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Cisplatin ototoxicity in children: implications for primary care providers.

The National Cancer Institute (2007) estimates that 12,500 children are diagnosed with cancer each year. Survival rates for childhood cancer have dramatically improved over the past two decades; 80.2% of young children diagnosed before age five, 78.3% of children diagnosed between ages 5 and 9 years, and 70.3% of children diagnosed with cancer during adolescence will survive (American Cancer Society, 2008). This increased survival rate for children with cancer has led to a need for primary care practitioners to become familiar with the long-term effects of cancer and cancer treatment protocols.

Most childhood malignancies are treated with a combination of intense chemotherapy agents, surgery, and/or radiation therapy. Although these treatments are largely successful in putting children's cancer into remission, they also expose children to related toxicities that may affect children's normal health and development. This article will review the long-term ototoxic effects of cisplatin, a common chemotherapy agent used to treat many childhood malignancies, ways to screen for auditory toxicity in the primary care setting, and current options for monitoring and managing these children's sensorineural hearing loss in the primary care setting.

Methodology

A literature review investigating cisplatin ototoxicity in children and childhood cancer survivors was conducted. The Cumulative Index to Nursing and Allied Health Literature (CINAHL, 1990-2008), PsychINFO (1967-2008), Ovid Medline (1990-2008), Google Scholar ([c] 2008), and Google ([c] 2008) databases were searched for all human studies and review articles published in English that included one or more of the following key words or search terms: "cisplatin," "ototoxicity," "hearing loss," "hearing impairment," "sensorineural hearing loss," "children," "cancer," "childhood cancer," and "childhood cancer survivors." Articles found were reviewed and included if they pertained to ototoxicity that occurred as a consequence of cisplatin treatment for childhood cancer. Ancestry searching of the references of these pertinent articles was also performed. Articles that referenced cisplatin ototoxicity in adults with cancer were excluded.

Review of Literature

Mechanism of Action of Cisplatin

Cisplatin or cis-diamminedichloridoplatinum (CDDP) is an antineoplastic platinum compound. It was the first drug of its class, and as such, it is the most widely studied. Other platinum-containing compounds currently used to treat cancer include carboplatin and oxaliplatin. Platinum agents exert their effect by interfering with cell division or mitosis. They do so by forming platinum complexes within cells. The complexes cause cross-linking between and within strands of DNA (Lehne, 2007; Li, 2006). This damages the DNA of cells and prevents cell mitosis from occurring. It also activates apoptosis pathways to cause cell death.

Current Usages of Cisplatin

Cisplatin is currently utilized in many childhood cancer clinical trials overseen by the Children's Oncology Group, which is the main research organization involved in developing pediatric oncology treatment protocols. Cisplatin and other platinum compounds are used in the treatment of cancers of the bone, connective tissue and muscles, brain and nerve tissues, head, neck, lungs, eyes, kidneys, adrenal glands, lymph tissues, liver, and reproductive organ tissues (see Figure 1) (CureSearch, National Childhood Cancer Foundation, & Children's Oncology Group, 2008; Mayo Clinic, 2008). For these treatment regimens, cisplatin is administered intravenously, and the timing and dosage of cisplatin is dependent on the specific type and grading of the cancer metastasis.
Figure 1.

Childhood Cancers Treated with Cisplatin and
Other Platinum Compounds

* Bone (osteosarcomas)

* Connective tissues and muscles (rhabdomyosarcomas)

* Lungs

* Eyes (retinoblastomas)

* Kidneys and adrenal glands (Wilms' tumor)

* Lymph tissues (non-Hodgkin's lymphoma)

* Liver (hepatoblastomas)

* Reproductive organ tissues (testicular, endometrial
ovarian, cervical cancers)

Sources: CureSearch, National Childhood Cancer Foundation,
& Children's Oncology Group, 2008; Mayo Clinic, 2008.


