This study investigates the risk of major congenital malformations (MCMs) in offspring of women with epilepsy (WWE) exposed to eight commonly used antiseizure medications (ASMs) during pregnancy. The study, conducted between 1999 and 2022, included 10,121 pregnancies where WWE were exposed to ASM monotherapy. The results showed that the lowest prevalence of MCMs was observed in offspring exposed to levetiracetam, oxcarbazepine, and lamotrigine, while higher risks were associated with phenytoin, valproate, carbamazepine, and phenobarbital, with dose-dependent increases in the latter three. The overall prevalence of MCMs decreased over time, from 6.1% in 1998-2004 to 3.7% in 2015-2022, which was linked to a decline in valproate and carbamazepine use and an increase in levetiracetam and lamotrigine use. The study highlights the importance of considering ASM type and dose when selecting treatment options for WWE during pregnancy. The findings have significant public health implications, emphasizing the need for continued monitoring of teratogenic outcomes to assess the safety of newer generation ASMs. The study also notes that while folate supplementation did not show a protective effect against MCMs, it may offer other benefits such as reduced risk of preterm birth and improved cognitive development in offspring. The results suggest that levetiracetam, lamotrigine, and oxcarbazepine are associated with lower risks of MCMs compared to valproate, particularly at lower doses. The study underscores the importance of understanding the comparative risks of different ASMs to guide safer treatment choices for WWE during pregnancy.This study investigates the risk of major congenital malformations (MCMs) in offspring of women with epilepsy (WWE) exposed to eight commonly used antiseizure medications (ASMs) during pregnancy. The study, conducted between 1999 and 2022, included 10,121 pregnancies where WWE were exposed to ASM monotherapy. The results showed that the lowest prevalence of MCMs was observed in offspring exposed to levetiracetam, oxcarbazepine, and lamotrigine, while higher risks were associated with phenytoin, valproate, carbamazepine, and phenobarbital, with dose-dependent increases in the latter three. The overall prevalence of MCMs decreased over time, from 6.1% in 1998-2004 to 3.7% in 2015-2022, which was linked to a decline in valproate and carbamazepine use and an increase in levetiracetam and lamotrigine use. The study highlights the importance of considering ASM type and dose when selecting treatment options for WWE during pregnancy. The findings have significant public health implications, emphasizing the need for continued monitoring of teratogenic outcomes to assess the safety of newer generation ASMs. The study also notes that while folate supplementation did not show a protective effect against MCMs, it may offer other benefits such as reduced risk of preterm birth and improved cognitive development in offspring. The results suggest that levetiracetam, lamotrigine, and oxcarbazepine are associated with lower risks of MCMs compared to valproate, particularly at lower doses. The study underscores the importance of understanding the comparative risks of different ASMs to guide safer treatment choices for WWE during pregnancy.