Extremely low gestation infants are at high risk

Extremely low gestation infants are at high risk for auditory neuropathy Lynn M. Iwamoto, MD; Konstantine Xoinis, MD; Yusnita Weirather, MA, CCC-A; Hareesh Mavoori, Ph. D; Steven Shaha, Ph. D Kapiolani Medical Center for Women & Children, Hawaii Pacific Health Center for Health Outcomes Honolulu, Hawaii

Faculty Disclosure Information • In the past 12 months, I have not had a significant financial interest or other relationship with the manufacturer(s) of the product(s) or provider(s) of the service(s) that will be discussed in my presentation. • This presentation will not include discussion of pharmaceuticals or devices that have not been approved by the FDA.

Auditory Neuropathy Auditory dys-synchrony (AD) n Transmission of sound to the brain is abnormal n Abnormal brainstem evoked responses (ABR) n Normal acoustic emissions (OAE) n Preserved cochlear microphonics n Acoustic reflex absent n n May be missed with OAE screening

Auditory Neuropathy n Pathophysiology Cochlear inner hair cells n Neural pathways: CN VIII n Brainstem n n Speech perception is impaired Fluctuating losses n Difficulty in background noise n n Prognosis is unpredictable n Optimum management is unclear

High risk neonates Sensorineural hearing loss is 10 times more prevalent n Auditory neuropathy (AN) n n Rance, et al 1999 n 1991 -1996 n 5199 infants screened (at risk population) n 2. 3/1000 AN n 11% of 109 SNHL n Berg, et al 2005 n Mar 2002 -Dec 2003 n 24. 1% of 432 NICU (regional perinatal center)

Risk Factors Family history n Prematurity n Hyperbilirubinemia n Ototoxic medications n Hypoxia n Hydrocephalus n Meningitis n

Objectives n Establish prevalence rate for auditory neuropathy in the high risk nursery n Differentiate infants with auditory neuropathy from those with cochlear hearing loss

Patient Population n Retrospective review 1999 -2003 n Kapiolani Medical Center for Women and Children Newborn Special Care Unit n n Sensorineural hearing loss n n Auditory neuropathy Gestational age-matched controls

Data Collected Demographics n n n Gestational age Birthweight Gender Ethnicity Apgar scores Severity of illness n n Length of hospitalization Chronic lung disease Intraventricular hemorrhage Necrotizing enterocolitis

Data Collected Risk Factors n Medications Furosemide n Aminoglycosides n Vancomycin n Dexamethasone n n Infections CMV n Toxoplasmosis n Meningitis n

Data Collected Risk Factors n Mechanical ventilation Conventional ventilation n High frequency ventilation n Hyperbilirubinemia n Pulmonary hypertension n n Nitric oxide

AN vs SNHL vs Control AN/AD SNHL Control (24) (71) (92) 28± 5† 33± 5 32± 5 1318± 894† 1968± 1006 1872± 996 58 61 53 1 min apgar 4. 8± 2. 5 6. 1± 2. 2 5. 6± 2. 3 5 min apgar 6. 7± 1. 6 7. 7± 1. 7 7. 3± 1. 7 117± 76*† 73± 89* 40± 62 Gestational age (wks) Birthweight (g) Male gender (%) Length of hospitalization (d) *p<0. 05 vs. Control †p<0. 05 vs. SNHL

Gestational Age Distribution High Risk Nursery 1999 -2003

PREVALENCE By Gestational Age Group

Exposure to Medications AN/AD SNHL Control (%) (%) Aminoglycosides 95. 8* 80. 3 70. 7 Furosemide 95. 8†* 50. 7* 32. 6 Vancomycin 79. 2†* 41. 4 27. 2 Dexamethasone 54. 2* 32. 4* 14. 1 *p<0. 05 vs control † p< 0. 05 vs SNHL

Neonatal Morbidities Peak Bilirubin (mg/dl) Ventilation (d) HFOV (%) CMV Infection (%) *p<0. 05 vs Control AN/AD SNHL Control 12. 7± 4. 2 13. 1± 6. 3* 10. 0± 3. 5 45± 42* 28± 31 19± 29 16. 7 28. 2* 8. 7 0 7. 0* 0

Neonatal Morbidities AN/AD SNHL Control (%) (%) BPD 66. 7†* 30. 0* 23. 9 IVH 16. 7 9. 9 3. 3 Hydrocephalus 4. 2 8. 5 3. 3 NEC 8. 3 8. 5 3. 3 * p<0. 05 vs. control † p < 0. 05 vs. SNHL

Summary n SNHL = 21/1000 in the NICU n AN/AD = 5. 3/1000 26% of hearing loss n 2/3 were ≤ 28 wks gestation n 44% of hearing loss for those ≤ 28 wks n

Summary n AN/AD vs. SNHL Younger gestation n Lower birthweight n Greater exposure to potential ototoxic medications n n Furosemide n Vancomycin Higher incidence of BPD n Longer hospitalization n

Conclusions n Auditory neuropathy is a significant problem in the high risk nursery population. n Extremely premature infants are at highest risk.

Perspective n Infants in the high risk nursery should be routinely screened by both ABR and OAE before hospital discharge. n Early identification of AN/AD will lead to a better understanding of the pathophysiology and the development of appropriate intervention strategies.