Malformation risk of new anti-epileptic drugs in women with epilepsy; observational data from the Kerala registry of epilepsy and pregnancy (KREP).

OBJECTIVES: We aim to report the major congenital malformation (MCM) rates for new and old anti-epileptic drugs (AED) exposures during the first trimester of pregnancy in women with epilepsy (WWE). METHODS: We extracted relevant data on drug exposure and malformation rate from the records of a prospective observational registry (Kerala Registry of Epilepsy and Pregnancy) for all completed pregnancies between 1998 and 2019. A comprehensive and uniform criterion with detailed guideline was used for assessment of malformations. We employed generalised linear model to generate adjusted incidence rate ratios (aIRR) of MCM in AED exposed group as compared to AED unexposed group, after adjustment for age and educational status of mothers' and epilepsy classification. RESULTS: The unadjusted MCM rate was 6.2% for all the infants included in the study (148/2328); 4.7% for the unexposed group (16/340), and 6.6% for the exposed group (132/1988). The aIRR of MCM as compared to unexposed group was similar for all monotherapies; lamotrigine (0.50; 95% CI 0.07-3.68), levetiracetam (1.16; 0.43-3.11), oxcarbazepine (1.61; 0.62-4.21) valproate (1.71, 0.93-3.19), phenytoin (1.21, 0.51-2.90), carbamazepine (0.99, 0.54-1.82), and phenobarbitone (1.20, 0.52-2.74). However, the point estimates suggest least risk with lamotrigine and highest risk with valproate. Polytherapy with high-dose valproate carried significantly higher risk of MCM as compared to the unexposed group (aIRR=4.12; 2.18-7.79, p<0.001). The aIRR of GTCS during pregnancy was 1.63 (95% CI 1.12-2.37, p = 0.011) for monotherapy with new AEDs (lamotrigine, levetiracetam or oxcarbazepine) as compared to old AEDs (phenobarbitone, phenytoin, carbamazepine, or valproate). CONCLUSION: The MCM risk was significantly higher for polytherapy with high dose valproate. It did not differ substantially between different AED monotherapies although point estimate was lowest with lamotrigine. Pregnant women on new AEDs report higher likelihood of GTCS than women on old AEDs during pregnancy.

Valproate usage in pregnancy: An audit from the Kerala Registry of Epilepsy and Pregnancy.

OBJECTIVE: This is an audit of the use of valproate (VPA) during pregnancy in women with epilepsy (WWE). METHODS: We identified all pregnancies exposed to VPA in the Kerala Registry of Epilepsy and Pregnancy between January 2010 and December 2019. Subjects' past usage of antiepileptic drugs (AEDs), seizure count before and during pregnancy, fetal outcome, and major congenital malformations (MCMs) were abstracted from the registry records. The presumed reason for usage of VPA was deducted from the clinical records. RESULTS: There were 221 pregnancies (17.75%) exposed to VPA (monotherapy, n = 149) during the audit period. The MCM rate for the completed pregnancies exposed to VPA was higher (n = 20, 10.36%) than that of VPA-unexposed pregnancies (n = 39, 4.96%). The relative risk for MCM with VPA exposure was 2.1 (95% confidence interval = 1.24-3.48, number needed to treat with VPA to result in MCM = 19). Reasons for using VPA during pregnancy (some women had more than one reason) were (1) VPA was the first AED prescribed and was effective (68, 29.06%), (2) other AEDs were ineffective (128, 54.70%), and (3) other AEDs were discontinued due to adverse effects (17, 7.28%). Other reasons (21, 8.97%) were (1) VPA was selected after the epilepsy classification was revised (3, 1.28%), (2) other AEDs were expensive (2, .85%), and (3) patient switched to VPA from other AEDs for unspecified reason (16, 6.83%). VPA was discontinued during pregnancy for 6 (2.71%) persons. Less than 10% of women were tried on lamotrigine or levetiracetam before switching to VPA. SIGNIFICANCE: Nine MCMs per thousand pregnancies can be avoided if VPA is not used in WWE. Safe and effective AEDs as alternatives to VPA are the need of the hour. Professional bodies and regulatory authorities need to implement updated guidelines on AED usage in girls and women.