{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,16]],"date-time":"2026-05-16T18:05:25Z","timestamp":1778954725719,"version":"3.51.4"},"reference-count":33,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2025,5,20]],"date-time":"2025-05-20T00:00:00Z","timestamp":1747699200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceuticals"],"abstract":"<jats:p>Background\/Objectives: Some product information on pregabalin suggests a potential risk for congenital anomalies (CAs), although evidence remains inconsistent and lacks clear patterns. This study aimed to provide additional safety information on pregabalin use in pregnancy by analyzing VigiBase, the World Health Organization\u2019s global pharmacovigilance database of individual case safety reports (ICSRs). Methods: The analysis included de-duplicated ICSRs related to pregabalin exposure in pregnancy, collected up to 16 January 2024. Reporting odds ratios (RORs) with 95% confidence intervals (CIs) were calculated for CA categories reported in at least 10 ICSRs, with a statistical threshold defined as a 95% CI lower bound &gt; 1. Results: Among 410 ICSRs, the majority originated from Europe (64.8%) and North America (26.5%). Of these, 59 (14.4%) ICSRs documented only pregabalin exposure in pregnancy, while 351 (85.6%) also reported adverse events in pregnancy. CAs occurred in 82 ICSRs (23.3%), most commonly involving heart defects (30), nervous system anomalies (18), and limb anomalies (12). No signals of disproportionate reporting were identified for these categories compared to the full database (heart defects: ROR 0.587, 95% CI 0.410\u20130.839; nervous system anomalies: ROR 0.588, 95% CI 0.370\u20130.933; limb anomalies: ROR 0.671, 95% CI 0.381\u20131.183). Conclusions: Future disproportionality analyses, along with pharmacovigilance and pharmacoepidemiological studies using patient registries and large-scale collaborative projects, are essential for the ongoing monitoring of pregabalin safety in pregnancy.<\/jats:p>","DOI":"10.3390\/ph18050759","type":"journal-article","created":{"date-parts":[[2025,5,20]],"date-time":"2025-05-20T11:50:31Z","timestamp":1747741831000},"page":"759","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Pregabalin Safety in Pregnancy: A Disproportionality Analysis of VigiBase Spontaneous Reporting System"],"prefix":"10.3390","volume":"18","author":[{"given":"Sarah","family":"Mondada","sequence":"first","affiliation":[{"name":"Division of Clinical Pharmacology and Toxicology, Institute of Pharmacological Sciences of Southern Switzerland, Ente Ospedaliero Cantonale, 6900 Lugano, Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8584-7408","authenticated-orcid":false,"given":"Francesca","family":"Bedussi","sequence":"additional","affiliation":[{"name":"Division of Clinical Pharmacology and Toxicology, Institute of Pharmacological Sciences of Southern Switzerland, Ente Ospedaliero Cantonale, 6900 Lugano, Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3494-9559","authenticated-orcid":false,"given":"Jonathan L.","family":"Richardson","sequence":"additional","affiliation":[{"name":"UK Teratology Information Service, Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne NE2 4AB, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4946-7926","authenticated-orcid":false,"given":"Roberta","family":"Noseda","sequence":"additional","affiliation":[{"name":"Division of Clinical Pharmacology and Toxicology, Institute of Pharmacological Sciences of Southern Switzerland, Ente Ospedaliero Cantonale, 6900 Lugano, Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4308-0405","authenticated-orcid":false,"given":"Alessandro","family":"Ceschi","sequence":"additional","affiliation":[{"name":"Division of Clinical Pharmacology and Toxicology, Institute of Pharmacological Sciences of Southern Switzerland, Ente Ospedaliero Cantonale, 6900 Lugano, Switzerland"},{"name":"Clinical Trial Unit, Ente Ospedaliero Cantonale, 6900 Lugano, Switzerland"},{"name":"Faculty of Biomedical Sciences, Universit\u00e0 della Svizzera Italiana, 6900 Lugano, Switzerland"},{"name":"Department of Clinical Pharmacology and Toxicology, University Hospital Zurich, 8091 Zurich, Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,5,20]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Spoendlin, J., Blozik, E., Graber, S., Rauch, M., Marxer, C., R\u00fcegg, S., Meier, C., Winterfeld, U., and Panchaud, A. (2021). Use of valproate in pregnancy and in women of childbearing age between 2014 and 2018 in Switzerland: A retrospective analysis of Swiss healthcare claims data. Swiss Med. Wkly., 151.","DOI":"10.4414\/smw.2021.20386"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1510","DOI":"10.1002\/pds.4897","article-title":"Prescription of antiepileptic medicines including valproate in pregnant women: A study in three European countries","volume":"28","author":"Morris","year":"2019","journal-title":"Pharmacoepidemiol. Drug Saf."