Large study captures risk of poor foetal growth after prenatal antiseizure meds exposure

Prenatal exposure to antiseizure medications is associated with increased risk of poor foetal growth, according to a large prospective study.

The study included 15,893 singleton livebirths of women with epilepsy on antiseizure medication and enrolled into the International Registry of Antiepileptic Drugs and Pregnancy (EURAP), among whom 12,911 were exposed prenatally to monotherapy and 2,982 to polytherapy. Follow-up data were collected after each trimester and at delivery.

Foetal growth indicators included birthweight centile (primary outcome), small for gestational age (SGA; birthweight <10th centile for gestational age), severe SGA (birthweight <3rd centile), and low birthweight (<2,500 g).

Compared with offspring prenatally exposed to monotherapy, those prenatally exposed to polytherapy had a lower birthweight centile (adjusted unstandardised model coefficient [b], –2.74) and around 50-percent greater odds of SGA (adjusted odds ratio [OR], 1.48, 95 percent confidence interval [CI], 1.29–1.70), severe SGA (OR, 1.49, 95 percent CI, 1.22 to 1.83), and low birthweight (OR, 1.50, 95 percent CI, 1.15–1.95). Birthweight centile decreased as the number of concomitant antiseizure medications increased (four antiseizure medications vs monotherapy: adjusted b, –14.18).

Among monotherapies, birthweight centile was lower with topiramate (adjusted b, –11.93), phenobarbital (adjusted b, –8.08), oxcarbazepine (adjusted b, –5.10), carbamazepine (adjusted b, –3.15), valproic acid (adjusted b, –2.54), and levetiracetam (adjusted b, –2.51) as compared with lamotrigine. Furthermore, birthweight centile was lower with prenatal exposure to carbamazepine and levetiracetam in combination than with lamotrigine monotherapy (adjusted b, –6.27.

The findings may inform preconception counselling and management, including risk prediction and individualized treatment selection.