{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,23]],"date-time":"2026-06-23T08:08:27Z","timestamp":1782202107825,"version":"3.54.5"},"reference-count":60,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2021,12,22]],"date-time":"2021-12-22T00:00:00Z","timestamp":1640131200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100007605","name":"Aarhus Universitet","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100007605","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Basic Clin Pharma Tox"],"published-print":{"date-parts":[[2022,3]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>With an increased prevalence of concurrent morbidities during pregnancy, polypharmacy has become increasingly common in pregnant women. The risks associated with polypharmacy may exceed those of individual medication because of drug\u2013drug interactions. This systematic review aims to evaluate the risk of congenital malformations in polymorbid pregnancies exposed to first\u2010trimester polypharmacy. PubMed, Embase and Scopus were searched to identify original human studies with first\u2010 trimester polypharmacy due to polymorbidity as the exposure and congenital malformations as the outcome. After screening of 4034 identified records, seven studies fulfilled the inclusion criteria. Four of the seven studies reported an increased risk of congenital malformations compared with unexposed or monotherapy, odds ratios ranging from 1.1 to &gt;10.0. Particularly, short\u2010term anti\u2010infective treatment combined with other drugs and P\u2010glycoprotein substrates were associated with increased malformation risks. In conclusion, knowledge is limited on risks associated with first\u2010trimester polypharmacy due to polymorbidity with the underlying evidence of low quantity and quality. Therefore, an increased focus on pharmacovigilance to enable safe drug use in early pregnancy is needed. Large\u2010scale register\u2010based studies and better knowledge of placental biology are needed to support the clinical management of polymorbid pregnancies that require polypharmacy.<\/jats:p>","DOI":"10.1111\/bcpt.13695","type":"journal-article","created":{"date-parts":[[2021,11,29]],"date-time":"2021-11-29T08:20:31Z","timestamp":1638174031000},"page":"394-414","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Polypharmacy in polymorbid pregnancies and the risk of congenital malformations\u2014A systematic review"],"prefix":"10.1111","volume":"130","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7180-3180","authenticated-orcid":false,"given":"Mette \u00d8stergaard","family":"Thunbo","sequence":"first","affiliation":[{"name":"Department of Clinical Medicine Aarhus University  Aarhus Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julie Hauer","family":"Vendelbo","sequence":"additional","affiliation":[{"name":"Department of Clinical Medicine Aarhus University  Aarhus Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9158-0893","authenticated-orcid":false,"given":"Tabia","family":"Volqvartz","sequence":"additional","affiliation":[{"name":"Department of Clinical Medicine Aarhus University  Aarhus Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel R.","family":"Witte","sequence":"additional","affiliation":[{"name":"Department of Public Health Aarhus University  Aarhus Denmark"},{"name":"Steno Diabetes Center Aarhus Aarhus University Hospital  Aarhus Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Agnete","family":"Larsen","sequence":"additional","affiliation":[{"name":"Department of Biomedicine Aarhus University  Aarhus Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lars Henning","family":"Pedersen","sequence":"additional","affiliation":[{"name":"Department of Clinical Medicine Aarhus University  Aarhus Denmark"},{"name":"Department of Biomedicine Aarhus University  Aarhus Denmark"},{"name":"Department of Obstetrics and Gynaecology Aarhus University Hospital  Aarhus Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2021,12,22]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajog.2011.02.029"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.semperi.2015.08.002"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1093\/humrep\/det369"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1089\/jwh.2005.14.401"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1067\/mob.2003.223"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1136\/bmjopen-2013-004365"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1002\/bdrc.21096"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12916-017-0845-1"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0198447"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tmaid.2019.01.008"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.4088\/JCP.18r12412"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1345\/aph.1P764"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.n71"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.n160"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1590\/S0104-11692007000300023"},{"key":"e_1_2_10_17_1","volume-title":"Covidence Systematic Review Software","author":"Veritas Health Innovation","year":"2021"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.1177\/2633556521993993"},{"key":"e_1_2_10_19_1","volume-title":"R: A Language and Environment for Statistical Computing","author":"R Core Team","year":"2021"},{"key":"e_1_2_10_20_1","unstructured":"Wells G. et al.The Newcastle\u2010Ottawa Scale (NOS) for assessing the