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"380","DOI":"10.1111\/ijcp.12791","article-title":"Pregabalin prescriptions in the United Kingdom: A drug utilisation study of The Health Improvement Network (THIN) primary care database","volume":"70","author":"Asomaning","year":"2016","journal-title":"Int. J. Clin. Pract."},{"key":"ref_4","unstructured":"Daugaard, C.A., Sun, Y., Dreier, J.W., and Christensen, J. (2019). Use of antiepileptic drugs in women of fertile age. Dan. Med. J., 66."},{"key":"ref_5","first-page":"e167","article-title":"Risks of 23 specific malformations associated with prenatal exposure to 10 antiepileptic drugs","volume":"93","author":"Raguideau","year":"2019","journal-title":"Neurology"},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Margulis, A.V., Hernandez-Diaz, S., McElrath, T., Rothman, K.J., Plana, E., Almqvist, C., D\u2019onofrio, B.M., and Oberg, A.S. (2019). Relation of in-utero exposure to antiepileptic drugs to pregnancy duration and size at birth. PLoS ONE, 14.","DOI":"10.1101\/574269"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"2020","DOI":"10.1212\/WNL.0000000000003959","article-title":"Pregabalin use early in pregnancy and the risk of major congenital malformations","volume":"88","author":"Patorno","year":"2017","journal-title":"Neurology"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"630","DOI":"10.1111\/bcp.15607","article-title":"A critical appraisal of controlled studies investigating malformation risks following pregabalin use in early pregnancy","volume":"89","author":"Richardson","year":"2023","journal-title":"Br. J. Clin. Pharmacol."},{"key":"ref_9","unstructured":"Upjohn UK Limited (2025, May 09). Summary of Product Characteristics: Lyrica 100 mg Hard Capsules. Available online: www.medicines.org.uk\/emc\/product\/10303\/smpc."},{"key":"ref_10","unstructured":"Food and Drug Adminstration (FDA) (2025, May 09). Pharmacology Review Lyrica\u00ae Pregabalin Capsules, Available online: www.accessdata.fda.gov\/drugsatfda_docs\/label\/2006\/021446s002,s003lbl.pdf."},{"key":"ref_11","unstructured":"European Medicines Agency (2025, May 09). Summary of the European Public Assessment Report: Lyrica Pregabalin. Available online: www.ema.europa.eu\/en\/medicines\/human\/EPAR\/lyrica."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1002\/bdrb.21174","article-title":"Embryo-Fetal Developmental Toxicity Studies with Pregabalin in Mice and Rabbits","volume":"107","author":"Morse","year":"2016","journal-title":"Birth Defects Res. Part B Dev. Reprod. Toxicol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"113","DOI":"10.2174\/1574886313666180402145645","article-title":"Teratogenic Effects of Third-Generation Antiepileptic Drug, Pregabalin: An In vivo Study","volume":"13","author":"Singh","year":"2018","journal-title":"Curr. Drug Saf."},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Bergman, J.E.H., Perraud, A., Bari\u0161i\u0107, I., Kinsner-Ovaskainen, A., Morris, J.K., Tucker, D., Wellesley, D., and Garne, E. (2024). Updated EUROCAT guidelines for classification of cases with congenital anomalies. Birth Defects Res., 116.","DOI":"10.1002\/bdr2.2314"},{"key":"ref_15","unstructured":"(2025, May 09). Re: Product Literature (SmPC and PIL) Pregnancy Section Updates for Pregabalin. Available online: https:\/\/www.entis-org.eu\/wp-content\/uploads\/2022\/06\/ENTIS-pregabalin-SmPC-updates.pdf."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"661","DOI":"10.1007\/s40264-023-01307-2","article-title":"Prenatal exposure to pregabalin, birth outcomes and neurodevelopment\u2014A population-based cohort study in four Nordic countries","volume":"46","author":"Dudukina","year":"2023","journal-title":"Drug Saf."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"2251","DOI":"10.1212\/WNL.0000000000002767","article-title":"Pregnancy outcome following maternal exposure to pregabalin may call for concern","volume":"86","author":"Winterfeld","year":"2016","journal-title":"Neurology"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"2241","DOI":"10.1016\/j.jacc.2011.08.025","article-title":"Birth prevalence of congenital heart disease worldwide: A systematic review and meta-analysis","volume":"58","author":"Konings","year":"2011","journal-title":"J. Am. Coll. Cardiol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1007\/s40265-020-01432-7","article-title":"Abuse and Misuse of Pregabalin and Gabapentin: A Systematic Review Update","volume":"81","author":"Evoy","year":"2021","journal-title":"Drugs"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"153","DOI":"10.1007\/s40263-024-01064-5","article-title":"Trends in Pregabalin Use and Prescribing Patterns in the Adult Population: A 10-Year Pharmacoepidemiologic Study","volume":"38","author":"Dressler","year":"2024","journal-title":"CNS Drugs"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1127","DOI":"10.1007\/s40264-024-01448-y","article-title":"Identification of Pregnancy Adverse Drug Reactions in Pharmacovigilance Reporting Systems: A Novel Algorithm Developed in EudraVigilance","volume":"47","author":"Zaccaria","year":"2024","journal-title":"Drug Saf."