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ObjectiveTo explore seizure control and offspring outcomes associated with antiseizure medication (ASM) withdrawal during the first trimester of pregnancy.MethodsBased on a prospective multicenter study in China, pregnancies followed up between 2009 and 2023 at the neurology outpatient clinic of 50 hospitals were included in this study. Information on demographics, epileptic characteristics, treatment during pregnancy, and offspring outcomes was collected. Pregnancies were categorized into an ASM withdrawal group and an ASM continuation group. Balance tests and univariate log‐binomial regression analysis were conducted to identify imbalanced factors between groups and potential risk factors for seizure deterioration during pregnancy. Multivariate log‐binomial regression was then used to estimate the adjusted effects of ASM withdrawal on seizure deterioration during pregnancy and fetal outcomes. In addition, exploratory subgroup analysis was conducted to identify high‐risk patients who should avoid ASM withdrawal.ResultsOf the 695 pregnancies enrolled, 14.2% withdrew ASMs in the first trimester of pregnancy. ASM withdrawal during this period was associated with a risk of seizure deterioration during pregnancy (adjusted risk ratio [aRR] 1.405, 95% confidence interval [CI] 1.009–1.876). Subgroup analysis revealed a significant risk of seizure deterioration in pregnancies with seizures in 9 months (aRR 1.590, 95% CI 1.079–2.344). After adjusting the folic acid dose, no evidence of protective effects on fetus after ASM withdrawal was observed compared to patients with continued treatment, whereas seizure deterioration during pregnancy increased the risk of fetal death (aRR 3.577, 95% CI 1.086–11.651).SignificanceASM withdrawal in the first trimester of pregnancy did not show a protective effect on fetal outcomes but rather resulted in increased seizure frequency during pregnancy. However, this finding requires a larger sample for validation. Furthermore, seizure deterioration during pregnancy was associated with an increased risk of fetal death.
ObjectiveTo explore seizure control and offspring outcomes associated with antiseizure medication (ASM) withdrawal during the first trimester of pregnancy.MethodsBased on a prospective multicenter study in China, pregnancies followed up between 2009 and 2023 at the neurology outpatient clinic of 50 hospitals were included in this study. Information on demographics, epileptic characteristics, treatment during pregnancy, and offspring outcomes was collected. Pregnancies were categorized into an ASM withdrawal group and an ASM continuation group. Balance tests and univariate log‐binomial regression analysis were conducted to identify imbalanced factors between groups and potential risk factors for seizure deterioration during pregnancy. Multivariate log‐binomial regression was then used to estimate the adjusted effects of ASM withdrawal on seizure deterioration during pregnancy and fetal outcomes. In addition, exploratory subgroup analysis was conducted to identify high‐risk patients who should avoid ASM withdrawal.ResultsOf the 695 pregnancies enrolled, 14.2% withdrew ASMs in the first trimester of pregnancy. ASM withdrawal during this period was associated with a risk of seizure deterioration during pregnancy (adjusted risk ratio [aRR] 1.405, 95% confidence interval [CI] 1.009–1.876). Subgroup analysis revealed a significant risk of seizure deterioration in pregnancies with seizures in 9 months (aRR 1.590, 95% CI 1.079–2.344). After adjusting the folic acid dose, no evidence of protective effects on fetus after ASM withdrawal was observed compared to patients with continued treatment, whereas seizure deterioration during pregnancy increased the risk of fetal death (aRR 3.577, 95% CI 1.086–11.651).SignificanceASM withdrawal in the first trimester of pregnancy did not show a protective effect on fetal outcomes but rather resulted in increased seizure frequency during pregnancy. However, this finding requires a larger sample for validation. Furthermore, seizure deterioration during pregnancy was associated with an increased risk of fetal death.
This report is the first comprehensive update on the activities of existing epilepsy‐pregnancy registries since 2010. The primary aim of these registries, which were initiated by independent international research groups some 25 years ago, has been to assess the risk of major congenital malformations (MCMs) in offspring exposed in utero to different antiseizure medications (ASMs). Progress reports are provided here from the five original registries (the International Registry of Antiepileptic Drugs and Pregnancy EURAP, the North American Antiepileptic Drug Pregnancy Registry, the UK and Ireland Epilepsy and Pregnancy Register, the Kerala Registry of Epilepsy and Pregnancy, and the Raoul Wallenberg Australian Pregnancy Register of Antiepileptic Drugs) plus the more recently initiated West China Registry. Since their inception, the registries have published a wealth of data revealing important differences in risks across the most frequently used ASM treatments, thereby facilitating rational management of women with epilepsy who are of childbearing potential. Although the number of pregnancies enrolled in the different registries has more than doubled since the 2010 report, many questions remain. These include outcomes following prenatal exposure to most of the newer ASMs or different ASM combinations, as well as associations with specific MCMs rather than MCMs as a collective. All the registries, therefore, remain active and continue to enroll pregnancies. Administrative health care databases have been utilized more recently for the assessment of MCM risks and other adverse pregnancy outcomes associated with in utero exposure to ASMs. Although these can provide population‐based complementary information, they cannot replace the specific epilepsy‐pregnancy registries with their more detailed validated individual information. Given the multiple newer ASMs that are increasingly used and the continuing multiple knowledge gaps for the older ASMs, epilepsy‐pregnancy registries will continue to play an important role in the future.
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.
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