Lamotrigine and the risk of malformations in pregnancy.
OBJECTIVE
To report the frequency of major malformations in lamotrigine-exposed pregnancies from September 1, 1992, through March 31, 2004, in the International Lamotrigine Pregnancy Registry.


METHODS
Health care professionals throughout the world can voluntarily enroll lamotrigine-exposed pregnancies in this observational study. Only pregnancies with unknown outcomes at the time of enrollment were included in the analysis. The percentage of outcomes with major birth defects was calculated as the total number of outcomes with major birth defects divided by the sum of the number of outcomes with major birth defects + the number of live births without defects.


RESULTS
Among 414 first-trimester exposures to lamotrigine monotherapy, 12 outcomes with major birth defects were reported (2.9%, 95% CI 1.6% to 5.1%). Among the 88 first-trimester exposures to lamotrigine polytherapy including valproate, 11 outcomes with major birth defects were reported (12.5%; 95% CI 6.7% to 21.7%). Among 182 first-trimester exposures to lamotrigine polytherapy excluding valproate, 5 outcomes with major birth defects were reported (2.7%, 95% CI 1.0% to 6.6%). No distinctive pattern of major birth defects was apparent among the offspring exposed to lamotrigine monotherapy or polytherapy.


CONCLUSIONS
The risk of all major birth defects after first-trimester exposure to lamotrigine monotherapy (2.9%) was similar to that in the general population and in other registries enrolling women exposed to antiepileptic monotherapy (3.3% to 4.5%). However, the sample size was too small to detect any but very large increases in specific birth defects.
Cunnington
Marianne
M
GlaxoSmithKline, Worldwide Epidemiology, Harlow, UK. Marianne.C.Cunnington@gsk.com
Tennis
Patricia
P
D000014:Abnormalities, Drug-Induced / Q000453:epidemiology*; D000927:Anticonvulsants / Q000009:adverse effects*; D005060:Europe / Q000453:epidemiology; D005260:Female; D006801:Humans; D015994:Incidence; D007231:Infant, Newborn; D000077213:Lamotrigine; D011247:Pregnancy; D011261:Pregnancy Trimester, First / Q000187:drug effects; D011297:Prenatal Exposure Delayed Effects / Q000453:epidemiology*; D012042:Registries / Q000706:statistics & numerical data; D018570:Risk Assessment; D018401:Sample Size; D014227:Triazines / Q000009:adverse effects*; D014481:United States / Q000453:epidemiology
D000927:Anticonvulsants; D014227:Triazines; D000077213:Lamotrigine