Plain English Summary
Background and study aims
The prevalence of acquired hearing loss in infants born before 32 weeks of gestation (very preterm) is ten times higher than in the normal paediatric population. There are several potential aetiological pathways, including the side effects of some regularly used medications on neonatal units, such as aminoglycosides. These are known to have toxic effects on the hearing system but, despite being at high risk of receiving aminoglycosides, there is little evidence for drug-induced ototoxicity in preterm children. The risk of hearing loss may be increased further in babies with a mutation of mitochondrial DNA, m.1555A>G. Individuals with this mutation who receive aminoglycosides suffer from rapidly progressive, profound hearing loss even when drug levels are maintained within normal limits; this interaction may be attenuated in the newborn period, but has not been formally studied.
This study will investigate the relationship between the m.1555A>G mutation, aminoglycosides and deafness in children born very prematurely.
Who can participate?
We aim to recruit 30-60 deaf children (cases) who were born at 31 weeks and 6 days of gestation or less. For every child with hearing loss we will recruit 5 children with normal hearing (controls). Groups will be matched according to gestational age, sex and the neonatal unit on which they were treated.
What does the study involve?
This is an observational study which will only involve saliva samples and access to medical notes.
Children with hearing loss will be invited to participate by their audiological paediatrician; ex-preterm children with normal hearing will be invited by their neonatologist. Saliva samples will be taken from children in both groups for genetic analysis of m.1555A>G. Clinical data including information on aminoglycoside exposure will be abstracted from medical notes.
What are the possible benefits and risks of participating?
The main benefit to participants with deafness is the opportunity to potentially identify a cause for their hearing loss. If the child has the mutation, it is likely that this is the cause. There is little benefit for control participants who have normal hearing, but they have genetic screening for the mutation and if they test positive they will be advised to avoid aminoglycoside antibiotics in the future to prevent the risk of hearing loss.
There are no anticipated risks for participants, although children could be nervous about having a saliva sample taken.
Where is the study run from?
The study has been set up at University College London (UK).
When is the study starting and how long is it expected to run for?
The study began in January 2013 and has started recruiting participants. It will run for 3 years, although for most participants there will only be a single contact for consent to be taken.
Who is funding the study?
Funding has been provided by Action on Hearing Loss (UK).
Who is the main contact?
Professor Maria Bitner-Glindzicz, email@example.com
Professor Neil Marlow, firstname.lastname@example.org
Gentamicin, genetic variation and deafness in preterm children: a case control study
We hypothesise that mutation (m.1555A>G) makes a significant contribution to deafness in babies born at 31 weeks and 6 days of gestation or less who receive treatment with aminoglycosides, even when drug levels were within the normal range.
NRES Ethics Committee London Central, 2 February 2012, Ref: 12/LO/0005
Case control study
Primary study design
Secondary study design
Patient information sheet
Causes of hearing loss in preterm infants
Genetic screening for mitochondrial mutation
Primary outcome measures
To determine the prevalence of the m.1555A>G mutation in very preterm children with deafness compared to controls. Children in both groups will have saliva samples collected and tested for the mutation by direct DNA sequencing.
Secondary outcome measures
To determine additional risk of subsequent hearing loss posed by gentamicin administration to very preterm children for presumed sepsis compared to other putative risk factors. Data from each childs medical notes, both cases and controls, will be retrospectively collected to compare risk factors.
Overall trial start date
Overall trial end date
Participant inclusion criteria
Cases babies born at 31 weeks and 6 days gestational age or less with hearing loss, treated on a neonatal unit within Greater London between 1st January 2009 31st December 2013
Controls - babies born at 31 weeks and 6 days gestational age or less with normal hearing, treated on a neonatal unit within Greater London between 1st January 2009 31st December 2013
Target number of participants
30 60 deaf children and 5 controls per deaf baby/child. Total 150-300 children
Participant exclusion criteria
Cases no exclusion criteria
Controls missing data in medication records
Recruitment start date
Recruitment end date
Countries of recruitment
Trial participating centre
30 Guilford Street
Action on Hearing Loss (UK) (ref: RNID G47)
Funding Body Type
private sector organisation
Funding Body Subtype
Results and Publications
Publication and dissemination plan
Not provided at time of registration
Intention to publish date
Participant level data
Not provided at time of registration
Results - basic reporting