Teratogenesis Risk Associated with Paired Antiseizure Medications in Pregnant Women with Epilepsy
Abstract number :
2.447
Submission category :
4. Clinical Epilepsy / 4E. Women's Issues
Year :
2022
Submission ID :
2232886
Source :
www.aesnet.org
Presentation date :
12/4/2022 12:00:00 PM
Published date :
Nov 22, 2022, 05:28 AM
Authors :
Terence O'Brien, Prof – Monash University and Alfred Hospital, Melbourne, Australia; Frank J. Vajda, MBBS, MD – The University of Melbourne; Janet Graham, RN – The Royal Melbourne Hospital; Alison Hitchcock, RN – The Royal Melbourne Hospital; Piero Perucca, MD, PhD – The University of Melbourne; Cecilie Lander, MBBS – University of Queensland; Mervyn Eadie, MBBS – University of Queensland
This is a Late Breaking abstract
Rationale: To assess the foetal malformation (FM) hazard associated with intrauterine exposure to paired combinations of antiseizure medications (ASMs), where both members, as individual agents, appear to be associated with increased hazards for FMs._x000D_
Methods: This analysis is based on pregnancies of women with epilepsy collected in the Raoul Wallenberg Australian Register of Antiepileptic Drugs in Pregnancy (APR) between 1999 and 2022. The primary purpose of the APR is to study the role of maternal intake of ASMs during pregnancy in relation to FMs, though information is also collected regarding other aspects. Data are recorded (1) at time of enrolment, (2) at approximately 28 weeks of pregnancy, (3) after the first post-partum month and (4) at the end of the first past-partum year. We examined FM rates for valproate (VPA), topiramate (TPM), carbamazepine (CBZ), lamotrigine (LTG) and levetiracetam (LEV), when used as monotherapy or in combination with each other. VPA, TPM and CBZ were designated as "moderately-to-highly teratogenic ASMs." Data from the APR were transferred to an Excel spreadsheet and analysed by simple statistical methods, employing the Stats Direct software for carrying out logistic regressions.
Results: We analysed 1904 pregnancies exposed to VPA, TPM, CBZ, LTG or LEV, either as monotherapy or in combination therapy. The FM hazard associated with each ASM used in combination therapy was increased relative to the ASM used in monotherapy in all instances apart from when VPA was paired with LTG or LEV (Table). For three pairs, i.e., TPM-LEV, CBZ-VPA and CBZ-TPM, the hazard was increased to a statistically significant extent. After adjusting for possible dosage-related effects, co-administering a second moderately-to-highly teratogenic ASM to a first increased the FM hazard. Adding LEV to any of the three moderately-to-highly teratogenic ASMs resulted in a minimal increase in hazard. Adding LTG to any of the moderately-to-highly teratogenic agents was associated with a notable decrease in FM rate.
Conclusions: Pairings of ASMs can produce an additive effect on the FM rate. A notable exception is the pairing of LTG with VPA, TPM or CBZ which yields a reduction in FM hazard.
Funding: None
Clinical Epilepsy