Pregnant women taking antiepileptic drugs have higher odds for preeclampsia, bleeding, labor induction, caesarean section, and major malformations of the newborn, Norwegian researchers have learned.
The findings, published May 11 in BJOG: An International Journal of Obstetrics and Gynaecology, add to mounting evidence that pregnancy risks for epileptic women may be linked to antiepileptic drugs (AEDs) rather than epilepsy itself.
In the study, Dr. Ingrid Borthen of Haukeland University Hospital, in Bergen, Norway, and her associates retrospectively compared obstetric outcomes for 205 deliveries by 170 women with a past or present history of epilepsy (57% of whom were taking AEDs) and 205 matched, nonepileptic control patients. The women in both groups had a mean age of 28 years.
Epileptic women taking AEDs had higher odds of severe preeclampsia (odds ratio [OR], 5.0; 95% CI, 1.3-19.9), bleeding in early pregnancy (OR, 6.4; 95% CI, 2.7-15.2), labor induction (OR, 2.3; 95% CI, 1.2-4.3), cesarean section (OR, 2.5; 95% CI, 1.4-4.7), and malformations in the offspring (OR, 7.1; 95% CI, 1.4-36.6). The comparisons of outcomes between the two groups were controlled for confounding factors, including smoking during pregnancy, mother’s age, highest maternal education, parity, body mass index of 30 kg/m2 or greater, diabetes and medical conditions, and previous caesarean section, bleeding, and preeclampsia on comparisons of birth outcomes.
Women with active epilepsy (defined as seizures within 5 years of conception) not using the drugs did not have increased odds for any of these outcomes; however, they did have higher odds for vaginal forceps delivery and preterm birth.
Which specific drugs may be implicated is still difficult to say, said Dr. Borthen, but the study showed that lamotrigine is associated with a higher risk (BJOG 2011 May 11 [doi: 10.1111/j.1471-0528.2011.03004.x]).
Two years ago, Dr. Borthen and her colleagues demonstrated that epileptic women taking AEDs had a significantly increased odds of experiencing preeclampsia and preterm delivery, compared with nonepileptic women, while epileptic women not using AEDs did not have higher odds for any outcomes (BJOG 2009;116:1736-42).
"In our study from 2009, carbamazepine was what was prescribed throughout Norway," Dr. Borthen said in an interview. In the current study, which enrolled women taking lamotrigine, carbamazepine, valproate, and polytherapies, women with lamotrigine monotherapy had an unadjusted OR of 7.5 (95% CI, 1.4-39.0) for severe preeclampsia. Women with polytherapy and with lamotrigine monotherapy had an increased risk of early bleeding (unadjusted OR, 8.6; 95% CI, 2.8-26.3 and OR, 6.2; 95% CI, 2.0-19.3, respectively).
"We use lamotrigine because it doesn’t harm the fetus. But maybe it harms the woman instead," Dr. Borthen said, adding that her team is now designing a new study that would enroll all women with epilepsy in Bergen, hoping for a finer picture of risk ascribable to individual drugs.
"It’s so interesting to see why the medication should have such an impact," Dr. Borthen said, adding that it was possible that interactions with folate could play a part. In this study, the vast majority of women with epilepsy and AED use were also taking folate.
Dr. Borthen and her colleagues noted that the proportion of women using AEDs during pregnancy may represent a larger group than epileptic women, as there is "growing use of AEDs for pain and psychiatric conditions."
One limitation of the study, Dr. Borthen and colleagues wrote in their analysis, was a lack of data on seizure type and severity. The study was funded by the Norwegian Research Council. Dr. Borthen and her colleagues declared that they had no conflicts of interest.