(A-286) Prenatal Exposure to Antiseizure Medications and Congenital Malformation Risk in Offspring

Background: Antiseizure medications (ASMs) are frequently prescribed during pregnancy, but their potential teratogenic effects remain a significant concern.

Objectives: To evaluate the association between prenatal ASM exposure and the risk of congenital malformations, considering epilepsy diagnosis, timing of exposure (trimester), specific ASMs, and the number of ASMs used.

Methods: A population-based cohort study was conducted using data from [Manitoba Research Data Repository (1998-2019)]. Pregnancies were classified by epilepsy diagnosis and ASM exposure. Generalized Estimating Equations models adjusted for maternal age and socioeconomic status were applied to assess risks for major congenital malformations (MCMs) and organ-specific defects.

Results: Among 297,734 pregnancies, 1.4% involved antiseizure medication (ASM) exposure during pregnancy. Major congenital malformation (MCM) rates were higher in ASM-exposed pregnancies (5.8% with maternal epilepsy, 4.4% without) compared to unexposed pregnancies (3.6%). ASM exposure increased overall MCM risk (OR = 1.21), with significant associations for circulatory system defects (OR = 1.48), cardiac malformations (OR = 1.49), and ventricular/atrial septal defects (OR = 1.84). First-trimester ASM exposure was associated with higher prevalence of circulatory system defects (5.5%), musculoskeletal defects (4.3%), and cardiac malformations (4.9%). Second or third trimester exposure showed slightly higher rates of circulatory system defects (6.4%) and cardiac malformations (5.8%). Valproate showed the highest MCM risk (9.9%), particularly for cardiac malformations (7.9%) and circulatory system defects (6.4%). Phenytoin (7.1%), phenobarbital (6.2%), carbamazepine (5%), topiramate (4.4%), gabapentin (4.8%), and clonazepam (4.6%) also showed elevated risks. Lamotrigine (3%) and levetiracetam (2.5%) had lower risks compared to other ASMs. Circulatory system defects were the most prevalent malformation type among exposed pregnancies (5.5%), followed by musculoskeletal defects (4.4%) and cardiac malformations (4.9%). Gabapentin was significantly associated with pyloric stenosis risk (OR = 3.17).

Conclusions: Prenatal exposure to ASMs is associated with an increased risk of congenital malformations in offspring, particularly affecting the circulatory system and cardiac structures, with risks varying by ASM type, timing of exposure, dosage, and combination therapy use. Valproic acid and phenytoin showed the highest risks, while lamotrigine and levetiracetam had lower teratogenic profiles. These findings emphasize the importance of careful selection of ASMs during pregnancy to minimize fetal risks while managing maternal epilepsy effectively.