Birth Defects Associated With Exposure to Lamotrigine in Pregnancy (EUROCAT)
September 29, 2014 updated by: GlaxoSmithKline
Monitoring of Specific Birth Defects Associated With Exposure to Lamotrigine in Pregnancy Through the EUROCAT Network
In 2007 a case control study was completed within the EUROCAT European network of congenital anomaly registers to test the hypothesis that first trimester lamotrigine monotherapy exposure is associated with an increased risk of isolated oral clefts.
This study found no statistically significant increased risk of oral clefts compared with other defects following lamotrigine exposure in the uterus.
The EUROCAT Antiepileptic Drug (AED) Database, established for the original case control study in 2007, will now be expanded to include an additional five to six years worth of data.
These data will provide greater power to investigate the risk of isolated oral clefts, specific cleft types and potential associations with additional specific malformation types (e.g.
neural tube defects).
Data on cases of isolated oral clefts registered between 1993 and 2012 will be extracted from EUROCAT member registers meeting set inclusion criteria (ensuring completeness of outcome and exposure data).
The primary comparison group will include all non oral cleft, non chromosomal malformations as the registers do not collect data on non malformed infants.
This study will also be powered to include a second control group of chromosomal malformations, very unlikely to be associated with medication exposure.
Data on exposure to anti-epileptic drugs (AEDs) during the first trimester of pregnancy will be extracted along with other key covariates including age of mother, history of epilepsy and gestational age of the infant.
Primary analyses, using logistic regression, will compare the lamotrigine monotherapy versus no AED use across case and control groups and a secondary analysis will compare lamotrigine monotherapy versus other AED monotherapy (with and without valproate).
Data will also be monitored for patterns of lamotrigine exposure across additional specific malformation groups of interest.
Study Overview
Status
Completed
Conditions
Study Type
Observational
Enrollment (Actual)
1
Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
- Child
- Adult
- Older Adult
Accepts Healthy Volunteers
No
Genders Eligible for Study
All
Sampling Method
Probability Sample
Study Population
All infants/fetuses with congenital malformations registered on EUROCAT anti-epileptic drug database between 1995 and 2012 (start date depends on date of lamotrigine registration in country of participating register).
EUROCAT is a European network of population-based congenital anomaly registers for surveillance. EUROCAT surveys 1.5 million births per year covering 29% of births in EU Member States.
In 2007, 19 population-based congenital malformation registers within EUROCAT participated in an initial study of the association of lamotrigine exposure in pregnancy and the risk of isolated oral clefts. These registries covered at least part of the population of Austria, Belgium, Croatia, Denmark, Finland, France, Germany, Ireland, Italy, Malta, Norway, Poland, Spain, Switzerland and Wales.
It is anticipated, that if these registers participate in the current study, the study will cover 8 million births and 200,000 congenital malformation registrations between 1995 and 2012.
Description
Inclusion Criteria:
- Individual population-based registers within EUROCAT are eligible to participate if:
- Anti-epileptic drug exposure is recorded for at least 3 per 1000 malformed infants/fetuses (figures below this threshold indicate potential under reporting of medication exposure).
- Specific drug names or complete 7 digit Anatomical Therapeutic Chemical (ATC) classification codes are available for at least 80% of AED exposed infants/fetuses.
Exclusion Criteria:
- As above
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Observational Models: Case-Control
- Time Perspectives: Retrospective
Cohorts and Interventions
Group / Cohort |
Intervention / Treatment |
|---|---|
|
Infants/foetuses w/malformations registered in EUROCAT network
Pregnancies resulting in foetus/infant with malformation registered through participating registers within the EUROCAT network
|
Exposure to lamotrigine monotherapy in the first trimester of pregnancy (time period from first day of menstrual period to 12th week of gestation).
No exposure to anti-epileptic drugs in the first trimester of pregnancy (time period from first day of menstrual period to 12th week of gestation).
Exposure to non lamotrigine monotherapy (with or without valproate) during the first trimester of pregnancy (time period from the first day of the menstrual period to the 12th week of gestation)
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Time Frame |
|---|---|
|
Non chromosomal, non monogenic, isolated oral clefts
Time Frame: Retrospective case control study. All isolated oral cleft malformations registered on congenital malformation registers participating in the EUROCAT anti-epileptic drug database will be extracted irrespective of timing of diagnosis pre- or post natally.
|
Retrospective case control study. All isolated oral cleft malformations registered on congenital malformation registers participating in the EUROCAT anti-epileptic drug database will be extracted irrespective of timing of diagnosis pre- or post natally.
|
Secondary Outcome Measures
Outcome Measure |
Time Frame |
|---|---|
|
Non oral cleft, non chromosomal malformations
Time Frame: Retrospective case control study. All non oral cleft, non chromsomal malformations recorded on congenital malformation registers participating in EUROCAT anti-epileptic drug database extracted irrespective of diagnosis timing pre or post-natal.
|
Retrospective case control study. All non oral cleft, non chromsomal malformations recorded on congenital malformation registers participating in EUROCAT anti-epileptic drug database extracted irrespective of diagnosis timing pre or post-natal.
|
|
All chromosomal malformations
Time Frame: This is a retrospective case control study. All chromosomal malformations recorded on congenital malformation registers participating in the EUROCAT anti-epileptic drug database will be extracted irrespective of timing of diagnosis pre- or post natally.
|
This is a retrospective case control study. All chromosomal malformations recorded on congenital malformation registers participating in the EUROCAT anti-epileptic drug database will be extracted irrespective of timing of diagnosis pre- or post natally.
|
Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start
May 1, 2009
Primary Completion (Actual)
December 1, 2013
Study Completion (Actual)
December 1, 2013
Study Registration Dates
First Submitted
January 21, 2010
First Submitted That Met QC Criteria
January 21, 2010
First Posted (Estimate)
January 25, 2010
Study Record Updates
Last Update Posted (Estimate)
October 1, 2014
Last Update Submitted That Met QC Criteria
September 29, 2014
Last Verified
September 1, 2014
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Congenital Abnormalities
- Physiological Effects of Drugs
- Molecular Mechanisms of Pharmacological Action
- Central Nervous System Depressants
- Antipsychotic Agents
- Tranquilizing Agents
- Psychotropic Drugs
- Membrane Transport Modulators
- Sodium Channel Blockers
- Calcium-Regulating Hormones and Agents
- Calcium Channel Blockers
- Lamotrigine
- Anticonvulsants
Other Study ID Numbers
- 113038
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