Abstract
Objective
Ondansetron, not approved for use in pregnancy, is increasingly being prescribed for
nausea and vomiting in pregnancy and hyperemesis gravidarum. A number of recent lawsuits
have highlighted the possibility that ondansetron may cause congenital malformations.
The aim of this study was to systematically review epidemiological evidence on the
potential association of prenatal exposure to ondansetron and congenital malformations.
Methods
Systematic searches in Medline and Embase were performed in June 2017 using controlled
vocabulary and key words, and references of search results were reviewed. Full papers
(RCTs, cohort, and case-control studies) were eligible for inclusion if they reported
fetal outcomes of prenatal ondansetron exposure in humans. Excluded were: case reports,
studies involving pre-medication with ondansetron prior to CS, animal studies, and
foreign languages studies.
Results
Ten epidemiologic studies were included: five large retrospective cohort studies,
two prospective observational studies, two population-based case-controls. and a retrospective
case series. Sample sizes ranged from 17 to 1 501 434 infants exposed to ondansetron.
A case-control study identified an association between prenatal exposure to ondansetron
and cleft palate, and one cohort study found an increased risk of cardiovascular defects.
These findings were not reproduced in the other studies.
Conclusion
While further investigation of the literature is needed, our results highlight the
paucity of evidence linking prenatal exposure to ondansetron to an increased risk
of congenital malformations. There is a need for additional epidemiologic studies
to confirm whether ondansetron represents a safe and effective alternative treatment
for nausea and vomiting in pregnancy and hyperemesis gravidarum.
Résumé
Objectif
L'ondansétron n'a pas été approuvé chez les femmes enceintes; or il est de plus en
plus prescrit pour traiter la nausée, les vomissements et l'hyperémèse associés à
la grossesse. Un certain nombre de poursuites en justice a souligné récemment la possibilité
que ce médicament soit à l'origine de malformations congénitales. Cette étude visait
à faire un examen systématique des données épidémiologiques sur l'association potentielle
entre l'exposition prénatale à l'ondansétron et les malformations congénitales.
Méthodologie
En juin 2017, nous avons mené des recherches systématiques dans Medline et Embase
à l'aide d'une terminologie et de mots-clés contrôlés, et avons examiné les références
des résultats obtenus. Les articles en texte intégral (ECR, études de cohorte, études
cas-témoin) étaient admissibles s'ils faisaient état des résultats de l'exposition
prénatale à l'ondansétron chez l'humain. Les déclarations de cas, les études portant
l'administration du médicament en vue d'une césarienne, les études sur des animaux
et les études de langue étrangère ont été exclues.
Résultats
Dix études épidémiologiques ont été retenues : cinq grandes études de cohorte rétrospectives,
deux études observationnelles prospectives, deux études cas-témoin basées sur des
populations et une étude de série de cas rétrospective. La taille des échantillons
allait de 17 à 1 501 434 bébés. Une étude cas-témoin a montré une association entre
l'exposition prénatale à l'ondansétron et la fente palatine, et une étude de cohorte
a mis en évidence un risque accru de malformations cardiovasculaires. Ces résultats
n'ont pas été observés dans les autres études.
Conclusion
Même si un examen plus poussé de la littérature serait nécessaire, nos résultats indiquent
un manque de données associant l'exposition prénatale à l'ondansétron et le risque
accru de malformations congénitales. D'autres études épidémiologiques devront être
menées pour déterminer si l'ondansétron constitue un traitement efficace et sécuritaire
de la nausée, des vomissements et de l'hyperémèse associés à la grossesse.
Key Words
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References
- Prevalence of nausea and vomiting of pregnancy in the USA: a meta analysis.J Popul Ther Clin Pharmacol. 2013; 20: e163-e170
- Quantifying the global rates of nausea and vomiting of pregnancy: a meta analysis.J Popul Ther Clin Pharmacol. 2013; 20: e171-e183
- The management of nausea and vomiting of pregnancy.J Obstet Gynaecol Can. 2002; 24 (quiz 32-3): 817-831
- Practice Bulletin Summary No. 153: Nausea and Vomiting of Pregnancy.Obstet Gynecol. 2015; 126: 687-688
- Management of nausea and vomiting in pregnancy.BMJ. 2011; 342: d3606
- Risk factors, treatments, and outcomes associated with prolonged hyperemesis gravidarum.J Matern Fetal Neonatal Med. 2012; 25: 632-636
- Secular trends in the treatment of hyperemesis gravidarum.Am J Perinatol. 2008; 25: 141-147
- Antiemetic use among pregnant women in the United States: the escalating use of ondansetron.Pharmacoepidemiol Drug Saf. 2017; 26: 592-596
- Off-label use of ondansetron in pregnancy in Western Australia.Biomed Res Int. 2013; 2013: 909860
- The safety of ondansetron for nausea and vomiting of pregnancy: a prospective comparative study.BJOG. 2004; 111: 940-943
- Ondansetron compared with doxylamine and pyridoxine for treatment of nausea in pregnancy: a randomized controlled trial.Obstet Gynecol. 2014; 124: 735-742
- Prescribing information: Zofran (ondansetron hydrochloride) 2010 [cited U.S. Food and Drug Administration].(Available at)http://www.accessdata.fda.gov/drugsatfda_docs/label/2010/020007s040,020403s018lbl.pdfDate accessed: December 21, 2017
- Ondansetron use in pregnancy and birth defects: a systematic review.Obstet Gynecol. 2016; 127: 878-883
- Cochrane handbook for systematic reviews of interventions.John Wiley & Sons, 2011
- Systematic reviews: CRD's guidance for undertaking reviews in health care.Lancet Infect Dis. 2010; 10: 226
- Use of antiemetic drugs during pregnancy in Sweden.Eur J Clin Pharmacol. 2005; 61: 899-906
- Medications used to treat nausea and vomiting of pregnancy and the risk of selected birth defects.Birth Defects Res Part A Clin Mol Teratol. 2012; 94: 22-30
- Ondansetron use during pregnancy: a case series.J Popul Ther Clin Pharmacol. 2012; 19: e1-10
- Ondansetron in pregnancy and risk of adverse fetal outcomes.N Engl J Med. 2013; 368: 814-823
- Use of ondansetron during pregnancy and congenital malformations in the infant.Reprod Toxicol. 2014; 50: 134-137
- The safety of ondansetron and chlorpromazine for hyperemesis gravidarum in first trimester pregnancy.Gynecol Obstet Reprod Med. 2016; 20
- Medication use in pregnancy in relation to the risk of isolated clubfoot in offspring.Am J Epidemiol. 2014; 180: 86-93
- Ondansetron in pregnancy and risk of adverse fetal outcomes in the United States.Reprod Toxicol. 2016; 62: 87-91
- Langman's medical embryology.12 ed. 2015
- Publishing negative findings and the challenge of avoiding type II errors in studies of suspect teratogens: example of a recent ondansetron publication.Reprod Toxicol. 2017; 67: 125-128
- The National Birth Defects Prevention Study: how to communicate data.Semin Fetal Neonatal Med. 2014; 19: 170-176
Article info
Publication history
Published online: May 10, 2018
Accepted:
October 10,
2017
Received:
July 21,
2017
Footnotes
Competing interests: The authors declare that they have no competing interests.
Identification
Copyright
Copyright © 2018 The Society of Obstetricians and Gynaecologists of Canada/La Société des obstétriciens et gynécologues du Canada. Published by Elsevier Inc. All rights reserved.
