Clinical manifestations

Presentation and course

Prior to the institution of universal newborn hearing screening, most children were identified with a possible hearing loss either from parental concerns, known risk factors, or delays in speech and language development. Since the 1990s, nearly all children with congenital hearing loss are detected though the universal newborn hearing screen program, in the absence of any clinical manifestations or symptoms. This factor has been vital in minimizing the neurocognitive effects of hearing loss, allowing for maximum intervention during the critical period of language development.

In order to meet the early detection and intervention guidelines, a diagnosis of newborn hearing loss should be completed prior to three months of age. When evaluating the hearing of infants and young children, the use of any one test alone is insufficient. Rather, a comprehensive assessment, including behavioral and physiologic measures, is indicated to fully assess the auditory system and determine the type, degree, and configuration of hearing loss for each ear.

Hearing loss can be identified by several audiologic methods, depending on the developmental age and cooperation level of the patient. Testing is usually characterized as either physiologic or behavioral. Infants younger than 6 months of developmental age cannot actively participate in testing and require physiologic measures such as otoacoustic emissions and auditory brainstem response testing to estimate their hearing threshold. Although 6 months is the average age at which good behavioral tests can first be achieved, physiologic testing is often done on children older than this (especially those with severe to profound hearing loss) to expedite diagnosis and intervention.

Physiologic testing. Most newborns are screened using a combination of auditory brainstem response and otoacoustic emission testing. Otoacoustic emissions measure output from the cochlea itself. Any process interfering with transmission of sound to and from the cochlea (ie, conductive hearing loss), or with the function of the cochlea itself, will result in abnormal otoacoustic emission results. Some infants with auditory dyssynchrony or central hearing loss with a normal functioning cochlea will be missed by this technique (false negative). Premature infants in particular have a high risk of auditory dyssynchrony and false-negative hearing screens if otoacoustic emissions are done in isolation. Auditory brainstem response testing evaluates the auditory pathway from external ear canal to brainstem and is now widely used as an initial screening test.

Otoacoustic emissions. The electromotility of the outer hair cells within the organ of Corti in the cochlea are thought to be responsible for the generation of otoacoustic emissions. When the cochlea is stimulated by sound, the outer hair cells vibrate, which generates a sound that passes through the middle ear in retrograde via the ossicular chain and eardrum, and can be recorded by placing a microphone in the ear canal. Otoacoustic emissions are generated exclusively by outer hair cells, which are more vulnerable to disease and damage than inner hair cells. Therefore, the presence of an emission provides a reasonable estimate that the hearing thresholds are 30 to 40 dB or better in the frequency range being tested. Extensive research has shown that the detection of normal otoacoustic emission signals is associated with normal to near-normal cochlear hearing (87).

Otoacoustic emissions are typically reported as “present” or “absent.” Thus, prediction of hearing levels in dB is not possible by measuring otoacoustic emissions. The absence of otoacoustic emissions can be associated with hearing loss of mild to moderate degree or greater, and their presence does not ensure normal hearing. The absence of otoacoustic emissions must be viewed within the context of the status of the middle ear because both the stimulus and the response pass through the middle ear. Therefore, the absence of an otoacoustic emission is diagnostically significant for cochlear hearing loss only when middle ear function is relatively normal. In addition, children with auditory dyssynchrony can “pass” otoacoustic emission testing, even in the presence of significant hearing impairment (11).

Auditory brainstem response. Auditory brainstem response testing measures the integrity of a portion of the auditory system from external canal to approximately the level of the midbrain. Audiologic stimuli are provided through ear canal inserts (for air conduction) and mastoid bone transmission (for bone conduction), and responses at the level of the inferior colliculus are measured by surface electrodes placed on the infant’s scalp. The auditory brainstem response can be used for both identification and assessment of hearing and can provide accurate estimates of threshold sensitivity in decibels (dB) (07). Under good recording conditions, and using frequency-specific stimuli, the auditory brainstem response can provide reliable estimates of sensitivity across the frequency range of hearing in children of all ages.

Threshold differences of greater than 15 dB with better bone conduction thresholds than air conduction thresholds are indicative of conductive hearing loss and warrant further evaluation by an otolaryngologist to assess the ear drum and middle ear.

Auditory brainstem response testing does not rely on the cooperation of the patient, and it tests the physiologic system, but not necessarily the patient’s direct experience. Testing should be confirmed with traditional behavioral responses in a sound booth as soon as the child is old enough to understand and cooperate with testing, if possible. Although it is well established that agreement exists between behavioral thresholds and auditory brainstem response thresholds for children with typical sensory hearing loss, there are instances where they will not agree and further investigation is necessary. Examples include patients with normal auditory brainstem response with no ability to recognize or use sound to "hear” (central or “cortical” hearing loss). Conversely, the absence of an identifiable waveform on an auditory brainstem response test does not necessarily equate to thresholds in the severe to profound range or to “no hearing,” due to limits of the auditory brainstem response equipment or inability of brainstem neurons to fire synchronously despite a normal cochlea. Patients with auditory neuropathy are characterized by normal otoacoustic emissions and an abnormal auditory brainstem response. These patients can often hear tones and sounds in the normal range, but their speech perception is worse than predicted based on the pure tone average.

The 2019 Joint Committee on Infant Hearing position statement recommends for a 2-stage or 2-tier screening, utilizing both otoacoustic emissions and auditory brainstem response testing. The recommendation is to first screen with otoacoustic emissions and to follow with auditory brainstem response if the patient fails the otoacoustic emissions screening. The exception to this recommendation is for children in the neonatal intensive care unit admitted for more than five days, who may be neurologically compromised. Auditory brainstem response testing, with or without otoacoustic emissions, is the preferred initial screening algorithm for these children.

