PHARMACOEPIDEMIOLOGY AND PRESCRIPTION
Exposure to cox-2 inhibitors (coxibs) during the first trimester
and pregnancy outcome: a prospective observational cohort study
Received: 29 August 2017 /Accepted: 26 November 2017 / Published online: 7 December 2017
Springer-Verlag GmbH Germany, part of Springer Nature 2017
Purpose 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.
Methods 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.
Results 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).
Conclusions 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.
Keywords Cox-2 inhibitors
Nonsteroidal anti-inflammatory drugs (NSAIDs) are widely
used in patients requiring analgesic, anti-pyretic and anti-
inflammatory therapy. Since anti-inflammatory as well as an-
algesic effects are mainly achieved by the inhibition of
cyclooxygenase (cox)-2, coxibs as selective cox-2 inhibitors
are potent drugs for the treatment of various pain symptoms
and rheumatic diseases. However, due to severe adverse ef-
fects including cardiovascular toxicity and artherothrombotic
events, their prescription has been restricted to defined indica-
tions taking into account individual risk factors [1–3].
Pregnant women may be exposed to coxibs for different
reasons, either intentional or inadvertently in an unplanned not
yet recognised pregnancy. However, it should be emphasised
that coxibs do not belong to the analgesics or anti-phlogistics
of choice during pregnancy because their effect on pregnancy
outcome is not well-studied. During the third trimester,
NSAIDs including coxibs should not be used. Their cox inhi-
bition may cause prostaglandin antagonistic premature closure
of the ductus arteriosus botalli and compromised foetal renal
function resulting in oligo- or anhydramnios [4–7].
Currently, data are scarce to assess possible teratogenic risks
after the use of coxibs in the first trimester which is the sensitive
period for disturbances of embryogenesis. There is no prospec-
tive or retrospective study with a particular focus on coxibs in
Electronic supplementary material The online version of this article
(https://doi.org/10.1007/s00228-017-2385-1) contains supplementary
material, which is available to authorized users.
* Katarina Dathe
Charité Universitätsmedizin Berlin, corporate member of Freie
Universität Berlin, Humboldt-Universität zu Berlin, and Berlin
Institute of Health, Pharmakovigilanz- und Beratungszentrum für
Embryonaltoxikologie, Institut für Klinische Pharmakologie und
Toxikologie, Augustenburger Platz 1, 13353 Berlin, Germany
Beuth Hochschule für Technik - University of Applied Sciences,
European Journal of Clinical Pharmacology (2018) 74:489–495