},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Noseda, R., M\u00fcller, L., Bedussi, F., Fusaroli, M., Raschi, E., and Ceschi, A. (2022). Immune checkpoint inhibitors and pregnancy: Analysis of the VigiBase\u00ae Spontaneous Reporting System. Cancers, 15.","DOI":"10.3390\/cancers15010173"},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Noseda, R., Bedussi, F., Gobbi, C., Ceschi, A., and Zecca, C. (2024). Calcitonin gene-related peptide antagonists in pregnancy: A disproportionality analysis in VigiBase\u00ae. J. Headache Pain., 25.","DOI":"10.1186\/s10194-024-01715-4"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"346","DOI":"10.1002\/cpt.3269","article-title":"Safety of Monoclonal Antibodies Inhibiting PCSK9 in Pregnancy: Disproportionality Analysis in VigiBase\u00ae","volume":"116","author":"Noseda","year":"2024","journal-title":"Clin. Pharmacol. Ther."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1116","DOI":"10.1007\/s43441-020-00130-6","article-title":"WHODrug: A global, validated and updated dictionary for medicinal information","volume":"54","author":"Lagerlund","year":"2020","journal-title":"Ther. Innov. Regul. Sci."},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Cutroneo, P.M., Sartori, D., Tuccori, M., Crisafulli, S., Battini, V., Carnovale, C., Rafaniello, C., Capuano, A., Poluzzi, E., and Moretti, U. (2024). Conducting and interpreting disproportionality analyses derived from spontaneous reporting systems. Front. Drug Saf. Regul., 3.","DOI":"10.3389\/fdsfr.2023.1323057"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"3242","DOI":"10.1044\/2023_JSLHR-22-00739","article-title":"Identifying Medications Underlying Communication Atypicalities in Psychotic and Affective Disorders: A Pharmacovigilance Study Within the FDA Adverse Event Reporting System","volume":"66","author":"Fusaroli","year":"2023","journal-title":"J. Speech Lang. Hear. Res."},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Sultana, J., Scondotto, G., Cutroneo, P.M., Morgante, F., and Trifir\u00f2, G. (2020). Intravitreal Anti-VEGF Drugs and Signals of Dementia and Parkinson-Like Events: Analysis of the VigiBase Database of Spontaneous Reports. Front. Pharmacol., 11.","DOI":"10.3389\/fphar.2020.00315"},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Tian, X., Chen, L., Gai, D., He, S., Jiang, X., and Zhang, N. (2022). Adverse Event Profiles of PARP Inhibitors: Analysis of Spontaneous Reports Submitted to FAERS. Front. Pharmacol., 13.","DOI":"10.3389\/fphar.2022.851246"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"999","DOI":"10.1007\/s40264-020-00957-w","article-title":"Risk Factor Considerations in Statistical Signal Detection: Using Subgroup Disproportionality to Uncover Risk Groups for Adverse Drug Reactions in VigiBase","volume":"43","author":"Sandberg","year":"2020","journal-title":"Drug Saf."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"601","DOI":"10.1007\/s40264-023-01306-3","article-title":"Identifying Safety Subgroups at Risk: Assessing the Agreement Between Statistical Alerting and Patient Subgroup Risk","volume":"46","author":"Mahaux","year":"2023","journal-title":"Drug Saf."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"575","DOI":"10.1007\/s40264-024-01421-9","article-title":"The Reporting of a Disproportionality Analysis for Drug Safety Signal Detection Using Individual Case Safety Reports in PharmacoVigilance (READUS-PV): Development and Statement","volume":"47","author":"Fusaroli","year":"2024","journal-title":"Drug Saf."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"585","DOI":"10.1007\/s40264-024-01423-7","article-title":"The REporting of A Disproportionality Analysis for DrUg Safety Signal Detection Using Individual Case Safety Reports in PharmacoVigilance (READUS-PV): Explanation and Elaboration","volume":"47","author":"Fusaroli","year":"2024","journal-title":"Drug Saf."}],"container-title":["Pharmaceuticals"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1424-8247\/18\/5\/759\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T17:36:03Z","timestamp":1760031363000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1424-8247\/18\/5\/759"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,5,20]]},"references-count":33,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2025,5]]}},"alternative-id":["ph18050759"],"URL":"https:\/\/doi.org\/10.3390\/ph18050759","relation":{},"ISSN":["1424-8247"],"issn-type":[{"value":"1424-8247","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,5,20]]}}}