Side Effects of Cisplatin

Common side effects of cisplatin include nausea, vomiting, decreased appetite, metallic taste, alopecia, and tinnitus (Mayo Clinic, 2008). It can also cause electrolyte disturbances in children, including hypomagnesaemia, hypokalemia, and hypocalcaemia (CureSearch et al., 2008; Mayo Clinic, 2008). Other more serious adverse effects of cisplatin include nephrotoxicity, peripheral neuropathy, acute bone marrow suppression, and ototoxicity (CureSearch et al., 2008; Lehne, 2007; Li, 2006; Mayo Clinic, 2008). During cisplatin treatment, children are monitored for most of these toxicities. Kidney function tests, including glomerular filtration rate, blood urea nitrogen, and creatinine clearance, are measured to monitor for nephrotoxicity; physical assessments are conducted to detect any peripheral neuropathies; and complete blood counts with differentials are drawn to monitor for cisplatin-induced myelosupression. Although in the past children's hearing was not monitored, today efforts are being made to routine]y assess children's hearing before, during, and after cisplatin treatment.

Cisplatin-Induced Sensorineurai Hearing Loss

Normal hearing physiology. Human ear anatomy is divided into outer, middle, and inner ear segments. The outer ear includes the pinna and external auditory canal; the middle ear consists of the tympanic membrane and the boney ossicles (malleus, incus, and stapes); and the inner ear consists of the oval window, the cochlea (which houses the organ responsible for hearing), the semicircular canals, and vestibule (which are responsible for balance and equilibrium) (Fontana & Porth, 2005).

Once a sound wave travels through the external auditory canal and into the middle ear, it causes the tympanic membrane to vibrate. The vibration of the tympanic membrane causes the ossicles to vibrate in turn, with the stapes eventually pressing upon the oval window of the inner ear. When the oval window begins to vibrate, it causes the fluid in the cochlea to oscillate along the Organ of Corti, which is lined with hair cells that serve as our hearing receptors. When the hair cells are stimulated by this fluid movement, they transmit nerve impulses through the cochlear nerve to cranial nerve VIII, the vestibulocochlear nerve. From there, the nerve impulses travel to the temporal lobe auditory processing centers of the brain, and audition is perceived (Fontana & Porth, 2005; Huether & Defriez, 2006).

Conductive vs. sensorineural hearing loss. Hearing loss is divided into two classifications: conductive or sensorineural. Conductive hearing loss occurs when there is a malfunction somewhere in the auditory pathway of the outer or middle ear sections, often a blockage in the outer canal due to excessive cerumen or fluid buildup in the middle ear space as a result of otitis media. Sensorineural hearing loss occurs when there is a malfunction in the auditory pathway in the inner ear. Research suggests that cisplatin causes damage to the hair cells that line the Organ of Corti in the inner ear, resulting in a sensorineural hearing loss (Garcia-Berrocal et al., 2007).

Mechanism of cisplatin-induced sensorineural hearing loss. Although scientists are still trying to elucidate the precise mechanism(s) of cisplatin-induced sensorineural ototoxicity in humans, animal models provide some insight into the underlying pathophysiology of cisplatin's ototoxicity. Researchers are using animal studies to determine if cisplatin activates apoptosis (or programmed cell death) in hair cells that line the Organ of Corti (Devarajan et al., 2002; Garcia-Berrocal et al., 2007; Husain, Scott, Whitworth, Somani, & Rybak, 2001). Garcia-Berrocal and colleagues (2007) examined the effect of cisplatin on 36 rats' inner ear hair cells and found that cisplatin increased the activity of a specific enzyme called capase-3/7. Capase-3/7 is an apoptotic enzyme that upon activation initiates a cascade of events that results in cell death in the cochlea.

Other researchers are using animal studies to establish the role reactive oxygen species (or oxygen free radicals) produced by cisplatin have in generating damage in the cochlea (Clerici, DiMartino, & Prasad, 1995; Lee et al., 2004; Rybak, 2007). They hypothesize that cisplatin produces oxygen free radicals in the cochlea. These reactive oxygen species decrease the endogenous antioxidant enzymes found in the cochlea, further increasing its susceptibility to damage caused by cisplatin-derived free radicals. Lee and colleagues (2004) found elevated levels of two potent oxygen free radicals, 4-hydoxynonel and nitrotyrosine, in mice following the administration of cisplatin; autopsies showed the radicals extensively damaged the cochlear hair cells of the mice.

