Abstract
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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.
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