Researchers Question The Use Of Antiepileptic Drugs During Pregnancy

Main Category: Epilepsy
Also Included In: Pregnancy / Obstetrics
Article Date: 30 Sep 2009 - 3:00 PDT

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New research to be published in BJOG: An International Journal of Obstetrics and Gynaecology reports the pregnancy complications experienced by women with epilepsy and examines the use of antiepileptic drugs (AED) for treatment during pregnancy.

Epileptic women (around 0.3-0.7% of the population) who become pregnant are classified as high-risk because prolonged fits can be dangerous for the baby as well as the mother. Current NICE guidelines state that an increase in seizure frequency in pregnant women (or during the first few months after birth) is unusual. Ideally, however, the woman should be seizure-free and thus it is important to optimise treatment during pregnancy. In order to achieve this, it is sometimes necessary to increase the amount of AEDs given. However, the guidelines also state that pregnant women with epilepsy must be given information about the harmful effects some AEDs pose to the developing fetus, so that the risks of the drugs vs the risks of seizures can be compared, allowing the woman to make an informed choice. Optimal care requires close liaison between the obstetrician and the epilepsy specialist (often a neurologist).

Norwegian researchers analysed the records of 365,107 singleton pregnancies in the Medical Birth Registry of Norway (MBRN) from December 1998 to October 2005. Within this group, 2,805 (0.8%) were recorded to have had a previous or present history of epilepsy while the rest (362,302) did not Confounding variables such as maternal age at delivery, smoking, diabetes and educational level were also noted and controlled for. In this study, 942 women with epilepsy were exposed to AED. The most commonly used AEDs were carbamazepine (46%), lamotrigine (25%) and sodium valproate (22%).

Pregnant women with epilepsy were found to be at significantly increased risk of developing pre-eclampsia (overall Odds Ratio (OR) 1.3; 1.4 for mild pre-eclampsia) when compared to non-epileptic women. Pre-eclampsia is a disease unique to pregnancy and is manifested as raised blood pressure and protein in the urine; in severe cases it also causes convulsions (eclampsia). No increased risks of placenta praevia, premature rupture of the membranes or eclampsia were found for pregnant women with epilepsy.

However, the increased risks of pre-eclampsia were confined to women using AEDs, (OR 1.5, mild pre-eclampsia 1.7). As with non-epileptic women, the risk was higher in the first pregnancy (OR 1.8). Women using AEDs also had an increased risk of gestational hypertension (OR 1.5, 2.4 in the first pregnancy), preterm delivery before the 34th week (OR 1.6) and an almost two-fold increased risk of late vaginal bleeding (OR 1.9). Women who were not treated with AEDs had no increased risks of any of these complications.

These results suggest that AEDs increase the incidence of pre-eclampsia, perhaps by affecting the placenta. However it is also possible that women who need to take AEDs while pregnant are significantly different in some way from the normal population to start with, whereas those not needing AEDs are not.

Co-author Dr Ingrid Borthen from the Department of Gynecology and Obstetrics at Haukeland University Hospital in Bergen, Norway said "Women with epilepsy have slightly increased risks during pregnancy and when giving birth. The risks include pre-eclampsia, non-proteinuric hypertension, bleeding in late pregnancy and delivery before week 34.

"Doctors should pay special attention to women with epilepsy using anti-epileptic drugs. It is important to emphasise that the increased risks are small and that the benefit of the drugs in preventing epilepsy is generally greater than the risks, although the balance of risk needs to be assessed on a case-by-case basis."

Professor Philip Steer, BJOG editor-in-chief said "Epilepsy during pregnancy poses significant challenges for mothers-to-be and the healthcare professionals who care for them. In the past, the use of AEDs during pregnancy was cautioned because of the way the drugs interact with existing levels of folic acid and vitamin K in the maternal body, the main concern being that the developing fetus is affected by AEDs and this can lead to significant congenital abnormalities.

"Although most women with epilepsy tend to have successful pregnancies, and the incidence of fits during pregnancy should be low with careful adjustment of AED dose, doctors and midwives must remain vigilant for residual risks, which are now seen to include pre-eclampsia, hypertension, and preterm birth. More research is needed to understand why this happens."

Notes

BJOG: An International Journal of Obstetrics and Gynaecology is owned by the Royal College of Obstetricians and Gynaecologists (RCOG) but is editorially independent and published monthly by Wiley-Blackwell. The journal features original, peer-reviewed, high-quality medical research in all areas of obstetrics and gynaecology worldwide. Please quote 'BJOG' or 'BJOG: An International Journal of Obstetrics and Gynaecology' when referring to the journal and include the website: http://www.bjog.org as a hidden link online.

Reference

"Complications during pregnancy in women with epilepsy: population-based cohort study."
Borthen I, Eide M, Veiby G, Daltveit A, Gilhus N.
BJOG 2009; DOI: 10.1111/j.1471-0528.2009.02354.x.

Source
Royal College of Obstetricians and Gynaecologists