The study of cisplatin-induced sensorineural hearing loss in animals is important. If researchers can isolate the mechanism(s) involved in cisplatin-induced cochlear damage in animal models, they can extrapolate the information to humans to determine how cisplatin exerts its ototoxic effects in children and hopefully develop a management technique to block or minimize these ototoxic effects. More research in this area is needed.

Prevalence of cisplatin-induced sensorineural hearing loss in childhood cancer survivors. Studies have shown that cisplatin causes irreversible ototoxicity in children (Bertolini et al., 2004; Coradini, Cigana, Selistre, Rosito, & Brunetto, 2007; Gilmer-Knight, Kraemer, & Neuwelt, 2005; Kushner, Budnick, Kramer, Modak, & Cheung, 2006; Lackner et al., 2000; Simon, Hero, Dupuis, Selle, & Berthold, 2002; Stohr et al., 2005). The prevalence rate or occurrence of cisplatin-induced sensorineural hearing loss varies in each of these studies, ranging from 10% to 85% of children studied.

One late effects study by Lackner and colleagues (2000) examined 223 children who were treated for childhood cancer with a median age at diagnosis of 7.2 years. The median time from treatment was 5 years. Twenty-two of the study's participants had received cisplatin, with a mean cumulative dosage of 367mg/[m.sup.2]. Pure tone audiometry testing for late effects showed that 18 of the 22 children (81%) had bilateral sensorineural hearing loss, with 5 using hearing aids. The study's results are limited by its small sample size.

Gilmer-Knight and colleagues (2005) looked at the incidence of hearing loss in children and young adults treated with cisplatin chemotherapy. They used pure tone audiometry to measure the hearing abilities of 67 children treated with cisplatin. The researchers were able to perform a baseline audiogram on these children prior to the beginning of their cisplatin chemotherapy. The children and young adults ranged in age from 8 months to 23 years of age. Serial audiological evaluations were performed throughout their treatment and up to 800 days after the initial administration of cisplatin. They found 41 of the 67 treated children (61%) experienced sensorineural hearing loss, and the median time to development of the hearing loss was 135 days. The progressive hearing loss was observed for up to 26 months after children completed their cancer treatments.

These occurrence rates may actually underestimate the prevalence of hearing loss in childhood cancer survivors. Coradini et al. (2007) found that using pure tone audiometry testing as a single measure is not as sensitive as using otoacoustic emissions testing, which identified hearing losses in 71% of the children, whereas pure tone audiometry only indicated hearing losses in 52% of the children. Further research using otoacoustic emissions testing is needed to examine the incidence of cisplatin-induced sensorineural hearing loss in childhood cancer survivors.

Characteristics of Cisplatin-Induced Ototoxicity In Childhood Cancer Survivors

High-frequency hearing loss. Cisplatin-induced ototoxicity results in high frequency hearing loss in children. Hearing loss is categorized by a grading system that ranges from Grade 1 to Grade 4 (Brock, Bellman, Yeomans, Pinkerton, & Pritchard, 1991). Grade 1 characterizes the least severe hearing loss where children have difficulty hearing only high frequency sounds, including those at 40 dB and greater than 8000 Hertz (Hz). Grade 4 characterizes the most severe hearing loss, where children have difficulty hearing both high and low frequency sounds, including those at 40 db between 1000 to 8000 Hz. Studies demonstrate that while children who receive cisplatin can develop varying degrees of hearing loss, most children develop Grade 1 ototoxicity or high frequency hearing loss (Bertolini et al., 2004; Gilmer-Knight et al., 2005; Kushner et al., 2006; Simon et al., 2002). Bertolini and colleagues (2004) found that of 52 children, 33 (63%) developed Grade 1 ototoxicity, 13 (25%) developed Grade 2 ototoxicity, and only 6 (12%) developed Grade 3 or 4 ototoxicity.

