Extremely low gestation Extremely low gestation infants are at high risk for infants are at high risk for

auditory neuropathyauditory neuropathy

Lynn M. Iwamoto, MD; Konstantine Xoinis, MD; Yusnita Lynn M. Iwamoto, MD; Konstantine Xoinis, MD; Yusnita Weirather, MA, CCC-A; Hareesh Mavoori, PhD; Steven Shaha, Weirather, MA, CCC-A; Hareesh Mavoori, PhD; Steven Shaha,

PhDPhD

Kapiolani Medical Center for Women & Children, Hawaii Pacific Kapiolani Medical Center for Women & Children, Hawaii Pacific Health Center for Health OutcomesHealth Center for Health Outcomes

Honolulu, HawaiiHonolulu, Hawaii

Faculty Disclosure InformationFaculty Disclosure Information

• In the past 12 months, I have not had a In the past 12 months, I have not had a significant financial interest or other significant financial interest or other relationship with the manufacturer(s) of the relationship with the manufacturer(s) of the product(s) or provider(s) of the service(s) product(s) or provider(s) of the service(s) that will be discussed in my presentation.that will be discussed in my presentation.

• This presentation will not include discussion This presentation will not include discussion of pharmaceuticals or devices that have not of pharmaceuticals or devices that have not been approved by the FDA.been approved by the FDA.

Auditory NeuropathyAuditory Neuropathy

Auditory dys-synchrony (AD)Auditory dys-synchrony (AD) Transmission of sound to the brain is Transmission of sound to the brain is

abnormalabnormal Abnormal brainstem evoked responses Abnormal brainstem evoked responses

(ABR)(ABR) Normal acoustic emissions (OAE)Normal acoustic emissions (OAE) Preserved cochlear microphonicsPreserved cochlear microphonics Acoustic reflex absentAcoustic reflex absent

May be missed with OAE screeningMay be missed with OAE screening

Auditory NeuropathyAuditory Neuropathy

PathophysiologyPathophysiology Cochlear inner hair cellsCochlear inner hair cells Neural pathways: CN VIIINeural pathways: CN VIII BrainstemBrainstem

Speech perception is impairedSpeech perception is impaired Fluctuating lossesFluctuating losses Difficulty in background noiseDifficulty in background noise

Prognosis is unpredictablePrognosis is unpredictable Optimum management is unclearOptimum management is unclear

High risk neonatesHigh risk neonates Sensorineural hearing loss is 10 Sensorineural hearing loss is 10

times more prevalenttimes more prevalent Auditory neuropathy (AN)Auditory neuropathy (AN)

Rance, et al 1999Rance, et al 1999 1991-1996 1991-1996 5199 infants screened (at risk population)5199 infants screened (at risk population) 2.3/1000 AN2.3/1000 AN 11% of 109 SNHL11% of 109 SNHL

Berg, et al 2005Berg, et al 2005 Mar 2002-Dec 2003Mar 2002-Dec 2003 24.1% of 432 NICU (regional perinatal 24.1% of 432 NICU (regional perinatal

center)center)

Risk FactorsRisk Factors

Family historyFamily history PrematurityPrematurity HyperbilirubinemiaHyperbilirubinemia Ototoxic medicationsOtotoxic medications HypoxiaHypoxia HydrocephalusHydrocephalus MeningitisMeningitis

ObjectivesObjectives

Establish prevalence rate for auditory Establish prevalence rate for auditory neuropathy in the high risk nurseryneuropathy in the high risk nursery

Differentiate infants with auditory Differentiate infants with auditory neuropathy from those with cochlear neuropathy from those with cochlear hearing losshearing loss

Patient PopulationPatient Population

Retrospective reviewRetrospective review 1999-20031999-2003 Kapiolani Medical Center for Women and Kapiolani Medical Center for Women and

Children Newborn Special Care UnitChildren Newborn Special Care Unit Sensorineural hearing lossSensorineural hearing loss

Auditory neuropathyAuditory neuropathy Gestational age-matched controlsGestational age-matched controls

Data CollectedData CollectedDemographicsDemographics

Gestational ageGestational age BirthweightBirthweight GenderGender EthnicityEthnicity Apgar scoresApgar scores Severity of illnessSeverity of illness

Length of hospitalizationLength of hospitalization Chronic lung diseaseChronic lung disease Intraventricular hemorrhageIntraventricular hemorrhage Necrotizing enterocolitisNecrotizing enterocolitis

Data CollectedData CollectedRisk FactorsRisk Factors

MedicationsMedications FurosemideFurosemide AminoglycosidesAminoglycosides VancomycinVancomycin DexamethasoneDexamethasone

