{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T15:14:59Z","timestamp":1790176499633,"version":"4.1.0"},"reference-count":28,"publisher":"Wiley","issue":"13","license":[{"start":{"date-parts":[[2019,9,18]],"date-time":"2019-09-18T00:00:00Z","timestamp":1568764800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81601186"],"award-info":[{"award-number":["81601186"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["obgyn.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["BJOG"],"published-print":{"date-parts":[[2019,12]]},"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>Oral fluconazole is used to treat vulvovaginal candidiasis during pregnancy. However, there are concerns regarding the pregnancy outcomes following exposure to fluconazole.<\/jats:p><\/jats:sec><jats:sec><jats:title>Objectives<\/jats:title><jats:p>To evaluate the pregnancy outcomes associated with exposure to oral fluconazole during the first trimester of pregnancy.<\/jats:p><\/jats:sec><jats:sec><jats:title>Search strategy<\/jats:title><jats:p>A systematic literature search was conducted to identify relevant studies published from inception until April 2019.<\/jats:p><\/jats:sec><jats:sec><jats:title>Selection criteria<\/jats:title><jats:p>Relevant English\u2010language citations using the terms oral fluconazole and pregnancy in humans.<\/jats:p><\/jats:sec><jats:sec><jats:title>Data collection<\/jats:title><jats:p>Two reviewers independently abstracted data and assessed study quality.<\/jats:p><\/jats:sec><jats:sec><jats:title>Main results<\/jats:title><jats:p>Oral fluconazole use during the first trimester of pregnancy was marginally associated with an increased risk of congenital malformations (odds ratio [<jats:styled-content style=\"fixed-case\">OR<\/jats:styled-content>] 1.09, 95% <jats:styled-content style=\"fixed-case\">CI<\/jats:styled-content> 0.99\u20131.2, <jats:italic>P\u00a0<\/jats:italic>=\u00a00.088; <jats:italic>n\u00a0<\/jats:italic>=\u00a06 studies), whereas in the subgroup analysis, this association existed only for high\u2010dose users (&gt;150\u00a0mg) (<jats:styled-content style=\"fixed-case\">OR<\/jats:styled-content> 1. 19, 95% <jats:styled-content style=\"fixed-case\">CI<\/jats:styled-content> 1.01\u20131.4, <jats:italic>P\u00a0<\/jats:italic>=\u00a00.039; <jats:italic>n\u00a0<\/jats:italic>=\u00a02). Exposure to fluconazole also increased the risk of heart malformations (<jats:styled-content style=\"fixed-case\">OR<\/jats:styled-content> 1.31, 95% <jats:styled-content style=\"fixed-case\">CI<\/jats:styled-content> 1.09\u20131.57, <jats:italic>P\u00a0<\/jats:italic>=\u00a00.003; <jats:italic>n\u00a0<\/jats:italic>=\u00a04), cardiac septal defects (<jats:styled-content style=\"fixed-case\">OR<\/jats:styled-content> 1.3, 95% <jats:styled-content style=\"fixed-case\">CI<\/jats:styled-content> 1.1\u20131.67, <jats:italic>P\u00a0<\/jats:italic>=\u00a00.047; <jats:italic>n\u00a0<\/jats:italic>=\u00a03), and tetralogy of Fallot (<jats:styled-content style=\"fixed-case\">OR<\/jats:styled-content> 3.39 95% <jats:styled-content style=\"fixed-case\">CI<\/jats:styled-content> 1.71\u20136.74, <jats:italic>P<\/jats:italic>\u00a0&lt;\u00a00.001; <jats:italic>n\u00a0<\/jats:italic>=\u00a02) in the offspring. In addition, exposure to fluconazole was significantly associated with an increased risk of spontaneous abortion (<jats:styled-content style=\"fixed-case\">OR<\/jats:styled-content> 1.99, 95% <jats:styled-content style=\"fixed-case\">CI<\/jats:styled-content> 1.38\u20132.88, <jats:italic>P\u00a0<\/jats:italic>&lt;\u00a00.001; <jats:italic>n\u00a0<\/jats:italic>=\u00a03).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Oral fluconazole use during the first trimester of pregnancy appears to be associated with heart malformations and spontaneous abortion, but a causal link cannot be proven.<\/jats:p><\/jats:sec><jats:sec><jats:title>Tweetable abstract<\/jats:title><jats:p>Oral fluconazole during the first trimester of pregnancy may be associated with unfavourable pregnancy outcomes.