Hearing in Schoolchildren After Neonatal Exposure to a High-Dose Gentamicin Regimen Dagny Hemmingsen, MD, a,c Camilla Mikalsen, MSc, a Alexander Rydland Hansen, MSc, a Jon Widding Fjalstad, MD, PhD, c Niels Christian Stenklev, MD, PhD, d Claus Klingenberg, MD, PhD b,c abstract OBJECTIVE: To assess the association between gentamicin exposure in the neonatal period and hearing in school age. METHODS: This study included children exposed to a high-dose (6 mg/kg) gentamicin regimen as neonates (2004–2012), invited for follow-up at school age, and a healthy age-matched control group. We assessed hearing with pure tone audiometry including the extended high-frequency (EHF) range. Outcomes were average hearing thresholds in the midfrequencies (0.5–4 kHz) and the EHFs (9–16 kHz). The measures of gentamicin exposure were cumulative dose and highest trough plasma concentration. We used linear regression models to assess the impact of gentamicin exposure, and other peri- and postnatal morbidities, on hearing thresholds. RESULTS: A total of 219 gentamicin-exposed and 33 healthy-control children were included in the audiological analysis. In the gentamicin cohort, 39 (17%) had a birth weight ,1500 g. Median cumulative doses and trough plasma concentrations were 30 (interquartile range 24–42) mg/kg and 1.0 (interquartile range 0.7–1.2) mg/L, respectively. Median hearing thresholds for the midfrequencies and the EHFs were 2.5 (0 to 6.3) dB hearing level and 21.7 (25.0 to 5.0) dB hearing level, both of which were within the normal range. In an adjusted analysis, increasing hearing thresholds were associated with lower birth weight and postnatal middle-ear disease but not level of gentamicin exposure. After adjusting for birth weight, there was no difference in hearing threshold between the gentamicin-exposed cohort and healthy controls. CONCLUSIONS: Exposure to a high-dose gentamicin regimen in the neonatal period was not associated with an increase in hearing thresholds in schoolchildren being able to complete audiometry. WHAT’S KNOWN ON THIS SUBJECT: Evidence for ototoxic hearing loss after gentamicin exposure is mainly from studies in adults and older children. Neonatal studies report low rates of ototoxicity but have commonly used only moderately sensitive hearing tests. WHAT THIS STUDY ADDS: We performed pure tone audiometry, including the extended high-frequency range, in 219 schoolchildren (median age 9 years) exposed to a high-dose gentamicin regimen in the neonatal period. We found no association between exposure to gentamicin and hearing levels. To cite: Hemmingsen D, Mikalsen C, Hansen AR, et al. Hearing in Schoolchildren After Neonatal Exposure to a High-Dose Gentamicin Regimen. Pediatrics. 2020;145(2): e20192373 Departments of a Otorhinolaryngology and Head and Neck Surgery and b Paediatrics and Adolescence Medicine, University Hospital of North Norway, Tromsø, Norway; c Paediatric Research Group, Faculty of Health Sciences, Univeristy of Tromsø-Arctic University of Norway, Tromsø, Norway; and d Ear-Nose-Throat Unit, Ishavsklinikken, Tromsø, Norway The raw data supporting the conclusion of this article will be made available by the authors, without undue reservation, to any qualified researcher. Dr Hemmingsen conceptualized and designed the study, conducted the initial analysis, wrote the first draft of the manuscript, had full access to all of the data in the study, and takes responsibility for the integrity of the data and the accuracy of the data analysis; Ms Mikalsen collected data and reviewed and revised the manuscript; Mr Hansen collected data, conducted the initial analysis, and reviewed and revised the manuscript; Dr Fjalstad reviewed all gentamicin data, established the cohort from the neonatal period, contributed to statistical analyses, and revised the manuscript; Dr Stenklev provided substantial contribution to the study design and interpretation of the data and reviewed and revised the manuscript; (Continued) PEDIATRICS Volume 145, number 2, February 2020:e20192373 ARTICLE Downloaded from http://publications.aap.org/pediatrics/article-pdf/145/2/e20192373/1078356/peds_20192373.pdf by guest on 07 February 2022