MONTEREY, CALIF. — Women who take the anticonvulsant lamotrigine during their first trimester of pregnancy have a 10-fold greater risk of having a baby with nonsyndromal cleft lip, cleft palate, or both, according to a peer-reviewed study.
Among 684 women enrolled in the North American Anti-Epileptic Drug (AED) Pregnancy Registry who reported taking lamotrigine monotherapy during their first trimester, there were 16 infants born with major malformations, Dr. Lewis B. Holmes said at the annual meeting of the Teratology Society. This translates to a rate of 2.3%, compared with a baseline rate of 1.6% in unexposed newborn infants (Neurology 2008;70:2152-8).
Although this difference in combined major malformation rates was not statistically significant, the investigators observed a significantly increased risk when they restricted the analysis to oral clefts.
Three of the infants had an isolated cleft palate, one had an isolated cleft lip, and one had bilateral cleft lip and palate, for an overall prevalence rate of 7.3/1,000 infants. In comparison, the rate was 0.7/1,000 for unexposed controls, yielding a significant relative risk of 10.4.
“That's a whopping increase,” said Dr. Holmes of Massachusetts General Hospital for Children, Boston. “You wonder if it's a sample size [effect], but it's certainly a point to be pursued in comparison to other databases.”
“A larger sample size is needed to see whether the rate of clefts is a 10-fold increase or as low as 4-fold, or somewhere in between,” Dr. Holmes said.
Dr. Holmes disclosed that he received a salary support from funds provided since 1997 by the six sponsors of the North American AED Registry: Abbott Laboratories, Eisai Co., GlaxoSmithKline Inc., Novartis, Ortho-McNeil Inc., and Pfizer Inc.