrome; and Tuberous sclerosis.

Management of patients with suspected autism spectrum disorder in the office

• • •

    Otoscopy (conductive component).

  • •

    Medical team orders the complete auditory test battery: Audiometry or assessment of auditory behavior; Transient-evoked and distortion-product OAE; Immittance testing or impedance audiometry; ABR; Steady-state response; and Tone-burst ABR.

Has an otolaryngologist seen the patient?

Scheduling team (call center/reception).

Tests require specific preparation. An otolaryngologist should see the patient because, if there is any impediment, the tests will not be performed.

The WHO warns that 1.1 billion young people are at risk of hearing loss due to prolonged and excessive exposure to loud sounds.39 Children, adolescents and young adults are at higher risk of developing hearing loss because of frequent exposure to loud music during leisure activities, on transport services, and while playing sports.40,41 Headphones improve the listening experience but also increase the risk of hearing loss, which is irreversible and manifests initially at 3, 4, and 6 kHz, extending to adjacent frequencies as it progresses.180

The use of portable music players such as MP3 players, iPods, smartphones, and similar devices has increased worldwide over the past few decades. They can produce sound pressure levels of up to 126 dBA.181 Most studies on noise-induced hearing loss began to be conducted in the 1950s and 1960s in the workplace and in the military. Recreational noise exposure is a recent concern. Exposure to portable music players has been shown to be associated with the development of noise-induced hearing loss and tinnitus in adolescents and young adults. The use of these devices has been associated with a 70% increased risk of mild-to-moderate hearing loss.182 Nightclubs and concerts are other common sources of noise, ranging from 104.3 to 112.4 dB HL, with an average level of 97.9 dB HL.183

In fitness sports, the use of loud music is widespread. A study conducted at an aerobics endurance tournament showed music intensity levels ranging from 101 to 119 dB during 120 min of activity.183 High-intensity music in gym classes has been shown to be related to enjoyment and motivation to work out. Exercisers generally do not consider it dangerously loud. Aerobic activities and their variants become high-risk activities for noise-induced hearing loss. Fitness instructors have experienced fluctuating hearing loss and tinnitus.184

Listening to music during sports activities enhances attention, reduces fatigue, and increases arousal. The more pleasurable a song is, the louder people wish to listen to it.185 Athletes perceive loud music as more pleasurable than less intense sounds.186

Loud music features 3 main elements of addictive substances, as it causes rapid and intense changes in mood and arousal level, reduces negative mood states, and makes individuals wish to listen to the music again.183 Prevention campaigns in gyms and for athletes focusing on the risks of loud music are rare.187 Listening to music during physical activity is associated with the risk of hearing loss, particularly when the activity is performed indoors.

Niskar et al.188 described the prevalence of hearing loss in US children aged 6 to 19 years and showed that 14.9% of 6166 participants had low-frequency or high-frequency hearing loss of at least 16 dB. Shargorodsky et al.189 compared the prevalence of hearing loss in adolescents aged 12 to 19 years between 2 different time periods. In 1988‒1994, 14.9% of the adolescents had hearing loss, whereas in 2005‒2006, 19.5% had hearing loss. Tung et al.190 found that 11.9% of 1878 first-year students at a university in Taiwan had unilateral or bilateral hearing thresholds above 25 dB. Balanay et al.191 reported that 39.6% of 2151 college students experienced at least one hearing symptom.

A study evaluating 5249 US adolescents aged 12 to 19 years showed that 15.9% had hearing deficits attributable to noise exposure.7 In the Netherlands, 14.2% of 5355 children aged 9 to 11 years had hearing impairment possibly correlated with noise-induced hearing loss.8 In Poland, 11.5% of 643 youths aged 13 to 18 years had hearing loss at 4 or 6 kHz, and it was significantly higher in those with heavy exposure to loud music (16.3%) than in those with mild exposure (10.7%).192

Exposure to moderate levels of noise, even in the short term, can cause extensive degeneration of inner hair cell synapses, but without hair cell degeneration. Audiometric testing is normal, but when evaluating a large number of noise-exposed people, on average, the thresholds are worse than those of people not exposed to noise.193,194 Cochlear synaptopathy can cause hidden hearing loss, which presents with a normal audiogram with difficulty in speech perception in noisy environments. Cochlear synapse degeneration may also impair auditory function in many aspects, such as neural adaptation, sound localization, and temporal speech processing. Degeneration of this synapse is observed in the early stage of age-related hearing loss and may accelerate its progression.195

Children and adolescents, even with minimal hearing loss, can have long-term consequences with adverse effects on language development and academic performance. Noise exposure in young people can negatively affect the auditory cortex and increase susceptibility to the effects of aging on hearing.196