title: Gentamicin, genetic variation and deafness in preterm children.
abstract: BACKGROUND
  Hearing loss in children born before 32 weeks of gestation is more prevalent than in full term infants. Aminoglycoside antibiotics are routinely used to treat bacterial infections in babies on neonatal intensive care units. However, this type of medication can have harmful effects on the auditory system. In order to avoid this blood levels should be maintained in the therapeutic range. However in individuals with a mitochondrial genetic variant (m.1555A > G), permanent hearing loss can occur even when drug levels are within normal limits. The aim of the study is to investigate the burden that the m.1555A > G mutation represents to deafness in very preterm infants.
  
  
  METHODS
  This is a case control study of children born at less than 32 completed weeks of gestation with confirmed hearing loss. Children in the control group will be matched for sex, gestational age and neonatal intensive care unit on which they were treated, and will have normal hearing. Saliva samples will be taken from children in both groups; DNA will be extracted and tested for the mutation. Retrospective pharmacological data and clinical history will be abstracted from the medical notes. Risk associated with gentamicin, m.1555A > G and other co-morbid risk factors will be evaluated using conditional logistic regression.
  
  
  CONCLUSIONS
  If there is an increased burden of hearing loss with m.1555A > G and aminoglycoside use, consideration will be given to genetic testing during pregnancy, postnatal testing prior to drug administration, or the use of an alternative first line antibiotic. Detailed perinatal data collection will also allow greater definition of the causal pathway of acquired hearing loss in very preterm children.
authors.affiliation: Genetics and Genomic Medicine, University College London Institute of Child Health and Great Ormond Street Hospital for Children, 30 Guilford Street, London WC1N 1EH, UK. maria.bitner@ucl.ac.uk.
authors.forename: Maria
authors.initials: M
authors.lastname: Bitner-Glindzicz
authors.forename: Shamima
authors.initials: S
authors.lastname: Rahman
authors.forename: Kathy
authors.initials: K
authors.lastname: Chant
authors.forename: Neil
authors.initials: N
authors.lastname: Marlow
mesh_terms: D000900:Anti-Bacterial Agents / Q000009:adverse effects*; D016022:Case-Control Studies; D003638:Deafness / Q000139:chemically induced* / Q000235:genetics*; D005260:Female; D014644:Genetic Variation; D005839:Gentamicins / Q000009:adverse effects*; D006801:Humans; D007231:Infant, Newborn; D007235:Infant, Premature, Diseases / Q000139:chemically induced* / Q000235:genetics*; D008297:Male; D009154:Mutation; D012189:Retrospective Studies
chemical_list: D000900:Anti-Bacterial Agents; D005839:Gentamicins