Tympanometry. Tympanometry assesses the movement of the tympanic membrane in response to mechanically varied air pressure and indirectly measures tympanic membrane mobility by measuring the amount of reflected sound. The use of a high-probe frequency (1000 Hz) is recommended for infants aged 6 months or younger in order to obtain data that most closely represent the status of the middle ear (13). Tympanometry can be very helpful in determining the status of the middle ear, and when combined with otoacoustic emission testing, can help determine if an absent otoacoustic emission response is due to poor transmission of a normal otoacoustic emission through an abnormal middle ear, or from a true lack of signal at the cochlear level.

Acoustic reflex testing. Acoustic reflex testing takes advantage of a brainstem reflex in response to loud sounds in order to test the integrity of the auditory system. Sound enters the external auditory canal, vibrates the tympanic membrane and ossicles, and is transmitted via the cochlea to the auditory nerve. From there, it travels to the brainstem where it synapses in the cochlear nucleus, at the bilateral superior olivary complexes, and bilateral facial nerve nuclei. An efferent signal is then sent along the facial nerve to contract the stapedius muscle on both sides, resulting in increased stiffness of the stapes bone and the increased impedance in the middle ear system that can be detected with the audiologic probe. A present reflex provides added support for normal middle-ear function as well as information about the integrity of this portion of the auditory pathway.

Behavioral testing. From the age of about 6 to 7 months, behavioral observation audiometry can be attempted. This method relies on the infant’s reflexive orienting behaviors in response to sound and is dependent on the observer’s impressions. It is less precise than auditory brainstem testing and can only provide information about both ears at the same time. Typically, results are reported for sound fields as representing the hearing status in “the better hearing ear.”

Between the ages of 6 and 30 months, many children are tested with a conditioned auditory response known as visual reinforcement audiometry to measure hearing threshold levels. This is an operant conditioning paradigm that reinforces a motor activity, usually a head turn, with an appealing visual display, usually a lighted or animated toy. The auditory stimulus cues the infant that a response (ie, a head turn) will result in reinforcement (121; 96). Visual reinforcement audiometry can be conducted using insert earphones and a bone conduction vibrator. If the child will not tolerate the use of earphones, results can be obtained using stimuli presented via speakers into the sound booth. This, again, is reported as frequency-specific information for at least the better hearing ear.

From 30 months to about 4 to 5 years of age, play audiometry is commonly used. In this method, the child is instructed to perform a task (eg, put this toy in the bucket) when they hear a sound. This method can be used in the sound field, or if the child is cooperative, headphones can be used to get ear-specific information. After the age of about five years, most children can cooperate with traditional audiometry, whereby each ear is tested separately and plotted on a graph of sound level versus frequency.

Prognosis and complications

Hearing loss in infants and children, when left undetected, can affect speech and language acquisition, leading to poor language and literacy skills. In addition, academic achievement and social and emotional development can be impacted (118; 25; 119). Even hearing loss that is unilateral or mild has been established to have an impact on academic performance and neural circuitry (64; 98; 51; 35; 119). More specifically, children with unilateral hearing loss can have difficulty with sound localization or hearing in complex auditory environments, even if they have normal hearing in the contralateral ear (95; 81). If hearing loss is detected early, however, poor outcomes can be diminished, and even eliminated, through early intervention. Studies have shown that communication skills comparable to age-matched hearing peers can be achieved when hearing loss is identified early and children receive early intervention services (75; 56).

A study by Harrison and Roush, conducted prior to universal newborn hearing screening, analyzed survey results from parents of children with hearing loss who were enrolled in early intervention programs (45). They found the age of identification of hearing loss varied with severity of hearing loss, but not with the presence of a risk factor for hearing loss. That is, for children without risk factors for hearing loss, the age that hearing loss was diagnosed was approximately 22 months if the loss was mild to moderate, but 13 months of age if the loss was severe to profound. Intervention and hearing aid fitting were affected in similar ways. Specifically, children with milder losses received intervention and hearing aid fittings at about 28 months for mild losses and 16 months for severe to profound losses. For children with known risk factors for hearing loss, the age of identification of hearing loss was not affected by degree of loss. The children with risk factors were identified at about 12 months of age. Fitting of hearing aids occurred earlier for those at-risk children with severe to profound loss (15 months) than those with mild to moderate hearing loss (22 months).

In an evaluation of the newborn hearing screening program in New York State, Dalzell and colleagues found the median age of diagnosis to be three months for a group of 85 infants identified by newborn hearing screening (24). Thirty-six of the infants were fit with amplification at a median age of 7.5 months. Infants who were screened for hearing loss at birth were diagnosed, fitted with amplification, and entered into early intervention at substantially younger ages than infants who were not screened. This dramatic reduction in age of diagnosis of hearing loss for those who receive newborn hearing screening was confirmed by Sininger and colleagues who reported the age of identification of hearing loss for those screened to be 2.4 months, with the age of hearing aid fitting reported at five months and the age at time of early intervention enrollment being nine months (107). They found that for infants screened compared to those unscreened, there was a 24.8-month difference in median age at diagnosis of hearing loss, a 23.6-month difference for fitting of amplification, and a 19.9-month difference for enrollment in intervention.

Finally, the 2019 Joint Committee on Infant Hearing recommends that regardless of previous hearing-screening outcomes, all infants with or without risk factors should receive ongoing surveillance of communicative development beginning at 2 months of age during well-child visits in the medical home (06). This recommendation provides an alternative, more inclusive strategy of surveillance of all children. In particular, this protocol permits the detection of children with either missed neonatal or delayed-onset hearing loss, irrespective of the presence of absence of a high-risk indicator.

Clinical vignette

[Note: This case is fictional.] Emily was a healthy newborn female who did not pass her newborn hearing screen in either ear at her birth hospital. She was born full-term at 8 lb. 2 oz. to a 30-year-old grava 2, para 1-2 mother with no complications during pregnancy, labor, or delivery. She had no risk factors for hearing loss, including no recognized intrauterine infections, perinatal antibiotics, jaundice, prematurity, or family history of early-onset hearing loss.

