Prenatal Exposure to Antiseizure Medications and Congenital Malformation Risk in Offspring:A Population-Based Study
Author(s)
Payam Peymani, Pharm.D, PhD1, Alekhya Lavu, PharmD, PhD1, Laila Aboulatta, PharmD1, Roxana Dragan, MSc2, Sherif Eltonsy, PhD1;
1College of Pharmacy, Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, MB, Canada, 2Manitoba Centre for Health Policy, Winnipeg, MB, Canada
1College of Pharmacy, Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, MB, Canada, 2Manitoba Centre for Health Policy, Winnipeg, MB, Canada
Presentation Documents
OBJECTIVES: Antiseizure medications (ASMs) are often prescribed during pregnancy, raising concerns about their teratogenic effects. This study aims to evaluate the association between prenatal ASM exposure and congenital malformations, considering epilepsy diagnosis, timing of exposure (trimester), specific ASMs, and the number of medications used.
METHODS: A population-based cohort study was conducted using data from [Manitoba Research Data Repository (1998-2019), including 297,734 pregnancies. Pregnancies were classified by epilepsy diagnosis and ASM exposure. Generalized Estimating Equations (GEE) models adjusted for maternal age and socioeconomic status were applied to assess risks for major congenital malformations (MCMs) and organ-specific defects. The effects of ASM exposure timing (trimester) and the number of ASMs were also analyzed.
RESULTS: In a study of 297,734 pregnancies, 1.4% involved antiseizure medication (ASM) exposure. 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), particularly for circulatory system and cardiac defects. First-trimester exposure showed higher prevalence of these defects. Valproate had the highest MCM risk (9.9%), while lamotrigine (3%) and levetiracetam (2.5%) had lower risks. Circulatory system defects were most prevalent among exposed pregnancies (5.5%). Gabapentin was associated with increased pyloric stenosis risk. MCM prevalence decreased from 6.1% to 3.7% between 1998 and recent years due to shifts towards safer ASMs.
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.
METHODS: A population-based cohort study was conducted using data from [Manitoba Research Data Repository (1998-2019), including 297,734 pregnancies. Pregnancies were classified by epilepsy diagnosis and ASM exposure. Generalized Estimating Equations (GEE) models adjusted for maternal age and socioeconomic status were applied to assess risks for major congenital malformations (MCMs) and organ-specific defects. The effects of ASM exposure timing (trimester) and the number of ASMs were also analyzed.
RESULTS: In a study of 297,734 pregnancies, 1.4% involved antiseizure medication (ASM) exposure. 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), particularly for circulatory system and cardiac defects. First-trimester exposure showed higher prevalence of these defects. Valproate had the highest MCM risk (9.9%), while lamotrigine (3%) and levetiracetam (2.5%) had lower risks. Circulatory system defects were most prevalent among exposed pregnancies (5.5%). Gabapentin was associated with increased pyloric stenosis risk. MCM prevalence decreased from 6.1% to 3.7% between 1998 and recent years due to shifts towards safer ASMs.
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.
Conference/Value in Health Info
2025-05, ISPOR 2025, Montréal, Quebec, CA
Value in Health, Volume 28, Issue S1
Code
CO117
Topic
Clinical Outcomes
Topic Subcategory
Relating Intermediate to Long-term Outcomes
Disease
SDC: Neurological Disorders, SDC: Pediatrics, SDC: Reproductive & Sexual Health, STA: Multiple/Other Specialized Treatments