Lamotrigine use in Pregnancy and Risk of Orofacial Clefts II

Study type

• Study topic:
  Disease /health condition

  Human medicinal product
• 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:
  Other
• Non-interventional study design, other:
  Case-malformed control study

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:
  • Paediatric Population (< 18 years)

    • Neonate

      • 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:
  10061059

Study design details

• Main study objective:
  To investigate more precisely whether first trimester exposure to lamotrigine (LTG) monotherapy is specifically associated with an increased risk of orofacial clefts (OCs) relative to other malformations, in a follow-up study involving 5 yearly updates (2009, 2010, 2011, 2012, and 2013).
• Outcomes:
  Odds of lamotrigine exposure among OC registrations (cases) was compared with the odds of lamotrigine exposure among malformed non-OC registrations (controls). Explore whether lamotrigine exposure may be associated with other malformations, and in particularly, assess independent evidence for the association with club foot signalled in the original study.
• Data analysis plan:
  Crude odds ratios (ORs) were calculated as well as ORs adjusted for maternal age, and adjusted for registry