No Evidence OnabutulinumtoxinA Exposure in Pregnancy Ups Risk for Birth Defects

Birth defects do not occur at a higher rate in onabotulinumtoxinA-exposed pregnancies, which suggests onabutulinumtoxinA may be a safe treatment for pregnant women with migraine. These are the findings of a longitudinal study published in Neurology.

OnabutulinumtoxinA is approved in the United States and the European Union for the treatment of 12 therapeutic and 3 aesthetic indications. As around 45% of pregnancies are unintended, there is a risk for pregnancies to be exposed to onabutulinumtoxinA, which may be concerning, as there is a paucity of data about the safety of onabutulinumtoxinA in pregnancy.

To better understand the safety profile of onabutulinumtoxinA in pregnancy, researchers sourced data for this study from the Allergan Global Safety Database. Between 1990 and 2018, pregnancies (N=397) exposed to onabutulinumtoxinA or botulinum toxin type A (BoNT/A) were evaluated for outcomes.

The pregnancies occurred among women younger than age 35 (54.4%); 64.7% of exposure events were for therapeutic indications, such as headache (30.3%); 78.6% of exposures occurred in the first trimester; and the most common onabutulinumtoxinA doses were less than 50 U (32.2%), 150-<200 U (26.9%), 100-<150 U (13.2%), and 50-<100 U (11.2%). Data from 202 of the pregnancies were collected retrospectively and 195 were collected prospectively.

In the prospective and retrospective cohorts, 77.1%-77.3% of pregnancies resulted in live births and 96.9%-97.4% of live births were normal.

Among all pregnancies, 69 were lost spontaneously. Using the prospective dataset, the 32 pregnancies that were lost spontaneously occurred more often among women who used onabutulinumtoxinA for aesthetic indications (72.4% vs 45.8%; P = .009) compared with pregnancies with live births, respectively.

In live births, the following occurred:

• 4 major fetal defects of a ventricular septal defect, tracheoesophageal fistula, cleft lip and cleft palate, and diaphragmatic hernia;
• 3 minor fetal defects of metatarsus adductus, innocent heart murmur, and laryngomalacia;
• 1 birth complication of Horner syndrome; and
• 1 significant adverse event of benign brain tumor.

In abortions, 2 occurred due to a major fetal defect of agenesis of corpus callosum and neural tube defect, 1 elective abortion occurred due to Down syndrome, and 1 spontaneous abortion was associated with Down syndrome.

Using the prospective data, the overall rate of fetal defects was 2.6% and major fetal defects was 0.7%. The rate of defects in pregnancies with preconception exposure was 3.1% compared with 2.0% for exposures in the first trimester.

This study may have been limited by combining onabutulinumtoxinA and BoNT/A exposures as well as prospective and retrospective data.

The researchers noted that “No discernible patterns in characteristics were observed in the 13 observed fetal defects, which were reported for prospective and retrospective pregnancies, cases of live birth and fetal loss, and patients treated for a variety of indications.” 

“This 29-year retrospective analysis of safety data in onabotulinumtoxinA-exposed mothers demonstrates that the prevalence rate of major fetal defects among live births is consistent with rates reported in the general population,” they concluded.

Disclosures: This research was supported by Allergan. Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.