From Allergan, an AbbVie Company (M.F.B., A.M.A., L.P., A.U., M.R.P.E., L.Y., I.Y.), Irvine, CA; Department of Neurology (M.F.B.), University of California, Irvine; College of Public Health (R.S.K.), University of South Florida, Tampa; Division of Medical Genetics (A.S.), Department of Pediatrics, University of California, San Francisco; Allergan, an AbbVie Company (L.R.); and University of Medicine and Pharmacy (L.R.), Carol Davila, Bucharest, Romania.
Neurology. 2023 Jul 11;101(2):e103-e113. doi: 10.1212/WNL.0000000000207375. Epub 2023 May 3.
A previous publication of pregnancy outcomes in onabotulinumtoxinA-exposed mothers demonstrated that the prevalence of major fetal defects (0.9%, 1/110) was comparable with background rates in the general population. There is continued interest to better understand the safety of onabotulinumtoxinA during pregnancy. This analysis evaluated pregnancy outcomes after onabotulinumtoxinA exposure to provide a cumulative 29-year update.
The Allergan Global Safety Database was searched from January 1, 1990, to December 31, 2018. Data from women (younger than 65 years or unknown) during pregnancy or ≤3 months before conception treated with onabotulinumtoxinA were assessed to estimate birth defect prevalence rates of live births only from prospective pregnancies.
Of 913 pregnancies, 397 (43.5%) were eligible with known outcomes. Maternal age was known in 215 pregnancies: 45.6% were 35 years or older. Indication was known in 340 pregnancies: most frequent were aesthetic (35.3%) and migraine/headache (30.3%). The timing of exposure was known in 318 pregnancies: 94.6% were before conception or during the first trimester. OnabotulinumtoxinA dose information was known in 242 pregnancies; most (83.5%) were exposed to <200 U. Of 195 prospective pregnancies with 197 fetuses, there were 152 (77.2%) live births and 45 (22.8%) fetal losses (32 spontaneous, 13 elective). Of 152 live births, 148 (97.4%) had normal outcomes and 4 had abnormal outcomes. Among the 4 abnormal outcomes, there were 1 major birth defect, 2 minor fetal defects, and 1 birth complication. The prevalence rate for overall fetal defects was 2.6% (4/152, 95% CI 1.0%-6.6%) and 0.7% (1/152, 95% CI 0.1%-3.6%) for major fetal defects (3%-6% in the general population). Among cases of live births and known determinable exposure times, there was 1 birth defect with preconception exposure and 2 with first-trimester exposure.
Although subject to reporting bias due to the nature of the postmarketing database review, this 29-year retrospective analysis of safety data in pregnant women exposed to onabotulinumtoxinA demonstrates that the prevalence rate of major fetal defects among live births is consistent with the rates reported in the general population. Although there are limited data available for second-trimester and third-trimester exposure, this updated and expanded safety analysis provides important real-world evidence to health care providers and their patients.
This analysis provides Class III data that demonstrate that the prevalence rate of major fetal defects among live births subsequent to in utero onabotulinumtoxinA exposure is comparable with the reported background rates.
先前有关昂丹司琼毒素 A 暴露母亲妊娠结局的出版物表明，主要胎儿缺陷的患病率（0.9%，1/110）与一般人群中的背景率相当。人们仍然有兴趣更好地了解妊娠期间昂丹司琼毒素 A 的安全性。本分析评估了昂丹司琼毒素 A 暴露后的妊娠结局，以提供长达 29 年的累积更新。
从 1990 年 1 月 1 日至 2018 年 12 月 31 日，检索 Allergan 全球安全数据库。评估了妊娠或受孕前≤3 个月期间接受过昂丹司琼毒素 A 治疗的女性（年龄<65 岁或未知）的数据，以仅从前瞻性妊娠中估计活产的出生缺陷患病率。
在 913 例妊娠中，397 例（43.5%）有已知结局，符合条件。已知 215 例妊娠的产妇年龄：45.6%为 35 岁或以上。已知 340 例妊娠的适应证：最常见的是美容（35.3%）和偏头痛/头痛（30.3%）。已知 318 例妊娠的暴露时间：94.6%在受孕前或孕早期。已知 242 例妊娠的昂丹司琼毒素 A 剂量信息：大多数（83.5%）接受了<200 U 的剂量。在 195 例有 197 个胎儿的前瞻性妊娠中，有 152 例（77.2%）活产和 45 例（22.8%）胎儿丢失（32 例自然流产，13 例选择性流产）。在 152 例活产中，有 148 例（97.4%）结局正常，4 例结局异常。在 4 例异常结局中，有 1 例主要出生缺陷，2 例轻微胎儿缺陷和 1 例出生并发症。总出生缺陷的患病率为 2.6%（4/152，95%CI 1.0%-6.6%），主要出生缺陷的患病率为 0.7%（1/152，95%CI 0.1%-3.6%）（一般人群为 3%-6%）。在活产和可确定的暴露时间已知的病例中，有 1 例先天暴露，2 例孕早期暴露。
尽管由于上市后数据库审查的性质存在报告偏倚，但这项对接受昂丹司琼毒素 A 暴露的孕妇进行的长达 29 年的安全性数据回顾性分析表明，活产儿中主要胎儿缺陷的患病率与一般人群报告的患病率一致。尽管关于中孕期和晚孕期暴露的可用数据有限，但本次更新和扩展的安全性分析为医疗保健提供者及其患者提供了重要的真实世界证据。
本分析提供了 III 类数据，证明了在宫内接触昂丹司琼毒素 A 后活产儿中主要胎儿缺陷的患病率与报告的背景率相当。
