Author	S. Man
Author	I. Nazareth
Author	I. Petersen
Abstract	Background Antiepileptic drugs are prescribed for chronic conditions such as epilepsy and bipolar disorder. Without adequate management, such conditions can have detrimental effects in pregnancy. However, first trimester use of some antiepileptic drugs is associated with a two-threefold increase in the risk of major congenital malformations. When women and their health care professionals consider treatment regimens, quantified relative risks can help decide which drug, if any, would be taken during pregnancy. Methods Three studies were performed using UK primary care data from The Health Improvement Network (THIN). Prescribing patterns of antiepileptic drugs in pregnancy were examined. A validation study for recording of major congenital malformations and perinatal death was performed. Lastly, a cohort study of pregnant women prescribed antiepileptic drugs prior to pregnancy was conducted to examine the risk of major congenital malformations or perinatal death in different first trimester antiepileptic drugs regimens. Results One in 200 women were prescribed antiepileptic drugs in pregnancy. Carbamazepine, sodium valproate and lamotrigine were the most commonly used antiepileptic drugs in pregnancy between 1994 and 2012. In this period, 353,171 pregnancies were identified in THIN. The incidence of major congenital malformations was 1.9% and perinatal death was 0.4%. Amongst 1,633 pregnant women regularly prescribed antiepileptic drugs before pregnancy, there were 54 cases of major congenital malformations and perinatal deaths (3.3%, 95% CI 2.5-4.3%). The risk amongst women prescribed sodium valproate polytherapy was 12% (95% CI 5.9-21.0%) - significantly greater than those prescribed carbamazepine monotherapy (IRR 2.72, 95% CI 1.23-5.99), 5 sodium valproate monotherapy (IRR 3.42, 95% CI 1.35-8.66) and lamotrigine monotherapy (IRR 5.03, 95% CI 1.99-12.74). Conclusions Women taking sodium valproate polytherapy face a greater risk of major congenital malformations or perinatal death compared to other common monotherapy regimens. Further research is needed to corroborate these findings, however women and their physicians should aim to avoid sodium valproate polytherapy if possible.