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

December 27, 2017, American Academy of Neurology

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 . 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 , 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 took topiramate during the first trimester, baby's risk of 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 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 lip or .

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 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 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 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.

Explore further: Epilepsy drug may not increase risk of birth defects

More information: Sonia Hernandez-Diaz et al, Topiramate use early in pregnancy and the risk of oral clefts, Neurology (2017).

Related Stories

Epilepsy drug may not increase risk of birth defects

April 6, 2016
Babies born to pregnant women taking the epilepsy drug lamotrigine may not be at an increased risk of birth defects, such as cleft lip, cleft palate or clubfoot, according to a study published in the April 6, 2016, online ...

Experimental drug achieves unprecedented weight loss

April 11, 2011
An investigational combination of drugs already approved to treat obesity, migraine and epilepsy produced up to a 10 percent weight loss in obese individuals participating in a one-year clinical trial, according to researchers ...

Anti-epileptic drug linked to birth defects when taken with other drugs

June 7, 2016
In an analysis of pregnancies in Australia from 1999 to 2014 in which women were taking anti-epileptic drugs, fetal malformation rates fell over time in pregnancies where only one drug was taken, but rates increased in pregnancies ...

Drug used for pain, anxiety may be linked to birth defects

May 18, 2016
A drug commonly used to treat pain, epilepsy, anxiety and other brain health disorders may be associated with an increased risk of major birth defects, according to a study published in the May 18, 2016, online issue of Neurology, ...

Recommended for you

Amygdala neurons increase as children become adults—except in autism

March 20, 2018
In a striking new finding, researchers at the UC Davis MIND Institute found that typically-developing children gain more neurons in a region of the brain that governs social and emotional behavior, the amygdala, as they become ...

Study IDs important role for specific gene in 16p11.2 deletion autism

March 20, 2018
In a new study of one of the most common genetic causes of autism, neuroscientists at MIT's Picower Institute for Learning and Memory have identified a specific molecular mechanism that appears to undermine the ability of ...

Why do some people 'hear' silent flashes?

March 20, 2018
Up to one in five people may show signs of a synaesthesia-like phenomenon in which they 'hear' silent flashes or movement, according to a new study from City, University of London.

'Missing mutation' found in severe infant epilepsy

March 20, 2018
Researchers have discovered a "missing mutation" in severe infant epilepsy—long-suspected genetic changes that might trigger overactive, brain-damaging electrical signaling leading to seizures They also found early indications ...

New research into letter-spacing could help improve children's reading

March 19, 2018
Increased letter spacing helps individuals read faster, but not due to visual processing, according to new research from Binghamton University, State University of New York.

Kids with severe brain injuries may develop ADHD: study

March 19, 2018
(HealthDay)—Young children who sustain a severe head injury may struggle with attention problems as they grow older, researchers say.


Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.