{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,27]],"date-time":"2026-07-27T18:17:45Z","timestamp":1785176265882,"version":"3.55.0"},"reference-count":59,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2025,10,29]],"date-time":"2025-10-29T00:00:00Z","timestamp":1761696000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["obgyn.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J of Obstet and Gynaecol"],"published-print":{"date-parts":[[2025,11]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>To evaluate valproic acid (VPA) safety in pregnancy versus other antiepileptic drugs (AEDs), focusing on fetal malformation risks.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>A literature search was conducted across PUBMED, MEDLINE, EMBASE, and Web of Science databases. Two researchers independently screened studies, extracted data, assessed quality, and analyzed VPA safety.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>This meta\u2010analysis of 25 safety studies showed that compared with other AEDs, VPA's teratogenic risks were as follows: combined major congenital malformations (RR\u2009=\u20092.36, 95% CI: 2.17\u20132.56), neural tube defects (RR\u2009=\u20096.54, 95% CI: 4.51\u20139.47), congenital heart defects (RR\u2009=\u20092.53, 95% CI: 2.16\u20132.96), cleft lip and\/or palate (RR\u2009=\u20094.31, 95% CI: 3.06\u20136.08), genitourinary anomalies (RR\u2009=\u20093.32, 95% CI: 2.67\u20134.14), and musculoskeletal anomalies (RR\u2009=\u20092.88, 95% CI: 1.98\u20134.19). Additional analyses stratified by calendar era yielded consistent results, with the corresponding RR values for the above malformations being 2.43 (95% CI: 2.13\u20132.77), 6.64 (95% CI: 4.50\u20139.79), 2.64 (95% CI: 2.14\u20133.26), 4.27 (95% CI: 2.98\u20136.12), 3.45 (95% CI: 2.76\u20134.31), and 2.99 (95% CI: 2.00\u20134.46), indicating a higher risk of multiple malformations with VPA.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>VPA monotherapy significantly increases teratogenic risk, especially for neural tube defects and cleft lip\/palate. Newer AEDs with lower risk profiles are preferred for epilepsy treatment during pregnancy. If VPA use is unavoidable, low doses and blood concentration monitoring are recommended to mitigate risk.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/jog.70121","type":"journal-article","created":{"date-parts":[[2025,10,30]],"date-time":"2025-10-30T00:31:47Z","timestamp":1761784307000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Safety of Valproic Acid Use in Pregnant Women: A Systematic Review and Meta\u2010Analysis"],"prefix":"10.1111","volume":"51","author":[{"given":"Xinying","family":"Yang","sequence":"first","affiliation":[{"name":"Department of Pharmacy, Beijing Friendship Hospital Capital Medical University  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yiqi","family":"Sun","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Beijing Friendship Hospital Capital Medical University  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zixin","family":"Hua","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Beijing Friendship Hospital Capital Medical University  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Taoran","family":"Li","sequence":"additional","affiliation":[{"name":"Big Data Center, Central China Subcenter of National Center for Cardiovascular Diseases, Henan Cardiovascular Disease Center, Fuwai Central China Cardiovascular Hospital Central China Fuwai Hospital of Zhengzhou University  Zhengzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xingang","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Beijing Friendship Hospital Capital Medical University  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6943-485X","authenticated-orcid":false,"given":"Pengqiang","family":"Du","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Fuwai Central China Cardiovascular Hospital, Henan Provincial People's Hospital Central China Fuwai Hospital of Zhengzhou University  Zhengzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,10,29]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(15)00045-8"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamaneurol.2017.1310"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamaneurol.2023.0148"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1111\/epi.13021"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(18)31672-6"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1002\/cpt.158"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1136\/bmjopen-2017-017248"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamaneurol.2024.0258"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.26561"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1002\/pds.3731"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000007696"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.seizure.2018.02.009"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.seizure.2021.10.015"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(18)30107-8"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.1320190303"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1528-1157.1988.tb03746.x"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.1136\/adc.66.3.320"},{"issue":"2","key":"e_1_2_10_19_1","first-page":"306","article-title":"Teratogenicity of Antiepileptic Drugs and Drug Specific