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Background: Evidence for the comparative teratogenic risk of antiepileptic drugs is insufficient, particularly in relation to the dosage used. Therefore, we aimed to compare the occurrence of major congenital malformations following prenatal exposure to the eight most commonly used antiepileptic drugs in monotherapy. Methods: We did a longitudinal, prospective cohort study based on the EURAP international registry. We included data from pregnancies in women who were exposed to antiepileptic drug monotherapy at conception, prospectively identified from 42 countries contributing to EURAP. Follow-up data were obtained after each trimester, at birth, and 1 year after birth. The primary objective was to compare the risk of major congenital malformations assessed at 1 year after birth in offspring exposed prenatally to one of eight commonly used antiepileptic drugs (carbamazepine, lamotrigine, levetiracetam, oxcarbazepine, phenobarbital, phenytoin, topiramate, and valproate) and, whenever a dose dependency was identified, to compare the risks at different dose ranges. Logistic regression was used to make direct comparisons between treatments after adjustment for potential confounders and prognostic factors. Findings: Between June 20, 1999, and May 20, 2016, 7555 prospective pregnancies met the eligibility criteria. Of those eligible, 7355 pregnancies were exposed to one of the eight antiepileptic drugs for which the prevalence of major congenital malformations was 142 (10·3%) of 1381 pregnancies for valproate, 19 (6·5%) of 294 for phenobarbital, eight (6·4%) of 125 for phenytoin, 107 (5·5%) of 1957 for carbamazepine, six (3·9%) of 152 for topiramate, ten (3·0%) of 333 for oxcarbazepine, 74 (2·9%) of 2514 for lamotrigine, and 17 (2·8%) of 599 for levetiracetam. The prevalence of major congenital malformations increased with the dose at time of conception for carbamazepine (p=0·0140), lamotrigine (p=0·0145), phenobarbital (p=0·0390), and valproate (p

The aim of this study was to investigate the relationships between oxcarbazepine (OXC) dosage, metabolite mono-hydroxy-derivative (MHD) serum concentrations, number of concomitant antiepileptic drugs, age and incidence of adverse events (AEs) in epileptic patients. A retrospective analysis was conducted of 414 consecutive epileptic patients on OXC alone or added-on to previous therapy. The sample was collected from the period 2001 to 2006. Statistical analysis was performed in two groups: with and without AEs. Eighty-seven patients (21%) experienced at least one AE. The most frequent was hyponatremia, reported in 9.2%. OXC was discontinued because of AEs in 27 cases. There were no important differences between patients with and without AEs, except for age (p=0.04). The categorization of patients into three different age ranges,20, 20-59 and (3)60 years, disclosed that the risk of AEs is notably lower in young (20 years) and adult (20-59 years) patients (OR 0.46 and 0.51, respectively). In particular, the patients who experienced hyponatremia were significantly older than those who did not (p=0.0045). The other variables showed no major changes according to age. The incidence of major AEs during OXC treatment, leading to withdrawal, was found to be low and influenced by age, but not by OXC dosage, MHD concentrations or number of concomitant antiepileptic drugs.