At three weeks of age, Emily and her parents had an appointment at the nearby children’s hospital with a pediatric audiologist for a repeat newborn hearing screening. The test results from this visit revealed absent transient-evoked otoacoustic emissions bilaterally, elevated acoustic reflexes, and normal tympanograms for both ears. These test findings suggested normal external and middle ear function and a possible cochlear cause due to the absent otoacoustic emissions. The next recommended step was a diagnostic auditory brainstem response.

At 2 months of age, Emily and her parents returned to the children’s hospital for diagnostic auditory brainstem response testing. The parents withheld Emily’s morning feeding, ensuring she was hungry when she arrived and hopefully ensuring she would fall asleep after feeding to allow for a quiet recording. Her head was cleaned, and 2-channel electrodes were applied with tape to her scalp. Earphone inserts were placed into both ears and a series of tones and clicks were played. The testing started with a 2000 Hz stimulus at 40 dB, and no brainstem response was obtained by the recording electrodes on her head. Intensity was increased to 70 dB, and two replicable well-formed brainstem responses were obtained twice to ensure validity. Two recordings presented at 60 dB to the left ear yielded replicable responses. When the sound level was decreased to 50 dB, no replicable responses were obtained. Testing was repeated in a similar way using tones at 500, 1000, and 4000 Hz. The right ear was then tested with all of the above stimuli, and similar thresholds were obtained, showing a flat moderate congenital sensorineural hearing loss in both ears.

Emily’s parents met with the audiologist to review the test findings. The pediatric audiologist obtained consent from the family to contact early intervention so that Emily could begin receiving hearing support services. The family was also referred to the children’s hospital otolaryngology department for a full medical work-up of the hearing loss.

Emily and her parents saw the pediatric otolaryngologist when she was three months of age. A full history was obtained, looking for potential causes of hearing loss (intrauterine infections, prematurity, low birth weight, perinatal antibiotics, jaundice, and other family members with early-onset hearing loss). A physical exam was performed, revealing no syndromic features, normal external ears, clear patent external auditory canals, normal ear drums, and the absence of an acute infection or middle ear fluid. Her family was counseled on potential causes, work-up, and treatment of hearing loss in newborns. Additional consultation with a pediatric geneticist was recommended to evaluate for genetic causes of hearing loss. A visit to a pediatric ophthalmologist was also strongly recommended because of an increased risk of visual abnormalities in babies with sensorineural hearing loss. The importance of supports to encourage normal language development, including the use of hearing aids and close involvement with early intervention and speech therapy, was stressed. A CT scan of the temporal bones was ordered to look for inner ear abnormalities. Several additional tests were discussed, including an MRI of the temporal bones, urinalysis, EKG, and thyroid function tests, but these were deferred due to her lack of syndromic features or any other concerning findings on history and physical exam. Emily’s eye exam was normal. Her geneticist initiated testing for genetic causes of hearing loss, and Emily tested positive for two pathogenic connexin 26/GJB2 mutations, the most common cause of bilateral genetic congenital hearing loss.

Emily and her family then returned to the pediatric audiology department for a hearing aid evaluation. At this appointment, communication options were discussed, and her parents indicated the desire for Emily to be fit with hearing aids. Earmold impressions were taken, styles and colors of hearing aids were discussed, and the family was instructed to schedule an appointment in 2 to 3 weeks to pick up the hearing aids. The need for another diagnostic auditory brainstem response was also discussed at this time, which would give the pediatric audiologist further information about the progression of Emily’s hearing loss over time.

At 4.5 months of age, Emily and her parents returned for the hearing aid dispensing visit. At this time, the family was instructed on the use and care of the hearing aids. An appointment was scheduled for 3 to 4 weeks later, at which point the pediatric audiologist would check the hearing aids and repeat the diagnostic auditory brainstem response to see if Emily’s hearing loss was stable or not. Emily was enrolled in early intervention and a speech and hearing therapist visited her at home on a weekly basis.

Ongoing monitoring of Emily’s hearing will always be necessary, usually every 3 to 6 months for the first 2 years during critical speech and language acquisition, and yearly after that if her hearing remains stable. Frequent visits will be required for new earmolds, as her ears will be growing and changing at a rapid rate while young. Emily is expected to do well with her hearing aids and speech and language development, as she was identified early, diagnosed early, and enrolled in early intervention.

Biological basis

Anatomic localization

Audiologic and diagnostic tests, including CT or MR imaging and genetic testing, can pinpoint the site, laterality, and degree of hearing loss, as well as a specific location of the causative abnormality in some cases.

Pathophysiology

The auditory system is broadly divided into a peripheral and a central portion. The peripheral portion of the auditory system is comprised of the external ear, middle ear, inner ear, and auditory nerve. The pinna, the outermost part of the auditory system, funnels sound waves from the environment into the external auditory meatus and to the tympanic membrane. Vibration of the tympanic membrane is picked up by the ear bones, or ossicles (malleus, incus, and stapes), which transfer the mechanical vibrations through the middle ear to the oval window of the inner ear. The cochlea then transforms these mechanical vibrations into fluid pressure waves that cause vibration of the basilar membrane and, subsequently, the cochlear hair cells. This results in the transduction of the vibrations into neural impulses. These neural impulses are then transmitted by the auditory nerve to the central portion of the auditory system, including the auditory brainstem and auditory cortex (40).

Damage to, or malformation of, any of these structures or systems can, therefore, result in hearing loss. The types of hearing loss can be categorized by where the damage or malformation occurs in the auditory system.

