Résumé
Tramadol is an opioid analgesic indicated for moderate to severe pain. The available data on the risks of use during pregnancy remain limited. Only two studies evaluating the malformative risk of tramadol have been published, and their results are controversial. The objective of this thesis, through a comparative study using the EFEMERIS database, was to provide additional data on its use in pregnant women, particularly concerning the risk of malformations and the risk of pregnancy termination. We compared 1 602 pregnancies exposed to tramadol (and 1 628 fetuses/newborns due to multiple pregnancies) with 6 311 exposed to codeine (6 406 fetuses/newborns) and 158 426 not exposed to tramadol and codeine (160 784 fetuses/newborns). The study showed an increase in the pregnancy termination rate in women exposed to tramadol compared to women exposed to codeine (aHR= 2.23 [1.64-3.03]) and non-exposed women (aHR= 1.86 [1.46-2.37]). Multivariate analysis did not show an increase in the rate of major congenital anomaly in fetuses/newborns exposed in utero to tramadol in the 1st trimester of pregnancy compared to fetuses/newborns exposed to codeine (ORa= 1.03 [0.67-1.57]) and those not exposed to these drugs (ORa= 1.24 [0.86-1.79]). This study found no association between prescription and dispensation of tramadol during the first trimester of pregnancy and an increased risk of major congenital anomalies. An association between tramadol use and the risk of pregnancy termination has been found. We cannot conclude that there is a causal link, because an indication bias is possible.