Study type

Study topic

Human medicinal product
Disease /health condition

Study type

Non-interventional study

Scope of the study

Assessment of risk minimisation measure implementation or effectiveness

Data collection methods

Secondary use of data
Non-interventional study

Non-interventional study design

Case-control
Study drug and medical condition

Anatomical Therapeutic Chemical (ATC) code

(N03AX09) lamotrigine
lamotrigine

Medical condition to be studied

Cleft lip and palate
Cleft palate
Population studied

Short description of the study population

Pregnant women who had first trimester exposure to the new anti-epileptic drug (AED) lamotrigine.

Age groups

Preterm newborn infants (0 – 27 days)
Term newborn infants (0 – 27 days)
Infants and toddlers (28 days – 23 months)

Special population of interest

Pregnant women

Estimated number of subjects

85563
Study design details

Main study objective

To investigate in a large dataset whether lamotrigine exposure in the first trimester of pregnancy is associated with an increased risk of orofacial clefts relative to other malformations

Outcomes

Odds of lamotrigine (LMT) exposure among OC registrations (cases) was compared with the odds of LTG exposure among malformed non-OC registrations (controls). An exploratory hypothesis-generating analysis compared the proportion of different malformation subgroups, according to EUROCAT subgroup definitions,among all nonchromosomal registrations, between lamotrigine exposed (all and mono) and AED unexposed registrations.

Data analysis plan

Crude ORs were calculated ignoring the registry of origin. In order to analyze the data taking into account the registry and including all registries (even if they had no exposure to lamotrigine (LMG) in either cases or controls) the WinBUGS computer package was used to fit multinomial responses with a logistic link. Maternal age was treated as a categorical variable. Due to the small numbers of exposures to LTG it was not possible to adjust simultaneously for both registry and maternal age.
Documents
Study publications
Dolk H, Jentink J, Loane M, Morris J, de Jong-van den Berg LTW and EUROCAT Anti…