“An initial study of this drug showed an increased risk for cleft lip or cleft palate, but a number of other studies since have not, and our previous study showed an increased risk of clubfoot,” said study author Helen Dolk, of Ulster University, in Northern Ireland.
The research, funded by the drug’s maker, Glaxo Smith Kline, was published April 6 in the journal.
In addition to being prescribed to control epileptic seizures, lamotrigine is used to prevent mood swings in people with bipolar disorder, the study authors said.
Controlling epilepsy during pregnancy is important because seizures may harm the fetus, the researchers noted.
Dolk’s team analyzed data on more than 10 million births over 16 years, including almost 227,000 babies with birth defects. Among those babies were 147 whose mothers took lamotrigine during the first trimester of pregnancy and had nongenetic birth defects.
Babies born with cleft lip, cleft palate or clubfoot were not significantly more likely than those with other birth defects to have been born to mothers who took lamotrigine in the first trimester of pregnancy, the study found.
In the general populations, one in every 700 babies is born with cleft lip or cleft palate, and nearly one in every 1,000 is born with clubfoot.
“We cannot exclude a small risk, but we estimate the excess risk of cleft lip or cleft palate among babies exposed to the drug to be less than one in every 550 babies,” Dolk said.
“Since excess risks of cleft lip or palate have been reported for a variety of anti-epileptic drugs, we recommend that for all mothers with epilepsy, whatever their drug exposure, special attention be given to examining the baby for cleft palate,” she added.
Also, Dolk stressed that “we did not have specific information on lamotrigine dosage, so additional study is recommended, especially of high doses.”
One expert believes the findings should reassure women with epilepsy.
Dr. Sean Hwang said the study was based on a “large multinational database, and [is] a significant contribution” to the literature on this issue.
“As this study reaffirms, lamotrigine [used alone] currently appears to be the safest anti-epileptic drug in pregnancy,” said Hwang, an attending neurologist at Northwell Health’s Comprehensive Epilepsy Care Center in Great Neck, N.Y.
However, he stressed that “the study was not designed to re-evaluate the overall risk of congenital malformations occurring with lamotrigine use in pregnancy, which has been observed to be slightly higher than in the general population.
“As the authors indicated, it also was not designed to assess dose-related effects, which has been shown in some studies to be an important risk factor,” Hwang said.