Dose-dependent ototoxicity related to cisplatin. Late effects studies have examined cisplatin ototoxicity and its relationship to different total cumulative dosages of the platinum agent (Allen et al., 1998; Li, Womer, & Silber, 2004; Simon et al., 2002). Simon and associates (2002) reviewed medical records of 1,170 children successfully treated for neuroblastoma and found 146 had documented hearing losses. They discovered that the presence of cisplatin-induced hearing impairments was associated with the stage at diagnosis of the neuroblastoma; children with more advanced disease received higher total cumulative dosages of cisplatin in comparison to children with less advanced disease. Children with non-metastatic neuroblastoma stage 1 disease received a total dose of 320mg/[m.sup.2]. Children with metastatic stage 4 disease received a total dose of 640mg/[m.sup.2], a significantly higher amount than children with stage 1 disease. The study's results indicated that only 1% of children who received 320mg/[m.sup.2] of cisplatin developed hearing impairments, as compared to 26.9% who received 640mg/[m.sup.2] of cisplatin. These results support the hypothesis that cisplatin-induced sensorineural hearing loss is dose dependent with lower cumulative dosages having less ototoxic effects.

Other late effects studies confirmed these findings (Coradini et al., 2007; Kushner et al., 2006; Stohr et al., 2005). Stohr and colleagues (2005) used pure tone audiometry to examine 74 individuals who were diagnosed with osteosarcoma and treated in childhood. Although no specific demographic information about the sample was provided, people currently above the age of 40 were excluded from the sample so that age-related hearing loss would not affect the results. The total cumulative dose of cisplatin in the study's sample ranged from 120 to 600mg/[m.sup.2]. Individuals who received a cumulative cisplatin dose of less than 240mg/[m.sup.2] displayed no significant hearing loss. However, people who received a cumulative cisplatin dose of greater than 360mg/[m.sup.2] demonstrated significant hearing impairments. Kushner and colleagues (2006) also studied the ototoxic effects of different cumulative doses of cisplatin. They used a more comprehensive assessment to evaluate the hearing abilities of 173 children with neuroblastoma treated with cisplatin therapy, including audiometry, visual reinforcement, and otoacoustic emissions testing. They found similar results to the aforementioned studies; higher dosages of cisplatin were associated with increased incidence of acquired sensorineural hearing loss. Hearing losses occurred more frequently once the total cumulative dose reached 300 to 400mg/[m.sup.2].

Clearly, the total cumulative dosage of cisplatin is a mediating factor in the child's development of ototoxicity. More research is needed to determine the exact total dosage amount that separates minimal hearing losses from severe hearing impairments.

Age-dependent ototoxicity related to cisplatin. It is hypothesized that administration of cisplatin to children at younger ages results in increased sensorineural hearing loss. In a landmark study examining cisplatin ototoxicity in 153 children treated with cisplatin, Li and colleagues (2004) found that even when the statistical analysis controlled for total cumulative dosages of cisplatin, the age at which the child received the cisplatin had a significant affect on whether or not the child developed sensorineural hearing loss. Specifically, they found that children younger than 5 years of age when they received cisplatin were 21 times more likely to develop moderate to severe hearing loss compared to children 15 to 20 years of age when they received cisplatin.

Kushner and colleagues (2004) divided the childhood cancer survivors successfully treated for neuroblastoma into three age group categories: those who received cisplatin before age 5, between the ages of 5 and 12, and after age 12. Children who received cisplatin before age 5 were significantly more likely than other children to have moderate to severe hearing loss. Children who received cisplatin before age 5 lost the ability to hear both high and low frequencies, even those in the normal speech frequency range (between 1000 to 2000 Hz). Being of an older age at the time of diagnosis and cisplatin administration appeared to be a protective factor against severe ototoxicity.

One study revealed results that contradicted these findings. Bertolini and associates (2004) examined 120 children who had been treated for neuroblastoma, osteosarcoma, hepatoblastoma, or germ cell tumors. The median age of diagnosis was 2.6 years, and the median age of follow up was 7 years post-treatment. The results showed that only 25% of children who were diagnosed and treated with cisplatin before the age of 36 months had significant hearing losses compared with 42% of children who were diagnosed and treated after 3 years of age. These results suggest that younger age (less than 3 years) could be a protective factor against cisplatin-induced ototoxicity. A possible explanation for this could be children less than 3 years of age still have plasticity to their neurons and cerebral cortex, allowing for recovery from the cellular effects of cisplatin. Further research is needed to elucidate the role that age has in mediating the ototoxic effects of cisplatin chemotherapy treatment.

