{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,28]],"date-time":"2026-07-28T09:02:56Z","timestamp":1785229376152,"version":"3.55.0"},"reference-count":45,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2026,7,24]],"date-time":"2026-07-24T00:00:00Z","timestamp":1784851200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Life"],"abstract":"<jats:p>Background and objectives: A migraine is a highly prevalent and disabling neurological disorder that mainly affects women of childbearing age. Treatment options for migraine prevention are limited during pregnancy and breastfeeding. Although OnabotulinumtoxinA (OnabotA) has proven efficacy and safety in chronic migraine prophylaxis in adults, its safety in pregnancy and breastfeeding remains understudied. Methods: Using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses methodology, this review systematically appraised the evidence on the use of OnabotA for chronic migraines and other neurological conditions during pregnancy and breastfeeding across four electronic databases between January 2000 and December 2025. Results: In summary, of the 555 OnabotA-exposed pregnancies, 80.2% resulted in full-term births, with a 17.5% loss rate (73 spontaneous, 21 elective, three unspecified) and 1.6% reporting foetal anomalies. These findings align with general population baselines for miscarriages (12.5\u201318.7%) and foetal anomalies (3\u20135%), respectively. Among 94 cases of reported breastfeeding, no adverse infant events or developmental delays were observed at 1 year. Maternal outcomes showed favourable symptom control without adverse effects. Conclusions: Although there is limited data on the use of OnabotA in pregnancy and breastfeeding, no significant adverse effects have been identified in pregnant mothers or neonates. OnabotA should therefore be considered on a case-by-case basis for treatment of various neurological conditions, including migraines, when there are no better safe alternatives.<\/jats:p>","DOI":"10.3390\/life16081228","type":"journal-article","created":{"date-parts":[[2026,7,27]],"date-time":"2026-07-27T01:26:23Z","timestamp":1785115583000},"page":"1228","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["The Safety of OnabotulinumtoxinA (OnabotA) During Pregnancy and Breastfeeding: Implications for Chronic Migraines"],"prefix":"10.3390","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6783-6839","authenticated-orcid":false,"given":"Sondos","family":"Eladawi","sequence":"first","affiliation":[{"name":"Department of Neurology, Queen Elizabeth Hospital Birmingham, University Hospitals Birmingham NHS Foundation Trust, Mindelsohn Way, Edgbaston, Birmingham B15 2GW, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9741-2578","authenticated-orcid":false,"given":"Prut","family":"Koonalintip","sequence":"additional","affiliation":[{"name":"Division of Neurology, Department of Internal Medicine, Prince of Songkla University, Hatyai 90110, Songkhla, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amelia","family":"Ngomuo","sequence":"additional","affiliation":[{"name":"Birmingham Medical School, College of Medicine and Health, University of Birmingham, Edgbaston, Birmingham B15 2TT, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emily","family":"Leech","sequence":"additional","affiliation":[{"name":"Birmingham Medical School, College of Medicine and Health, University of Birmingham, Edgbaston, Birmingham B15 2TT, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7772-2157","authenticated-orcid":false,"given":"Mark","family":"Thaller","sequence":"additional","affiliation":[{"name":"Department of Neurology, Queen Elizabeth Hospital Birmingham, University Hospitals Birmingham NHS Foundation Trust, Mindelsohn Way, Edgbaston, Birmingham B15 2GW, UK"},{"name":"Institute of Metabolism and Systems Research, College of Medicine and Health, University of Birmingham, Edgbaston, Birmingham B15 2TT, UK"},{"name":"Department of Neurology, Sandwell and West Birmingham NHS Trust, West Bromwich B71 4HJ, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Benjamin R.","family":"Wakerley","sequence":"additional","affiliation":[{"name":"Department of Neurology, Queen Elizabeth Hospital Birmingham, University Hospitals Birmingham NHS Foundation Trust, Mindelsohn Way, Edgbaston, Birmingham