quality of nonrandomised studies in meta\u2010analyses.2019. Available from:http:\/\/www.ohri.ca\/programs\/clinical_epidemiology\/oxford.asp"},{"key":"e_1_2_10_21_1","unstructured":"Howick J. et al.The Oxford 2011 levels of evidence.2011. Available from:https:\/\/www.cebm.ox.ac.uk\/resources\/levels-of-evidence\/ocebm-levels-of-evidence"},{"key":"e_1_2_10_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0890-6238(01)00178-2"},{"key":"e_1_2_10_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.reprotox.2004.11.012"},{"key":"e_1_2_10_24_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40264-015-0299-3"},{"key":"e_1_2_10_25_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0173530"},{"key":"e_1_2_10_26_1","doi-asserted-by":"publisher","DOI":"10.1111\/bcp.14191"},{"key":"e_1_2_10_27_1","doi-asserted-by":"publisher","DOI":"10.1111\/epi.14539"},{"key":"e_1_2_10_28_1","doi-asserted-by":"publisher","DOI":"10.3233\/JRS-1996-8307"},{"key":"e_1_2_10_29_1","doi-asserted-by":"publisher","DOI":"10.1124\/jpet.107.121772"},{"key":"e_1_2_10_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bcp.2004.05.014"},{"key":"e_1_2_10_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bcp.2008.01.004"},{"key":"e_1_2_10_32_1","doi-asserted-by":"publisher","DOI":"10.1248\/bpb.b13-00369"},{"key":"e_1_2_10_33_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamapediatrics.2013.4914"},{"key":"e_1_2_10_34_1","doi-asserted-by":"publisher","DOI":"10.1002\/pds.3940"},{"key":"e_1_2_10_35_1","doi-asserted-by":"publisher","DOI":"10.1136\/bmjopen-2017-018390"},{"key":"e_1_2_10_36_1","doi-asserted-by":"publisher","DOI":"10.1111\/bcpt.13396"},{"key":"e_1_2_10_37_1","doi-asserted-by":"publisher","DOI":"10.1067\/mob.2002.127376"},{"key":"e_1_2_10_38_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0022174"},{"key":"e_1_2_10_39_1","doi-asserted-by":"publisher","DOI":"10.1097\/AOG.0b013e3181c52616"},{"issue":"3","key":"e_1_2_10_40_1","first-page":"217","article-title":"Advanced maternal age and the risk of major congenital anomalies","volume":"34","author":"Goetzinger KR","year":"2017","journal-title":"Am J Perinatol"},{"key":"e_1_2_10_41_1","doi-asserted-by":"publisher","DOI":"10.1111\/aogs.12433"},{"key":"e_1_2_10_42_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2018.10.050"},{"key":"e_1_2_10_43_1","doi-asserted-by":"publisher","DOI":"10.2147\/CLEP.S298748"},{"key":"e_1_2_10_44_1","doi-asserted-by":"publisher","DOI":"10.1002\/uog.18932"},{"key":"e_1_2_10_45_1","doi-asserted-by":"publisher","DOI":"10.1002\/bdra.20393"},{"key":"e_1_2_10_46_1","doi-asserted-by":"publisher","DOI":"10.1093\/oxfordjournals.aje.a009758"},{"key":"e_1_2_10_47_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-018-21917-6"},{"key":"e_1_2_10_48_1","doi-asserted-by":"publisher","DOI":"10.1111\/bcp.12292"},{"key":"e_1_2_10_49_1","doi-asserted-by":"publisher","DOI":"10.1080\/14740338.2018.1546841"},{"issue":"3","key":"e_1_2_10_50_1","first-page":"241","article-title":"Association between anti\u2010thyroid peroxidase antibody and asthma in women","volume":"11","author":"Samareh Fekri M","year":"2012","journal-title":"Iran J Allergy Asthma Immunol"},{"key":"e_1_2_10_51_1","doi-asserted-by":"publisher","DOI":"10.3390\/nu12051434"},{"issue":"1","key":"e_1_2_10_52_1","first-page":"11s","article-title":"Influence of febrile disease on the pharmacokinetics of veterinary drugs","volume":"21","author":"Miert A","year":"1990","journal-title":"Ann Rech Vet"},{"key":"e_1_2_10_53_1","doi-asserted-by":"publisher","DOI":"10.1080\/17425255.2018.1499726"},{"key":"e_1_2_10_54_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0014-2999(00)00743-3"},{"key":"e_1_2_10_55_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpregu.00173.2005"},{"key":"e_1_2_10_56_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40262-020-00867-1"},{"key":"e_1_2_10_57_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0890-6238(98)00027-6"},{"key":"e_1_2_10_58_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11095-016-2028-8"},{"key":"e_1_2_10_59_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.placenta.2015.08.007"},{"key":"e_1_2_10_60_1","doi-asserted-by":"publisher","DOI":"10.1210\/clinem\/dgaa660"},{"key":"e_1_2_10_61_1","article-title":"Transfer learning for non\u2010image data in clinical research: a scoping review","author":"Ebbehoj A","year":"2021","journal-title":"medRxiv"}],"container-title":["Basic &amp; Clinical Pharmacology &amp; Toxicology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/bcpt.13695","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/bcpt.13695","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/bcpt.13695","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,8,22]],"date-time":"2023-08-22T21:02:50Z","timestamp":1692738170000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/bcpt.13695"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,12,22]]},"references-count":60,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2022,3]]}},"alternative-id":["10.1111\/bcpt.13695"],"URL":"https:\/\/doi.org\/10.1111\/bcpt.13695","archive":["Portico"],"relation":{},"ISSN":["1742-7835","1742-7843"],"issn-type":[{"value":"1742-7835","type":"print"},{"value":"1742-7843","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,12,22]]},"assertion":[{"value":"2021-06-15","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2021-11-19","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2021-12-22","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}