Conductive. Conductive hearing loss results from a blockage in transmission of the sound waves from the external environment to the cochlea. Common causes include middle ear fluid, aural atresia, tympanic membrane perforation, or fixation of the ossicles. The degree, or amount, of hearing loss can vary extensively, from air-conduction thresholds in the minimal range of hearing to a maximum conductive loss of around 60 dB.

Sensorineural. Sensorineural hearing loss is due to disease or disruption of the cochlea or auditory nerve. In the pediatric population, genetic hearing losses are prevalent, with greater than half of all prelingual hearing losses in children having a hereditary cause (61). The inheritance pattern for these hearing losses can be autosomal dominant, autosomal recessive, x-linked, or mitochondrial (43). Most congenital hearing loss due to genetic causes is autosomal recessive and not associated with a syndrome. Mutations in the GJB2 gene are responsible for approximately 50% of sensorineural hearing loss (61). GJB2 encodes the protein connexin 26, which is a gap-junction protein that forms intracellular channels. These channels are thought to be critical to potassium circulation between the hair cells in the cochlea and the stria vascularis (110; 61).

The remaining 40% to 50% of prelingual sensorineural hearing loss in children is attributed to environmental factors. The most common cause of congenital nongenetic hearing loss is intrauterine cytomegalovirus infection, affecting approximately 1 in 200 children (57; 27).

Environmental and genetic factors can also combine to cause prelingual or postlingual hearing loss, as seen by the increasing prevalence of hearing loss with age (61).

Unilateral hearing loss. Congenital causes account for approximately 45% of infants and children with unilateral sensorineural hearing loss (39). Of these, cochlear nerve deficiency seems to be the most common, accounting for up to 50% of children with congenital severe-to-profound unilateral hearing loss (117; 116).

Central. In central hearing loss, the problem lies in the brain with the inability to process auditory information. The process of interpreting speech is a complex task. With central hearing losses, people can hear well, but have trouble interpreting or understanding what is being said.

Epidemiology

Congenital hearing loss is the most common condition screened for at birth. In the United States, it is estimated that about 8000 to 12,000 babies are born each year with permanent hearing loss (National Institute on Deafness and Other Communication Disorders). Approximately 3 out of every 1000 babies are born with hearing loss, mostly to normal-hearing parents (73). Many of these children are minorities and are born into low-income or non-English-speaking households, which may have implications for language development (73; 52). Comparatively, the combined incidence of all other diseases that are screened for at birth is about 1.2 per 1000 (72). Unilateral hearing loss occurs in another 1 in 1000 infants and up to 1 in 5 adolescents (73; 103), and studies have shown that even unilateral loss contributes to deficits in auditory perception, with resulting effects on speech, language, and academic success (54; 116). Combining all cases of permanent, progressive, unilateral, and conductive hearing loss, as many as 15 per 1000 will have some degree of hearing dysfunction during childhood (112).

Differential diagnosis

There are many causes of hearing loss in children, and identifying a specific diagnosis can be challenging. Even with a full medical evaluation, including history and physical exam, imaging, and laboratory and genetic testing, sometimes a cause is still not identified. Patients and families should be counseled appropriately to prepare them for this uncertainty. Knowing the cause of the hearing loss can be helpful in predicting the course of the hearing loss and can help in counseling families. Below are some of the common causes of hearing loss in children.

Confusing conditions

Acquired conductive hearing loss.

Otitis media with effusion. This is the most common cause of conductive hearing loss in children, with an estimated 85% to 96% of all children in the United States affected by at least one episode of otitis media with effusion by their first birthday. By three years of age, approximately one-third of all children have had multiple episodes of otitis media with effusion, also known as chronic serous otitis media (114). Chronic middle ear fluid can be present from birth due to amniotic fluid filling the ears, nose, and mouth, or can develop in older infants and toddlers as a result of eustachian tube dysfunction. Without adequate pressure equalization by the eustachian tube, negative pressure develops in the middle ear, and a transudative fluid is pulled from the mucus membranes lining the middle ear. This fluid blocks sound transmission by the ossicular chain and predisposes children to otitis media. If fluid is present for a prolonged period of time, the resultant fluctuating hearing loss, typically in the range of 20 to 40 dB, can interfere with adequate speech and language development (114). Diagnosis is based on otoscopic examination showing visible fluid behind the ear drum and a lack of ear drum movement using pneumatic otoscopy. Findings can be confirmed with tympanometry, which typically shows a flat tracing that indicates poor movement of the tympanic membrane in response to the stimulus pulse (40).

Ear drum perforation. A hole in the eardrum can be caused by trauma, infection, or postsurgical treatment (iatrogenic). If the perforation is large, sound escapes through the hole, and the eardrum vibrates with a lower amplitude, resulting in reduced transmission of sound to the ossicular chain and a smaller fluid wave in the cochlea (74).

Cholesteatoma. A cholesteatoma is a collection of squamous debris, or keratin, in the middle ear. Over time, cholesteatoma can erode the ossicular chain and surrounding bone. They may be either congenital or acquired and can result in a conductive hearing loss. Diagnosis is typically dependent on physical exam and imaging studies (115).

Acquired sensorineural hearing loss causes.

Bacterial meningitis. Bacterial meningitis is the most common cause of sensorineural hearing loss due to an acquired infection after the neonatal period. It can cause any degree of sensorineural hearing loss and may progress with time (40). Audiologic evaluation is recommended as soon as possible after a diagnosis of meningitis. If the hearing loss is severe to profound bilaterally, cochlear implantation can be considered and should be done as soon as is feasible because ossification of the cochlea often occurs over time and can interfere with successful insertion of the cochlear implant electrode.

Hyperbilirubinemia. Elevated bilirubin levels have been correlated with an increased risk of sensorineural hearing loss and auditory neuropathy (91; 100; 106). Auditory dyssynchrony presents with varying degrees and configurations of hearing loss and is often not detectable with otoacoustic emission screening tests. Otoacoustic emissions are often present while auditory brainstem responses (and behavioral responses) are abnormal (93).

