Does dosing of drug for mom make a difference for baby's risk of cleft lip, palate?

December 27, 2017

MINNEAPOLIS - Taking a higher dose of topiramate during the first three months of pregnancy may increase a baby's risk of cleft lip or cleft palate more than when taking a lower dose, according to a study published in the December 27, 2017, online issue of Neurology®, the medical journal of the American Academy of Neurology.

Topiramate is prescribed to prevent seizures in people with epilepsy. It is also used to prevent migraine headaches or treat bipolar disorder. In combination with phentermine, it may be prescribed for weight loss.

"While topiramate is not recommended for pregnant women, unplanned pregnancies are common, so it's important to fully examine any possible risk," said Sonia Hernandez-Diaz, MD, DrPH, of the Harvard T.H. Chan School of Public Health in Boston. "Our study found that when pregnant women took topiramate during the first trimester, baby's risk of cleft lip or palate was three times greater than if mom was not taking the drug. The risk was higher when the mother took high doses of the drug than when she took lower doses."

For the study, researchers looked at Medicaid data and identified nearly 1.4 million women who gave birth to live babies over a 10-year period. Women who filled a prescription for topiramate during their first three months of pregnancy were compared with women who did not fill a prescription for any anti-seizure drug. They were also compared to women who filled a prescription for lamotrigine, another drug used to reduce seizures in epilepsy. There were 2,425 pregnancies in the topiramate group, 2,796 in the lamotrigine group, and more than 1.3 million in the group not taking anti-seizure drugs. Researchers then looked at how many women in each group gave birth to a baby diagnosed with cleft lip or cleft palate.

Researchers found that among the more than 1.3 million pregnancies in the group not taking anti-seizure drugs, 1,501 babies had cleft lip or cleft palate which translates to a risk of 1.1 per 1,000. For the 2,425 babies born to mothers who filled a prescription for topiramate during the first trimester of pregnancy, the risk of cleft lip or cleft palate was 4.1 per 1,000. The risk was 1.5 per 1,000 in the babies born to the 2,796 women taking lamotrigine.

Compared to the group not taking anti-seizure medications, women with epilepsy on topiramate had an eight times greater risk of giving birth to a baby with cleft lip or cleft palate, while the women taking the drug for other conditions had a 50 percent higher risk. Women with epilepsy took a higher dose of the drug than those with other conditions. The average daily dose for women with epilepsy was 200 milligrams, while the average for women without epilepsy was 100 milligrams. Additionally, the risk of cleft lip or cleft palate for those taking more than 100 milligrams for any reason was five times greater than those not taking anti-seizure drugs, while those taking less than 100 milligrams had a 60 percent greater risk than those not taking anti-seizure drugs. Results were similar when women taking topiramate were compared with those taking lamotrigine.

"Our results suggest that women with epilepsy on topiramate have the highest relative risk of giving birth to a baby with cleft lip or cleft palate, likely due to the higher doses of topiramate when used for controlling seizures," said Hernandez-Diaz. "The best course may be to avoid prescribing high doses of topiramate to women of childbearing age unless the benefits clearly outweigh the risks."

A limitation of the study is that topiramate doses were not randomly assigned to patients and therefore women on high doses may be different from those on low doses for reasons incompletely measured by the investigators, such as severity of epilepsy.
-end-
The study was supported by the National Institute of Mental Health.

To learn more about epilepsy, visit http://www.aan.com/patients.

The American Academy of Neurology is the world's largest association of neurologists and neuroscience professionals, with over 34,000 members. The AAN is dedicated to promoting the highest quality patient-centered neurologic care. A neurologist is a doctor with specialized training in diagnosing, treating and managing disorders of the brain and nervous system such as Alzheimer's disease, stroke, migraine, multiple sclerosis, concussion, Parkinson's disease and epilepsy.

For more information about the American Academy of Neurology, visit http://www.aan.com or find us on Facebook, Twitter, Google+, LinkedIn and YouTube.

Media Contacts: Renee Tessman, rtessman@aan.com, (612) 928-6137
Michelle Uher, muher@aan.com, (612) 928-6120

American Academy of Neurology

Related Epilepsy Articles from Brightsurf:

Focal epilepsy often overlooked
Having subtler symptoms, a form of epilepsy that affects only one part of the brain often goes undiagnosed long enough to cause unexpected seizures that contribute to car crashes, a new study finds.

Antibodies in the brain trigger epilepsy
Certain forms of epilepsy are accompanied by inflammation of important brain regions.

Breaching the brain's defense causes epilepsy
Epileptic seizures can happen to anyone. But how do they occur and what initiates such a rapid response?

Using connectomics to understand epilepsy
Abnormalities in structural brain networks and how brain regions communicate may underlie a variety of disorders, including epilepsy, which is one focus of a two-part Special Issue on the Brain Connectome in Brain Connectivity, a peer-reviewed journal from Mary Ann Liebert, Inc., publishers.

Epilepsy: Triangular relationship in the brain
When an epileptic seizure occurs in the brain, the nerve cells lose their usual pattern and fire in a very fast rhythm.

How concussions may lead to epilepsy
Researchers have identified a cellular response to repeated concussions that may contribute to seizures in mice like those observed following traumatic brain injury in humans.

Understanding epilepsy in pediatric tumors
A KAIST research team led by Professor Jeong Ho Lee of the Graduate School of Medical Science and Engineering has recently identified a neuronal BRAF somatic mutation that causes intrinsic epileptogenicity in pediatric brain tumors.

Can medical marijuana help treat intractable epilepsy?
A new British Journal of Clinical Pharmacology review examines the potential of medicinal cannabis -- or medical marijuana -- for helping patients with intractable epilepsy, in which seizures fail to come under control with standard anticonvulsant treatment.

Fertility rates no different for women with epilepsy
'Myth-busting' study among women with no history of infertility finds that those with epilepsy are just as likely to become pregnant as those without.

Do women with epilepsy have similar likelihood of pregnancy?
Women with epilepsy without a history of infertility or related disorders who wanted to become pregnant were about as likely as their peers without epilepsy to become pregnant.

Read More: Epilepsy News and Epilepsy Current Events
Brightsurf.com is a participant in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for sites to earn advertising fees by advertising and linking to Amazon.com.