Levetiracetam use during pregnancy poses no significant risks of birth defects, miscarriage

Expectant mothers who use the antiseizure medication levetiracetam as monotherapy do not appear to have increased overall risk of major birth defects or miscarriage, as reported in a study.

Data from 690 pregnancies with first trimester exposure to either levetiracetam (n=221) or lamotrigine (n=469) showed that major birth defects occurred in 5.8 percent of pregnancies in the levetiracetam monotherapy group and in 3.8 percent of those in the lamotrigine monotherapy group. Of note, birth weight of male neonates was significantly lower after exposure to levetiracetam monotherapy. Meanwhile, spontaneous abortion occurred in 13.6 and 16.8 pregnancies in the respective groups. [Epilepsia 2024;65:26-36]

Compared with lamotrigine, levetiracetam monotherapy was not associated with heightened risk of either major birth defects (adjusted odds ratio [aOR], 1.41; 95 percent confidence interval [CI], 0.58–3.44) or spontaneous abortion (aHR, 0.80; 95 percent CI, 0.34–1.86).

When compared with the comparison cohort consisting of 729 pregnancies without exposure to antiseizure medications, the overall levetiracetam cohort (pregnancies exposed to levetiracetam monotherapy, n=221; pregnancies exposed to levetiracetam plus lamotrigine, n=80) showed a similar rate of spontaneous abortion (21.9 percent vs 22.5 percent; aHR, 1.29; 95 percent CI, 0.81–2.07) but a higher rate of birth defects (5.6 percent vs 4.5 percent; aOR, 1.21; 95 percent CI, 0.61–2.38), especially cardiac defects (3.4 percent vs 1.7 percent; aOR, 2.55; 95 percent CI, 0.98–6.66).

“Approximately half of the cardiac defects occurred after concomitant exposure to lamotrigine,” the investigators noted.

Further analysis showed that dual therapy with levetiracetam plus lamotrigine was associated with a significantly increased risk of spontaneous abortion (aHR, 3.01; 95 percent CI, 1.43–6.33) and a nonsignificant effect estimate for major birth defects (aOR, 1.47; 95 percent CI, 0.48–4.47) compared with nonexposure to antiseizure medications.

“In general, polytherapy with antiseizure medication during pregnancy is avoided but might be required for seizure control,” with the increased risks following polytherapy being mainly related to teratogens like valproate or topiramate, as the investigators pointed out.

“The high overall risk of birth defects after dual therapy with levetiracetam and lamotrigine in our study was unexpected. But [the risk was] attenuated after adjustment for confounders and was not significantly increased compared to the comparison and lamotrigine monotherapy cohorts,” they added.

The present study, according to the investigators, validates the suitability of levetiracetam as an antiepileptic drug for pregnant women. However, further investigation is required to shed light on the lower birthweight in male neonates following maternal levetiracetam monotherapy as well as the increased risk of spontaneous abortion and birth defects when levetiracetam was combined with lamotrigine.