Comparing the Safety of Antiepilepsy Drugs in Pregnancy

Evidence is lacking about the comparative safety of AEDs during pregnancy. Because AEDs cross the placenta, can increase the risk of miscarriage and birth defects. What are the risk of birth defects and perinatal outcomes for infants exposed to various AEDs in utero?

To determine outcomes for infants exposed to AEDS in utero, Veroniki and colleagues[1] searched databases for studies that compared mono- or polytherapy AEDs to controls or other AEDs. They found 96 studies comprising 58,461 patients: 92 cohort studies, 3 case control studies, and one randomized clinical trial (RCT).

Gabapentin, lamotrigine, and levetiracetam were not associated with statistically significant increased risk of MCMs. And, compared with controls levetiracetam and lamotrigine were significantly less likely to be linked to cardiac malformations.

Gabapentin, lamotrigine, and levetiracetam were not associated with statistically significant increased risk of MCMs. And, compared with controls levetiracetam and lamotrigine were significantly less likely to be linked to cardiac malformations.

Although newer generation lamotrigine and levetiracetam were not significantly linked to major birth defects, the results do not imply that these AEDs are completely harmless. Clinicians should counsel women of childbearing age and pregnant women deciding whether to continue on AEDs about the risk of birth defects. Treatment options include switching from polytherapy to monotherapy with lower risk AEDs, and avoiding AEDs consistently linked to birth defects (eg, valproate). In making treatment decisions, the risk of birth defects should be balanced against harm associated with inadequate seizure control.

1. Veroniki AA, Cogo E, Rios P, et al. Comparative safety of anti-epileptic drugs during pregnancy: a systematic review and network meta-analysis of congenital malformations and prenatal outcomes. BMC Med. 2017;15:95.