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

Abstract

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.

Trends and patterns of antiseizure medication prescribing during pregnancy between 1995 and 2018 in the United Kingdom: A cohort study

“…Towards the end of the study period, lamotrigine was the most common ASM in women with epilepsy and bipolar disorder, and gabapentin and pregabalin were more common in women with other indications. Similar rates of ASM prescription during pregnancy have been found in other western countries, with increasing prevalence in recent time periods 6,17–20 . The overall increase in ASM prescription, in this study and others, was driven by prescription for indications other than epilepsy, 20,21 and prescription of ASMs with more evidence of teratogenicity decreased (specifically valproate, phenytoin, and carbamazepine) 6,19,22–24 …”

“…Similar rates of ASM prescription during pregnancy have been found in other western countries, with increasing prevalence in recent time periods 6,17–20 . The overall increase in ASM prescription, in this study and others, was driven by prescription for indications other than epilepsy, 20,21 and prescription of ASMs with more evidence of teratogenicity decreased (specifically valproate, phenytoin, and carbamazepine) 6,19,22–24 …”

“…6,[17][18][19][20] The overall increase in ASM prescription, in this study and others, was driven by prescription for indications other than epilepsy, 20,21 and prescription of ASMs with more evidence of teratogenicity decreased (specifically valproate, phenytoin, and carbamazepine). 6,19,[22][23][24] Discontinuation of ASMs during pregnancy was common, particularly among women with indications other than epilepsy. Factors with evidence for an association with discontinuation of ASMs included older age at conception and greater social deprivation.…”

“…ASM polypharmacy was observed in 10% of women using ASMs during the first trimester of pregnancy, similar to findings using Dutch data that showed 12% of pregnancies exposed to ASMs included polytherapy. 19…”

GPs awareness of pregnancy: trends and association with hazardous medication use

“… 3 For example, they are still responsible for the large majority of drug prescriptions during pregnancy, including medication with potential safety risks, in one-third of Dutch pregnancies. 5 , 6 A substantial part of repeat prescribing by GPs occurs without any direct patient contact, thus without assessing pregnancy status or intention. 7 , 8 This underscores the GPs’ vital role in optimisation of pregnancy care.…”