Anti-epileptic drug and folic acid usage during pregnancy, seizure and malformation outcomes: Changes over two decades in the Kerala Registry of Epilepsy and Pregnancy

Abstract

Background: This study was carried out to determine changes over time in use of folic acid, anti-epileptic drugs (AED), seizures during pregnancy and malformation rate over two decades in women with epilepsy enrolled in the Kerala registry of Epilepsy and Pregnancy (KREP).

Methods: All completed pregnancies with known outcome between 1998 and 2017 (n = 1962) were analyzed for the use of folic acid and AEDs in the first trimester, seizure count for the entire pregnancy and the presence of major congenital malformation (MCM). The results were presented for three epochs (1998-2004, 2005-2011 and 2012-2017).

Results: There was significant increase (p = .001) in the use of folic acid 5 mg/day or more in pre-pregnancy month (43.9 to 81 %) and first trimester (52.7 to 86.6 %). Occurrence of seizures during pregnancy had declined significantly (57.2 to 32.9 %, p = 0.001) over time. Those who were off AEDs during pregnancy declined from 17.4 to 8.5 % (p = .001). Newer AEDs - lamotrigine, levetiracetam, oxcarbazepine and topiramate) were increasingly preferred in the last seven years instead of older AEDs (phenobarbitone, phenytoin and clonazepam). There was no significant change in the use of carbamazepine or valproate. MCM rates did not show any significant change (7.5 to 7.3 %).

Conclusion: Seizure control and high dose folic acid usage during pregnancy had improved over two decades. Despite the changes in the AED usage over time the MCM rates had remained unchanged probably due to continued use of valproate, increased use of topiramate and clobazam that are associated with higher MCM rates and lack of reduction in polytherapy.

Keywords: AED; Safety; Teratogenicity; Trend; Women with epilepsy.