B15 2GW, UK"},{"name":"Institute of Metabolism and Systems Research, College of Medicine and Health, University of Birmingham, Edgbaston, Birmingham B15 2TT, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,7,24]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"137","DOI":"10.1186\/s10194-020-01208-0","article-title":"Lifting The Burden: The Global Campaign Against Headache. Migraine remains second among the world\u2019s causes of disability, and first among young women: Findings from GBD2019","volume":"21","author":"Steiner","year":"2020","journal-title":"J. Headache Pain"},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"American Headache Society (2019). The American Headache Society position statement on integrating new migraine treatments into clinical practice. Headache J. Head Face Pain, 59, 1\u201318.","DOI":"10.1111\/head.13456"},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Headache Classification Committee of the International Headache Society (IHS) (2018). The International Classification of Headache Disorders, 3rd edition. Cephalalgia, 38, 1\u2013211.","DOI":"10.1177\/0333102417738202"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1001","DOI":"10.1111\/ene.12701","article-title":"Migraine and risk of ischaemic heart disease: A systematic review and meta-analysis of observational studies","volume":"22","author":"Sacco","year":"2015","journal-title":"Eur. J. Neurol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1007\/s10072-016-2746-z","article-title":"Migraine and the risk of stroke: An updated meta-analysis of prospective cohort studies","volume":"38","author":"Hu","year":"2017","journal-title":"Neurol. Sci."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"197","DOI":"10.1046\/j.1468-2982.2003.00480.x","article-title":"Course of migraine during pregnancy and postpartum: A prospective study","volume":"23","author":"Sances","year":"2003","journal-title":"Cephalalgia"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1783\/147118907780254312","article-title":"Migraine in pregnancy and lactation: A clinical review","volume":"33","author":"MacGregor","year":"2007","journal-title":"J. Fam. Plan. Reprod. Health Care"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"3331024241229410","DOI":"10.1177\/03331024241229410","article-title":"How migraine and its associated treatment impact on pregnancy outcomes: Umbrella review with updated systematic review and meta-analysis","volume":"44","author":"Phillips","year":"2024","journal-title":"Cephalalgia"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"3331024251414634","DOI":"10.1177\/03331024251414634","article-title":"Migraine, associated treatments and risk of miscarriage: A matched cohort study and nested case-control study using the CPRD pregnancy register","volume":"46","author":"Phillips","year":"2026","journal-title":"Cephalalgia"},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Phillips, K., Koonalintip, P., and Wakerley, B.R. (2024). Migraine and Pregnancy. Life, 14.","DOI":"10.3390\/life14101224"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"405.e1","DOI":"10.1016\/j.ajog.2012.07.008","article-title":"Use of topiramate in pregnancy and risk of oral clefts","volume":"207","author":"Margulis","year":"2012","journal-title":"Am. J. Obstet. Gynecol."},{"key":"ref_12","unstructured":"(2026, July 15). Headaches in over 12s: Diagnosis and Management (Clinical Guideline CG150). Available online: https:\/\/www.nice.org.uk\/guidance\/cg150."},{"key":"ref_13","unstructured":"NICE (2023). Rimegepant for Treating Migraine; TA919, NICE. Available online: https:\/\/www.nice.org.uk\/guidance\/ta919\/resources."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1007\/164_2019_271","article-title":"The History of Botulinum Toxins in Medicine: A Thousand Year Journey","volume":"Volume 263","author":"Whitcup","year":"2021","journal-title":"Botulinum Toxin Therapy"},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Chamani, G., Jasim, H., Minston, A., Dias, M.F., Poluha, R.L., Gon\u00e7alves, D.A.G., Christidis, M., Al-Moraissi, E.A., Christidis, N., and De la Torre Canales, G. (2026). Botulinum Toxin Type A for the Prevention of Migraines: An Umbrella Review of Systematic Reviews. Toxins, 18.","DOI":"10.3390\/toxins18010033"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"239","DOI":"10.1097\/PRS.0000000000005111","article-title":"Botulinum toxin versus placebo: A meta-analysis of prophylactic treatment for migraine","volume":"143","author":"Bruloy","year":"2019","journal-title":"Plast. Reconstr. Surg."