{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,27]],"date-time":"2026-08-27T19:57:08Z","timestamp":1787860628831,"version":"build-2784847793"},"reference-count":46,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2024,5,7]],"date-time":"2024-05-07T00:00:00Z","timestamp":1715040000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100007281","name":"National Drug and Alcohol Research Centre","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100007281","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100007281","name":"National Drug and Alcohol Research Centre","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100007281","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003921","name":"Department of Health and Aged Care, Australian Government","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100003921","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["associationofanaesthetists-publications.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Anaesthesia"],"published-print":{"date-parts":[[2024,9]]},"abstract":"<jats:title>Summary<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Prescribed opioid analgesics are frequently used to manage pain in pregnancy. However, the available literature regarding the teratogenic potential of opioid use during pregnancy has not been systematically summarised. This systematic review and meta\u2010analysis aimed to assess the quality of the evidence on these potential risks and calculate a pooled estimate of risk for any opioid analgesic and individual opioids.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We searched PubMed, Embase and CINAHL for published studies assessing the risk of major congenital malformations in infants following first\u2010trimester exposure to opioid analgesics compared with a reference group, excluding studies examining opioid agonist therapy or illicit opioid use. We assessed the risk of bias using the Risk of Bias in Non\u2010Randomised Studies of Intervention tool. We pooled adjusted risk estimates from studies rated at serious risk of bias or better in a random\u2010effects meta\u2010analysis.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Of 12 identified studies, 11 were at high risk of bias (eight serious; three critical). Relative to unexposed infants, those exposed to any opioid use during the first trimester of pregnancy were not at an increased risk of major congenital malformations overall (relative risk 1.04, 95%CI 0.98\u20131.11); cardiovascular malformations (relative risk 1.07, 95%CI 0.96\u20131.20); or central nervous system malformations (relative risk 1.06, 95%CI 0.92\u20131.21). Raised risk estimates were observed for gastrointestinal malformations (relative risk 1.40, 95%CI 0.38\u20135.16) and cleft palate (relative risk 1.57, 95%CI 0.48\u20135.13) following any opioid exposure and atrial septal defects (relative risk 1.20, 95%CI 1.05\u20131.36) following codeine exposure.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Although the meta\u2010analysis did not indicate substantial increased risk for most malformations examined, this risk remains uncertain due to the methodological limitations of the included studies. Healthcare professionals and pharmaceutical regulators should be aware of the issues related to the quality of research in this field.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/anae.16307","type":"journal-article","created":{"date-parts":[[2024,5,8]],"date-time":"2024-05-08T00:24:29Z","timestamp":1715127869000},"page":"967-977","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Opioid analgesic exposure during the first trimester of pregnancy and the risk of major congenital malformations in infants: a systematic review and meta\u2010analysis\n                    <sup>\u2020<\/sup>"],"prefix":"10.1111","volume":"79","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0611-6018","authenticated-orcid":false,"given":"Bianca","family":"Varney","sequence":"first","affiliation":[{"name":"School of Population Health, Faculty of Medicine and Health UNSW Sydney  Sydney NSW Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonathan","family":"Brett","sequence":"additional","affiliation":[{"name":"School of Population Health, Faculty of Medicine and Health UNSW Sydney  Sydney NSW Australia"},{"name":"St. Vincent's Clinical School St. Vincent's Hospital  Sydney NSW Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Helga","family":"Zoega","sequence":"additional","affiliation":[{"name":"School of Population Health, Faculty of Medicine and Health UNSW Sydney  Sydney NSW Australia"},{"name":"Centre of Public Health Sciences, Faculty of Medicine University of Iceland  Reykjavik Iceland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Malcolm B.","family":"Gillies","sequence":"additional","affiliation":[{"name":"School of Population Health, Faculty of Medicine and Health UNSW Sydney  Sydney NSW Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Madeline","family":"Powell","sequence":"additional","affiliation":[{"name":"School of Population Health, Faculty of Medicine and Health UNSW Sydney  Sydney NSW Australia"},{"name":"National Drug and Alcohol Research Centre, Faculty of Medicine and Health UNSW Sydney  Sydney NSW Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brian T.","family":"Bateman","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, Perioperative and Pain Medicine Stanford University  Stanford CA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonia W.","family":"Shand","sequence":"additional","affiliation":[{"name":"Department of Maternal Fetal Medicine Royal Hospital for Women  Randwick, Sydney NSW Australia"},{"name":"Faculty of Medicine and Health Children's Hospital at Westmead Clinical School  Sydney NSW Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sallie\u2010Anne","family":"Pearson","sequence":"additional","affiliation":[{"name":"School of Population Health, Faculty of Medicine and Health UNSW Sydney  Sydney NSW Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alys","family":"Havard","sequence":"additional","affiliation":[{"name":"School of Population Health, Faculty of Medicine and Health UNSW Sydney  Sydney NSW Australia"},{"name":"National Drug and Alcohol Research Centre, Faculty of Medicine and Health UNSW Sydney  Sydney NSW Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,5,7]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11096\u2010016\u20100322\u20105"},{"key":"e_1_2_6_3_1","unstructured":"Australian Government Therapeutic Goods Administration.Nonsteroidal anti\u2010inflammatory drugs (NSAIDs) and spontaneous abortion. 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