Context and objectives
Prenatal exposure to certain anti-epileptic drugs (MAES) is associated with proven or suspected risks of congenital malformations and neurological development disorders. Large -scale and real -life data are essential to guide efforts to mitigate these risks. Our goal was to assess the trends in prenatal exposure to the MAES in the last decade in France according to medication safety profiles.
Methods
This national study is based on the exhaustive data of the French national register mother-child Epi-Meres. All pregnancies exposed to MAES which ended between 2013 and 2021 were included. The frequency and characteristics of pregnancies exposed to MAES (maternal and morbid socio -demographic data, resulting from pregnancy, treatment methods by MAES) were evaluated taking into account the 3 categories of MAE classified according to their safety profile: (i) MAES considered as the least risky (lamotrigine, letiracetam); (ii) Maes at uncertain risks, including pregabalin, gabapentine, and the most recent macs (eg lacosamide and zonisamide); (iii) recognized risks, including valproic acid, valpromide, carbamazepine and topiramate.
Results
Between 2013 and 2021, 55,801 pregnancies were exposed to more or less 1 MAE. The number of pregnancies exposed to the least risky MAES increased by 30 % over this period. In parallel, prenatal exposure to valproic acid and valpromide has decreased considerably due to the decline in the number of pregnancies exposed (-84% and -89%, respectively), increase in the rate of interruption of exposed pregnancies ( +23% and +28%, respectively) and, among those which ended with childbirth, the decrease in the number of pregnancies having been the subject of several issues Valproate (-86% and -93%, respectively) or a sustained exposure throughout pregnancy (-91% and -96%, respectively).
The prenatal exhibition at carbamazepine and topiramate has decreased very slightly, with nearly 600 newborns still exposed to each of these MAES in 2019-2021. The pregabalin and gabapentine were widely used during pregnancy, which led to an increasingly important prenatal exposure of newborns (+28 %) and, for pregabalin, more and more multiple deliveries (+65 %) and a sustained exposure throughout pregnancy (+171 %).
The number of pregnancies and newborns exposed to the most recent MAES has also increased sharply ( +140% and +60%, respectively). Overall, prenatal exposure to MAES at proven or uncertain risks disproportionately concerns pregnant women at low level of resources (18.5% and 17.9%, respectively, against 13-14% among the pregnancies exposed to the least risky or not exposed to MAES).
Discussion
Despite the Valproate passage to less risky anti-epileptic drugs, prenatal exposure to other MAES presenting recognized or uncertain risks has persisted, or even increased, in particular among the most disadvantaged populations on the social level, which requires additional risk minimization measures.