Plain English Summary
Background and study aims:
Exposure in the womb to certain medications is associated with an increased risk of both physical and developmental problems. Reductions in developmental functioning can have lifelong implications for the child, including poor educational achievement and lower skilled occupational prospects in adult life. Effects on development are not always apparent at birth and problems may go unnoticed for many years after a medication has received its licence. There are methods of investigating adverse effects of exposure to medications in the womb but typically they only look at the physical development of the child and they cover very large regions. Typically, when measuring development the child is assessed in person. This poses financial and time limitations for assessing large numbers of individuals from a large region or entire country. This study seeks to investigate the reliability of using questionnaires filled in by the parents of children known to have been exposed to medications in the womb. If such measures are reliable then they would offer a cost effective way to assess large numbers of children across large regions and would speed up the information which can be collected on medications which are commonly used during pregnancy.
Who can participate?
Pregnant women in their first or second trimester, diagnosed with epilepsy and are either taking antiepileptic medications or not.
What does the study involve?
The study involves interviewing each participant briefly during their pregnancy about their health and background. Once the child is born, details about the child’s physical health are taken from hospital records. Each mother is then asked to complete two questionnaires about their child’s development when they are a year old and again when they are 2 years old. When the child is 2 years old, they are visited at home by a member of the study team to complete a developmental assessment with their child.
What are the possible benefits and risks of participating?
There may be no direct benefits to participants. However, following the assessment when the child is 2 years old, each parent is provided with brief feedback regarding their child’s assessment. This letter will also be copied to their GP and kept on the child’s file. If there are any concerns about specific areas of a child’s development, these are discussed with the parent and their GP and Health Visitor.
Where is the study run from?
The study is run by the University of Manchester in collaboration with Central Manchester University Hospitals NHS Foundation Trust and other collaborating hospitals.
When is the study starting and how long is it expected to run for?
July 2014 to March 2019
Who is funding the study?
National Institute for Health Research (UK)
Who is the main contact?
Dr Rebecca Bromley
name.study@cmft.nhs.uk
Trial website
Contact information
Type
Public
Primary contact
Dr Rebecca Bromley
ORCID ID
http://orcid.org/0000-0003-4008-0917
Contact details
University of Manchester
Institute of Human Development
6th Floor
St Mary’s Hospital
Oxford Road
Manchester
M13 9WL
United Kingdom
+44 161 7019139
Rebecca.bromley@cmft.nhs.uk
Additional identifiers
EudraCT number
ClinicalTrials.gov number
Protocol/serial number
16727
Study information
Scientific title
Neurodevelopment of Babies Born to Mothers with Epilepsy (NaME): a observational cohort study
Acronym
NaME
Study hypothesis
1.1. Question: Is the utilisation of parental reporting for neurodevelopmental outcome feasible in large populations of children exposed to teratogens in utero?
1.2. Hypothesis: The utilisation of parental reporting for neurodevelopmental outcome will be feasible in large populations of children exposed to teratogens in utero.
2.1. Question: Is the Ages and Stages Questionnaire (ASQ) or the Vineland Adaptive Behaviour Scales (VABS) a reliable measure of neurodevelopmental impairment in populations prenatally exposed to known and unknown teratogens? Is one method more reliable than the other when considered against the Bayley Scales of Infant and Toddler Development?
2.2. Hypothesis: Parental ratings of neurodevelopment will be reliable in their detection of infants with impaired neurodevelopment. It is anticipated that the VABS is likely to be more reliable than the ASQ.
3.1. Question: Are the ratings made by parents on either the VABS or the ASQ at 12 months predictive of ratings at 24 months of age?
3.2. Hypothesis: Parental ratings of neurodevelopment will predict outcomes at 24 months of age.
4.1. Question: What is the neurodevelopmental outcome of children prenatally exposed to newer AEDs?
4.2. Hypothesis: Prenatal exposure to newer antiepileptic drugs will demonstrate different safety and risk profiles pertaining to the neurodevelopment of the child.
Ethics approval
North West - Greater Manchester Central Research Ethics Committee, 22/04/2014, ref: 14/NW/0193
Study design
Observational cohort study
Primary study design
Observational
Secondary study design
Cohort study
Trial setting
Not specified
Trial type
Treatment
Patient information sheet
Not available in web format, please use the contact details below to request a patient information sheet
Condition
Specialty: Reproductive health and childbirth, Primary sub-specialty: Reproductive and sexual medicine; UKCRC code/ Disease:
Intervention
Surveillance for neurodevelopmental teratogenic effects of pharmacological treatment during pregnancy is limited, the consequence of which is that treatment is unlikely to be optimised for maternal or fetal safety. This study aims to investigate the feasibility and reliability of parental reporting methods for the screening of neurodevelopmental outcomes following prenatal exposure to medications across large populations. Antiepileptic drugs (AEDs) provide a means through which to investigate such methods due to the documented outcomes for the older AEDs. Women with epilepsy, who are in their first or second trimester, will be invited to consent into this follow up study. Demographics and health information will be collected during gestation. When the child is 12 months of age the parent will complete the Ages and Stages Questionnaire (ASQ) and the Vineland Adaptive Behavior Scale (VABS). At 24 months of age the child will be assessed using the Bayley Scales of Infant and Toddler Development (Bayley Scales) and reassessed with the ASQ and VABS. Diagnostic efficiency statistics of sensitivity (percentage of children that are impaired and are classified correctly), specificity (percentage of children who are not impaired and who are classified correctly) and false positive/negative predictive values will be calculated for the parental measures in comparison to the Bayley Scales. The kappa statistic will be calculated to determine level of agreement between measures. This investigation will also provide critical information regarding neurodevelopmental outcome following prenatal exposure to newer AEDS, for which safety remains uncertain. Bayley scores at 24 months will be analysed utilising multiple regression, adjusting for confounding variables, to address this issue.
