Study Confirms Valproic Acid and Topiramate as Teratogenic

Spina Bifida, Cleft Lip Among Defects Caused by Antiepilectics

A study just published in Neurology reports that a number of major congenital malformations, including spina bifida and cleft lip, are associated with exposure to valproic acid and topiramate.

Researchers from the French National Health Insurance (CNAM) conducted a nationwide cohort study of all pregnancies ≥ 20 weeks and ending between January 2011 and March 2015 to examine the correlation between exposure to monotherapy with 10 different antiepileptic drugs during the first two months of pregnancy and the risk of 23 major congenital malformations (MCMs).

Among 1,886,825 pregnancies, 2,997 were exposed to lamotrigine; 1,671 to pregabalin; 980 to clonazepam; 913 to valproic acid; 579 to levetiracetam; 517 to topiramate; 512 to carbamazepine; 365 to gabapentin; 139 to oxcarbazepine; and 80 to phenobarbital.

Exposure to valproic acid was associated with eight specific types of MCMs, including spina bifida (odds ratio [OR], 19.4; 95% CI, 8.6–43.5), and cleft lip was associated with exposure to topiramate (OR, 6.8; 95% CI, 1.4–20.0). Women were considered to have been exposed if they had received an antiepilectic drug between one month before and two months after the beginning of pregnancy. 

Three other signals were also identified, but the researchers have urged interpreting this data with caution because of the small numbers of cases involved and possible confounding.

No significant associations were found for lamotrigine, levetiracetam, carbamazepine, oxcarbazepine, or gabapentin.

Because of the widespread prescription of antiepilectic drugs, as well as the number of unplanned pregnancies, the researchers wanted to examine the drugs’ safety with a large study.

Source: MedicalXpress, June 13, 2019