{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,11]],"date-time":"2026-07-11T22:49:40Z","timestamp":1783810180354,"version":"3.55.0"},"reference-count":40,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2026,1,30]],"date-time":"2026-01-30T00:00:00Z","timestamp":1769731200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,1,30]],"date-time":"2026-01-30T00:00:00Z","timestamp":1769731200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100000024","name":"Canadian Institutes of Health Research","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000024","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Pharmacoepidemiology and Drug"],"published-print":{"date-parts":[[2026,2]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Ondansetron, a selective 5\u2010hydroxytryptamine type 3 serotonin receptor antagonist, is the most prescribed medication to treat hyperemesis gravidarum in the United States. However, certain characteristics of ondansetron, such as QT interval prolongation and its ability to cross the placenta, may suggest possible fetal harm following maternal exposure.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>To assess the association between ondansetron use and risk for spontaneous abortion and stillbirth in pregnant women affected by hyperemesis gravidarum.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Design<\/jats:title>\n                    <jats:p>Retrospective cohort study.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Setting<\/jats:title>\n                    <jats:p>Electronic healthcare databases from over 500 healthcare facilities across the United States between 2001 and 2016.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Participants<\/jats:title>\n                    <jats:p>Pregnant women affected by hyperemesis gravidarum are eligible for evaluation of spontaneous abortion and stillbirth, respectively.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Measurements<\/jats:title>\n                    <jats:p>The hazard ratios (HRs) and 95% confidence intervals (CIs) for spontaneous abortion and stillbirth were estimated for women exposed to ondansetron versus women not exposed to an antiemetic in a time\u2010dependent manner, using a Cox proportional\u2010hazards regression model. Dose\u2013response relationships between ondansetron use and respective outcomes were assessed, with ondansetron doses categorized as no use, 1\u20134, 5\u201315, and \u2265\u200916\u2009mg. We conducted post hoc analyses to compare the risks of spontaneous abortion and stillbirth among ondansetron users with those exposed to other antiemetics, as well as with those exposed only to the two most frequently used antiemetics, promethazine and metoclopramide.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>There were 34\u2009273 and 50\u2009862 pregnant women affected by hyperemesis gravidarum, eligible for evaluation of spontaneous abortion and stillbirth, respectively. Following propensity score matching on a 1:1 ratio between women solely exposed to ondansetron and women not exposed to antiemetics, a total of 10\u2009238 and 13\u2009585 pairs were included in the main analysis of spontaneous abortion and stillbirth, respectively. Exposure to ondansetron was associated with a decreased risk for spontaneous abortion compared with women not exposed to an antiemetic (adjusted HR 0.82, 95% CI 0.73, 0.91) under the time\u2010dependent Cox model. There was no significant dose\u2010dependent relationship between spontaneous abortion and ondansetron exposure. There was no association between ondansetron exposure and stillbirth. The adjusted HR for stillbirth with time\u2010dependent defined exposure was 1.34 (95% CI 0.87\u20132.08) in mild cases and 0.72 (95% CI 0.23\u20132.26) in severe cases. A reduction in spontaneous abortion risk with ondansetron users compared to other antiemetic users was also observed (aHR 0.85, 95% CI 0.73\u20130.98).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Obstetric use of ondansetron suggested a decreased risk of spontaneous abortion, with no increased risk of stillbirth among pregnant women affected by hyperemesis gravidarum.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/pds.70335","type":"journal-article","created":{"date-parts":[[2026,1,30]],"date-time":"2026-01-30T12:26:17Z","timestamp":1769775977000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Ondansetron Use for Women With Hyperemesis Gravidarum and Risks of Spontaneous Abortion and Stillbirth: A Retrospective Cohort Study"],"prefix":"10.1002","volume":"35","author":[{"given":"Jianzhou","family":"Yang","sequence":"first","affiliation":[{"name":"School of Publich Health Changzhi Medical College  Changzhi China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miao","family":"Hong","sequence":"additional","affiliation":[{"name":"Clinical Data Center, Institute of Pediatrics, Guangzhou Women and Children's Medical Center Guangzhou Medical University  Guangzhou Guangdong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Feng","family":"Liang","sequence":"additional","affiliation":[{"name":"Clinical Data Center, Institute of Pediatrics, Guangzhou Women and Children's Medical Center Guangzhou Medical University  Guangzhou Guangdong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yujie","family":"Han","sequence":"additional","affiliation":[{"name":"School of Publich Health Changzhi Medical College  Changzhi China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rihua","family":"Xie","sequence":"additional","affiliation":[{"name":"Foshan Fetal Medicine Institute, the Affiliated Foshan Maternity &amp; Child Healthcare Hospital Guangdong Medical University  Foshan Guangdong China"},{"name":"School of Nursing Guangdong Medical University  Foshan Guangdong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel","family":"Krewski","sequence":"additional","affiliation":[{"name":"Risk Sciences International  Ottawa Ontario Canada"},{"name":"School of Epidemiology and Public Health University of Ottawa  Ottawa Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Donald","family":"Mattison","sequence":"additional","affiliation":[{"name":"Risk Sciences International  Ottawa Ontario Canada"},{"name":"Department of Epidemiology and Biostatistics Arnold School of Public Health University of South Carolina  Columbia South Carolina USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel J.","family":"Corsi","sequence":"additional","affiliation":[{"name":"School of Epidemiology and Public Health University of Ottawa  Ottawa Ontario Canada"},{"name":"Ottawa Hospital Research Institute Methodology and Implementation Research Program  Ottawa Ontario Canada"},{"name":"Department of Obstetrics and Gynecology University of Ottawa Faculty of Medicine  Ottawa Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark","family":"Walker","sequence":"additional","affiliation":[{"name":"School of Epidemiology and Public Health University of Ottawa  Ottawa Ontario Canada"},{"name":"Ottawa Hospital Research Institute Methodology and Implementation Research Program  Ottawa Ontario Canada"},{"name":"Department of Obstetrics and Gynecology University of Ottawa Faculty of Medicine  Ottawa Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Darine","family":"El\u2010Cha\u00e2r","sequence":"additional","affiliation":[{"name":"School of Epidemiology and Public Health University of Ottawa  Ottawa Ontario Canada"},{"name":"Ottawa Hospital Research Institute Methodology and Implementation Research Program  Ottawa Ontario Canada"},{"name":"Department of Obstetrics and Gynecology University of Ottawa Faculty of Medicine  Ottawa Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Doug","family":"McNair","sequence":"additional","affiliation":[{"name":"Bill &amp; 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