Implications for Primary Care

Importance of Hearing in Children's Development

Children's ability to hear facilitates many domains of their development, including their cognitive development. In young children, hearing and auditory processing play key roles in language acquisition (including vocabulary, phoneme, morpheme, syntax, and grammar development), and the development of literacy and reading skills. Undetected or uncorrected hearing loss in early childhood can interfere with children's normal speech and language development (Kiese-Himmel, 2008; Moeller, Tomblin, Yoshinaga-Itano, Connor, & Jerger, 2007). Children who acquire hearing losses after the language acquisition years can be affected in slightly different ways. They can have trouble attending to or cognitively processing information at school, which can lead to academic difficulties. In a study of childhood neuroblastoma survivors, Gurney and colleagues (2007) found that children with hearing impairments secondary to their cancer treatments were more than twice as likely to have difficulties with reading, math, or attention skills than children who did not acquire any hearing losses from treatment.

Children's social development can also be affected by hearing losses. Young children learn to read other's social cues as they develop peer interaction and communication skills. Social cues and communication with others can be done in both verbal and non-verbal ways. If children are unable to hear or process these verbal cues, they do not attend to them and may respond inappropriately to their peers (Brinton & Fujiki, 2002; Brown, Bortoli, Remine, & Othman, 2008). This puts children with undetected hearing impairments at risk for developing social difficulties with peer relations, which can negatively influence their socioemotional development. For a detailed description of the impact of hearing impairments on children's social development, see Brinton and Fujiki, 2002.

Monitoring Hearing in Primary Care

When to monitor hearing. Since children's ability to hear is crucial to their cognitive, social, and language development, universal guidelines for hearing screening have been established. As part of the Recommendations for Preventive Pediatric Health Care, Bright Futures and the American Academy of Pediatrics (2008) recommend formal hearing screening in newborns and all children of ages of 4, 5, 6, 8, and 10 years. At all other ages and preventive health care visits, they advocate for the clinician to conduct hearing risk assessments, and if appropriate, follow up by performing a hearing screen measure, such as otoacoustic emissions testing or pure tone audiometry.

Since childhood cancer survivors treated with cisplatin are at increased risk for developing hearing impairments, primary care clinicians need to monitor their hearing more closely. Typically, children's hearing will be monitored by their oncology team during their chemotherapy treatment. Once children complete treatment, they may seek follow-up care in their regional cancer survivorship clinics or from their primary care doctor. Children followed in late effects clinics may have their hearing tested there; those not followed in late effects clinics must be regularly screened in primary care. The Children's Oncology Group's (2006) long-term follow-up guidelines for cancer survivors recommend yearly clinical histories of any hearing difficulties, otoscopic examinations of outer and middle ear structures, and sensorineural hearing screening for children who received cisplatin chemotherapy. If any hearing loss is detected or if results of the screening tests are inconclusive, children need to be referred directly to an audiologist who is familiar with the late effects of childhood cancer chemotherapy. Since cisplatin hearing loss is progressive, the audiologist determines how often children with hearing loss must be re-tested based on their total cumulative dose of cisplatin and their age when it was administered.

How to monitor hearing. The Children's Oncology Group recommends using otoacoustic emissions, pure tone audiograms, or auditory-evoked response tests to monitor for cisplatin-induced sensorineural hearing loss in cancer survivors. However, in studies of childhood cancer survivors, distortion-product otoacoustic emissions (DPOAE) testing was found to be a more sensitive screening tool for hearing losses than pure tone audiometry and transient-evoked otoacoustic emissions testing (Dhooge et al., 2006; Knight, Kraemer, Winter, & Neuwelt, 2007; Stavroulaki, Apostolopoulos, Segas, Tsakanikos, & Adamopoulos, 2001). These studies advocate for DPOAE testing to become the preferred method to monitor inner ear cochlear function and detect sensorineural hearing losses related to cisplatin ototoxicity.