InfectionsInfections CMVCMV ToxoplasmosisToxoplasmosis MeningitisMeningitis

Mechanical ventilationMechanical ventilation Conventional ventilationConventional ventilation High frequency ventilationHigh frequency ventilation

HyperbilirubinemiaHyperbilirubinemia Pulmonary hypertensionPulmonary hypertension

Nitric oxideNitric oxide

Data CollectedData CollectedRisk FactorsRisk Factors

AN vs SNHL vs ControlAN vs SNHL vs ControlAN/ADAN/AD

(24)(24)

SNHLSNHL(71)(71)

ControlControl(92)(92)

Gestational age Gestational age (wks)(wks)

28±528±5†† 33±533±5 32±532±5

Birthweight (g)Birthweight (g) 1318±8941318±894†† 1968±10061968±1006 1872±9961872±996

Male gender (%)Male gender (%) 5858 6161 5353

1 min apgar1 min apgar 4.8±2.54.8±2.5 6.1±2.26.1±2.2 5.6±2.35.6±2.3

5 min apgar5 min apgar 6.7±1.66.7±1.6 7.7±1.77.7±1.7 7.3±1.77.3±1.7

Length of Length of hospitalization (d)hospitalization (d)

117±76117±76**†† 73±8973±89** 40±6240±62

*p<0.05 vs. Control†p<0.05 vs. SNHL

Gestational Age DistributionHigh Risk Nursery 1999-2003

PREVALENCEBy Gestational Age Group

Exposure to MedicationsExposure to Medications

AN/ADAN/AD(%)(%)

SNHLSNHL(%)(%)

ControlControl(%)(%)

AminoglycosidAminoglycosideses

95.895.8** 80.380.3 70.770.7

FurosemideFurosemide 95.895.8††** 50.750.7** 32.632.6

VancomycinVancomycin 79.279.2††** 41.441.4 27.227.2

DexamethasoDexamethasonene

54.254.2** 32.432.4** 14.114.1

*p<0.05 vs control† † pp< 0.05 vs SNHL

Neonatal MorbiditiesNeonatal Morbidities

AN/ADAN/AD SNHLSNHL ControlControl

Peak Bilirubin Peak Bilirubin (mg/dl)(mg/dl)

12.7±4.212.7±4.2 13.1±6.313.1±6.3** 10.0±3.510.0±3.5

Ventilation (d)Ventilation (d) 45±4245±42** 28±3128±31 19±2919±29

HFOV (%)HFOV (%) 16.716.7 28.228.2** 8.78.7

CMV Infection CMV Infection (%)(%)

00 7.07.0** 00

*p<0.05 vs Control

Neonatal MorbiditiesNeonatal Morbidities

AN/ADAN/AD(%)(%)

SNHLSNHL(%)(%)

ControlControl(%)(%)

BPDBPD 66.766.7††** 30.030.0** 23.923.9

IVHIVH 16.716.7 9.99.9 3.33.3

HydrocephalHydrocephalusus

4.24.2 8.58.5 3.33.3

NECNEC 8.38.3 8.58.5 3.33.3

* p<0.05 vs. control† p < 0.05 vs. SNHL

SummarySummary

SNHL = 21/1000 in the NICUSNHL = 21/1000 in the NICU

AN/AD = 5.3/1000AN/AD = 5.3/1000 26% of hearing loss26% of hearing loss 2/3 were ≤ 28 wks gestation2/3 were ≤ 28 wks gestation 44% of hearing loss for those ≤ 28 wks44% of hearing loss for those ≤ 28 wks

SummarySummary

AN/AD vs. SNHLAN/AD vs. SNHL Younger gestationYounger gestation Lower birthweightLower birthweight Greater exposure to potential ototoxic Greater exposure to potential ototoxic

medicationsmedications FurosemideFurosemide VancomycinVancomycin

Higher incidence of BPDHigher incidence of BPD Longer hospitalizationLonger hospitalization

ConclusionsConclusions

Auditory neuropathy is a significant Auditory neuropathy is a significant problem in the high risk nursery problem in the high risk nursery population.population.

Extremely premature infants are at Extremely premature infants are at highest risk.highest risk.

PerspectivePerspective

Infants in the high risk nursery should Infants in the high risk nursery should be routinely screened by both ABR and be routinely screened by both ABR and OAE before hospital discharge.OAE before hospital discharge.

Early identification of AN/AD will lead to Early identification of AN/AD will lead to a better understanding of the a better understanding of the pathophysiology and the development pathophysiology and the development of appropriate intervention strategies.of appropriate intervention strategies.