Background: Antiepileptic drugs (AEDs) are prescribed for several conditions which are common among pregnant women. Due to uncertain or worrisome safety data, risk minimization measures have been strengthened over the past decade to limit the risks associated with in utero exposure to AEDs.
Objectives: To assess the level and characteristics of AEDs use during pregnancy in France and their evolution over the period 2010-2021.
Methods: We used data of the EPI-MERES Register, built from the National Health Data System and covering 98% of deliveries in France since 2010. All pregnancies ended between April 2010 and December 2021 were included. Comprehensive information on maternal socio-demographic and health characteristics and on pregnancy course and outcome was available. Any pregnancy with ≥1 AED (ATC code N03A) dispensation within 30 days before pregnancy start and/or during pregnancy was considered exposed. Frequency and characteristics of AED-exposed pregnancies were described overall and by time sub-periods.
Results: Among a total of 11,467,412 pregnancies, 76,428 (0.7%) were exposed to AEDs. Overall, 26,543 pregnancies were exposed to lamotrigine (LTG), 15,197 to pregabalin (PGB), 11,537 to valproate (VPA), 10,476 to levetiracetam (LTC), 6616 to clonazepam (CLZ), 4,879 to carbamazepine (CBZ), 4,616 to topiramate (TPM) and 3,825 to gabapentin (GBP). The most common reported indications were epilepsy and/or mood disorders for LTG, VPA, LTC, CLZ, and CBZ, pain for PGB and GBP, and migraine for TPM. There were marked increases over time in the numbers of pregnancies exposed to LTG (from 5,200 in 04/2010-12/2012 to 7,481 in 01/2019-12/2021), PGB (from 2,663 to 4,662), LTC (from 1,648 to 3,426) and GBP (from 667 to 1,061). In contrast, the numbers of pregnancies exposed to VPA and CLZ steadily decreased (from 4,967 to 764 and from 4,975 to 407, respectively); pregnancies exposed to CBZ and TPM also decreased, though less markedly (from 1,512 to 913 and from 1,214 to 996, respectively). Exposure was generally limited to the 1st trimester of pregnancy (56.2% overall), except for LTG and LTC (68.5% and 67.3% exposed beyond the 1st trimester, respectively). Pregnancy termination (elective/therapeutic abortion) occurred in 23.4% of exposed pregnancies (vs. 19.8% of unexposed), reaching 32% among those exposed to VPA or to TPM and 27% among those exposed to CBZ.
Conclusions: Over the past decade, the use of LTG and LTC for the treatment of epilepsy or mood disorders during pregnancy has increased at the expense primarily of VPA and CLZ, and to a lesser extent CBZ. Meanwhile, in pregnant women the use of PGB and GBP for pain management has substantially increased and the use of TPM for migraine has barely decreased.