Pharmacological ototoxicity. Pharmacological ototoxicity can cause permanent or reversible sensorineural hearing loss. It is usually bilateral and symmetric in the high frequencies, with varying degrees of severity and progression (93). Common causes include gentamicin administration in the newborn period and platinum-based chemotherapeutic agents. Audiologic screening and monitoring before, during, and after treatment is essential (55). Genetic factors can influence sensitivity to ototoxic drugs, such as the mitochondrial A1555G mutation in the MTNR1/12srRNA gene that increases susceptibility to hearing loss secondary to aminoglycosides (77).

Noise-induced hearing loss. Noise-induced hearing loss is an environmental cause of sensorineural hearing loss that can be temporary or permanent. The hallmark audiologic presentation of noise-induced hearing loss is a “noise notch,” which is a unilateral or bilateral presence of poorer thresholds in the 3000 to 6000 Hz frequency region. This is a growing issue in the pediatric population. Research has estimated that approximately 12.5% of children in the United States aged 6 to 19 years have unilateral or bilateral noise-induced hearing loss. An update reported similar rates of noise-induced hearing loss in all children over time, but an increase in recreational exposure to noise, decreased hearing-protection use, and increased threshold shifts in young females (80; 103; 48).

Associated or underlying disorders

Conductive hearing loss.

Microtia or aural atresia. Congenital malformations of the external ear can cause significant conductive hearing loss. These malformations can range from a small malformed pinna and external ear canal (microtia) to absence of an external ear canal (atresia) (40). Microtia or atresia can be due to environmental factors during early fetal development or can be associated with a congenital syndrome (09).

Ossicular chain fixation. Some children have congenital fixation of one of the ossicles, either due to overgrowth of the surrounding bone or failure to separate from the bony wall of the middle ear during development (83). If severe, this can result in a maximum conductive hearing loss in the affected ear.

Sensorineural hearing loss. Sensorineural hearing loss can range from minimal to profound, at a greater than 90 dB hearing level.

Genetic, nonsyndromic. This type of hearing loss is present at birth in the absence of any other clinical features or physical exam findings. Clinical manifestations can vary, such as age of onset, severity, configuration, and inheritance pattern. Approximately 50% of these cases are due to mutations in the GJB2 and GJB6 genes, which encode gap-junction (connexin) proteins (61).

Genetic, syndromic. Many syndromes are associated with hearing loss and present with various clinical manifestations. Pendred syndrome is the most common cause of congenital genetic syndromic sensorineural hearing loss, which can be any type or severity, and may be unilateral or bilateral. Pendred syndrome results from mutations in the SLC26A4 gene, which encodes for the pendrin protein, an ion transporter (49). It is associated with the presence of an enlarged vestibular aqueduct in one or both ears, which can be identified with a temporal bone CT or MRI scan. The other clinical feature of Pendred syndrome is the development of a goiter later in life. Diagnosis in the past relied on an abnormal thyroid perchlorate discharge test. This test is rarely performed now, and diagnosis is typically made by screening for the genetic mutations affecting the SLC26A4 gene (110; 49).

In utero infection. The group of infectious diseases that cause congenital sensorineural hearing loss can be remembered with the pneumonic “TORCHES” (Toxoplasmosis, Others, Rubella, Cytomegalovirus, Herpes, and Syphilis). Congenital cytomegalovirus is the most common cause of nongenetic prelingual sensorineural hearing loss (77; 27). The hearing loss tends to be severe to profound and may have a delayed onset with fluctuations and progression over time (41). Hearing loss is detected at birth in approximately 10% of babies with symptomatic congenital cytomegalovirus infection. Another 10% of infants will be diagnosed with hearing loss later in childhood (30; 27). Cytomegalovirus has been detected in the cochlear perilymphatic fluid and epithelial cells of the scala tympani, as well as in auditory spiral ganglion neurons (08; 27). It is typically diagnosed by obtaining a sample of saliva (ie, cheek swab) and testing using traditional shell vial culture or polymerase chain reaction. The virus is ubiquitous in our environment, and children who are tested later in life present a diagnostic dilemma in determining if they have a congenital infection (which can affect hearing) or have acquired the virus after birth (with no hearing implications). Children with confirmed sensorineural hearing loss in the newborn period should be tested for cytomegalovirus as soon as possible, as this is a potentially treatable disease. Research has shown that initiating antiviral treatment such as intravenous ganciclovir or oral valganciclovir may halt progression of the hearing loss in the first several months of life (60; 26). Longer duration therapy of six months compared to six weeks may result in improved long-term hearing and developmental outcomes (59).

Central hearing loss.

Auditory processing disorder. Children with central auditory processing disorder can present with hearing in the normal range for detection of sounds, yet have increased difficulty understanding speech, especially in the presence of background noise or competing talkers. There is some controversy in the literature about whether this represents a deficit in the auditory neurologic pathway, or if it can be better explained by deficits in working memory and attention. Testing for central auditory processing disorder is done when the child can cooperate with more sophisticated testing, usually around nine years of age (76).

Diagnostic workup

Once the degree, configuration, and characteristics of hearing loss have been described by audiometry for an individual patient, there are several further recommendations in order to achieve a comprehensive work-up of the patient with hearing loss. New guidelines from the International Pediatric Otolaryngology Group provide an evidence-based algorithm for diagnostic work-up in children with newly identified hearing loss (65).