DPOAE testing is a non-invasive test where a small probe is inserted into the outer ear canal of the child. The probe itself is connected to a small portable computer device. The otoacoustic emissions device is programmed to emit acoustic sounds at variable frequencies and digitally measure the response of the hair cells in the cochlea to those sounds. DPOAE testing differs from other forms of otoacoustic emissions screening because it measures the hair cell's response to two sounds of different frequencies emitted simultaneously (Stavroulaki et al., 2001; Wagner, Heppelmann, Vonthein, & Zenner, 2008). After conducting the test, the computer device digitally analyzes the cochlear response and determines whether the child's hearing requires further assessment. Usually, the DPOAE device summarizes its findings into "pass" or "refer" results. Complex DPOAE devices that communicate to office computer networks are available, and these devices enable the provider to print out the digital analysis or electronically transfer the test results into children's medical records. While the cost of the portable DPOAE computer device can range from $4,000 to $25,000 depending on its degree of technological sophistication, the cost of the disposable probe covers needed for each patient is only about $0.50 to $1.00 per child (National Center for Hearing Assessment and Management, 2008).

The DPOAE test offers many advantages to other traditional forms of hearing assessment, such as pure tone audiometry. First, it is a sensitive screening tool with high test-retest reliability (Wagner et al., 2008). Test sensitivity of the DPOAE is superior to pure tone audiometry; it is able to detect drug-induced sensorineural hearing losses before pure tone audiometry measures can (Lonsbury-Martin & Martin, 2003; Stavroulaki et al, 2002). Second, DPOAE testing can be used with children of all ages, from newborns to adolescents, for regular assessment of their hearing in primary care settings. Third, it is a fast, efficient computerized method to screen children's hearing. Although the test must be done separately for each ear, it takes less than 1 minute to perform on each child, taking approximately 15 to 30 seconds per ear (Stowe, 2009). Fourth, unlike pure tone audiograms that depend on the child's cooperation to indicate when he or she hears a sound, DPOAE testing does not depend on children's verbal or physical responses (for example, saying yes or raising their hand to indicate they heard a sound). The only requirement is that children stay relatively still for the few seconds the probe is in each ear. Fifth, medical assistants and/or nursing staff can be trained to use the device and administer the testing. They can incorporate it into their normal routine with children. Typically, a practice will only need one DPOAE device. Since the DPOAE device is portable, the medical and/or nursing staff can do the testing in the quiet environment of an examination room. Finally, computerized testing will also provide analysis and guidelines for when to refer children to an audiologist for further hearing assessment. Although other forms of hearing screening are available, DPOAE testing provides many benefits and is practical for primary care settings. The major disadvantage to DPOAE testing is the cost of the equipment; it is markedly more expensive than pure tone audiometers, which range in price from $500 to $1500 (American Speech-Language Hearing Association [ASHA], 2009c).

Family Education

Primary care clinicians have a responsibility to educate childhood cancer survivors and their families about the necessity of continual hearing assessments. They must explain to parents what is known about the long-term ototoxic effects of cisplatin and how a DPOAE test in the primary care office can screen for hearing losses. Clinicians should clarify that it is only a screening test and that the results will help determine if the child needs further audiological assessment. Families and children may have difficulty talking about the cancer treatment and its persistent affect on their lives (Fuemmeler, Mullins, Van Pelt, Carpentier, & Parkhurst, 2005; Santacroce & Lee, 2006). Clinicians need to provide concrete information about the potential for hearing impairments while remaining sensitive to the family's emotional status and coping abilities.

When referring children to audiologists, clinicians should inform families about what to expect during their appointment. The audiologist will use a battery of tests, including otoacoustic emissions, pure tone audiometry, speech audiometry, and auditory brainstem response tests to thoroughly assess the child's hearing (ASHA, 2009b). The audiologist will measure the degree and type of hearing loss, and develop an audiogram that outlines the specific frequencies (pitch) and intensities (loudness) that the child can and cannot hear. Once the hearing profile is developed, management options will be presented.

Management of Hearing Loss

Primary care clinicians need to educate childhood cancer survivors and their families about the potential implications of hearing loss on children's language, speech, social, and academic abilities. They need to encourage families to view hearing loss as a significant problem that must be addressed. Primary care clinicians need to be knowledgeable about the range of management options for pediatric hearing impairments. Management of children's hearing loss will depend on its severity. Children with moderate to severe hearing impairments may require hearing aid devices and classroom accommodations, while children with mild hearing impairments may not require hearing aids but still require educational accommodations. Although hearing impairments are managed by the audiologist, the primary care clinician provides the medical home, oversees the child's care, and acts as a resource for the family. There is a range of management options for hearing loss in children, including various hearing aids, cochlear implants, assistive listening devices, and educational accommodations.

