Antiseizure Medicines Linked to Foetal Growth Differences

ANTISEIZURE medication use during pregnancy was associated with differences in foetal growth, with risks varying by treatment regimen and individual medicine, according to a large prospective international cohort study. 

Polytherapy Associated with Greater Growth Risk 

The study analysed 15,893 offspring exposed to antiseizure medications during pregnancy, including 12,911 exposed to monotherapy and 2,982 exposed to polytherapy. The researchers examined birthweight centile as the primary outcome, alongside small for gestational age, severe small for gestational age and low birthweight. 

Compared with monotherapy, prenatal exposure to polytherapy was associated with a lower birthweight centile and approximately 50% higher odds of several measures of poor foetal growth. The adjusted odds ratio for small for gestational age was 1.48 (95% CI: 1.29–1.70), while the corresponding estimates were 1.49 (95% CI: 1.22–1.83) for severe small for gestational age and 1.50 (95% CI: 1.15–1.95) for low birthweight. 

The association also appeared to strengthen as the number of concomitant antiseizure medications increased. Among the small group exposed to four medicines, birthweight centile was substantially lower than among those receiving monotherapy. 

Differences Identified Between Individual Medicines 

The analysis also found variation between antiseizure medication monotherapies. Compared with lamotrigine, birthweight centile was lower among offspring exposed to topiramate, phenobarbital, oxcarbazepine, carbamazepine, valproic acid and levetiracetam. 

The largest difference was observed with topiramate, which was associated with an adjusted birthweight centile coefficient of −11.93 (95% CI: −16.72 to −7.15). Lower birthweight centiles were also associated with phenobarbital, oxcarbazepine, carbamazepine, valproic acid and levetiracetam. 

However, the findings were not uniform across combinations. Offspring exposed to carbamazepine and levetiracetam together had a lower birthweight centile than those exposed to lamotrigine monotherapy, while no difference was identified between lamotrigine alone and lamotrigine combined with either levetiracetam or valproic acid. 

Implications For Pregnancy Management 

The researchers said poor foetal growth should be considered alongside congenital malformations and neurodevelopmental effects when assessing the potential adverse outcomes associated with prenatal antiseizure medication exposure. 

The findings could have implications for preconception counselling and treatment selection, particularly when considering the number and combination of antiseizure medications required to control epilepsy during pregnancy. 

Importantly, the observational design means the findings identify associations rather than establishing that individual medicines directly caused poor foetal growth. The researchers concluded that risk prediction and treatment selection should account for differences between individual antiseizure medications and combinations, supporting a more individualised approach to managing epilepsy during pregnancy. 

Reference  

Perucca P et al.; EURAP Collaborators. Antiseizure medication use in pregnancy and the risk of poor fetal growth in the EURAP international registry: a prospective cohort study. Lancet Neurol. 2026;25(9):8 

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