Trends in maternal deaths from epilepsy in the United Kingdom: a 30-year retrospective review

Kapoor, Dipti; Wallace, Suzanne

doi:10.1177/1753495x14553257

Cited by 21 publications

(13 citation statements)

References 22 publications

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“…Maternal mortality is almost 10 times greater for women with epilepsy than for those without epilepsy (100 versus 11/100 000 pregnancies) 57. Maternal mortality has fallen, but epilepsy related deaths increased over the past 30 years 58. Valproate had been stopped before pregnancy in two of the nine cases of sudden unexpected death in epilepsy reported in the UK during 2013-15 59…”

Section: Arguments For Restricted Usementioning

confidence: 99%

Weighing the risks of valproate in women who could become pregnant

Angus‐Leppan

Liu

2018

BMJ

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Section: Arguments For Restricted Usementioning

confidence: 99%

Weighing the risks of valproate in women who could become pregnant

Angus‐Leppan

Liu

2018

BMJ

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“…Furthermore, a review of similar deaths over 30 years concluded that between 1979 and 2008, the proportion related to epilepsy have increased although maternal deaths have decreased. 29 Put bluntly, restricting efficacious drugs from women increases their risk of dying from their epilepsy. Even when a woman is not pregnant, epilepsy confers a twentyfold increase in death because of SUDEP.…”

Section: Valproate Is An Effective Drugmentioning

confidence: 99%

Valproate: life-saving, life-changing

Thomas

2018

Clinical Medicine

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s1-s8 LINACRE LECTURE both the widespread harm caused to an estimated 10,000 children worldwide and the battle to recognise this risk and restrict its use. The drug had (and still has) many important medical uses, but when taken in early pregnancy to combat hyperemesis, affected children were born with significant limb deficits. Although withdrawn in the UK in 1961, it took a long campaign and press support before there was a compensation settlement. Therefore, when The Daily Telegraph headline on 30 July 2009 stated that valproate was responsible for 'worst child poisoning case since thalidomide' the connotation was stark and emotional (Fig 1 ). I will discuss the many reasons why the thalidomide comparison is understandable, but also why the circumstances are significantly different. This will be with the specific aim of promoting the unanimous advice about valproate in pregnancy from many august agencies, while also recognising that there are important evidence gaps. Valproate exposure in uteroValproate is a recognised teratogen and the major cause of fetal anticonvulsant syndrome. An estimated 10.7% of children exposed to valproate in utero are born with a major congenital malformation (that is, a structural abnormality that is recognisable at birth) in comparison to an estimated 2% of unexposed infants. 1This produces the first two problems: 1 doctors are often poor at explaining risk 2 patients are inexperienced in balancing these risks. This is exacerbated when the research evidence produces population risks ( ' a certain percent of affected children') whereas what we need is individualised risk ('your chance of having an affected baby is'). Equally, our prior experiences as physician and parent will sway the way we deal with perceived risk. The second issue is this: the fact that the concern regarding major malformations and valproate is so well known it has blinded us to the new scandal, the new relationship. We, as adult physicians have had 'change blindness' -we have failed to see that the threat of valproate is no longer limited to malformations at birth, but more far-reaching and life-changing developmental issues.The easiest associations to recognise are when infrequent exposures (unusual drug x) causes a dramatic, instant and frequently occurring outcome. A much more challenging situation is when a drug that has been available since the late 1960s, such as valproate, produces a delayed and variable effect, such as poorer cognition. Recognition is even harder when the effect is in the patients' offspring. This in part explains why the epilepsy community was so slow to recognise the extent of the risks.Antiepileptic medications, and valproate principally, are commonly prescribed teratogens. There is significant concern that we are not doing enough to educate clinicians and potential parents about the risks of valproate in pregnancy. There is clear advice from the Medicines and Healthcare products Regulatory Agency and the International League Against Epilepsy about the risks of valproate exposure in...

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“…An enquiry from the maternal deaths registry in the United Kingdom showed that women with epilepsy are 10 times more likely to die while pregnant compared to women without epilepsy, and sudden unexpected death in epilepsy (SUDEP) is the major cause of death in pregnant and postpartum women with epilepsy . Multiple risk factors are suspected, including frequent generalized tonic‐clonic seizures, poor adherence to antiepileptic drug (AED) treatment, nocturnal seizures, and early onset of epilepsy.…”

mentioning

confidence: 99%

Are doses of lamotrigine or levetiracetam adjusted during pregnancy?

et al. 2017

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SummarySubtherapeutic levels of lamotrigine and levetiracetam are more likely to occur during pregnancy owing to the effect of pregnancy on their pharmacokinetics. This can lead to suboptimal control of epilepsy, and guidelines recommend proactive dose adjustment in the second and third trimesters alongside therapeutic drug monitoring (TDM). This retrospective cohort study using administrative databases aimed to investigate whether prescribers adjust the dose of lamotrigine or levetiracetam during and after pregnancy and whether TDM is used to manage dose adjustment. In 460 individual pregnancies, 232 women (61.4%) had their lamotrigine dose increased in the second and third trimesters and 44 women (53.7%) had their levetiracetam dose increased. Only 57 women (12.4%) had any TDM. The dose was not always decreased postpartum, and 157 women (56.9% of those who had escalated doses during pregnancy) had dose reduced following birth. Between 2012 and 2015, 29 women had an epilepsy‐coded hospital discharge during pregnancy and were more likely to have had their dose of lamotrigine or levetiracetam increased. Overall, doses of lamotrigine and levetiracetam were not increased during pregnancy in 40% of the study population, dose changes were not often guided by TDM, and doses were not always reduced postpartum.

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Trends in maternal deaths from epilepsy in the United Kingdom: a 30-year retrospective review

Cited by 21 publications

References 22 publications

Weighing the risks of valproate in women who could become pregnant

Weighing the risks of valproate in women who could become pregnant

Valproate: life-saving, life-changing

Are doses of lamotrigine or levetiracetam adjusted during pregnancy?

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