Anti-seizure medication prescription during preconception period and pregnancy with risk of orofacial clefts in offspring

: A UK CPRD GOLD population-based study

Abstract

Background
Anti-seizure medications (ASM) are widely used during pregnancy to prevent adverse maternal and foetal outcomes resulting from inadequate seizure management and non-epileptic conditions. As the knowledge of ASM teratogenicity expands, practitioners face a challenge in balancing the detrimental effects of ASM use during pregnancy. Our study aims to evaluate the association between epilepsy and ASM prescriptions as monotherapy and polytherapy in women during the preconception and pregnancy period with the risk of orofacial clefts (OFCs) in offspring.
Methods
A population-based cohort study was conducted using the United Kingdom (UK) Clinical Practice Research Datalink (CPRD) GOLD database, with cohort including women having pregnancy start date between 1st January 1995 and 31st December 2018. The final cohort consisted of 518,050 livebirths. Epilepsy in women and ASM prescriptions as monotherapy and/or polytherapy during the preconception period, pregnancy, and first trimester were evaluated with OFC in offspring as the primary outcome, using logistic regression models.
Findings
Valproate prescription during preconception (aOR=4.34, 95% CI=0.45-42.27), and pregnancy (aOR=4.97, 95% CI=0.51-48.38) was associated with an increased risk of OFCs in offspring. However, strength of the evidence for an association was lacking. Prescription with carbamazepine, pregabalin, lamotrigine, and levetiracetam presented with raised odds, but the wide confidence intervals suggested lack of strong evidence for association. No evidence was found for gabapentin, phenytoin, and topiramate prescriptions.
Interpretation
Our study did not discover substantial evidence for relationship between epilepsy and ASM prescriptions in women with OFC in offspring, indicating further research to evaluate the ASM safety during pregnancy.

Date of Award	8 Nov 2022
Original language	English
Awarding Institution	University of Bristol
Supervisor	Sarah J Lewis (Supervisor), Amy J V Davies (Supervisor), Paul C Madley-Dowd (Supervisor) & Dheeraj Rai (Supervisor)