Malformations","volume":"47","author":"Kaneko S.","year":"1993","journal-title":"Japanese Journal of Psychiatry and Neurology"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0920-1211(98)00084-9"},{"key":"e_1_2_10_21_1","doi-asserted-by":"publisher","DOI":"10.1053\/seiz.1998.0239"},{"key":"e_1_2_10_22_1","doi-asserted-by":"publisher","DOI":"10.1002\/1531-8249(199911)46:5<739::AID-ANA9>3.0.CO;2-2"},{"key":"e_1_2_10_23_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1528-1157.1999.tb00851.x"},{"key":"e_1_2_10_24_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM200104123441504"},{"key":"e_1_2_10_25_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1651-2227.2004.tb00701.x"},{"key":"e_1_2_10_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.yebeh.2003.11.020"},{"key":"e_1_2_10_27_1","doi-asserted-by":"publisher","DOI":"10.1212\/01.WNL.0000163771.96962.1F"},{"issue":"2","key":"e_1_2_10_28_1","first-page":"53","article-title":"Pregnancy and Teratogenicity of Antiepileptic Drugs","volume":"108","author":"Eroglu E.","year":"2008","journal-title":"Acta Neurologica Belgica"},{"key":"e_1_2_10_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.seizure.2009.11.008"},{"key":"e_1_2_10_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(11)70107-7"},{"key":"e_1_2_10_31_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0b013e3182574f39"},{"key":"e_1_2_10_32_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.reprotox.2013.04.002"},{"key":"e_1_2_10_33_1","doi-asserted-by":"publisher","DOI":"10.1136\/jnnp-2013-306318"},{"key":"e_1_2_10_34_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-0404.1988.tb03655.x"},{"key":"e_1_2_10_35_1","doi-asserted-by":"publisher","DOI":"10.2165\/00023210-200216100-00003"},{"key":"e_1_2_10_36_1","doi-asserted-by":"publisher","DOI":"10.1212\/CON.0000000000000289"},{"issue":"12","key":"e_1_2_10_37_1","article-title":"Antiepileptic Drug Monotherapy for Epilepsy: A Network Meta\u2010Analysis of Individual Participant Data","volume":"12","author":"Nevitt S. J.","year":"2017","journal-title":"Cochrane Database of Systematic Reviews"},{"key":"e_1_2_10_38_1","doi-asserted-by":"publisher","DOI":"10.1002\/bdra.23277"},{"key":"e_1_2_10_39_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1528-1167.2009.02128.x"},{"key":"e_1_2_10_40_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40262-019-00845-2"},{"key":"e_1_2_10_41_1","doi-asserted-by":"publisher","DOI":"10.1212\/01.wnl.0000289511.20864.2a"},{"key":"e_1_2_10_42_1","doi-asserted-by":"publisher","DOI":"10.1002\/acn3.29"},{"key":"e_1_2_10_43_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.yebeh.2014.02.011"},{"key":"e_1_2_10_44_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000006240"},{"key":"e_1_2_10_45_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa0907328"},{"key":"e_1_2_10_46_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0b013e3181a6b312"},{"key":"e_1_2_10_47_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0b013e31827f0874"},{"key":"e_1_2_10_48_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12916-017-0845-1"},{"key":"e_1_2_10_49_1","doi-asserted-by":"publisher","DOI":"10.1111\/epi.12109"},{"key":"e_1_2_10_50_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.seizure.2020.10.018"},{"key":"e_1_2_10_51_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.seizure.2016.10.004"},{"key":"e_1_2_10_52_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.seizure.2017.05.004"},{"key":"e_1_2_10_53_1","doi-asserted-by":"publisher","DOI":"10.5603\/GP.a2017.0053"},{"key":"e_1_2_10_54_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.nrleng.2019.02.010"},{"key":"e_1_2_10_55_1","doi-asserted-by":"publisher","DOI":"10.1007\/s13311-016-0464-0"},{"key":"e_1_2_10_56_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ebr.2020.100419"},{"key":"e_1_2_10_57_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.seizure.2015.02.030"},{"issue":"11","key":"e_1_2_10_58_1","article-title":"Monotherapy Treatment of Epilepsy in Pregnancy: Congenital Malformation Outcomes in the Child","volume":"11","author":"Weston J.","year":"2016","journal-title":"Cochrane Database of Systematic Reviews"},{"key":"e_1_2_10_59_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00404-017-4404-y"},{"key":"e_1_2_10_60_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000209279"}],"container-title":["Journal of Obstetrics and Gynaecology Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/obgyn.onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/jog.70121","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,11,26]],"date-time":"2025-11-26T06:01:45Z","timestamp":1764136905000},"score":1,"resource":{"primary":{"URL":"https:\/\/obgyn.onlinelibrary.wiley.com\/doi\/10.1111\/jog.70121"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,10,29]]},"references-count":59,"journal-issue":{"issue":"11","published-print":{"date-parts":[[2025,11]]}},"alternative-id":["10.1111\/jog.70121"],"URL":"https:\/\/doi.org\/10.1111\/jog.70121","archive":["Portico"],"relation":{},"ISSN":["1341-8076","1447-0756"],"issn-type":[{"value":"1341-8076","type":"print"},{"value":"1447-0756","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,10,29]]},"assertion":[{"value":"2025-08-06","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-10-13","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-10-29","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70121"}}