Electronic hearing aids. There are three different types of hearing aids available for children: behind-the-ear, in-the-ear, and completely in-the-canal aids (The Children's Hearing Institute, 2009; National Institute on Deafness and Other Communication Disorders, 2009). Behind-the-ear aids include an ear mold that sits in the outer ear and is connected to a plastic case that is placed behind the ear. With behind-the-ear aids, sounds are amplified in the plastic case and travel through the ear mold into the ear. In-the-ear aids are smaller than behind-the-ear aids, and the whole device fits into the outer ear. In general, in-the-ear aids are avoided in children because they are difficult to fit precisely in the outer ear and often need to be re-made as the child grows (The Children's Hearing Institute, 2009). As their name implies, completely in-the-canal aids sit entirely in the ear canal and are the least visible hearing aids. Audiologists can advise families on what type of aid will work best for their child and whether the child needs an analog or digital version.

Cochlear implants. Children with severe sensorineural hearing loss may be eligible for cochlear implants. Cochlear implants involve external and internal components that are surgically inserted into the child's cochlea (The Children's Hearing Institute, 2009). The external part is similar to a behind-the-ear hearing aid and acts as processor and transmitter of acoustic signals, which are received by the internal component that transmits the information into electrical signals read by the cranial auditory nerve (ASHA, 2005, 2009b). Children have to undergo extensive testing by a cochlear implant center to determine their eligibility for the procedure.

Assistive listening devices. Audiologists sometimes recommend that children use assistive listening devices alone or in combination with hearing aids. One common assistive listening device is a personal frequency modulation (FM) system. Children use FM systems to aid in their hearing in group-like settings, such as school classrooms. FM systems include a microphone for the speaker to use and a portable FM receiver that looks like a small radio for the child to use. The FM receiver amplifies the sound waves so that the child can better understand the auditory input (ASHA, 2009a). Other common assistive listening devices are telephone amplification systems and one-to-one communicators.

Educational and school support for young children. Young children with hearing impairments may qualify to receive early intervention services. Primary care clinicians are responsible for referring children and their families for these services and coordinating their care. Early intervention services are critical for language and speech development (Moeller, 2000).

Educational and school support for school-age children and adolescents. Children with hearing impairments may need special accommodations for school. Primary care clinicians can collaborate with the family and school to develop an individualized education program for the child. Accommodations can include preferential classroom seating, the use of personal FM systems in the classroom, and auditory-visual curriculum adaptation. With the family's permission, clinicians can also communicate with teachers about the child's specific learning needs.

Resources for parents. There are several associations and Web sites that provide information about hearing impairments in children, hearing aids, and other support measures as well as promoting healthy child development (see Figure 2).
Figure 2.

Resources for Parents

* American Speech-Language Hearing Association
(www.asha.org)

* American Hearing Aid Associates
(www.ahaanet.com/children.asp)

* The Children's Hearing Institute
(www.childrenshearing.org)

* Hearing Loss Education Center
(www.hearinglosseducation.com)

* Information on School Services
(www.hearinglossweb.com)

* The Let Them Hear Foundation
(www.letthemhear.org/hearing/pediatric.php)

* National Center for Hearing Assessment and Management
(www.infanthearing.org)

* National Institute on Deafness and Other Communication Disorders
(www.nidcd.nih.gov)

* State and Local Departments of Education
(www.education.com)


Conclusion

As survival rates for childhood cancer continue to improve, there is a growing need for pediatric practitioners to offer health care surveillance for the long-term effects of chemotherapy, including cisplatin-induced ototoxicity, in primary care settings. Primary care clinicians can use distortion-product otoacoustic emissions testing to regularly screen childhood cancer survivors for cisplatin-induced sensorineural hearing loss. If evidence of hearing loss is present, clinicians must refer children and their families to an audiologist for a complete hearing evaluation. Permanent hearing impairments can be a traumatic discovery for the family. Primary care pediatric settings oversee children's care and serve as support systems for the family. Pediatric clinicians need to be knowledgeable about current management options for hearing impairments in children. They need to educate families about local, state, and school resources, national organizations, and other support services that are available to help their child.

