Prescription of antiepileptic medicines including valproate in pregnant women: A study in three European countries

Hurault‐Delarue, Caroline; Morris, Joan K.; Charlton, Rachel; Gini, Rosa; Loane, Maria; Pierini, Anna; Puccini, Aurora; Neville, Amanda J.; Snowball, Julia; Damase‐Michel, Christine

doi:10.1002/pds.4897

Cited by 25 publications

(29 citation statements)

References 35 publications

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“…Recent studies have confirmed that there were in excess of four million prescriptions of anti-seizure medications provided annually to United States women between 15 and 40 years of age ( Adedinsewo et al, 2013 ). While the prevailing consensus in the literature is that changes in prescribing trends globally has shifted to safer, less teratogenic ASMs, the clinical concern is accordingly lessened ( Hurault-Delarue et al, 2019 ). In fact, ASM usage and exposure during pregnancy continues to rise from 15.7 to 21.9 per 1,000 deliveries over a 10-year period ending in 2009 ( Bobo et al, 2012 ).…”

Section: Discussionmentioning

confidence: 99%

Gene Environment Interactions in the Etiology of Neural Tube Defects

et al. 2021

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Human structural congenital malformations are the leading cause of infant mortality in the United States. Estimates from the United States Center for Disease Control and Prevention (CDC) determine that close to 3% of all United States newborns present with birth defects; the worldwide estimate approaches 6% of infants presenting with congenital anomalies. The scientific community has recognized for decades that the majority of birth defects have undetermined etiologies, although we propose that environmental agents interacting with inherited susceptibility genes are the major contributing factors. Neural tube defects (NTDs) are among the most prevalent human birth defects and as such, these malformations will be the primary focus of this review. NTDs result from failures in embryonic central nervous system development and are classified by their anatomical locations. Defects in the posterior portion of the neural tube are referred to as meningomyeloceles (spina bifida), while the more anterior defects are differentiated as anencephaly, encephalocele, or iniencephaly. Craniorachischisis involves a failure of the neural folds to elevate and thus disrupt the entire length of the neural tube. Worldwide NTDs have a prevalence of approximately 18.6 per 10,000 live births. It is widely believed that genetic factors are responsible for some 70% of NTDs, while the intrauterine environment tips the balance toward neurulation failure in at risk individuals. Despite aggressive educational campaigns to inform the public about folic acid supplementation and the benefits of providing mandatory folic acid food fortification in the United States, NTDs still affect up to 2,300 United States births annually and some 166,000 spina bifida patients currently live in the United States, more than half of whom are now adults. Within the context of this review, we will consider the role of maternal nutritional status (deficiency states involving B vitamins and one carbon analytes) and the potential modifiers of NTD risk beyond folic acid. There are several well-established human teratogens that contribute to the population burden of NTDs, including: industrial waste and pollutants [e.g., arsenic, pesticides, and polycyclic aromatic hydrocarbons (PAHs)], pharmaceuticals (e.g., anti-epileptic medications), and maternal hyperthermia during the first trimester. Animal models for these teratogens are described with attention focused on valproic acid (VPA; Depakote). Genetic interrogation of model systems involving VPA will be used as a model approach to discerning susceptibility factors that define the gene-environment interactions contributing to the etiology of NTDs.

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Section: Discussionmentioning

confidence: 99%

Gene Environment Interactions in the Etiology of Neural Tube Defects

et al. 2021

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“…Contrary to the Danish study, however, our results are based on a relatively small sample of the Swiss population (15%), and thus our estimates may be subject to variability introducing some uncertainty. Reported prevalence of in utero valproate exposure vary by country and region; the Italian region of Tuscany reported that 15/10,000 pregnancies were exposed to valproate between 2007 and 2016 [26]. The French national agency of drug safety revealed a valproate exposure prevalence of 25/10,000 pregnancies in 2007, which declined to 14/10,000 pregnancies in 2014, and to 3/10,000 pregnancies in 2018 [27,28], based on an Original article analysis of national claims data.…”

Section: Discussionmentioning

confidence: 99%

“…The French national agency of drug safety revealed a valproate exposure prevalence of 25/10,000 pregnancies in 2007, which declined to 14/10,000 pregnancies in 2014, and to 3/10,000 pregnancies in 2018 [27,28], based on an Original article analysis of national claims data. However, an EMA funded study suggested that valproate exposure prevalence in France was lower (11/10,000 pregnancies) as of 2011 [26].…”

