Abstracts

Rationale: Pregnant women with epilepsy on antiepileptic drugs (AEDs) may experience a reduction in serum AED levels. This has the potential to worsen seizure control. We wanted to see what additional benefit may be conferred by therapeutic drug monitoring in pregnancy and conducted a clinical trial comparing early 21st century practice in the United Kingdom, in which decisions were made without knowing the serum AED level, to a strategy of therapeutic drug monitoring and allowing the participant and epilepsy professional to know the serum AED level and so influence clinical decision making.  Methods: The trial design meant that all those participants who did not have a significant fall in AED serum levels, determined as 25% or less, were blinded to the serum level and half of those who had significant serum AED fall were blinded, while in the other randomised half the treating professionals and participants knew of the fall. Seizures data was collected prospectively by seizure diaries, along with a battery of maternal and foetal outcomes until 6 weeks post-delivery.  Results: The results of the clinical trial have been presented elsewhere. Fifty obstetric and epilepsy clinics in secondary and tertiary care units in the UK were involved and some 650 women were recruited. The great majority of participants were taking either lamotrigine or levetiracetam. In comparison with the group with stable serum AED levels (odds ratio 0.93, 95% CI 0.56 to 1.5),there were no significant increases in seizures when there was a significant fall in AED levels (odds ratio 0.93, 95% CI 0.56 to 1.5), this was the same whether the epilepsy professional and participant knew of the fall or was randomised to the blinded cohort . Maternal and neonatal outcomes were similar in both groups, except for higher cord blood levels of lamotrigine (MD 0.55 mg/l, 95% CI 0.11 to 1 mg/l) or levetiracetam (MD 7.8 mg/l, 95% CI 0.86 to 14.8 mg/l) when the epilepsy professional and participant knew the serum AED level compared to when they did not.  Conclusions: These results challange current practice. The physiological AED falls seen in pregnancy of lamotrigine and levetiracetam were not seen to cause worse seizure outcomes when compared to stable levels. This data was collected in a blinded systematic manner and for lamotrigine contain many more observed participants than has been previously published. Knowing that there has been a fall in serum AED levels resulted in a management strategy that led to an increase in exposure of AED to the unborn child, without measurable benefit to mother or child of improved seizure outcomes.  Funding: NIHR grant UK.