| アブストラクト | Importance: Ondansetron is frequently used to treat nausea and vomiting during pregnancy. Although some studies reported important safety signals, few studies have been sufficiently large to assess rare pregnancy outcomes. Objective: To study the association between ondansetron exposure during pregnancy and the risks of spontaneous abortion, stillbirth, and major congenital malformations. Design, Setting, and Participants: This is a cohort study conducted in 3 countries, with a meta-analysis. Participants included women and girls aged 12 to 55 years who experienced spontaneous abortion, induced abortion, stillbirth, or live birth between April 2002 and March 2016, as recorded in administrative data from 5 Canadian provinces (British Columbia, Alberta, Saskatchewan, Manitoba, and Ontario), the US IBM MarketScan Research Databases, and the UK Clinical Practice Research Datalink. The statistical analysis was completed in October 2020. Exposures: Exposure to ondansetron during pregnancy was compared with exposure to other commonly used antiemetics to minimize confounding by indication. Main Outcomes and Measures: The primary outcome was fetal death, defined as either spontaneous abortion or stillbirth. Secondary outcomes were the 2 components of the primary outcome and major congenital malformations identified during the year after a live birth. Adjusted hazard ratios were estimated using Cox proportional hazards models with time-dependent drug exposures and were adjusted using high-dimensional propensity scores. For major congenital malformations, adjusted odds ratios were estimated from logistic models. Site-level results were pooled using random-effects meta-analysis. Sensitivity analyses considered second-line antiemetic exposure and exposure specifically during 4 to 10 weeks of gestation. Results: Data from 456963 pregnancies were included in this study of fetal death (249787 [54.7%] in Canada, 197913 [43.3%] in the US, and 9263 [2.0%] in the UK; maternal age, </=24 years, 93201 patients [20.4%]; 25-29 years, 149117 patients [32.6%]; 30-34 years, 142442 patients [31.2%]; and >/=35 years, 72203 patients [15.8%]). Fetal death occurred in 12907 (7.9%) of 163810 pregnancies exposed to ondansetron, and 17476 (5.7%) of 306766 pregnancies exposed to other antiemetics. The adjusted hazard ratios were 0.91 (95% CI, 0.67-1.23) for fetal death with time-dependent ondansetron exposure during pregnancy, 0.82 (95% CI, 0.64-1.04) for spontaneous abortion, and 0.97 (95% CI, 0.79-1.20) for stillbirth. For major congenital malformations, the estimated odds ratio was 1.06 (95% CI, 0.91-1.22). Results of sensitivity analyses were generally consistent with those of the primary analyses. Conclusions and Relevance: In this large, multicenter cohort study, there was no association between ondansetron exposure during pregnancy and increased risk of fetal death, spontaneous abortion, stillbirth, or major congenital malformations compared with exposure to other antiemetic drugs. |
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| 投稿日 | 2021/4/24 |
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| 投稿者 | Dormuth, Colin R; Winquist, Brandace; Fisher, Anat; Wu, Fangyun; Reynier, Pauline; Suissa, Samy; Dahl, Matthew; Ma, Zhihai; Lu, Xinya; Zhang, Jianguo; Raymond, Colette B; Filion, Kristian B; Platt, Robert W; Moriello, Carolina; Paterson, J Michael |
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| ジャーナル名 | JAMA network open |
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| 組織名 | Department of Anesthesiology, Pharmacology and Therapeutics, University of;British Columbia, Vancouver, British Columbia, Canada.;College of Medicine, University of Saskatchewan, Saskatoon, Saskatchewan, Canada.;Saskatchewan Health Quality Council, Saskatoon, Saskatchewan, Canada.;ICES, Toronto, Ontario, Canada.;Center for Clinical Epidemiology, Jewish General Hospital, Lady Davis Institute,;Montreal, Quebec, Canada.;Department of Epidemiology, Biostatistics and Occupational Health, McGill;University, Montreal, Quebec, Canada.;Manitoba Centre for Health Policy, University of Manitoba, Winnipeg, Manitoba,;Canada.;Department of Medicine, Cumming School of Medicine, University of Calgary,;Calgary, Alberta, Canada.;Department of Medicine, McGill University, Montreal, Quebec, Canada.;Department of Pediatrics, McGill University, Montreal, Quebec, Canada.;Institute of Health Policy, Management and Evaluation, University of Toronto,;Toronto, Ontario, Canada. |
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| Pubmed リンク | https://www.ncbi.nlm.nih.gov/pubmed/33890993/ |
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