Dr Helen Dolk of Ulster University in Ireland and her team looked at the data from more than 10 million births over 16 years. Their sample included 226,806 babies with birth defects.
Previously the drug lamotrigine, which is used to control seizures, had been feared to increase the risk of a baby developing a cleft lip, cleft palate or clubfoot.
The researchers found mothers who took lamotrigine in the first trimester of pregnancy were "not significantly more likely" to have a baby born with cleft lip, cleft palate or clubfoot, than mothers who had not taken the drug.
"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," Dr Dolk wrote in the medical journal 'Neurology'.
"An initial study of this drug showed an increased risk for cleft lip or cleft palate, but this study does not."
In the general population, one in every 700 babies is born with cleft lip or cleft palate, and nearly one in every 1,000 is born with clubfoot.
However, in the sample involved in the new study 147 babies, who were exposed to lamotrigine within the first trimester of pregnancy, were born with birth defects that were not genetic.
The researchers did not have specific information on the dose of lamotrigine given to pregnant women in the study and they have called for more research to be carried out to see if high doses of the drugs have any effect on babies.
"The study shows that the risk of having a baby with a malformation may not be significantly higher for women who are taking lamotrigine," he told The Huffington Post UK.
"We now need further studies to assess the association between risk and dosage of the drug.
"It is true that women with epilepsy have a slightly higher chance of having a baby with a birth defect than those who do not have the condition, but the risk is small and must be put into context."
Professor Sander explained there is a risk some epilepsy drugs could affect the development of the baby in the first 12 weeks when their main organs and skeleton are forming.
"Lamotrigine is one of the anti-epileptic drugs thought to have the lowest recorded risk, depending on dosage," he added.
"Whatever medication a woman is taking during pregnancy, it is important that she discusses this with her epilepsy specialist."
The NHS advises pregnant women taking anti-epileptic drugs to continue taking their medication and discuss any changes with their neurologist or GP.