SUDEP and pregnancy

[Part 3: Challenges; Nashef L]

 

 

SUDEP is uncommon. Getting a handle on how often it occurs in pregnancy is difficult as data are limited. Based on the UK Confidential Enquiries into Maternal Deaths, Adab et al (2004) estimated a tenfold increase in mortality in pregnancy in the UK in women with epilepsy (WWE), compared to women without. More recently, using the 2011 report of the Confidential Enquiries (CMACE, 2011), this exercise has been repeated with similar results (Edey et al., 2014), as summarised here. Amongst 2,291,493 maternities (2006-2008), an estimated 0.6% (Burn et al., 2000; Fairgrieve et al., 2000) or 13,978 were in WWE. Fourteen deaths were epilepsy-related, of which 11 (79%) were sudden and unexpected (SUDEP). Nine occurred during pregnancy and five postpartum. An estimated 1:1000 women died from epilepsy (mostly SUDEP) during or shortly after pregnancy. Thus, epilepsy-related mortality appears to be a significant risk in pregnancy. Similar population-based data are needed from other countries to confirm or refute this estimate. How this compares to epilepsy-related mortality in women of child-bearing age who are not pregnant is uncertain. A general population-based study of SUDEP observed an incidence of 0.35 per 1,000 person-years (Ficker et al., 1998) with much higher rates in intractable cohorts (Tomson et al., 2013). Possibly, women who fall pregnant are less likely to have intractable epilepsy with serious or multiple co-morbidities. These data raise the possibility that pregnancy for WWE may carry a greater risk than the non-pregnant state.

 

Amongst the deaths observed, nine (64%) were in women taking Lamotrigine, seven as monotherapy. Given that Lamotrigine is believed to have a lower risk of teratogenicity than some other anti-epileptic drugs (AEDs), this observation may simply reflect UK prescribing practice during the period in question, and not an association between epilepsy-related deaths and Lamotrigine use. However, observations from the EURAP epilepsy pregnancy registry, whereby women on Lamotrigine, the levels of which significantly decrease in pregnancy, had more difficulties with epilepsy control argue against this being the sole explanation. Compared with other AEDs used as monotherapy, women exposed to Lamotrigine monotherapy in pregnancy were significantly less likely to be seizure-free, had more GTCS and a greater likelihood of deterioration in seizure control from first to second or third trimesters, and were more likely to require an increase in drug load (Battino et al., 2013).

 

The levels of some, but not all, AEDs decrease significantly in pregnancy because of increased clearance (Reisinger et al., 2013; Tomson et al., 2013) and the effect of pregnancy on the pharmacokinetics of AEDs is difficult to predict (Sabers & Tomson, 2009). More data are needed to clarify the clinical significance of changes in drug levels with different medications and reduce important gaps in current knowledge (Sabers & Tomson, 2009). Nevertheless, given the potential risks of uncontrolled epilepsy including SUDEP, every attempt should be made to prevent seizures, particularly convulsive, during pregnancy and in the postpartum period. Being proactive in checking and maintaining Lamotrigine levels during pregnancy is supported by some (Tomson et al., 2013), and advocated by this author, to reduce the risk of seizures and their complications.

 

Another study (Kapoor and Wallace, 2014), also based on the United Kingdom Confidential Enquiry into Maternal Deaths, analysed trends and causes of maternal death from epilepsy in the UK over the last 30 years with a retrospective review of 10 triennial Confidential Enquiry into Maternal Death reports (1979–2008), encompassing 21,514,457 maternities. The study concluded that the proportion of total maternal deaths from epilepsy over 30 years was 3.7% (95% CI 3.0–4.5) which showed an increasing trend. The study concluded that women with epilepsy should be looked after by specialist combined obstetric and medical or neurological teams in pregnancy to improve maternal and fetal outcomes. 

 

 

Lina Nashef

Consultant Neurologist

King's College Hospital, London, UK

Dec 2014

 

 

How to cite:

Nashef L. SUDEP and pregnancy. In: Hanna J, Panelli R, Jeffs T, Chapman D, editors. Continuing the global conversation [online]. SUDEP Action, SUDEP Aware & Epilepsy Australia; 2014 [retrieved day/month/year]. Available from: www.sudepglobalconversation.com.

 

 

References

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Adab N, Kini U, Vinten J, Ayres J, Baker G, Clayton-Smith J, et al. The longer term outcomes of children born to mothers with epilepsy. J Neurol Neurosurg & Psych 2004;75:1575-83.

Battino D, Tomson T, Bonizzoni E, Craig J, Lindhout D, Sabers A, et al. Seizure control and treatment changes in pregnancy: observations from the EURAP epilepsy pregnancy registry. Epilepsia 2013:54:1621-27.

Centre for Maternal and Child Enquiries (CMACE). Saving mothers’ lives: reviewing maternal deaths to make motherhood safer: 2006–2008. The eighth report of the confidential enquiries into maternal deaths in the United Kingdom. BJOG 2011;118s1:1-203.

CMACE - see Centre for Maternal and Child Enquiries.

Edey S, Moran N, Nashef L. SUDEP and epilepsy-related mortality in pregnancy. Epilepsia. 2014;55(7):e72-4.

Fairgrieve SD, Jackson M, Jonas P, Walshaw D, White K, Montgomery TL, et al. Population based, prospective study of the care of women with epilepsy in pregnancy. BMJ 2000;321:7262.

Ficker DM, So EL, Shen WK, Annegers JF, O’Brien PC, Cascino GD, et al. Population-based study of the incidence of sudden unexplained death in epilepsy. Neurology 1998; 51:1270-74.

Harper A. How can we improve the care of pregnant women with epilepsy? MSc dissertation 2012, King’s College London.

Kappoor D, Wallace S. Trends in maternal deaths from epilepsy in the United Kingdom: a 30-year retrospective review. Obstet Med 2014;7(4):160-64.

Reisinger TL, Newman M, Loring DW, Pennell PB, Meador KJ. Antiepileptic drug clearance and seizure frequency during pregnancy in women with epilepsy. Epilepsy & Behav 2013: 29:13-18.

Sabers A, Tomson T. Managing antiepileptic drugs during pregnancy and lactation. Curr Opin Neurol. 2009 Apr;22(2):157-61.

Tomson T, Landmark CJ, Battino D. Antiepileptic drug treatment in pregnancy: changes in drug disposition and their clinical implications. Epilepsia 2013: 54:405-13.

Tomson T, Nashef L, Ryvlin P. Sudden unexpected death in epilepsy: current knowledge and future directions. Lancet Neurol 2008;7(11):1021–31.

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Despite being reassured by her doctors that epilepsy in itself was not life threatening, Dianne died in her sleep suddenly and unexpectedly in March 1989, aged 32...

My daughter Kristen was diagnosed with epilepsy when she was nearly 15 years old.  For ten years her epilepsy had been fairly well controlled with medication...  That changed when she became pregnant...

Kirsty was one of a pair.  She has an identical twin sister - a mirror twin - a wonderful constant reminder.  Kirsty’s first episode of epilepsy was at the age of 18...

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