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"921","DOI":"10.1111\/j.1526-4610.2010.01678.x","article-title":"OnabotulinumtoxinA for treatment of chronic migraine: Pooled results from the double-blind, randomized, placebo-controlled phases of the PREEMPT clinical program","volume":"50","author":"Dodick","year":"2010","journal-title":"Headache J. Head Face Pain"},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Ahmed, F., Gaul, C., Kollewe, K., Singh, R.C., and Sommer, K. (2025). Real-World Safety and Efficacy of 156 U\u2013195 U OnabotulinumtoxinA in Adults With Chronic Migraine: Results From the REPOSE Study. BMC Neurol., 25.","DOI":"10.1186\/s12883-025-04087-7"},{"key":"ref_19","unstructured":"National Institute for Health and Care Excellence (NICE) (2012). Botulinum Toxin Type A for the Prevention of Headaches in Adults with Chronic Migraine, NICE. Technology Appraisal Guidance [TA260]."},{"key":"ref_20","unstructured":"Electronic Medicines Compendium (emc) (2026, March 21). BOTOX 50 Allergan Units Powder for Solution for Injection\u2014Summary of Product Characteristics (SmPC). Available online: https:\/\/www.medicines.ie\/medicines\/botox-50-allergan-units-powder-for-solution-for-injection-31465\/spc."},{"key":"ref_21","unstructured":"Electronic Medicines Compendium (emc) (2026, March 21). BOTOX 100 Allergan Units Powder for Solution for Injection\u2014Summary of Product Characteristics (SmPC). Available online: https:\/\/www.medicines.org.uk\/emc\/product\/859\/smpc#gref."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"n160","DOI":"10.1136\/bmj.n160","article-title":"PRISMA 2020 explanation and elaboration: Updated guidance and exemplars for reporting systematic reviews","volume":"372","author":"Page","year":"2021","journal-title":"BMJ"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"n71","DOI":"10.1136\/bmj.n71","article-title":"The PRISMA 2020 statement: An updated guideline for reporting systematic reviews","volume":"372","author":"Page","year":"2021","journal-title":"BMJ"},{"key":"ref_24","unstructured":"Eladawi, S., Ngomuo, A., Leech, E., and Wakerley, B. (2026, July 15). The Safety of Using OnabotulinumtoxinA (BoNT-A) in Managing Chronic Migraines in Pregnancy. PROSPERO 2026 CRD420251245233. Available online: https:\/\/www.crd.york.ac.uk\/PROSPERO\/view\/CRD420251245233."},{"key":"ref_25","unstructured":"Santana, K. (2026, March 21). Icahn School of Medicine at Mount Sinai. Levy Library Guides: Evidence Based Medicine: The PICO Framework. Available online: https:\/\/libguides.mssm.edu\/ebm\/ebp_pico."},{"key":"ref_26","unstructured":"US Food and Drug Administration, Center for Drug Evaluation and Research (2019). Evaluating the Risks of Drug Exposure in Human Pregnancies, FDA."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"E103","DOI":"10.1212\/WNL.0000000000207375","article-title":"Pregnancy Outcomes in Patients Exposed to OnabotA Treatment: A Cumulative 29-Year Safety Update","volume":"101","author":"Brin","year":"2023","journal-title":"Neurology"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1186\/s10194-020-01196-1","article-title":"OnabotA for chronic migraine during pregnancy: A real world experience on 45 patients","volume":"21","author":"Wong","year":"2020","journal-title":"J. Headache Pain"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"03331024251327387","DOI":"10.1177\/03331024251327387","article-title":"OnabotA treatment for chronic migraine in pregnancy: An updated report of real-world headache and pregnancy outcomes over 14 years in Hull","volume":"45","author":"Wong","year":"2025","journal-title":"Cephalalgia"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1136\/jnnp.2005.063792","article-title":"Botulinum toxin A during pregnancy: A survey of treating physicians","volume":"77","author":"Morgan","year":"2006","journal-title":"J. Neurol. Neurosurg. Psychiatry"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1384","DOI":"10.1002\/mds.20205","article-title":"Botulinum toxin type A therapy during pregnancy","volume":"19","author":"Newman","year":"2004","journal-title":"Mov. Disord."