Imaging of the temporal bone. In children with symmetric, bilateral, sensorineural hearing loss, temporal bone imaging is of low yield and is not included in the initial diagnostic work-up. For those with asymmetric, unilateral, or mixed hearing loss, imaging should be considered (65). Obtaining either a CT scan or an MRI of the temporal bones bilaterally is recommended. In children who have congenital hearing loss severe enough for consideration of a cochlear implant, a CT scan should be obtained prior to one year of age in order to identify any structural abnormalities of the middle or inner ear, and to assist with surgical planning. In children who do not meet cochlear implant criteria, imaging can still be helpful in identifying a cause of the hearing loss in some cases (86). A CT scan is the optimal imaging study to identify abnormalities in the bony ear structures such as the cochlea, ossicles, and semicircular canals. MRI scanning is more helpful in delineating soft tissue abnormalities, such as a mass lesion or hypoplastic auditory nerve. The decision to obtain imaging should be individualized for each patient, with an awareness of potential harm from exposure to radiation and/or sedation, health care costs, and diagnostic yield. Choice of imaging modality and timeframe of imaging are directed by the differential diagnosis, treatment plan, and each clinician’s preference (63; 53; 105).

Ophthalmologic examination. Several reports have addressed the comorbidities of children diagnosed with sensorineural hearing loss. The estimated incidence of ophthalmologic abnormalities ranges from 20% to 50% (102; 122), including both refractive and nonrefractive abnormalities. In older children, retinal abnormalities may be identified, which may lead to a diagnosis of Usher syndrome. Because children with hearing loss have impaired sensory input from one domain, it is very important that they maximize input from other senses, such as vision, in order to facilitate learning and development. The current recommendation is that every child with a new diagnosis of sensorineural hearing loss should be seen by an ophthalmologist as part of their work-up.

Genetic evaluation. The role of genetics in the diagnostic evaluation of sensorineural hearing loss has undergone tremendous expansion over the past several decades, as our collective knowledge of the genetic basis of disease has increased. Comprehensive genetic testing has been more accessible and attainable since the advent of new genetic testing platforms based on massively parallel sequencing (MPS) in 2010. In fact, genetic testing now has the highest diagnostic yield for bilateral sensorineural hearing loss, after the basic audiogram (65; 109; 89). Genetic counseling and evaluation can provide a possible etiologic diagnosis and helps identify potential comorbidities that require additional referrals and screening (01). In the past, hearing loss was diagnosed as hereditary (genetic) based on patterns of inheritance among families. We now know that up to two-thirds of early-onset hearing loss is due to genetic causes, and the majority of patients with genetic hearing loss are born to hearing parents, making a recessive inheritance pattern more likely (49). Genetic testing to diagnose a cause of the hearing loss therefore plays a larger role. It is estimated that greater than 500 genes with multiple types of mutations per gene may contribute to hearing loss (66). In particular, genes that participate in hair cell development and adhesion, ion transport, and neurotransmitter release are implicated in malfunction of the hearing mechanism (36). The most common defects are in the GJB2 gene, which encodes for the gap junction protein connexin 26; and the SLC26A4 gene, which has been implicated in patients with Pendred syndrome (50; 49). Currently, protocols for genetic screening, counseling, and testing vary by state and by medical center. Two general practices include selective screening for a specific mutation and full gene sequencing of a selected group of genes (66). Sloan-Heggen and colleagues performed comprehensive genetic testing with targeted genomic enrichment and massively parallel sequencing on 1119 patients with hearing loss, and they were able to identify a genetic cause in 39% of patients (109). The diagnostic rate varied greatly depending on clinical phenotype and was highest for patients with a positive family history.

Current guidelines from the American College of Medical Genetics recommend testing for GJB2 and GJB6 as an initial cost-effective strategy for suspected nonsyndromic hearing loss. The 2019 Joint Committee on Infant Hearing guidelines also recommend a genetic evaluation for newborns with congenital hearing loss. For children with confirmed connexin-related hearing loss, imaging of the temporal bone may be deferred (23). If syndromic hearing loss is suspected, testing may be targeted toward a specific syndrome or a group of the most common syndromes, such as testing for SLC26A4 mutations in Pendred syndrome. In addition, comprehensive genetic testing for deafness has been able to be completed on fresh and archived dried blood spots (104). They can be very helpful in identifying a genetic cause of hearing loss, but cannot predict who will develop hearing loss in the general population; thus, they are not used as a screening tool for all infants at this time (66).

Cytomegalovirus testing. Congenital cytomegalovirus is the most common cause of nongenetic prelingual sensorineural hearing loss occurring in 0.2% to 2% of live births worldwide (14; 94; 31). About 25,000 infants are born each year in the United States with congenital cytomegalovirus infection, 10% to 15% of whom develop sensorineural hearing loss (14). Presently in the United States, there is no national standard of care or routine protocols regarding congenital cytomegalovirus screening at birth. However, as of April 2022, 11 states have laws in place that mandate education, hearing-targeted screening, or both. Many other states are in progress of passing legislation, and even so many individual hospitals have hearing-targeted congenital cytomegalovirus screening policies in place. Connecticut, Florida, Iowa, Kentucky, New York, Utah, and Virginia require each newborn that fails the newborn hearing screening to be tested for congenital cytomegalovirus (the option is provided but not required in Illinois). Minnesota is the first state to enact universal congenital cytomegalovirus screening for all newborns, which will go into effect in 2023 (44; 16; 90). Testing is typically done by obtaining a cheek swab for culture or polymerase chain reaction. Current guidelines recommend that PCR or shell viral culture be obtained in the first three weeks of life if the newborn hearing screen is failed in both ears (65).

Outside the 3-week time window, dried blood spot testing has been investigated as a method of retrospectively diagnosing congenital cytomegalovirus infection. However, the sensitivity of dried blood spot testing ranges from 28.3% using a single-primer PCR assay to 34.4% using a 2-primer assay, with a specificity of 99.9% (12). Given the poor sensitivity, dried blood spot real-time PCR is not recommended as a primary test to diagnose or screen for cytomegalovirus but may be useful in the work-up of children who present with sensorineural hearing loss.

