One of a mother’s most basic instincts entails the protection of her child. She will go to great lengths to ensure her offspring have everything they need, particularly when they are at the more helpless, younger stages of life. But what if the maternal instinct to protect is in conflict with self-preservation? What if the mother has a medical condition demanding treatment that may inadvertently harm the fetus? This is the conundrum faced by pregnant women afflicted with epilepsy, and it is an issue that Page Pennell, MD, director of research for the Division of Epilepsy, BWH Department of Neurology, seeks to resolve.
“Epilepsy is the biological tendency to have recurrent seizures,” said Pennell.
Epilepsy is typically diagnosed after one or two seizures, which will continue if treatment is not sought. It affects a variety of ages, from childhood onwards. Severity is different in each patient, with some having up to 100 seizures a day while others have one every 10 years. Several treatments are available, including medication, nerve-stimulating devices, and surgery to remove the seizure focus in the brain.
In pregnant women with epilepsy, an obvious danger is seizures that may physically harm the mother, fetus or both. Hence, medication is necessary. However, in addition to increasing the risk for major congenital malformations (e.g., birth defects), “these medications can have potential negative effects on the developing fetal brain,” said Pennell. This arises because most medications inhibit neural activity in order to control the seizures, but neural activity is necessary for the proper development of the fetal brain. Thus, the aforementioned conundrum facing the mother is one of balancing seizure protection of self with protection of normal fetal brain development.
Resolution through Research
Pennell believes that this dilemma can be resolved through research. She is one of two principal investigators of a broad observational study entitled “Maternal Outcomes and Neurodevelopmental Effects of Antiepileptic Drugs (MONEAD),” which is being conducted with a host of other investigators across the United States. The study will enroll 350 pregnant women with epilepsy, 100 pregnant women without epilepsy, and 100 women with epilepsy who are not pregnant for a total of 550 subjects. The purpose is to determine the effect of different anti-epilepsy drugs (AEDs), including carbamazepine, lamotrigine and levetiracetam, on the mother’s epilepsy and health during pregnancy and on the child’s cognitive development.
To that end, several primary outcomes will be measured. In mothers, it will be determined whether they have increased seizures during pregnancy, if C-section rate is increased, and if they are at greater risk for depression during the pregnancy or post-partum period. Blood samples will be taken from patients to determine medication levels. Moreover, IQ tests will be given to parents to predict that of the child, and such factors as background and socioeconomic status are taken into account.
In the children, verbal intellectual abilities and other neurobehavioral outcomes will be tracked until the age of six years. Additionally, other adverse neonatal outcomes, such as small size, will be assessed, along with the effect of breastfeeding while taking AEDs. Umbilical cord blood will also be collected to measure medication levels.
“We are halfway through enrollment,” said Pennell. “Our hope is that the study will provide more information to patients and doctors about how to find the perfect balance of medication use and maintenance of fetal health.”
On a more sociological note, there is often a stigma against women with epilepsy. In some regions they are told they cannot have families, even to the point of legal enforcement. Pennell wants to erase that stigma and help women suffering from epilepsy understand that they can have a healthy family with the proper treatment.
According to Pennell, “It’s a way to alleviate fear with knowledge.”