Unplanned pregnancy in women who have epilepsy may double the risk for spontaneous fetal loss, according to a new study.
Investigators from the Harvard Neuroendocrine Unit at Massachusetts General Hospital in Boston, Massachusetts, examined the Epilepsy Birth Control Registry (EBCR) in order to determine whether a planned pregnancy is a determinant for spontaneous fetal loss in women with epilepsy. They also hoped to assess other risk factors that could potentially be modified, such as maternal age, pregnancy spacing, and antiepileptic drug categories.
The team pulled demographic, epilepsy, antiepileptic drug, contraceptive, and reproductive data from the EBCR between 2010 and 2014 and found 1144 female patients with epilepsy between the ages of 18 and 47 years to include in their analysis.
Further analysis revealed that 65% of pregnancies in women with epilepsy included in the study were unplanned, the investigators wrote. This rate was higher than the 45% to 51% range seen in the general US population between 2001 and 2011. Minority race and younger age were risk factors for both cohorts and a third of the pregnancies occurred when the women were not taking contraception.
European predictions indicate that maternal exposure to antiepileptic drug polytherapy, the presence of major congenital malformation in 1 parent, previous spontaneous fetal loss, and maternal age are risk factors for spontaneous fetal loss.
The investigators used the following predicted risk factors: pregnancy planning, age, and antiepileptic drugs use. Spontaneous fetal loss was the outcome for 180 of 794 pregnancies the investigators studied. The risk of spontaneous fetal loss was greater for unplanned vs planned pregnancies. Furthermore, the risk of spontaneous fetal loss was greater when unplanned pregnancies were entered alone, and when adjusted for maternal age, interpregnancy interval, and antiepileptic drug category. Additionally, maternal age and interpregnancy interval were independent risk factors. The use of antiepileptic drugs was not an independent risk factors, according to the investigators.
Those women younger than 18 years had the highest rate of spontaneous fetal loss while the risks for the other cohorts varied. Women aged 18 to 27 years had a 29% risk; women 28 to 37 years, had a 20% risk; and women 38 to 47 years had a 25% risk.
Of the 368 women with epilepsy who had more than 1 pregnancy, the risk for spontaneous fetal loss was greater when the time between pregnancies was less than 1 year, compared with latencies greater than 1 year, the study authors wrote.
The frequencies of spontaneous fetal loss among women with epilepsy who did and did not use antiepileptic drugs during pregnancies were similar, at 28% and 27%, respectively. About a quarter of women received monotherapy, while another quarter received polytherapy.
Despite practice guidelines suggestions that women with epilepsy achieve seizure control prior to conception—which requires planning—about two-thirds of these pregnancies are unplanned. Thus, the investigators shared that “unplanned pregnancy may increase the risk of spontaneous fetal loss in women with epilepsy and identifies pregnancy planning, maternal age, and interpregnancy interval as significant modifiable variables.”
“In view of the finding of increased risk for spontaneous fetal loss in unplanned pregnancies in women with epilepsy, and because a history of spontaneous fetal loss in women with epilepsy may increase the risk that subsequent live-born offspring will develop epilepsy, the finding warrants prospective investigation with medical record verification of pregnancy outcomes,” the authors concluded.
The study “Association of Unintended Pregnancy with Spontaneous Fetal Loss in Women with Epilepsy,” was published in JAMA Neurology.
Source: MedMag.com Byy R R. Lutz
A follow-up study of Danish babies with neonatal hyperbilirubinaemia* who had been treated with phototherapy discovered a modest increase in the risk of childhood epilepsy. The finding has now been replicated in a large database analysis from the United States. Phototherapy is associated with an increase in the likelihood of epilepsy by 30% to 40% and the risk seems to be greater in boys than girls.
Phototherapy (light treatment) is the process of using light to eliminate bilirubin in the blood, many time used on newborn babies with jaundice.
* A condition characterized by an abnormal increase of BILIRUBIN in the blood, which may result in JAUNDICE. Bilirubin, a breakdown product of HEME**, is normally excreted in the BILE or further catabolized before excretion in the urine.
**An iron-containing compound of the porphyrin class that forms the nonprotein part of hemoglobin and some other biological molecules.
Study finds significant changes in how seizure medications are metabolized during the different trimesters of pregnancy
During pregnancy, the numerous physiological changes a woman’s body undergoes can alter the way medications are metabolized, the rate at which they are cleared, and their overall effectiveness. Many women continue taking antiepileptic drugs (AEDs) during pregnancy, but while many studies address their safety, it has been unclear if the drug’s effectiveness may be altered during pregnancy. A new study by investigators from Brigham and Women’s Hospital examined whether pregnancy-related changes may influence how effectively five common AEDs prevent seizures and found that AED clearance significantly changes by the first trimester for the most commonly used medication and by the second trimester for two others. Their results are published in Neurology.
“We want to be able to give the exact dose of a drug that keeps a woman seizure-free and keeps her and her baby safe, but there are relatively few studies that have examined pregnancy-related changes in AED metabolism for us to know how to adjust this dose,” said lead author P. Emanuela Voinescu, MD, PhD, associate neurologist in the Department of Neurology at BWH. “We sought to fill that gap about changes in AED metabolism during the different trimesters of pregnancy.”
The team investigated five commonly used drugs, including levetiracetam – one of the most widely used medications during pregnancy – oxcarbazepine, topiramate, phenytoin, and valproate.
