Birth Defects Associated With Exposure to Lamotrigine in Pregnancy (EUROCAT)
Status:
Completed
Trial end date:
2013-12-01
Target enrollment:
Participant gender:
Summary
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.