P r e g n a n c y , E p i l e p s y a n d A n t i e p i l e p t i c d r u g s : N e e d F o r T e r a t o v i g i l a n c e Dwajani S, Errol Fernandez, Chanda Kulkarni, GRK Sarma Clinical Pharmacology & Department of Neurology, St .Johns Medical College and Hospital, Bangalore , INDIA. I N T R O D U C T I O N R E S U L T S Every drug has a potential to induce adverse effects, a few may have teratogenic effect, with 2.00% infants having major birth defects. The long term effects of use of newer drugs as a part of post marketing surveillance, called as ‘Teratovigilance’ is therefore gaining attention. The present study was therefore carried out to examine influence of AEDs on pregnancy and neonatal outcomes among women with epilepsy [WWE]. Disposition data of WWE Pattern of AED Monotherapy used in WWE No. of WWE with Seizure control at different trimesters Total Patients Enrolled N = 143 Type of AED No. of WWE Total % Older Drugs : Carbamazepine Phenobarbitone Phenytoin Sodium valproate Oxcarbamazepine 34 [ 40.47%] 16 [ 19.04%] [ 11.90%] 07 [ 8.33%] 05 [ 5.96% ] 85.70% Newer Drugs: Zonisamide Levetiracetam Topiramate Lamotrigine Clobazam 04 [ 4.39%] 03 [ 3.29%] 02 [ 2.19%] 01 [ 1.09%] 14.28% Total 91 [100%] 100% 114 Completed 29 Lost for follow up Total number of patients N = 114 To determine the outcome of pregnancy in women with epilepsy on antiepileptic drugs To identify the pattern of malformations if any associated with AEDs individually or in combination O B J E C T I V E S No Seizures during entire pregnancy n = 85 (74.56%) Seizure 1st, 2nd and 3rd Trimesters n =29 ( 22.80% ) Ethical clearance was obtained from Institutional Ethical Review Board Study design - Cross sectional, prospective/retrospective, observational study Study site – Division of clinical Pharmacology &Dept of Neurology OPD (St John’s Medical College and Hospital) Inclusion criteria - - Female patients > 18 years of age - Women with epilepsy receiving AEDs - Women with epilepsy and confirmed pregnancy - Women who have consented to participate Source-Collected data in specially designed CRF modified from European Registry for Epilepsy and Pregnancy [EURAP]. Following details were recorded – Demographic data – Height, Weight, maternal age, economic status, level of education and employment etc., Pregnancy data–All pregnancies irrespective of multiple pregnancies, gravida, parity, LMP, EDD, consanguinity, type of deliveries, Maternal risk factors, progression of delivery, pregnancy and fetal outcome was noted Disease data regarding epilepsy – type, frequency, duration, family history and co-existing medical conditions, etc. AED treatment data – Generic name, dose, frequency, duration, administration schedule, drug treatment for other medical conditions, Complimentary Alternative Medications on AEDs prior to, at the time of conception and/or during pregnancy. Investigational data – AED blood level monitoring, fetal USG, [MRI], Alfa Feto Protein [AFP] etc when available. Follow up visits – WWE were followed up every trimester to collect data prospectively or retrospectively depending on stage at which woman enrolled/reported and to record the progress of gestation during entire pregnancy. Fetal/neonatal outcome – The health of the new born after delivery was reviewed through personal interview pregnancy charts, birth reports, medical records and discharge notes. Statistical analysis -Data was analyzed using descriptive statistical analysis M E T H O D S NOTE: All Pregnant women with epilepsy received FOLIC ACID throughout their pregnancy AED Exposure during pregnancy in WWE Mode of Delivery in WWE Pregnancy/Neonatal outcomes in WWE (n=8) Pregnancy/ Neonatal outcomes AED use Total daily dose Neonatal Seizure [n=2] Lamotrigine [1] Phenytoin [1] 25-50 300 Abortion [ n=3] Carbamazepine [2] Phenytoin[1] 400-600 Perinatal Death [PD] [n=3] Phenobarbitone + Clobazam[1] Phenobarbitone[1] Sodium valproate[1] 60+50 60 500 Total Number of patients = 114 AED Mono therapy n = 91 ( 79.82 % ) AED Dual therapy n = 18 ( 15.78 % ) AED Poly therapy n = 5 ( 4.38 % ) CBZ n= 34 CBZ + PB n= 8 CBZ + PB + CLB n= 3 Abnormal Neonatal Outcomes in pregnant WWE (n = 112) Neonatal outcome in (n=7) Congenital anomalies / malformations AED use Total daily dose Hydronephrosis secondary to PUJ obstruction [1] Carbamazepine 400 - 600 Mild pelvicaliectasis and PUJ obstruction [1] Polydactyly [1] Phenytoin 200 - 300 Hypo plastic ear, facial palsy [1] Phenobarbitone + Clobazam 45 + 400 Club feet [1] Lamotrigine 1000 Intrauterine death (IUD) with multiple anomalies [1] Lamotrigine + Clonazepam 100-300 + 0.25-0.5 Hip dysplasia [1] 200 Total number Births No. neonates with low birth weight Total neonates with low Apgar score Total neonates with congenital malformations 112 births with a win delivery n = 33 ( 28.94%) n= 1 ( 0.82%) n = 7 (6.41% ) Remaining all other neonates were normal C O N C L U S I O N S Despite adequate monitoring practices, supplementation of folic acid and use of AEDs in recommended doses, there were adverse neonatal outcomes. Few WWE did not have control of seizures during pregnancy. Hence careful evaluation through ‘Teratovigilance’ programs may assist not only in counseling but also in achieving improved pregnancy and neonatal outcomes Acknowledgment : Sanofi Aventis for financial assistance and Dr. Sheela CN, Prof, OBG, SJMCH. Indian Epilepsy Association & Indian Epilepsy Society – EPILEPSY CONFERENCE – 2013, Hyderabad, India