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OnabotulinumtoxinA in Pregnant Migraineurs Appears Safe for Babies

The babies of pregnant women who received onabotulinumtoxinA (Botox) injections to treat migraine do not appear to face a greater risk of fetal abnormalities, suggested an abstract from the virtual annual scientific meeting of the American Headache Society.

In 2013, the researchers had accessed the Allergan safety database (1990-2013) and found that at that time the prevalence of fetal defects in onabotulinumtoxinA-exposed mothers before and during pregnancy was 2.7 percent, which was similar to the rate of the general population. 

The present study aimed to provide a cumulative 29-year update of these findings, including additional data through December 31, 2018. And it found that the risk for abnormalities in babies whose mothers had the injections was no greater than the risk of birth defects, 2 to 4 percent, in the general population.

Babies whose mother had the injections had a 3.9 percent prevalence rate for overall fetal defects and a 1.3 percent rate for major fetal defects, reported Mitchell Brin, MD, senior vice president and chief scientific officer for Botox & Neurotoxins at Allergan in Irvine, CA.

The Allergan Global Safety Database contains reports of onabotulinumtoxinA administration before and during pregnancy, including prospective and retrospective cases, Dr. Brin said. The research team searched the database for eligible cases, where treatment occurred during pregnancy or within three months prior to conception. To minimize reporting bias, overall prevalence rates and major birth defect prevalence rates were estimated from prospective cases only and included cases of live births as well as cases of unknown birth types. Any undetermined abnormal birth outcome was classified as a major birth defect for this analysis.

The researchers identified 914 pregnancies in mothers-to-be who had been exposed to onabotulinumtoxinA. Of that group, 400 pregnancies were included in the study, where outcomes were known.

Dr. Brin said patients received onabotulinumtoxinA most frequently for cosmetic indications (30.3 percent), migraine/headache (25.8 percent), and movement disorders (10.5 percent). Of the 196 prospective cases, 76.8 percent (152) were live births; 22.2 percent (44) ended in fetal loss—32 to spontaneous abortions and 12 elective abortions.

In other data, 148 (97.4 percent) were normal live births, four were live births with abnormal outcomes, and two birth types were unknown with abnormal outcomes. The two unknown birth types were reported as a minor fetal malformation and as an undetermined abnormality/possibly a hole in heart, which was conservatively classified for this analysis as a major birth defect.

"Although the results from this analysis are encouraging, and the prevalence rates are consistent with those reported in our previous publication, it is important that we continue surveillance of exposure to onabotulinumtoxinA during pregnancy and remain vigilant in assessing the safety profile of onabotulinumtoxinA across both therapeutic and cosmetic indications," Dr. Brin told Neurology Today At the Meetings.

"OnabotulinumtoxinA should only be used to treat pregnant women if the benefits outweigh the potential risks. Therefore, women who are pregnant should consult their physician prior to initiating, or continuing, onabotulinumtoxinA treatment."

He suggested that the findings with onabotulinumtoxinA should not be translated to other products. "Botulinum toxin type A products are not interchangeable," Dr. Brin said.

"Differences in manufacturing, formulation, and potency evaluation can impact dose and biological activity, resulting in a specific set of interactions between each product and the tissue that is injected. These differences can impact preclinical dose response curves and clinical dosing, efficacy, duration of action, and safety/adverse events."

Overall, he said the updated results should be comforting to patients and clinicians. "This 29-year retrospective analysis of safety in onabotulinumtoxinA-exposed mothers, which included over 30 percent of cases of women with migraine or headache, demonstrated that the prevalence rate of major abnormal birth outcomes was comparable to that reported in the general population," he said.

"There were no consistent types of malformation by indication or organ observed, with no new safety signals identified. The findings from this analysis, in addition to other available information, such as that in the Package Insert, provides an additional resource for physicians who utilize onabotulinumtoxinA to treat patients for therapeutic or cosmetic indications," Dr. Brin said.

In commenting on the study, Nina Riggins, MD, PhD, assistant clinical professor of neurology at University of California, San Francisco, said: "This study gives us hope that onabotulinumtoxinA is safe to use during pregnancy."

"In this study only about 26 percent of participants received treatment for migraine, which could mean that lower doses and/or different frequency could be given for cosmetic and other indications," Dr. Riggins said. "We use about 155 units every three months for chronic migraine treatment. Variability in dose and timing gives a possibility of a different outcome." 

"We need to continue to evaluate available treatments of migraine to make sure they are safe during pregnancy," she said. "We need more information and dedicated controlled randomized clinical trials with statistically significant results to relax surveillance in pregnancy for use of botulinum toxin."

Dr. Riggins suggested that the current study would only apply to onabotulinumtoxinA. "I believe that each botulinum toxin formulation needs to be studied individually as there can be differences in safety and efficacy."  

Disclosures: Dr. Brin is an employee of Allergan, which sponsored the study. Dr. Riggins had no relevant disclosures.

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AHS Abstract: Brin M, Manack Adams A, Parker L, et al. Pregnancy outcomes following exposure to onabotulinumtoxinA update—29 years of safety observation.