Other tests. In previous years, additional testing to identify syndromic causes of hearing loss were recommended, including a urinalysis to look for Alport syndrome, complete blood count to evaluate for leukemia or Fechner syndrome, and an electrocardiogram to identify patients with Jervell Lange Nielsen, a rare disease that causes a prolonged QT interval as well as sensorineural hearing loss. Because these syndromes are very rare, identification of patients was infrequent. Routine testing of all patients with sensorineural hearing loss is no longer recommended. Additional testing is now based on a greater level of suspicion for an individual patient, such as gross hematuria (Alport), a family history of sudden cardiac death (Jervell Lange Nielsen), or any systemic signs such as unexplained bleeding, and bone or joint pain (69; 86; 46).

Management

The goals of management for childhood hearing loss are 3-fold: to correct those disorders that are amenable to treatment, to support the child and family with amplification and educational support, and initiation of electrical hearing with a cochlear implant or possibly auditory brainstem implant, if indicated.

Conductive hearing loss. Conductive hearing loss is often a temporary and treatable disorder. The primary management strategy for most newly diagnosed cases of conductive hearing loss due to middle ear fluid is conservative management and observation over time. The majority of patients will be able to clear the fluid without intervention, resulting in normal hearing. For children with persistent middle ear fluid and conductive hearing loss in one ear for six months, or both ears for three months, surgical placement of tympanostomy tubes should be considered. During the procedure, an incision is made in the ear drum and the often thick and viscous fluid is suctioned from the middle ear. Placement of the tympanostomy tube ensures that the pressure between the middle ear and external environment is equal, thus, preventing the development of negative pressure in the middle ear and preventing the reaccumulation of transudative fluid in this space. The tubes typically extrude spontaneously over the course of approximately 9 to 18 months. They are highly effective in correcting the conductive hearing loss if fluid is the cause. There are some children who continue to have a conductive hearing loss with functional tubes in place, and a more thorough search for other causes of conductive hearing loss should ensue.

Other causes of conductive hearing loss in children are also often amenable to surgical treatment, such as patching of a tympanic membrane perforation or removal of cholesteatoma. Congenital fixation of the ossicles may also be surgically correctable, but treatment carries a risk of permanent hearing loss in the operated ear. Typically, a hearing aid is employed during childhood, and the decision for surgery is postponed until the patient is mature enough to weigh the risks and benefits and can choose the course of action with which they feel most comfortable.

Sensorineural hearing loss. Management of permanent sensorineural hearing loss in children starts first with counseling the family about the hearing loss, supporting their emotional needs as they deal with the diagnosis, helping them to understand the modes of communication available, and finding opportunities for practical and financial support. The only factor that has been shown to slow the progression of hearing loss is the administration of antiviral medications to patients with congenital cytomegalovirus infection, and this entity should be diagnosed and treated with high priority in the newborn period (60; 26). Even if detected, the treatment of children with isolated sensorineural hearing loss is unclear. The 2017 published consensus recommendations for the prevention, diagnosis, and treatment of cCMV states, “Antiviral therapy is not routinely recommended for cCMV infection with isolated sensorineural hearing loss and otherwise asymptomatic” (92). However, a review in 2018 shows some evidence that valganciclovir is beneficial in these patients (84). Overall, antiviral treatment in children with isolated sensorineural hearing loss, as well as initiating treatment beyond one month of life, are areas of ongoing investigation. Treatment of these children should be determined on a case-by-case basis, and referral to an infectious disease specialist should be considered to review the risks and benefits of antiviral therapy (67).

Choosing an educational program geared toward helping develop communication for those with hearing loss. Often this consists of enrolling the patient in a program such as early intervention, where they have ongoing evaluation and support for speech development. Children with a diagnosis of hearing loss can often qualify for services immediately and do not need to “test into” the program. This translates into earlier monitoring and support, which can often prevent communication delays, rather than treating a speech or articulation disorder once it has already developed. Children with more severe hearing loss may be eligible to work with a teacher of the deaf, or to attend a school for the deaf, where American Sign Language and alternative communication strategies are taught, often in parallel with oral communication development.

In counseling patients and families about hearing loss, a key component is careful exploration of the family’s wishes regarding communication. It is critical to ensure that their choices are respected while also trying to achieve accuracy in their understanding of the hearing loss and what options are currently available for their child.

Amplification. The majority of families opt to provide amplification for their child. Advances in technology have resulted in better hearing and speech outcomes for children with hearing loss. In general, hearing aids have become smaller and stay on small ears better, have more programming and stylistic options, and work better in background noise. Programming strategies such as frequency compression and frequency transposition can shift or compress the frequency range so that it fits into regions of better hearing, allowing for better amplification of high-frequency sounds. Bone anchored hearing aids are approved for children with conductive or mixed hearing loss, and are particularly useful for children with congenital malformations of the ear such as microtia or canal atresia (71). There have been recent advances in bone anchored hearing aid technology, and there are now several options from which to choose. Historically these first developed as percutaneous, direct-connect bone conduction implants that eliminated the dampening effects of skin or tissue on the vibrational system. Subsequent efforts to reduce abutment-related skin complications led to the development of transcutaneous (non-skin penetrating) systems where the skin remained intact with an external sound processor connected magnetically. However, these systems had limitations with higher frequencies due to attenuation of vibratory energy passing through soft tissue. In 2018, efforts to circumvent these limitations have led to the development of transduction implants, which are also implanted under the skin but the vibratory mechanism is in the implanted portion itself rather than the external processor, improving high frequency amplification compared to previous models (42).

