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.
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.
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 Rs. 11.93 (95% CI: Rs. 16.72 to Rs. 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.
(European Medical Journal)