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TOPLINE:

Prenatal exposure to safer antiseizure medications (ASMs) increased and valproate use decreased, but the use of newer medications with uncertain risks surged.

METHODOLOGY:

• Researchers analysed 55,801 ASM-exposed pregnancies (from 2013 to 2021) out of 8,669,502 total pregnancies documented in the French National Mother-Child Register.
• ASMs were categorised into three safety tiers: those considered the safest (lamotrigine and levetiracetam), those with uncertain risk (pregabalin, gabapentin, clonazepam, oxcarbazepine, and newer ASMs), and those with acknowledged risk (valproic acid, valpromide, carbamazepine, topiramate, phenobarbital, phenytoin, and primidone).
• The maternal age was 15-49 years; socioeconomic status was assessed via health insurance, and diagnoses were confirmed using the International Statistical Classification of Diseases and Related Health Problems, 10th Revision codes.
• Maternal and pregnancy characteristics, along with ASM treatment characteristics, were analysed over the study period (2013-2021) and by subperiods (2013-2015, 2016-2018, and 2019-2021).
• The outcome was the temporal change in prenatal ASM exposure rates across safety categories, analysed on the basis of year, diagnosis, and social indicators.

TAKEAWAY:

• Between 2013 and 2021, prenatal exposures to valproic acid and valpromide declined by 84% and 89%, respectively, but terminations rose (+23% and +28%, respectively), and multiple valproate dispensations and sustained live birth exposures fell drastically (valproic acid: -86% and -91% and valpromide: -93% and -96%, respectively).
• The use of the safest ASMs (lamotrigine and levetiracetam) rose by +30%. The use of ASMs with uncertain risks rose by +33%, notably pregabalin (+49%), gabapentin (+27%), and newer ASMs (+140%).
• The use of carbamazepine and topiramate decreased to a lesser extent (-40% and -34%, respectively), with nearly 600 newborns exposed to each of these medications between 2019 and 2021; among women with a low level of resources, exposure to ASMs with uncertain or acknowledged risks was higher (18.5% and 17.9%, respectively) than exposure to the safest ASMs or unexposed (13.8% and 13.5%, respectively).
• Lamotrigine use linked to mood disorders rose by +51%, correlating with a +35% rise in termination rates. Terminations also rose with ASMs with acknowledged risks.

IN PRACTICE:

"Additional measures are needed to further reduce perinatal exposure to ASMs with acknowledged or uncertain risks, especially among the most socially deprived populations," the authors wrote.

SOURCE:

This study, led by Pouneh Shahriari, EPI-PHARE Scientific Interest Group in Epidemiology of Health Products (French National Agency for the Safety of Medicines and Health Products, French National Health Insurance), Saint-Denis, France, was published online on July 23, 2025, in Neurology.

LIMITATIONS:

This study was limited by the reliance on prescription claims to determine exposure to ASMs and the absence of data on clinical indications for treatment. However, prior research using this dataset supports its reliability for assessing prenatal exposure to ASMs.

DISCLOSURES:

This study did not report any targeted funding. The authors declared having no conflicts of interest.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.