Related Experiment Video
Updated: Jan 10, 2026
Assessment and Evaluation of the High Risk Neonate: The NICU Network Neurobehavioral Scale
Published on: August 25, 2014
Late Pregnancy Antiseizure Medication Exposure and Offspring Neurodevelopmental Risk: A Multi-Child Cohort Study
Odile Sheehy1, Vanina Tchuente1, Sherif Eltonsy2
1CHU Sainte-Justine, Research Center, Montreal, Canada.
Insights
Prenatal exposure to antiseizure medications (ASMs) is linked to a higher risk of neurodevelopmental disorders (NDDs) in children. This association highlights the need for careful consideration of ASM use during pregnancy.
Area of Science:
- Neuroscience
- Developmental Pediatrics
- Pharmacology
Background:
- Antiseizure medication (ASM) use during pregnancy has risen, yet its impact on offspring neurodevelopment remains debated.
- Existing evidence on prenatal ASM exposure and neurodevelopmental disorders (NDDs) is inconsistent.
- This study addresses the need for clearer data on the association between prenatal ASM exposure and NDDs.
Purpose of the Study:
- To evaluate the association between prenatal exposure to antiseizure medications (ASMs) and the risk of neurodevelopmental disorders (NDDs) in children.
- To analyze data from large, population-based mother-child cohorts in Canada and the United States.
- To provide evidence for informed decision-making regarding ASM use in pregnant individuals.
Main Methods:
- Analysis of 5 population-based cohorts (Canadian Mother-Child Cohort [CAMCCO] and AM-PREGNANT).
- ASM exposure defined by maternal prescription fills within 60 days before birth.
- NDDs identified using validated algorithms based on ICD-9/10 codes; Cox proportional hazards models and meta-analysis were employed.
Main Results:
- Prenatal ASM exposure in 0.47% of 2,910,206 children was associated with a 29% increased risk of NDDs (pooled-adjusted hazard ratio [p-aHR]: 1.29).
- Specific ASMs showed varied risks: carbamazepine (p-aHR: 1.50), clonazepam (p-aHR: 1.22), topiramate (p-aHR: 1.56), and valproic acid (p-aHR: 1.38).
- Polytherapy showed a trend towards higher risk than monotherapy, but this was not statistically significant.
Conclusions:
- Prenatal exposure to certain ASMs is consistently linked to elevated risks of NDDs in offspring.
- Findings underscore the importance of individualized risk-benefit assessments for ASM use during pregnancy.
- Careful decision-making is crucial to mitigate potential neurodevelopmental risks in children exposed to ASMs prenatally.
Objective:
Antiseizure medication (ASM) use during pregnancy has increased over the past decade. However, evidence linking prenatal ASM exposure to neurodevelopmental disorders (NDDs) in offspring remains inconsistent. This study evaluated whether prenatal ASM exposure increases the risk of NDDs in children.
Methods:
We analyzed data from 5 population-based cohorts of live-born children in Canada (Alberta, Manitoba, Ontario, Quebec; the Canadian Mother-Child Cohort [CAMCCO] cohorts) and the United States (AM-PREGNANT cohort). ASM exposure was defined as maternal prescription fills overlapping the 60 days before birth. NDDs were identified using validated algorithm based on the International Classification of Disease-9/10 codes from inpatient and outpatient records. Within each cohort, Cox proportional hazards models were applied, with adjustment performed separately using (1) covariates and (2) propensity scores. Pooled estimates were obtained using random-effects meta-analysis.
Results:
Of 2,910,206 children, 0.47% were exposed to ASMs in the 60 days before birth. Prenatal ASM exposure was associated with a 29% increased risk of NDDs (pooled-adjusted hazard ratio [p-aHR], 1.29; 95% CI: 1.22-1.37; 1,805 exposed cases). In the Canadian cohorts, risks of combined NDDs varied by medication: carbamazepine (p-aHR: 1.50; 95% CI: 1.20-1.87; 262 exposed cases), clonazepam (p-aHR 1.22; 95% CI: 1.12-1.33; 585 exposed cases), topiramate (p-aHR 1.56; 95% CI: 1.04-2.34; 69 exposed cases), and valproic acid (p-aHR 1.38; 95% CI: 1.16-1.65; 134 exposed cases). Although point estimates were higher for polytherapy than monotherapy, the difference was not statistically significant.
Interpretation:
Prenatal exposure to certain ASMs was consistently associated with increased risks of NDDs in offspring. These findings support careful, individualized decision-making regarding prenatal ASM use to minimize neurodevelopmental risks. ANN NEUROL 2026;99:761-776.
Related Concept Videos
01:07Teratogenicity
01:24Epilepsy and Seizures: Overview
Various factors can trigger epilepsy, including genetic factors, brain damage, metabolic causes, and unknown etiology. Diagnosis of epilepsy involves electroencephalography (EEG), which...
01:20Antiepileptic Drugs: Modulators of Neurotransmitter Release Mediated by SV2A Protein
SV2A is a transmembrane glycoprotein located predominantly in the brain, modulating the release of neurotransmitters for neuronal communication. Both levetiracetam and brivaracetam exhibit a high affinity for...
01:14Antiepileptic Drugs: Glutamate Antagonists
01:18Antiepileptic Drugs: GABAergic Pathway Potentiators
The key GABA pathway potentiators used in epilepsy management are as follows.
Benzodiazepines are a well-known class of drugs used for...
01:29Drug Dosing: Infants and Children