<\/jats:p><\/jats:sec>","DOI":"10.1111\/1471-0528.15913","type":"journal-article","created":{"date-parts":[[2019,8,25]],"date-time":"2019-08-25T06:58:27Z","timestamp":1566716307000},"page":"1546-1552","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":35,"title":["The safety of oral fluconazole during the first trimester of pregnancy: a systematic review and meta\u2010analysis"],"prefix":"10.1111","volume":"126","author":[{"given":"Z","family":"Zhang","sequence":"first","affiliation":[{"name":"Department of Urology College of Medicine The First Affiliated Hospital Zhejiang University Hangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"X","family":"Zhang","sequence":"additional","affiliation":[{"name":"Collaborative Innovation Centre for Diagnosis and Treatment of Infectious Diseases State Key Laboratory for Diagnosis and Treatment of Infectious Diseases School of Medicine the First Affiliated Hospital Zhejiang University Hangzhou Zhejiang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Y\u2010y","family":"Zhou","sequence":"additional","affiliation":[{"name":"Department of Child Psychiatry Hangzhou Seventh People's Hospital Hangzhou Zhejiang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C\u2010m","family":"Jiang","sequence":"additional","affiliation":[{"name":"Department of Paediatrics the Affiliated Hangzhou First People's Hospital Zhejiang University School of Medicine Hangzhou Zhejiang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7601-7827","authenticated-orcid":false,"given":"H\u2010y","family":"Jiang","sequence":"additional","affiliation":[{"name":"Collaborative Innovation Centre for Diagnosis and Treatment of Infectious Diseases State Key Laboratory for Diagnosis and Treatment of Infectious Diseases School of Medicine the First Affiliated Hospital Zhejiang University Hangzhou Zhejiang China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2019,9,18]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.68.2.651-657.2000"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(07)60917-9"},{"key":"e_1_2_6_4_1","first-page":"1","article-title":"Sexually transmitted diseases treatment guidelines, 2015","volume":"64","author":"Workowski KA","year":"2015","journal-title":"MMWR Recommend Rep"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1439-0507.2012.02185.x"},{"key":"e_1_2_6_6_1","first-page":"554","article-title":"The teratogenic effects of 5\u2010fluorocytosine in the rat","volume":"29","author":"Chaube S","year":"1969","journal-title":"Can Res"},{"key":"e_1_2_6_7_1","doi-asserted-by":"publisher","DOI":"10.1002\/bdra.10022"},{"key":"e_1_2_6_8_1","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1096-8628(19971031)72:3<253::AID-AJMG1>3.0.CO;2-S"},{"key":"e_1_2_6_9_1","doi-asserted-by":"publisher","DOI":"10.1093\/clinids\/22.2.336"},{"key":"e_1_2_6_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0002-9378(96)70119-9"},{"key":"e_1_2_6_11_1","doi-asserted-by":"publisher","DOI":"10.1592\/phco.19.3.221.30919"},{"key":"e_1_2_6_12_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2125.1999.00989.x"},{"key":"e_1_2_6_13_1","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/dkn157"},{"key":"e_1_2_6_14_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1301066"},{"key":"e_1_2_6_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.reprotox.2015.02.009"},{"key":"e_1_2_6_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajog.2015.11.022"},{"key":"e_1_2_6_17_1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2015.17844"},{"key":"e_1_2_6_18_1","doi-asserted-by":"publisher","DOI":"10.1503\/cmaj.180963"},{"key":"e_1_2_6_19_1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.283.15.2008"},{"key":"e_1_2_6_20_1","unstructured":"Higgins.Cochrane Handbook for Systematic Reviews of Interventions version 5.1.0. 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