Twenty-year trends in the use of anti-seizure medication among pregnant women in the Netherlands.

BACKGROUND: Anti-seizure medications (ASMs) are used to treat conditions such as epilepsy and bipolar disorder. Some of these drugs are associated with an increased risk of congenital malformations and adverse developmental outcomes. OBJECTIVES: To examine trends in use of ASMs among pregnant women in the Netherlands according to medication safety profile. METHODS: Using population-based data from the PHARMO Perinatal Research Network, we assessed trends in use of ASMs among pregnant women in the Netherlands between 1999 and 2019, stratified by medication safety profile. Individual treatment patterns were also assessed. RESULTS: In total, 671,709 pregnancies among 446,169 women were selected, of which 2405 (3.6 per 1000) were ASM-exposed. Over the study period, a significant increase was observed for use of known safest ASMs (0.7-18.0 per 10,000 pregnancies) as well as for those with uncertain risk (5.3-13.4 per 10,000 pregnancies). Use of ASMs with higher risk of congenital malformations decreased significantly (24.8-14.5 per 10,000 pregnancies), except for topiramate (0-6.7 per 10,000 pregnancies). Switches between ASM safety risk categories before and during pregnancy were uncommon; women rather discontinued treatment or switched within the same category. There was no clear change for the proportion using polytherapy during pregnancy (12% overall), however a non-significant trend toward inclusion of known safest ASMs was observed over time (1.9-3.6%). CONCLUSIONS: Over the last two decades, there has been an increase in use of known safest ASMs among pregnant women, together with a trend toward newer ASMs with uncertain risk. Only a small proportion of women switched to a safer alternative before or during pregnancy. Altogether, this highlights the need for an expansion of ASM risk knowledge and communication to healthcare providers and women of reproductive age to improve preconception counseling.

Use of antiepileptic drugs by trimester.

OBJECTIVE: To determine which antiepileptic drugs pregnant women receive by trimester. METHODS: This retrospective cohort study using the IBM Watson Health MarketScan Research Databases evaluated which antiepileptic drugs pregnant women with epilepsy received by trimester. Women with aged 15-54 years with a history of seizure disorder who underwent a delivery hospitalization between 2008 and 2017 were included in the analysis. Descriptive statistics were performed. RESULTS: Of 34,144 women with a seizure disorder diagnosis and a delivery hospitalization, 10,289 (30.1%) received an anti-epileptic medication during pregnancy of which more than half received lamotrigine or levetiracetam. Other antiepileptic medications used by >5% of the population during any one trimester in the study period included carbamazepine, clonazepam, and topiramate. In evaluating medication use in the 1st trimester versus the 2nd trimester, clonazepam use decreased 32.0% (95% CI 60.0%, 77.0%) from 5.6% to 3.8% of patients receiving antiepileptics from the 1st to the 2nd trimester, gabapentin deceased 22.1% (95% CI 0.68%, 0.90%) from 4.1% to 3.2%, and topiramate decreased 30.0% (95% CI 62.8%, 77.9%) from 7.2% to 5.1%. In comparison, levetiracetam increased from 22.5% to 33.3% between the 1st and 3rd trimester and lamotrigine 22.2% to 27.5% between the 1st and 3rd trimester, 48.3% and 24.0% increases respectively. CONCLUSION: Antiepileptic drugs with less favorable fetal risk profiles such as topiramate decreased by trimester while medications with more favorable fetal risk profiles such as lamotrigine and levetiracetam increased. These findings broadly support that there are opportunities to improve pre-conceptional counseling of women with epilepsy.

Maternal morbidity and mortality associated with epilepsy.

OBJECTIVE: Prior research demonstrated large increased risk for maternal mortality among women with epilepsy. The objective of this study was to estimate risk for adverse maternal outcomes during delivery hospitalizations among women with epilepsy. METHODS: Truven Health MarketScan databases were used to compare risk for adverse maternal outcomes during delivery hospitalizations based upon whether there was diagnosis of epilepsy and receipt of anti-epileptic drugs prior to delivery. Outcomes included: (i) death during delivery hospitalization, (ii) severe maternal morbidity, (iii) cesarean delivery, (iv) postpartum hemorrhage, (v) placental abruption, (vi) preeclampsia, (vii) preterm delivery, (viii) premature rupture of membranes, and (ix) stillbirth. Adjusted models including hospital and demographic factors were performed with adjusted risk ratios (aRR) with 95% CIs as measures of effect. RESULTS: Women with epilepsy prior to delivery who received antiepileptic drugs (n = 6019) during pregnancy were not at increased risk for mortality with no deaths occurring in this group (p = .27). Risk for severe maternal morbidity in this group was approximately double (aRR 2.16, 95% CI 1.86-2.51) with risks for other outcomes including placental abruption (aRR 1.29, 95% CI 1.04-1.60), cesarean delivery (aRR 1.14, 95% CI 1.10-1.18), and preterm delivery (aRR 1.25, 95% CI 1.15-1.35) slightly increased compared to women without seizures. CONCLUSION: No significant difference in mortality risk was found for women with epilepsy. Increased risk for other adverse maternal outcomes for women with epilepsy on antiepileptics was modest.