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"e703","DOI":"10.7205\/MILMED-D-13-00477","article-title":"OnabotA Successfully Used as Migraine Prophylaxis During Pregnancy: A Case Report","volume":"179","author":"Robinson","year":"2014","journal-title":"Mil. Med."},{"key":"ref_33","first-page":"e53326","article-title":"Dramatic Effect of Botox Injection in Disabling Chronic Migraine Secondary to Inoperable Cerebral Arteriovenous Malformation","volume":"16","author":"Mezaal","year":"2024","journal-title":"Cureus"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1658","DOI":"10.1016\/S0140-6736(21)00682-6","article-title":"Miscarriage matters: The epidemiological, physical, psychological, and economic costs of early pregnancy loss","volume":"397","author":"Quenby","year":"2021","journal-title":"Lancet"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"2515","DOI":"10.1001\/jama.2016.18425","article-title":"Association Between the Birth of an Infant With Major Congenital Anomalies and Subsequent Risk of Mortality in Their Mothers","volume":"316","author":"Cohen","year":"2016","journal-title":"JAMA"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"658","DOI":"10.1016\/S0022-3476(75)80871-7","article-title":"Observations of an infant born to a mother with botulism","volume":"87","author":"Clair","year":"1975","journal-title":"J. Pediatr."},{"key":"ref_37","unstructured":"Centers for Disease Control and Prevention (CDC) (1995). Wound botulism\u2014California, 1995. MMWR Morb. Mortal. Wkly. Rep., 44, 889\u2013892."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1016\/S0140-6736(05)66139-9","article-title":"Botulism and pregnancy","volume":"348","author":"Polo","year":"1996","journal-title":"Lancet"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"823","DOI":"10.1056\/NEJM199609123351117","article-title":"Botulism in a Pregnant Woman","volume":"335","author":"Robin","year":"1996","journal-title":"N. Engl. J. Med."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1111\/j.1365-2044.2005.04434.x","article-title":"Botulism in a pregnant intravenous drug abuser","volume":"61","author":"Morrison","year":"2006","journal-title":"Anaesthesia"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"284","DOI":"10.3181\/00379727-107-26604","article-title":"Distribution and Particle Size of Type A Botulinum Toxin in Body Fluids of Intravenously Injected Rabbits","volume":"107","author":"Hildebrand","year":"1961","journal-title":"Exp. Biol. Med."},{"key":"ref_42","first-page":"1183","article-title":"Botulinum toxin type A in pregnancy","volume":"59","author":"Tan","year":"2013","journal-title":"Can. Fam. Physician Med. Fam. Can."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"523","DOI":"10.1089\/fpsam.2023.0326","article-title":"Analysis of breast milk samples in lactating women after undergoing botulinum toxin injections for facial rejuvenation: A pilot study","volume":"26","author":"Hudson","year":"2024","journal-title":"Facial Plast. Surg. Aesthetic Med."},{"key":"ref_44","doi-asserted-by":"crossref","unstructured":"Gu, H., Xu, Z., Koviazina, R., Tan, P., Zheng, C., Kappes, F., Kotsifaki, D.G., Shen, F., and Tsigkou, A. (2025). Detection of nontoxic BoNT\/A levels in post-facial botox injection breastmilk. Front. Drug Saf. Regul., 4.","DOI":"10.3389\/fdsfr.2024.1480515"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1007\/s11916-016-0545-0","article-title":"Botulinum toxin: Pharmacology and therapeutic roles in pain states","volume":"20","author":"Patil","year":"2016","journal-title":"Curr. Pain Headache Rep."}],"container-title":["Life"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2075-1729\/16\/8\/1228\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,28]],"date-time":"2026-07-28T08:15:17Z","timestamp":1785226517000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2075-1729\/16\/8\/1228"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,7,24]]},"references-count":45,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2026,8]]}},"alternative-id":["life16081228"],"URL":"https:\/\/doi.org\/10.3390\/life16081228","relation":{},"ISSN":["2075-1729"],"issn-type":[{"value":"2075-1729","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,7,24]]}}}