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Risk of Pregnancy Termination and Congenital Anomalies After Domperidone Exposure: A Study in the EFEMERIS Database

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Abstract

Introduction

Domperidone is widely used during pregnancy, although the risks associated with pregnant women have not been adequately evaluated.

Objective

The objective of this study was to compare the rate of pregnancy outcomes and congenital anomalies between pregnant women exposed and unexposed to domperidone during pregnancy.

Methods

We conducted a retrospective cohort study comparing pregnant women exposed and unexposed to domperidone during pregnancy. We used the EFEMERIS database containing the prescriptions and dispensing of drugs to pregnant women in Haute-Garonne, who had a pregnancy outcome between July 2004 and December 2017. We compared pregnant women who were exposed to domperidone at least once during pregnancy to unexposed pregnant women. Logistic regression and Cox proportional risk models were applied.

Results

Overall, 13,964 pregnancies (10.3% of pregnancies) were given domperidone. A reduction in the number of pregnant women exposed to domperidone (2004: 17.1% to 2017: 1.2%) was noted. More than 75% of pregnancies were exposed to domperidone in the first trimester of pregnancy. The rate of natural pregnancy termination in pregnant women exposed to domperidone was lower than that in unexposed pregnant women (adjusted hazard ratio = 0.78 [0.71–0.87]). The malformation rate in fetuses/newborns exposed in utero (first trimester) to domperidone is comparable to that of unexposed fetuses/newborns (adjusted odd ratio = 0.89 [0.77–1.03]).

Conclusions

This is the first comparative study to enrol a large number of pregnant women exposed to domperidone. Data regarding the malformation rate following exposure to domperidone during the first trimester of pregnancy are reassuring. Women exposed to domperidone during pregnancy have a decreased risk for natural pregnancy termination, probably owing to an indication bias.

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Acknowledgments

We thank our data providers, who made anonymised data available for our research institution: the Haute-Garonne Health Insurance System, the Haute-Garonne Mother and Child Protection Centre, the Prenatal Diagnosis Centre and the Haute-Garonne hospital medical information system of the Toulouse University Hospital Centre.

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Authors and Affiliations

  1. Réseau REGARDS, Laboratoire de Pharmacologie Médicale et Clinique (Medical and Clinical Pharmacology Laboratory), Centre Hospitalier Universitaire de Toulouse (Toulouse University Hospital Centre), Centre d’Epidémiologie et de Recherche en santé des POPulations (Center for Epidemiology and Research in POPulation health, CERPOP), INSERM UMR 1295, Equipe SPHERE: Study of Perinatal, paediatric and adolescent Health: Epidemiological Research and Evaluation, Faculté de Médecine de Toulouse (Toulouse Faculty of Medicine), 37 allées Jules Guesde, 31000, Toulouse, France

    Mélanie Araujo, Clémentine Vabre, Justine Benevent, Christine Damase-Michel, Caroline Hurault-Delarue & Isabelle Lacroix

  2. Réseau REGARDS, Laboratoire de Pharmacologie Médicale et Clinique (Medical and Clinical Pharmacology Laboratory), CIC 1436, Centre Hospitalier Universitaire de Toulouse (Toulouse University Hospital Centre), Centre d’Epidémiologie et de Recherche en santé des POPulations (Center for Epidemiology and Research in POPulation health, CERPOP), INSERM UMR 1295, Equipe SPHERE: Study of Perinatal, paediatric and adolescent Health: Epidemiological Research and Evaluation, Faculté de Médecine de Toulouse (Toulouse Faculty of Medicine), 37 allées Jules Guesde, 31000, Toulouse, France

    Agnès Sommet

Authors
  1. Mélanie Araujo
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  2. Clémentine Vabre
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  3. Justine Benevent
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  4. Agnès Sommet
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  5. Christine Damase-Michel
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  6. Caroline Hurault-Delarue
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  7. Isabelle Lacroix
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Corresponding author

Correspondence to Mélanie Araujo.

Ethics declarations

Funding

The present study is part of the REproduction Gestation And Reproduction (REGARDS) research programme funded by the Agence Nationale de Sécurité du Médicament et des produits de santé (ANSM) [French National Agency for the Safety of Medicines and Health Products]. This programme aims to improve drug monitoring in pregnant women, in France. Allocation of funding did not impact the study design and conduct, data collection, management, analysis and interpretation or the preparation, review and approval of the manuscript. This publication represents the views of the authors and does not necessarily represent the opinion of the French Medicines Agency.

Conflict of interest/Competing interests

Mélanie Araujo, Clémentine Vabre, Justine Benevent, Agnès Sommet, Christine Damase-Michel, Caroline Hurault-Delarue and Isabelle Lacroix have no conflicts of interest that are directly relevant to the content of this article.

Ethics approval

The EFEMERIS cohort was approved by the French Data Protection Agency on 7 April, 2005 (authorisation number 05-1140). This study was performed on anonymised patient data.

Consent to participate

The women included in EFEMERIS were informed of their inclusion and of the potential use of their anonymised data for research purposes. They can oppose the use of their data at any time.

Consent for publication

The women included in EFEMERIS know that their gathered and anonymised data can be used for medical research purposes and can thus be published.

Availability of data and material

Because of the nature of this research, participants of this study did not agree for their data to be shared publicly, thus supporting data are not available.

Code availability

Not applicable.

Authors’ contributions

Study design: MA, CH-D, IL. Data acquisition, analysis or interpretation: MA, CV, CH-D, IL. Drafting of the manuscript: MA, CH-D, IL. Critical review of the manuscript for significant intellectual content: MA, CV, CH-D, AS, CD-M, JB, IL. All authors had full access to all study data and are responsible for the integrity of the data and the accuracy of the data analysis. All authors have read and approved the final version.

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Araujo, M., Vabre, C., Benevent, J. et al. Risk of Pregnancy Termination and Congenital Anomalies After Domperidone Exposure: A Study in the EFEMERIS Database. Drug Saf 44, 787–796 (2021). https://doi.org/10.1007/s40264-021-01077-9

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  • DOI: https://doi.org/10.1007/s40264-021-01077-9

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