Babies who are born too early have an increased risk for hearing, speech and language problems. While hearing is screened at birth, screening may miss milder degrees of loss. Children may be screened for speech and language problems by their doctors or schools, but therapy is rarely started until age 3 or 4 years. About 40% of babies born earlier than 32 weeks of gestation have major speech and language problems. We are researching hearing, speech and language development in babies who are very or extremely premature in a 5-year longitudinal study funded by the National Institutes of Health.

The primary aim of the study is to predict later hearing, speech and language problems using MRI, auditory and EEG measures at birth. The long-term goal is to uncover brain differences that highly predict children at risk so that they can receive intervention as soon as possible after birth.

Infants born preterm are at higher risk for hearing loss, particularly in the high frequencies, due to treatment with ototoxic drugs, hypoxia-ischemia, mechanical ventilation, and jaundice. However, current newborn screening methods may miss slight-mild and high frequency hearing loss. Our hypothesis is that all degrees of hearing loss important for speech perception can be detected using age-appropriate tests of the inner ear called distortion product otoacoustic emissions (DPOAE), validated by audiometry in at-risk 2–3-year-old children.

We have found a very high prevalence of hearing loss (11% of children) in 2–3-year-old preterm graduates. About half of the hearing loss was permanent, while the other half was due to temporary, middle ear problems that could be treated medically. Only 1/5 cases with permanent sensorineural loss had referred on newborn hearing screening. Age-appropriate combined DPOAE levels were highly predictive of hearing loss. Wideband absorbance was an effective method to determine presence of middle ear dysfunction. These data reinforce Joint Committee on Infant Hearing 2019 recommendations to follow-up babies cared for in the NICU.

Project Details

• Collaborators: Jennifer Vannest, PhD, University Of Cincinnati; Nehal Parikh, DO; David Moore, PhD; Ernie Pedapati, MD; Lauren Petley, PhD, Clarkson University, New York
• Funding: National Institutes of Health (R01DC018734)

Prevention of Ototoxicity with Effective Monitoring (POEM) Study

Patients treated with life-saving aminoglycoside antibiotics frequently experience adverse side effects of ototoxicity – permanent hearing loss and degraded speech communication. Currently, most patients at risk are not monitored for ototoxic hearing loss. The lack of monitoring is primarily due to lack of availability and awareness of early detection methods, as well as treatment alternatives that can preserve hearing. There are critical gaps in our understanding of individual susceptibility for ototoxicity and access to effective tests that identify those at higher risk. Cystic fibrosis (CF) is the most common life-threatening genetic disease in Caucasians and causes persistent lung infections in childhood that are frequently treated with aminoglycoside (AG) antibiotics, thus is an important patient group to target for prevention of ototoxicity.

The long-term goal of this research program is to develop a predictive model using novel auditory tests and pharmacodynamics for early detection and prevention of sensorineural hearing loss (SNHL) in at-risk individuals receiving aminoglycoside (AG) antibiotics. This project will evaluate new methods to detect onset of ototoxicity using extended high frequency (EHF) transient otoacoustic emissions (TEOAE) tests of inner ear function and digits in noise (DIN) tests, compared with longitudinal PD measures of drug clearance.

Project Details

• Collaborators: Patrick Feeney, PhD, National Center for Rehabilitative Audiologic Research and Oregon Health and Science University; Angela Garinis, PhD, Oregon Health and Science University; Dawn Konrad-Martin, PhD, Oregon Health and Science University; Min Dong, PhD; David Moore, PhD; Gary McPhail, MD; Ron Rubenstein, MD, PhD, Washington University-St. Louis Pulmonary Medicine; Sander Vinks, PhD
• Funding: National Institutes of Health (R01DC017867)

Genetics of Hearing Loss in Cystic Fibrosis

Drug-induced ototoxicity is a leading cause of acquired, permanent sensorineural hearing loss (SNHL), and individuals with cystic fibrosis (CF) are particularly at risk for SNHL due to obligate intravenous (IV) delivery to aminoglycoside (AG) antibiotics. These IV-AG medications are commonly used because of their efficacy for treating bacterial lung infections (pulmonary exacerbations), or for prolonged duration to treat infections by difficult-to-treat organisms such as atypical mycobacteria.

While most patients with CF suffer substantial hearing loss, it remains unclear why a significant fraction of patients retain normal hearing despite high cumulative IV-AG dosing. This bimodal distribution is highly suggestive of genetic susceptibility to (or protection from) AG ototoxicity. Identifying genetic variants associated with susceptibility to, or protection from, AG-induced hearing loss, will provide critical knowledge to develop a genetic screen to identify patients at high-risk for drug-induced SNHL.

Prospective identification of these individuals will permit individually-tailored antibiotic therapy to ameliorate ototoxicity and permit optimal (and earlier) allocation of auditory rehabilitation resources when AG exposure is obligatory. Preventing hearing loss, including high frequency hearing loss, is crucial to maintain quality of life, particularly for children acquiring the listening and spoken language skills essential for communication, emotional growth and academic success.

Project Details

• Funding: Cystic Fibrosis Foundation (PI: Angela Garinis, PhD, Oregon Health and Science University, Ron Rubenstein, MD, PhD, Washington University-St. Louis)
• Further Reading: Cystic Fibrosis and Ototoxic Meds Linked with Hearing Loss