Effect of dose on the frequency of major birth defects following fetal exposure to lamotrigine monotherapy in an international observational study.

Data from the International Lamotrigine Pregnancy Registry were analyzed to examine the effect of maximal first-trimester maternal dose of lamotrigine monotherapy on the risk of major birth defects (MBDs). Among 802 exposures, the frequency of MBDs was 2.7% (95% confidence interval [CI] 1.8-4.2%). The distribution of dose did not differ between infants with and those without MBDs (mean 248.3 milligrams per day [mg/day] and 278.9 mg/day, respectively, median 200 mg/day for both groups). A logistic regression analysis showed no difference in the risk of MBDs as a continuous function of dose (summary odds ratio [OR] per 100 mg increase =0.999, 95% CI 0.996-1.001). There was also no effect of dose, up to 400 mg/day, on the frequency of MBDs.