Pregnancy Outcomes in Patients Exposed to OnabotulinumtoxinA Treatment: A Cumulative 29-Year Safety Update.

BACKGROUND AND OBJECTIVES: 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. METHODS: 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. RESULTS: 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. DISCUSSION: 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. CLASSIFICATION OF EVIDENCE: 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.

Importance of education and the role of the patient and family in the care of anorectal malformations.

During this early part of the 21st century online technology has prompted many major advances in medical care. In this section we argue that this is particularly evident in the treatment and care of patients born with Anorectal Malformation (ARM) and Hirschsprung's Disease (HD). Our stories show that anyone born with these complex colorectal conditions in the 20th century was destined to a life of isolation and stigma. Here we explore the lack of understanding and recognition of the psychological effects on children and families which has characterised this period. We show that advances in clinical practice has been supported by developing social media platforms. There has been a rapid creation of online support groups for patients and families which has enabled survivors' greater access to patient and parent organizations across the globe and thereby stimulated a sense of belonging and solidarity. Online technology and social media platforms have also opened up the opportunity for pediatric medical professionals to provide a greater level of patient education. There is no doubt families have become much more aware of the complexities of ARM & HD and achieved greater comfort and understanding of their needs. We have generated "lightbulb moments" for pediatric providers with adult ARM & HD patients, enabling them to share their lived experiences in a therapeutic exchange. In the past survivors felt they were abandoned by the adult healthcare system. We are seeing evidence-based research of major psychosocial issues experienced by adult patients and, as a result, improved understanding of how to treat ARM & HD survivors across their whole of life journey. The winds of change continue to direct our cohorts to a mature approach based on improving levels of interactive communication and education. We argue that this maturity has mostly been facilitated by the use of online technology and the ensuing collaboration between providers and patient and parent organizations.

Pregnancy outcomes following exposure to onabotulinumtoxinA.

PURPOSE: To evaluate pregnancy outcomes following onabotulinumtoxinA (US Food and Drug Administration pregnancy category C product) exposure using the Allergan safety database. METHODS: The Allergan Global Safety Database contains reports of onabotulinumtoxinA administration before/during pregnancy, including both prospective (reported before outcome) and retrospective (outcome already known) cases. The database was searched from 1/1/90 to 12/31/13 for eligible cases where treatment occurred during pregnancy or ≤3 months before conception. To minimize reporting bias, prevalence rates were focused on prospective cases. RESULTS: Of 574 pregnancies with maternal onabotulinumtoxinA exposure, 232 were eligible with known outcomes. Patients received onabotulinumtoxinA most frequently for cosmetic indications (50.5%), movement disorders (16.8%), and pain disorders (14.2%). Of the 137 with dose information, 40.1% received <50U, 14.6% 50U to <100U, 27.7% 100U to <200U, and 17.5% ≥200U. Among 146 cases with known maternal age, 47.9% were ≥35 years. Most (96.0%) fetal exposures occurred during/before the first trimester. Of the 137 prospective cases (139 fetuses), 110 (79.1%) were live births; 29 (20.9%; 95% CI, 14.0-30.0%) ended in fetal loss (21 spontaneous, 8 induced abortions). Among live births, 106 (96.4%) were normal, with four abnormal birth outcomes (1 major fetal defect, 2 minor fetal malformations, 1 birth complication), giving a 2.7% (3/110; 95% CI, 0.6-8.0%) prevalence rate for overall fetal defects. CONCLUSIONS: A 24-year retrospective review of the Allergan safety database shows that the prevalence of fetal defects in onabotulinumtoxinA-exposed mothers before/during pregnancy (2.7%) is comparable with background rates in the general population. Pregnancy outcome monitoring in onabotulinumtoxinA-exposed women continues.

Skin contact transfer of three fragrance residues from candles to human hands.

The dermal hand transfer of three fragrance materials (cinnamic aldehyde, d-limonene and eugenol) from scented candles was determined in 10 subjects (i.e., 20 hands) after grasping scented candles for 5 consecutive 20s exposures/grasps. The fragrance materials from each subject's hands were recovered by isopropyl alcohol wipes and subsequent extractions. Removal efficiencies for both cinnamic aldehyde and eugenol placed directly on the hands were not concentration dependent and ranged from 103% to 106%. The removal efficiency of d-limonene showed an inverse relation with 74.3% removed at the low concentration of 50 microg and 63.8% removed at the high concentration of 500 microg. The residue/transfer of d-limonene from the candles to the hands was below the limit of detection of 50 microg. The residue/transfer of cinnamic aldehyde and eugenol to each subject's hands was consistent between subjects as well as between each exposure/grasp. The total mean residues of cinnamic aldehyde and eugenol transferred per grasp from the candles to the hands were 0.255 microg/cm(2) and 0.279 microg/cm(2), respectively.