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Plasma gentamicin concentrations and exposure in neonates cooled for suspected hypoxic-ischaemic encephalopathy and association with later permanent childhood hearing impairment: a case-control study

Presented at the Neonatal Society 2018 Autumn Meeting (programme).

Dabbour S1, Jones J1, Cane C2, Murray-Smith C2, Fitzgerald J2, Clarke P1,3

1 Neonatal Intensive Care Unit, Norfolk and Norwich University Hospitals NHS Foundation Trust, Norwich, UK
2 Department of Audiology, Norfolk and Norwich University Hospitals NHS Foundation Trust, Norwich, UK
3 Norwich Medical School, University of East Anglia, Norwich, UK.

Background: Perinatal asphyxia and aminoglycoside antibiotic therapy are both recognised risk factors for permanent childhood hearing impairment (PCHI). Therapeutic hypothermia (TH) is known to be neuroprotective. Our hypothesis was that the risk of aminoglycoside ototoxicity associated with raised gentamicin concentrations in babies with suspected hypoxic-ischaemic encephalopathy (HIE) is modulated by concurrent reception of TH.

Methods: Retrospective review and case control study. Neonates who received TH for suspected HIE in our tertiary-level unit between 2007 and 2017 were sub-grouped according to newborn hearing screening and later audiological test results and categorised as having a diagnosis of PCHI or ‘normal hearing’ outcomes (non PCHI). First-week highest trough gentamicin concentrations and proportions with a raised gentamicin concentration (>2 mg/L) were compared in the PCHI versus normal hearing sub-groups. Infants with PCHI were then matched for asphyxial severity with two control HIE infants who received TH and had normal hearing outcomes. We then examined the potential affects of gentamicin cumulative exposure on PCHI risk in the presence of TH in PCHI versus controls.

Results: Of 218 eligible babies, 35 were excluded (22 died; 13 alive but had no gentamicin data). Complete follow up data were available for 183 infants of whom 13 (7%) had PCHI and 170 (93%) had normal hearing. Highest gentamicin trough concentrations (median [IQR]) were similar in infants with later PCHI as in those with normal hearing (PCHI: 2.2 mg/L [2.0–3.0 mg/L] vs. normal: 1.9 mg/L [1.5–2.6 mg/L], p value=0.16,) as were proportions with a raised gentamicin >2 mg/L (PCHI: 8/13 [61.5%] vs. normal: 78/170 [46%], p value=0.18). The Table shows gentamicin concentrations and exposure in the 13 PCHI cases compared with 26 matched controls:

Conclusion: Ours is the largest cohort to date of audiological outcomes in neonates cooled for HIE. We found no association between first-week gentamicin concentrations, raised gentamicin >2mg/L, or cumulative gentamicin exposure and risk of later PCHI. Other factors may be more important in the aetiology of PCHI, and TH may modulate risk.

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