Condition category
Ear, Nose and Throat
Date applied
Date assigned
Last edited
Retrospectively registered
Overall trial status
Recruitment status
No longer recruiting

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,
Professor Neil Marlow,

Trial website

Contact information



Primary contact

Prof Maria Bitner-Glindzicz


Contact details

30 Guilford Street
United Kingdom

Additional identifiers

EudraCT number number

Protocol/serial number


Study information

Scientific title

Gentamicin, genetic variation and deafness in preterm children: a case control study



Study hypothesis

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.

Ethics approval

NRES Ethics Committee London – Central, 2 February 2012, Ref: 12/LO/0005

Study design

Case control study

Primary study design


Secondary study design

Case-control study

Trial setting


Trial type


Patient information sheet



Causes of hearing loss in preterm infants


Genetic screening for mitochondrial mutation

Intervention type



Not Specified

Drug names


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 child’s medical notes, both cases and controls, will be retrospectively collected to compare risk factors.

Overall trial start date


Overall trial end date


Reason abandoned


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

Participant type


Age group




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

United Kingdom

Trial participating centre

30 Guilford Street
United Kingdom

Sponsor information


University College London - Institute of Child Health (UK)

Sponsor details

30 Guilford Street
United Kingdom

Sponsor type




Funder type


Funder name

Action on Hearing Loss (UK) (ref: RNID G47)

Alternative name(s)

Funding Body Type

private sector organisation

Funding Body Subtype

other non-profit


United Kingdom

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

Publication summary

Publication citations

Additional files

Editorial Notes