Objective: To assess the effects of in-utero exposure to antiepileptic drug monotherapy on children’s neurodevelopment.

Methods: This is a blinded cohort study with controls. Participants were children born to mothers registered with the UK Epilepsy and Pregnancy Register who were taking sodium valproate or carbamazepine or lamotrigine monotherapy throughout pregnancy. Controls, whose mothers were not taking medications in pregnancy, were recruited from the child health system. Exclusion criteria were children born before 35 weeks gestation, maternal comorbidity and/or polytherapy. Children were assessed using Bayley’s or Griffiths’ scales.

Results: A total of 186 children (99 male, 87 female), comprising 142 born to mothers taking antiepileptic drugs (58 sodium valproate, 49 carbamazepine, 35 lamotrigine) and 42 controls were assessed. 23/58 children exposed to sodium valproate demonstrated a delayed performance (five significant, 18 mild). 10/49 children exposed to carbamazepine (two significant and eight mild delay), one of 35 children exposed to lamotrigine (mild) and two of 42 control children (one mild, one significant) demonstrated delay. An ordinal regression model adjusting for confounding variables including gender, birth weight, age, socioeconomic status, maternal educational attainment and the occurrence of five or more generalised tonic–clonic seizures in pregnancy revealed that in-utero exposure to either sodium valproate or carbamazepine was an independent risk factor for impaired neurodevelopment (p<0.001). In-utero exposure to lamotrigine was not shown to have a statistically significant detrimental effect on children’s development (p = 0.053).

Conclusions: In-utero exposure to either sodium valproate or carbamazepine monotherapy risks significant neurodevelopmental impairment.