First-trimester use of antiseizure medications and the risk of miscarriage: a population-based cohort study

Abstract

BackgroundAntiseizure medications (ASMs) during the first trimester of pregnancy have been associated with an increased risk of miscarriage.MethodsWe carried out a population-based cohort study using routinely collected healthcare data from the UK, 1995–2018. Pregnancies were identified in the Clinical Practice Research Datalink and we estimated the HR of miscarriage associated with prescriptions of ASMs during the first trimester of pregnancy, using Cox regression, adjusting for potential confounders, including ASM indications.ResultsASMs were prescribed during the first trimester in 7832 (0.8%) of 1 023 787 included pregnancies. 14.5% of pregnancies with first-trimester exposure to ASMs ended in miscarriage, while 12.2% without ASM exposure in the first trimester ended in miscarriage; after adjustment, there was a 1.06-fold relative hazard of miscarriage (95% CI 1.00 to 1.13) in women with first-trimester ASM use. After restricting to women with specific ASM indications, this association was not evident in women with epilepsy (adjusted HR 0.98, 95% CI 0.89 to 1.08), but was observed in women with bipolar or other psychiatric conditions (1.08, 95% CI 1.00 to 1.16) although CIs overlapped. Compared with discontinuation of ASMs prior to pregnancy, there was no evidence of increased risk of miscarriage for first-trimester ASM use in women with bipolar or other psychiatric conditions (1.02, 95% CI 0.87 to 1.20).ConclusionWe found no clear evidence to suggest that first-trimester ASM use increased the risk of miscarriage. Taken together, our analyses suggest that apparent associations between first-trimester ASM use and miscarriage may be the result of confounding by the presence of a bipolar disorder or associated unmeasured variables.

Antiseizure medication and early pregnancy loss: should we be worried?

“…Forbes and colleagues report findings from a cohort study based on data on more than 1 million pregnancies in the UK from 1995 to 2018, suggesting that first-trimester ASM use does not increase the risk of miscarriage. 2 To understand how they reach their conclusion, one must be familiar with a common type of bias in pharmacoepidemiological studies, known as confounding by indication-a bias that arises when the indication for using a particular drug is independently associated with the outcome of interest. Forbes and colleagues initially demonstrate that the three main indications for ASM use in their pregnant population are all associated with an increased risk of miscarriage (regardless of ASM use), thereby emphasising the need to account for this type of bias.…”