Cochlear implantation. Children with severe to profound hearing loss may be candidates for cochlear implantation, where an electrical prosthetic device is surgically implanted into the cochlea to stimulate the auditory nerve. The United States Food and Drug Administration approval for cochlear implants was received in the early 1980s for children aged two years and older with profound hearing losses and little to no benefit from traditional hearing aids. These criteria have changed over time, as the benefit of cochlear implants for hearing and speech development have been more widely recognized and supported by years of research. Several studies in the early part of this century began to show that earlier implantation results in near normal speech and language development compared to later implantation (70; 113; 17; 97). The literature has also supported improvements in quality-of-life scores, including self-reliance and social relationships, for children receiving cochlear implants (02). Furthermore, the 2019 Joint Committee on Infant Hearing recommendations included consideration of reduction in the FDA-approved age for cochlear implantation to less than 12 months. Subsequently, in March 2020, the FDA approved lowering the age of cochlear implantation from 12 months to 9 months for children with bilateral, profound sensorineural hearing loss (82). The current criteria are for children ages 9 to up to 24 months with profound hearing loss, and children two years and older with severe to profound hearing loss. However, many surgeons advocate for earlier implantation, as soon as six months. Patients who have bilateral hearing loss confirmed in the severe to profound range, whose parents desire cochlear implantation, undergo a thorough evaluation to determine their candidacy. The team of specialists includes an audiologist, otolaryngologist, speech language pathologist, and psychologist. The first step is a trial of traditional amplification with a hearing aid. Children are tested for pure tone responses and word recognition with the hearing aids in place over a period of 3 to 6 months, and their performance is compared to typical results for children who have received cochlear implants (68). If a patient receives minimal benefit from hearing aids, he or she is referred for medical evaluation by the otolaryngologist to confirm that the ears are otherwise healthy. A CT or MRI scan of the temporal bones is required to define the cochlear anatomy and confirm that an auditory nerve is present. The patient should be enrolled in an appropriate program to support oral communication strategies. Finally, parents and caregivers should have realistic expectations about the possible benefits their child might receive from a cochlear implant. Following the surgical procedure, the implant is activated and mapped about 2 to 4 weeks postoperatively, and support continues for hearing habilitation. Research supports placement of bilateral cochlear implants, either simultaneously or in sequence, for better auditory performance, localization of sound, and improved speech perception in noisy environments (33; 62; 120). The child’s success with a cochlear implant depends on having a multidisciplinary team to support the child and family throughout the selection process, surgical procedure, programming of the device, and rehabilitation of hearing.

Unilateral hearing loss. Mild to moderate unilateral sensorineural hearing loss in children is often managed with hearing aids, whereas conductive hearing loss can be treated with bone anchored hearing aids (111; 79). However, a now established body of research has supported management of severe to profound unilateral hearing loss with cochlear implantation, with improvements cited in localization, speech understanding in quiet and in noise, and quality of life (37; 28; 29; 108; 38). An increasing number of adults and children with severe to profound unilateral hearing loss have received a cochlear implant over the past decade (22), especially when in July 2019, significant unilateral hearing loss was approved as an FDA indication for cochlear implantation for both children and adults. Specifically, cochlear implants are now approved for people five years and older with single-sided deafness who have profound sensorineural hearing loss in one ear and normal hearing or mild sensorineural hearing loss in the other ear. They are also approved for people five years and older with asymmetric hearing loss who have profound sensorineural hearing loss in one ear and mild to moderately severe sensorineural hearing loss in the other ear, with a difference of at least 15 dB in pure tone averages between ears. These have shown mixed to positive results in maximizing language development, improving quality of life, and promoting more normal neural cortical development (47; 32; 101; 22; 124). Furthermore, systematic review and metaanalysis performed after FDA approval found that cochlear implantation for children with single sided deafness was associated with clinically meaningful improvement in speech perception (both in noise and quiet) and sound localization (10).

Auditory brainstem implant. Patients with severe to profound hearing loss who are not candidates for cochlear implantation due to cochlear or auditory nerve pathology may benefit from insertion of an auditory brainstem implant (20). This includes patients with neurofibromatosis type 2 and bilateral vestibular schwannomas, bilateral temporal bone fractures, and those with ossification of the cochlea due to meningitis (99). A case series specifically looking at pediatric patients included those with cochlear aplasia/hypoplasia, cochlear nerve aplasia/hypoplasia, common cavity deformity, prematurity, and CHARGE syndrome (88). This device bypasses the cochlea and auditory nerve and provides auditory stimulation to the cochlear nucleus in the brainstem. Colletti and Shannon have shown high levels of speech recognition in adults using auditory brainstem implants (21). In children, auditory brainstem stimulation appears to be sufficient for development of the auditory cortex (19). There are currently no U.S. FDA-approved indications for auditory brainstem implant placement in children, but outcome data showing significant improvements in auditory perception and a low rate of complications are promising (18; 78; 88).

Gene therapy. Inner ear gene therapy has shown early promise in animal models, including modification, silencing, replacing, or inhibiting abnormal or absent gene function. Because of this, gene therapy delivery and hair cell regeneration have been a recent focus in sensorineural hearing loss therapeutics. However, despite encouraging findings in animal models, there are still many obstacles to successful human implementation (58).

Outcomes

Improvements are being seen not only in hearing screening, but also in better systems of care for those children who do not pass their hearing screen or who are at risk for delayed onset of hearing loss, such as better and more timely evaluation of hearing, better ability to assess middle ear function more reliably for very young infants, and better amplification and other habilitation options. As a result of newborn hearing screening and earlier diagnosis of hearing loss, techniques used to determine hearing levels in young infants have been refined over the last decade, and efforts to recruit and train professionals to assess hearing in this young population have increased. There are also improved technologies for those identified with hearing loss, including more precise goals and measures for fitting amplification devices, and better training for those who provide habilitation. Coupling technology with improved awareness and better training of professionals who work with children with hearing loss has helped to improve outcomes for these children.