{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,28]],"date-time":"2026-10-28T03:07:33Z","timestamp":1793156853851,"version":"4.5.0"},"reference-count":12,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2025,3,25]],"date-time":"2025-03-25T00:00:00Z","timestamp":1742860800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Pharmacoepidemiology and Drug"],"published-print":{"date-parts":[[2025,4]]},"abstract":"ABSTRACT<\/jats:title>Purpose<\/jats:title>The aim of the study was to assess the risk of pregnancy termination and major congenital anomalies with tramadol by comparing women exposed to tramadol during pregnancy with women exposed to codeine and unexposed women, using the French EFEMERIS database.<\/jats:p><\/jats:sec>Methods<\/jats:title>The study was based on the EFEMERIS (\u00c9valuation chez la Femme Enceinte des M\u00c9dicaments et de leurs RISques<\/jats:italic>) database, which contains reimbursed medications prescribed and dispensed to pregnant women, dates of conception and pregnancy outcome, and data on the children (congenital anomalies, neonatal diseases, etc.). Women were considered to be exposed if they were prescribed and dispensed tramadol or codeine at least once during pregnancy. Women who had a pregnancy outcome between July 1, 2004 and December 31, 2020 and living in Haute\u2010Garonne (south\u2010west France) were included in this study.<\/jats:p><\/jats:sec>Results<\/jats:title>We compared 1602 (1.0%) pregnancies exposed to tramadol (including 1628 fetuses\/newborns due to multiple pregnancies) with 6311 (3.8%) exposed to codeine (including 6406 fetuses\/newborns) and 158\u2009426 (95.2%) unexposed to tramadol and codeine (including 160\u2009784 fetuses\/newborns). The rate of pregnancies exposed to tramadol increased sevenfold between 2004 and 2020. The study showed an increase in the rate of spontaneous pregnancy termination in women exposed to tramadol compared with women exposed to codeine (aHR [95% CI]\u2009=\u20092.23[1.64\u20133.03]) and unexposed women (aHR [95% CI]\u2009=\u20091.86[1.46\u20132.37]), after adjustment for maternal age, dispensation of folic acid, teratogenic drugs, NSAIDs, presence of hypertension, diabetes, and long\u2010term Illness. Multivariate analysis did not show an increased rate of major congenital anomalies in fetuses\/newborns exposed in utero to tramadol during the first trimester of pregnancy compared with fetuses\/newborns exposed to codeine (ORa [95% CI]\u2009=\u20091.03 [0.67\u20131.57]) and those not exposed to these medications (ORa [95% CI]\u2009=\u20091.24 [0.86\u20131.79]).<\/jats:p><\/jats:sec>Conclusion<\/jats:title>This study found an association between tramadol use and the risk of spontaneous pregnancy termination. We cannot conclude that there is a causal link because of a possible indication bias. No association between prescription and dispensation of tramadol during the first trimester of pregnancy and an increased risk of major congenital anomalies has been found.<\/jats:p><\/jats:sec>","DOI":"10.1002\/pds.70143","type":"journal-article","created":{"date-parts":[[2025,3,28]],"date-time":"2025-03-28T08:14:29Z","timestamp":1743149669000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Tramadol During Pregnancy: Risk of Adverse Pregnancy Outcome and Major Congenital Anomalies. A Comparative Study in the EFEMERIS<\/scp> Database"],"prefix":"10.1002","volume":"34","author":[{"ORCID":"https:\/\/orcid.org\/0009-0004-0143-0130","authenticated-orcid":false,"given":"Eva","family":"Ferrer","sequence":"first","affiliation":[{"name":"R\u00e9seau REGARDS, Service de Pharmacologie M\u00e9dicale et Clinique, Facult\u00e9 de M\u00e9decine CHU de Toulouse, INSERM 1295 CERPOP Toulouse France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laurane","family":"Delteil","sequence":"additional","affiliation":[{"name":"R\u00e9seau REGARDS, Service de Pharmacologie M\u00e9dicale et Clinique, Facult\u00e9 de M\u00e9decine CHU de Toulouse, INSERM 1295 CERPOP Toulouse France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anthony","family":"Caillet","sequence":"additional","affiliation":[{"name":"R\u00e9seau REGARDS, Service de Pharmacologie M\u00e9dicale et Clinique, Facult\u00e9 de M\u00e9decine CHU de Toulouse, INSERM 1295 CERPOP Toulouse France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fatiha","family":"Karam","sequence":"additional","affiliation":[{"name":"Cellule \u201cReproduction Grossesse et Allaitement\u201d ANSM Saint\u2010Denis France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7344-7282","authenticated-orcid":false,"given":"Isabelle","family":"Lacroix","sequence":"additional","affiliation":[{"name":"R\u00e9seau REGARDS, Service de Pharmacologie M\u00e9dicale et Clinique, Facult\u00e9 de M\u00e9decine CHU de Toulouse, INSERM 1295 CERPOP Toulouse France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,3,25]]},"reference":[{"issue":"4","key":"e_1_2_10_2_1","first-page":"395","article-title":"Tramadol, Pharmacology, Side Effects, and Serotonin Syndrome: A Review","volume":"18","author":"Beakley B. D.","year":"2015","journal-title":"Pain Physician"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.reprotox.2015.10.007"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1097\/AOG.0000000000004714"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00228-009-0647-2"},{"key":"e_1_2_10_6_1","volume-title":"Etat des lieux de la consommation des antalgiques opio\u00efdes et leurs usages probl\u00e9matiques","author":"Monzon E.","year":"2019"},{"key":"e_1_2_10_7_1","volume-title":"Avis tramadol (chlorhydrate de)","author":"Commission de la Transparence","year":"2016"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.2515\/therapie\/2011004"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1111\/1753-6405.12762"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1111\/aogs.13920"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijoa.2011.03.002"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.322.7281.266"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.327.7411.368"}],"container-title":["Pharmacoepidemiology and Drug Safety"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/pds.70143","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,4,24]],"date-time":"2025-04-24T01:57:00Z","timestamp":1745459820000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/pds.70143"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,3,25]]},"references-count":12,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2025,4]]}},"alternative-id":["10.1002\/pds.70143"],"URL":"https:\/\/doi.org\/10.1002\/pds.70143","archive":["Portico"],"relation":{},"ISSN":["1053-8569","1099-1557"],"issn-type":[{"value":"1053-8569","type":"print"},{"value":"1099-1557","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,3,25]]},"assertion":[{"value":"2024-07-31","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-03-14","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-03-25","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70143"}}