Zonisamide serum concentrations during pregnancy.

PURPOSE: To investigate the change in zonisamide (ZNS) serum concentration and its consequences in pregnant women with epilepsy. METHODS: Six hospitals in Norway and Denmark screened their records for women who had been using ZNS during pregnancy. Absolute serum concentrations as well as concentration/dose (CD)-ratios were compared to non-pregnant values. Descriptive data on seizure control and obstetrical data were also collected. RESULTS: 144 serum concentrations from 23 pregnancies in 15 individual women with epilepsy were included (six on monotherapy). The mean ZNS serum concentration fell to a minimum of 58.6 ±â€¯15.1%, while the C/D-ratio fell to as low as 55.1 ±â€¯15.3% of the non-pregnant-value. The lowest values were seen in gestational months six to nine, and the individual nadir varied considerably (range: 24-81% of the non-pregnant value). Four out of ten previously seizure-free patients experienced breakthrough seizures. Gestational age, weight at birth and head circumference of the newborns were within the reference ranges. CONCLUSIONS: ZNS serum concentrations may fall by over 40% during pregnancy, with large interindividual variability. In some patients, this may lead to worsened seizure control. These findings are in line with reports on other AEDs and suggest that regular therapeutic drug monitoring and dose adjustments may be useful.

[Antiepileptic drugs and congenital malformations]. / Antiepileptika og medfødte misdannelser.

BACKGROUND: In pregnant women with epilepsy the use of antiepileptic drugs may increase the risk of harming the foetus. For the treating neurologist it may be challenging to find a balance between optimal seizure control and the lowest possible drug dosage. The aim of this study was to assess the prevalence and type of congenital malformations in children exposed to antiepileptic drugs during pregnancy. MATERIAL AND METHOD: In Norway we have prospectively followed 813 pregnancies in women with epilepsy as part of an international cohort study. The women had three check-ups during the pregnancy, and the children were followed up twice during their first year of life. RESULTS: We found a total of 34 congenital malformations in the children, of which 12 were heart defects, yielding a malformation rate of 4.5%. Six of the malformations (18%) were detected prenatally, 20 (59%) were reported immediately after birth, and eight (24%) were discovered during the child's first year of life. INTERPRETATION: Our study shows that 95.5%.of the women included who used antiepileptic drugs during pregnancy gave birth to a healthy child. This Norwegian cohort is too small to evaluate the teratogenic risk associated with the individual drugs.