Exposure to cox-2 inhibitors (coxibs) during the first trimester and pregnancy outcome: a prospective observational cohort study
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Cox-2-inhibitors (coxibs) are not recommended in pregnancy but early exposure may occur, for instance in unplanned pregnancies. Experience in pregnancy is limited leading to concerns in patients and their health care providers. Therefore, further data on coxibs and their effects on embryogenesis are needed.
This observational cohort study evaluates pregnancies ascertained in Germany during the study period from January 2000 to January 2016. A cohort of 174 women exposed to coxibs in the first trimester was compared to a randomly selected cohort of 521 women without exposure to coxibs, other nonsteroidal anti-inflammatory drugs or known teratogens.
The overall rate of major birth defects was not significantly increased in the study cohort (2.9 vs. 2.7%, OR 1.08, 95% CI 0.34–3.42; OR adjusted 0.96, 95% CI 0.28–3.26). The cumulative incidence of spontaneous abortions was nonsignificantly lower in the exposed cohort (14.3 vs. 20.0%; HR, 0.90, 95% CI 0.51–1.58; HR adjusted, 0.87; 95% CI, 0.49–1.56). Elective terminations of pregnancies (ETOP), mainly for ‘social’ reasons, were more frequent in the coxib cohort (17.5 vs. 7.0%, HR, 2.31; 95% CI, 1.26–4.24; HR adjusted 2.12, 95% CI 1.13–3.97).
Our study results support the assumption that coxibs are not major teratogens. Considering the still limited evidence basis on coxib exposure during pregnancy, well-established alternatives should be preferred.
KeywordsCox-2 inhibitors Coxibs Pregnancy outcome Birth defects Spontaneous abortions Pharmacovigilance
We would like to thank our colleagues from the German Embryotox Pharmacovigilance Institute for counselling patients and their attending physicians. The thorough documentation of each case is an indispensable prerequisite to obtain a high data quality of the study population. This study is part of the thesis of Luisa-Maria Köhler.
Contribution of authors
KD, SP, SH, RM and CS designed the study. KD, SP, LMK and KM validated and analysed the data. AKF and TTD performed the statistical analyses and RM provided expert interpretation of the analyses. KD, SP, SH, CS, AKF, TTD, RM, KD and CS participated in the result interpretation. KD and CS wrote the first draft of the manuscript and all authors critically revised subsequent manuscript drafts and contributed essential discussion points. The listed authors approved the final version of this manuscript and they are responsible for the accuracy of this work.
This work was supported by the German Federal Institute for Drugs and Medical Devices (BfArM). The funder had no role in study design, data collection and analysis, decision to publish or preparation of the manuscript.
Compliance with ethical standards
Conflict of interest
The authors declare that they have no conflicts of interest.
Ethics approval was obtained from the ethics committee of the Charité Universitätsmedizin Berlin, Germany (no. EA4/029/16). The study was registered in the German Clinical Trials Register (no. DRKS00011140).
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