The prospective, observational study, started by senior author Page Pennell, MD, while at Emory University, consisted of 40 women with epilepsy who were planning to conceive or were less than 16 weeks pregnant, and who chose to continue their AEDs during pregnancy. Study visits occurred every one to three months and for the first postpartum year. Drug clearance values, the dose required to maintain a certain blood serum concentration, were obtained via blood draw at baseline and during pregnancy. Seizure occurrence and frequency were recorded throughout the study.
Researchers found that the metabolic changes affecting levetiracetam started early, in the first trimester, and drug clearance remained elevated during the second and third trimesters. In contrast, they found that oxcarbazepine and topiramate had elevated clearance starting in the second trimester. This is important because if drug clearance increases, patients may need to be prescribed a higher or more frequent dose of their antiepileptic medication.
“It is already a challenge to be pregnant and our patients have to deal with epilepsy on top of it. It requires a little more work because of all the frequent blood draws and medication adjustments” said Voinescu. “It would be nice to be able to simplify their management by having more scientific guidelines in place regarding how to adjust medication doses during pregnancy to keep them seizure-free and to keep their babies safe.”
Funding for this work was supported by an NIH Specialized Center of Research (P50MH 68036) NCRR M01-RR00039, NINDS and NICHD (U01 NS038455), the American Brain Foundation, American Epilepsy Society and the Epilepsy Foundation as the Susan Spencer Clinical Research Training Fellowship and the Karger Fund.
Paper cited: Voinescu, E et al. “Antiepileptic drug clearances during pregnancy and clinical implications for women with epilepsy” Neurology DOI:10.1212/WNL.0000000000006240
The rate of miscarriage was doubled in women with epilepsy whose pregnancies were unplanned, a survey of Epilepsy Birth Control Registry participants found.
Among women with epilepsy, spontaneous fetal loss occurred in 35% of unplanned versus 16% of planned pregnancies, reported Andrew Herzog, MD, MSc, of Beth Israel Medical Center in Boston, and colleagues in JAMA Neurology.
“This is important because unplanned pregnancy is very common among women with epilepsy, more common than in the general population,” Herzog told MedPage Today.
About 65% of pregnancies in women with epilepsy are unplanned, despite epilepsy practice guidelinesthat suggest these women “plan pregnancies to occur when they have achieved optimal seizure control on the minimum effective dosage of antiepileptic drugs and take folic acid supplement before conception to achieve optimal maternal and fetal outcomes,” Herzog added.
Reasons behind these practice guidelines have been evident for years: prenatal exposure to valproate (Depakote) has been tied to autism and impaired cognitive development in children, prompting FDA warnings about using the drug during pregnancy. And while research indicates that newer anti-epileptic drugs like levetiracetam (Keppra) or topiramate (Topamax) during pregnancy are not linked to reduced cognitive abilities in children, a recent study showed that women on anti-seizure medications who did not take folic acid supplements before conceiving had a substantially increased risk of children with autistic traits.
“Discussion about the importance of planned pregnancies should be part of standard care by neurologists carrying for teens and women with epilepsy,” said Page Pennell, MD, of Brigham and Women’s Hospital in Boston, who was not involved with the study.
“To increase the likelihood of a planned pregnancy, the neurologist should also be directly engaged in education of the patient and her other healthcare providers if the anti-seizure medicine prescribed interacts with hormonal contraceptives and lowers their efficacy,” Pennell told MedPage Today. “In those situations, long-acting reversible contraceptives such as intrauterine devices should be encouraged.”
In this study, researchers conducted a web-based retrospective survey from 2010 to 2014 on women with epilepsy from the Epilepsy Birth Control Registry. The average age of survey respondents was 28.5 years; nearly 4 in 10 had household incomes of $25,000 or less, and minority women represented 8.7% of participants.
Respondents reported that 794 pregnancies had occurred: 530 were unplanned (66.8%) and 264 were planned (33.2%). Among 653 unaborted pregnancies, the risk for spontaneous fetal loss was greater for unplanned (n=137 of 391, 35.0%) than planned (n=43 of 262, 16.4%) pregnancies (RR 2.14, 95% CI 1.59-2.90, P<0.001).
Regression analysis identified an interpregnancy interval of less than 1 year and conception age under 18 or over 37 years as predictors of spontaneous fetal loss. Miscarriage frequencies were comparable among women who did and did not use antiepileptic drugs during pregnancy.
“The Epilepsy Birth Control Registry has previously published that a substantial minority of women with epilepsy do not use highly effective contraception despite their increased risk for having offspring with major congenital malformations,” Herzog said. “The current findings strengthen the need for the education of patients and healthcare providers in this regard.”
The researchers listed several important limitations to the study, including its reliance on self-reported information not verified by medical records. Stigmatized health information tends to be underreported, they pointed out, and it’s possible women reported fewer induced abortions in favor of miscarriage, despite survey anonymity and the option to not answer questions about pregnancy outcome. Minority women also were underrepresented in the sample.
This study was funded by the Epilepsy Foundation and Lundbeck. Researchers reported relationships with the Epilepsy Foundation and Lundbeck.
Source: By J. George MedPage Today
Not using folic acid before and during pregnancy increased risks substantially.
Supplemental folic acid before pregnancy and during the first trimester may limit language development problems in children exposed to anti-epileptic drugs in utero.
Note that the study suggests that beginning supplemental folic acid prior to pregnancy and continuing it through at least the first trimester does have substantial benefit for children of women with epilepsy on anti-epileptic drugs. (more…)