Additional Reading

Cunningham, M., Cox, E.O., & the American Academy of Pediatrics' Committee on Practice and Ambulatory Medicine and the Section on Otolaryngology and Bronchoesophagology. (2003). Hearing assessment in infants and children: Recommendations beyond neonatal screening. Pediatrics, 111(2), 436-440.

References

Allen, G., Tiu, C., Koike, K., Ritchey, K., Kurs-Lasky, M., & Wax, M. (1998). Transient-evoked otoacoustic emissions in children after cisplatin chemotherapy. Otolaryngology-Head and Neck Surgery, 118(5), 584-588.

American Cancer Society. (2008). Cancer statistics presentation 2008. Retrieved February 20, 2009, from http://www.cancer.org/docroot/LPRO/content/ PRO_1_1_Cancer_Statistics_2008_Presentation.asp

American Speech-Language Hearing Association [ASHA]. (2005). Audiology information series: Cochlear implants. Retrieved February 20, 2009, from http://www.asha.org/NR/rdonlyres/ F1DBFB69-2400-4019-89FC-AD5263209F7C/0/InfoSeries Cochlearlmplants.pdf

American Speech-Language Hearing Association [ASHA]. (2009a). Assistive technology: What are assistive listening devices? Retrieved February 20, 2009, from http://www.asha.org/public/ hearing/treatment/assist_tech.htm

American Speech-Language Hearing Association [ASHA]. (2009b) Cochlear implants. Retrieved February 20, 2009, from http://www.asha.org/public/hearing/treatment/cochlear_implant.htm

American Speech-Language Hearing Association [ASHA]. (2009c). Guidelines for manual pure-tone threshold audiometry. Retrieved February 20, 2009, from http://www.asha.org/docs/html/GL2005 00014.html

Bertolini, P., Lassalle, M., Mercier, G., Raquin, M., Izzi, G., Carradini, N., et al. (2004). Platinum compound-related ototoxicity in children: Long-term follow-up reveals continuous worsening of hearing loss. Journal of Pediatric Hematology and Oncology, 26(10), 649-655.

Bright Futures, & American Academy of Pediatrics. (2008). Bright futures: Guidelines for health supervision of infants, children, and adolescents (3rd ed.). Elks Grove Village, IL: Author.

Brinton, B., & Fujiki, M. (2002). Social development in children with specific language impairment and profound hearing loss. In P.K. Smith & C.H. Hart (Eds.), Blackwell handbook of childhood social development (pp. 588-603). Malden, MA: Blackwell Publishing.

Brock, P., Bellman, S., Yeomans, E., Pinkerton, C., & Pritchard, J. (1991). Cisplatin ototoxicity in children: A practical grading system. Medical Pediatric Oncology, 19, 295-300.

Brown, M., Bortoli, A., Remine, M., & Othman, B. (2008). Social engagement, attention and competence of preschoolers with hearing loss. Journal of Research in Special Educational Needs, 8(1), 19-26.

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Children's Oncology Group. (2006). Establishing and enhancing services for childhood cancer survivors: Long term follow-up program resource guide. Retrieved on February 20, 2009, from http://www.survivorshipguidelines.org/pdf/LTFUResourceGuide.pdf

Clerici, W., DiMartino, D., & Prasad, M. (1995). Direct effect of reactive oxygen species on cochlear outer hair cells. Hearing Research, 84, 30-40.

Coradini, R, Cigana, L., Selistre, S., Rosito, L., & Brunetto, A. (2007). Ototoxicity from cisplatin therapy in childhood cancer. Journal of Pediatric Hematology and Oncology, 29(6), 355-360.

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Jessica Helt-Cameron, MSN, MA, RN, is a Pediatric Nurse Practitioner, Graduate, Yale University, School of Nursing, New Haven, CT, and holds a MA degree from Tufts University.

Patricia Jackson Allen, MS, RN, PNP, FAAN, is a Professor and the Director of the Pediatric Nurse Practitioner Specialty, Yale University School of Nursing, New Haven, CT, and a Member of Pediatric Nursing's Editorial Board.
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Title Annotation:Primary Care Approaches
Author:Helt-Cameron, Jessica; Allen, Patricia Jackson
Publication:Pediatric Nursing
Geographic Code:1USA
Date:Mar 1, 2009
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