Abstract
Introduction
Nimesulide is the most prescribed non-steroidal anti-inflammatory drug in Italy, and it is currently marketed in about 50 countries worldwide. The association between the use of nimesulide in early pregnancy and the risk of birth defects was investigated in a large cohort of pregnant women from Italy.
Methods
Data were from the healthcare utilization databases of the Italian region of Lombardy. The cohort of 353,081 newborns occurring in Lombardy during the period 2005–2010 was investigated. Exposure to nimesulide during the first trimester of pregnancy, and congenital malformations detected at presentation and within 90 days after birth (outcome), were investigated. Exposure–outcome association was measured by the ratio between the prevalence of congenital malformations among users and non-users of nimesulide. Propensity score stratification was used to control for potential confounders, including maternal medical comorbidities, concomitant medications and sociodemographic characteristics.
Results
The 627 (0.18%) women who filled prescriptions for nimesulide in the first trimester of pregnancy had a 2.6-fold risk of having children with congenital urinary tract anomalies compared to those who did not (adjusted prevalence ratio 2.6; 95% CI 1.2–5.7). Weaker and non-significant evidence for congenital malformations as a whole was found (adjusted prevalence ratio 1.2, 95% CI 0.9–1.6).
Conclusion
Our study suggests that the use of nimesulide in early pregnancy may result in a greater risk of having births with congenital urinary tract anomalies.
Funding
This study was funded by grants from the Italian Ministry of the Education, University and Research (’Fondo d’Ateneo per la Ricerca’ portion, year 2015).
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Acknowledgements
The authors wish to acknowledge the Pedianet Project for the support provided to the Laboratory of Healthcare Research and Pharmacoepidemiology with reference to the research carried out in paediatrics and the participants of this study.
Funding
This study was funded by grants from the Italian Ministry of the Education, University and Research (’Fondo d’Ateneo per la Ricerca’ portion, year 2015). The funding source had no involvement on the study. Anna Cantarutti confirm that had full access to all the data in the study and had final responsibility for the decision to submit for publication. Article processing charges were funded by the authors.
Authorship
All named authors meet the International Committee of Medical Journal Editors (ICMJE) criteria for authorship for this article, take responsibility for the integrity of the work as a whole, and have given their approval for this version to be published.
Authorship Contributions
Anna Cantarutti, Matteo Franchi, and Federico Rea performed statistical analyses. Anna Cantarutti and Giovanni Corrao wrote the paper. Luca Merlino authorized data utilization. Giovanni Corrao was responsible for designing the study. Anna Cantarutti, Matteo Franchi, Federico Rea, Luca Merlino and Giovanni Corrao read and approved the final version of the manuscript.
Disclosures
Giovanni Corrao received research support from the European Community (EC), the Italian Agency of Drug (AIFA), and the Italian Ministry for University and Research (MIUR). He took part to a variety of projects that were funded by pharmaceutical companies (i.e., Novartis, GSK, Roche, AMGEN and BMS). He also received honoraria as member of Advisory Board from Roche. Anna Cantarutti, Matteo Franchi, Federico Rea and Luca Merlino have nothing to disclose.
Compliance with Ethics Guidelines
According to the rules from the Italian Medicines Agency (available at: http://www.agenziafarmaco.gov.it/sites/default/files/det_20marzo2008.pdf) retrospective studies without direct contact with patients do not need a written consent to process personal data when they are used for research aims. This article does not contain any studies with human participants or animals performed by any of the authors.
Data Availability
The datasets generated during and/or analyzed during the current study are not publicly available due confidentiality but are available from the corresponding author on reasonable request.
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Cantarutti, A., Franchi, M., Rea, F. et al. Use of Nimesulide During Early Pregnancy and the Risk of Congenital Malformations: A Population-Based Study from Italy. Adv Ther 35, 981–992 (2018). https://doi.org/10.1007/s12325-018-0735-8
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DOI: https://doi.org/10.1007/s12325-018-0735-8