Intervention type
Other
Phase
Drug names
Primary outcome measures
1. Sensitivity and specificity of the Ages and Stages Questionnaire for assessing child development (collected at 12 and 24 months of age)
2. Behaviour and cognitive skills, assessed using Vineland Adaptive Behaviour Scale-II (collected at 12 and 24 months of age)
3. Child development, assessed using Bayley Scales of Infant and Toddler Development-III (collected at 24 months of age)
Secondary outcome measures
Child development, assessed using the Bayley Scales of Infant and Toddler Development-III (collected at 24 months of age) across individual antiepileptic drugs treatments.
Overall trial start date
07/07/2014
Overall trial end date
30/03/2019
Reason abandoned
Eligibility
Participant inclusion criteria
1. A diagnosis of epilepsy and either:
1.1. On antiepileptic drug treatment (experimental group)
1.2. Not on treatment (control group)
2. Living within the North West, North East of England or Northern Ireland.
3. Able to provide informed consent
4. In their first or second trimester of pregnancy
Participant type
Patient
Age group
Adult
Gender
Both
Target number of participants
Planned Sample Size: 385; UK Sample Size: 385
Participant exclusion criteria
1. Significant learning disability (defined as not able to live independently).
2. Taking non-AED medications which are known to be teratogenic (e.g. warfarin)
3. Unable to understand written or verbal English (due to the standardised assessments in use)
Recruitment start date
07/07/2014
Recruitment end date
31/03/2016
Locations
Countries of recruitment
United Kingdom
Trial participating centre
Central Manchester University Hospitals NHS Foundation Trust (Lead Centre)
Oxford Road
Manchester
M13 9WL
United Kingdom
Trial participating centre
Belfast Health and Social Care Trust
Royal Hospitals
Grosvenor Road
Belfast
BT12 6BA
United Kingdom
Trial participating centre
Lancashire Teaching Hospitals NHS Foundation Trust
Royal Preston Hospital
Sharoe Green Lane
Preston
PR2 9HT
United Kingdom
Trial participating centre
Liverpool Women’s Hospital NHS Foundation Trust
Crown Street
Liverpool
L8 7SS
United Kingdom
Trial participating centre
Salford Royal NHS Foundation Trust
Stott Lane
Salford
M6 8HD
United Kingdom
Trial participating centre
City Hospitals Sunderland NHS Foundation Trust
Sunderland Royal Hospital
Kayll Road
Sunderland
SR4 7TR
United Kingdom
Trial participating centre
Newcastle Upon Tyne Hospitals NHS Foundation Trust
Royal Victoria Hospital
Queen Victoria Road
Newcastle Upon Tyne
NE1 4LP
United Kingdom
Trial participating centre
South Tees Hospitals NHS Foundation Trust
Marton Road
Middlesbrough
TS4 3BW
United Kingdom
Trial participating centre
Walton Centre for Neurology and Neurosurgery NHS Foundation Trust
Lower Lane
Liverpool
L9 7LJ
United Kingdom
Trial participating centre
South Tyneside NHS Foundation Trust
South Tyneside District General Hospital
Harton Lane
South Shields
NE34 0PL
United Kingdom
Trial participating centre
Northumbria Healthcare NHS Foundation Trust
Rake Lake
North Shields
Tyne and Wear
NE29 8NH
United Kingdom
Trial participating centre
University Hospitals of Morecambe Bay NHS Foundation Trust
Lancaster Royal Infirmary
Ashton Road
Lancaster
LA1 4RP
United Kingdom
Trial participating centre
Warrington and Halton Hospitals NHS Foundation Trust
Lovely Ln
Warrington
Cheshire
WA5 1QG
United Kingdom
Trial participating centre
Countess of Chester Hospital NHS Foundation Trust
The Countess Of Chester Health Park
Liverpool Rd
Chester
Cheshire
CH2 1UL
United Kingdom
Trial participating centre
East Lancashire Hospitals NHS Foundation Trust
Royal Blackburn Hospital
Haslingden Rd
Blackburn
BB2 3HH
United Kingdom
Trial participating centre
Mid Cheshire Hospitals NHS Foundation Trust
Leighton Hospital
Crewe
Cheshire
CW1 4QJ
United Kingdom
Trial participating centre
York Teaching Hospitals NHS Foundation Trust
Wigginton Rd
York
North Yorkshire
YO31 8HE
United Kingdom
Trial participating centre
Leeds Teaching Hospitals NHS Foundation Trust
St James Hospital
Beckett Street
Leeds
LS9 7TF
United Kingdom
Trial participating centre
Southport and Ormskirk Hospitals NHS Trust
Wigan Rd
Ormskirk
Lancashire
L39 2AZ
United Kingdom
Trial participating centre
Harrogate and District Hospitals NHS Trust
Lancaster Park Rd
Harrogate
HG2 7SX
United Kingdom
Trial participating centre
County Durham and Darlington NHS Foundation Trust
North Rd
Durham
DH1 5TW
United Kingdom
Funders
Funder type
Government
Funder name
National Institute for Health Research
Alternative name(s)
NIHR
Funding Body Type
government organisation
Funding Body Subtype
Federal/National Government
Location
United Kingdom
Results and Publications
Publication and dissemination plan
Not provided at time of registration
Intention to publish date
30/03/2020
Participant level data
To be made available at a later date
Results - basic reporting
Publication summary