Condition category
Pregnancy and Childbirth
Date applied
11/04/2016
Date assigned
26/04/2016
Last edited
26/04/2016
Prospective/Retrospective
Retrospectively registered
Overall trial status
Ongoing
Recruitment status
No longer recruiting

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

Sponsor information

Organisation

The University of Manchester

Sponsor details

Oxford Road
Manchester
M13 9PL
United Kingdom

Sponsor type

Hospital/treatment centre

Website

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

Publication citations

Additional files

Editorial Notes