Section: Discussionmentioning

confidence: 99%

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Use of valproate in pregnancy and in women of childbearing age between 2014 and 2018 in Switzerland: a retrospective analysis of Swiss healthcare claims data

et al. 2021

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AIMS OF THE STUDY: The prevalence of the use of valproate during pregnancy and by women of childbearing age in Switzerland is not known. We aimed to study the use of antiseizure drugs by these women in Switzerland, with a particular focus on valproate. METHODS:We conducted a retrospective descriptive study using the healthcare claims database of the Swiss health insurance Helsana (2014-18). We established two separate study populations: (1) a cohort of pregnancies leading to a delivery, and (2) all women of childbearing age (15-45 years) who were insured with Helsana for at least one year during the study period. We identified the dispensation of valproate, lamotrigine, carbamazepine, levetiracetam, topiramate, pregabalin, gabapentin, phenobarbital, and phenytoin (1) between delivery and three months prior to the estimated date of the last menstrual period, and (2) by calendar year. We quantified exposure prevalence of each antiseizure drug as the number of women with ≥1 prescription fill per 10,000 (1) pregnancies, and (2) women by calendar year. Results were weighted for the demographic distribution of the Helsana population relative to the Swiss population.RESULTS: We identified a weighted pregnancy population of 387,418 pregnancies, with a mean maternal age at delivery of 31.9 years (standard deviation 5.1). Lamotrigine was the most frequently dispensed antiseizure drug during pregnancy (20/10,000), followed by levetiracetam (11/ 10,000), and pregabalin (3.8/10,000). Valproate was dispensed to 1.9/10,000 women during pregnancy and to 1.3/ 10,000 women within 90 days prior to the last menstru-al period but not during pregnancy. The weighted study population of women aged 15-45 years consisted of 2,781,151 women, of whom 74,080 (270/10,000) were exposed to ≥1 of the evaluated antiseizure drugs. Pregabalin was the most frequently dispensed antiseizure drug (64/ 10,000), followed by lamotrigine (46/10,000), topiramate (32/10,000), and valproate (25/10,000). The use of valproate decreased from 28/10,000 women in 2014 to 21/ 10,000 women in 2018. CONCLUSIONS:The prevalence of exposure to valproate during pregnancy was comparable to Denmark and lower than in other European countries. Despite decreasing exposure prevalence, the use of valproate in women of childbearing age in Switzerland seems higher than the actual clinical need.

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“…In such a context, the relationship between changes in antiepileptic drug prescribing during pregnancy and risk of malformation has become a public health interest in a few countries. [16][17][18][19][20][21][22] We performed a descriptive, population-based pharmacoepidemiological study using data from administrative healthcare databases aimed to evaluate prescription profiles of AEDs in an Italian population of women in childbearing age and pregnant women.…”

Section: Introductionmentioning

confidence: 99%

Changes in antiepileptic drug prescriptions over a decade in childbearing women in Lombardy region, Italy

Clavenna

Campi

Putignano

et al. 2021

Brit J Clinical Pharma

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Aims To describe the antiepileptic drug (AED) prescription pattern in pregnant women and women of childbearing age in the 2010–2019 period in the Lombardy region, Italy. Methods The Lombardy region administrative healthcare databases (2010–2019) were analysed. AEDs were classified as drugs belonging to the N03A subgroup of the Anatomical Therapeutic Chemical Classification System. Women aged 15–49 years were considered as being of childbearing age, while exposure during pregnancy was estimated taking into account the 12 months before delivery (International Classification of Diseases, Ninth Revision, Clinical Modification, ICD‐9‐CM codes in the diagnosis record from 650 to 659). Results During 2019, 16 605 women of childbearing age (prevalence: 14.8‰) received at least 1 AED prescription. Pregabalin was the most widely used antiepileptic in women of childbearing age (22.3%), followed by valproic acid (20.0%). In 2010, the prevalence of valproic acid prescription to women of childbearing age was 30.2%; in 2019 this was 20.0%. In pregnant women, this prevalence was 24.9% in 2010 and 14.1% in 2019. Starting from 2017, levetiracetam and lamotrigine were the most commonly drugs prescribed to pregnant women. Conclusion Despite the decrease in valproic acid prescription over time, this drug is still among the most used AEDs, in particular in women of childbearing age. Educational interventions for healthcare professionals and women are needed in order to reduce the risk of unplanned pregnancy.

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Prescription of antiepileptic medicines including valproate in pregnant women: A study in three European countries

Cited by 25 publications

References 35 publications

Gene Environment Interactions in the Etiology of Neural Tube Defects

Gene Environment Interactions in the Etiology of Neural Tube Defects

Use of valproate in pregnancy and in women of childbearing age between 2014 and 2018 in Switzerland: a retrospective analysis of Swiss healthcare claims data

Changes in antiepileptic drug prescriptions over a decade in childbearing women in Lombardy region, Italy

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