1. Minimum prevalence of non-compliance recorded in an audit of antenatal care in a district general hospital joint obstetric epilepsy clinic
Smyth C, Gornall A, Bowen J
Shrewsbury & Telford NHS Hospitals Trust
Introduction
Prevalence of epilepsy in pregnant women has been estimated at % (1). The management of epilepsy in pregnancy poses the duel challenge of balancing the risk of seizures and teratogenic exposure to the foetus (2). Epilepsy remains one of the leading indirect causes of mortality in pregnancy (3), with SUDEP accounting for the majority of deaths (4). AED concordance in the epilepsy population has been documented as only 75% (5) with an observational study reporting 15% of WWE discontinuing AED in pregnancy (8). Moreover, a study analysing hair during pregnancy reported that four (15%) of 26 WWE discontinued medication during pregnancy, with only one patient acknowledging having done so (6). NIHCE advises that measuring serum levels of certain AEDs may be useful during pregnancy, reflecting pharmacokinetic alterations which may occur during pregnancy (7).
This audit examined adherence with AED in WWE attending a joint obstetric antenatal clinic. The importance of preconception counselling (4) and early intervention from epilepsy services is highlighted to promote increased awareness of the importance of seizure control during pregnancy.
Figure 2
Findings / recommendations
The majority of WWE (73%) were prescribed 1 AED with 61% being prescribed Lamotrigine, in keeping with evidence that Lamotrigine at the lowest dose possible, has a low risk of congenital malformations (8).
Despite limitations inherent to retrospective studies, our findings are consistent with previous reports of suboptimal AED compliance in pregnancy. We documented undetectable AED levels in around 1 in 5 of those tested. Potential reasons for non-compliance were not explored systematically though all WWE with undetectable levels at booking reported good compliance and 60% subsequently had therapeutic levels following intervention from EPSN.
We found only 1 / 36 (3%) WWE lost seizure control after a dose adjustment following fall in serum concentration by >25%. Whether seizures would have occurred in the other 35 WWE without dose adjustments remains unknown.
Of 11 seizure free patients relapsing in pregnancy, 3/11 (27%) had undetectable AEDs at booking. In comparison the relapse rate amongst patients with detectable AEDs at booking was lower (8/46;17%).
Poor or non-compliance has been identified as a risk factor for mortality of WWE in pregnancy (3). Lamotrigine and Levetiracetam levels may fall in pregnancy (8).
Joint antenatal clinics provide an appropriate environment for WWE to be cared for during their pregnancy. This audit has shown that a significant minority of Mums are non compliant with AEDs when presenting at booking clinic and hints that it may be a modifiable risk factor for seizure breakthrough in pregnancy. AED level testing at booking and a planned approach to dose adjustment as described proved acceptable to WWE.
A prospective study is planned.
Methodology
A retrospective case review of patients attending a joint obstetric / epilepsy clinic at a DGH during was undertaken. Analysis of clinical letters, notes and review of electronic results system allowed for collection of data pertaining to seizure control or occurrence, medication prescribed prior to and during pregnancy, adherence with treatment plan and serum levels of AEDs. Collection of serum level was limited to Lamotrigine and Levetiracetam.
Figure 1
Drug combinations during pregnancy
Results
143 WWE were reviewed. Established diagnoses were primary generalised epilepsy (50), focal epilepsy (75 ) and dissociative seizures (18) . A mean of 3 contacts per pregnancy with the EPSN took place. Excluding dissociative seizures 87/125 (70%) patients reported seizure freedom for at least one year prior to conception.
Booking took place around 12 weeks gestation when the majority had been prescribed monotherapy of which Lamotrigine (72) & Levetiracetam (32) were the most common (Figure 3). A minority were prescribed 2 AEDs (8%) or more (1%) AEDs (Figure 1). Almost 18% (25/143) patients were not taking any AED of whom 14/25 had epileptic seizures and 11/25 had dissociative seizures (Figure 2).
All WWE prescribed Lamotrigine or Levetiracetam were invited to have levels checked at booking and throughout. AED levels were checked on 57 consecutive patients (57/125) (Lamotrigine - 48 : Levetiracetam – 9) and were undetectable in 10/57 (17.5%). Subsequent testing later in pregnancy found 6 of these to have appropriate serum AED levels.
Universal acceptance of AED measurement & proposal to dose adjustments to level falling > 25% was achieved and the majority of WWE felt reassured that serum levels were being checked and all agreed to increases when a >25% drop were noted.
Stage of gestation at seizure breakthrough varied from 3 – 35 weeks.
Number of WWE
(87)
Seizures during pregnancy
Adjustments made to AED
AED levels available
AED levels undetectable 54 No
24/54 22
Yes
22/22 7 11
11/11 3
87 WWE Seizure free > 12 months prior to pregnancy
Total WWE –
125
38 WWE not Seizure free > 12 months prior to pregnancy
Medications charted for patients during pregnancy (125/143)
Figure 3
1.Kulaga, S. et al. (2011) Antiepileptic drug use during pregnancy: Perinatal outcomes. Seizure, 20, pp
2. Borthen, I. (2015) Obstetric complications in women with epilepsy. Seizure, 28, pp
3. Saving Lives, Improving mothers care - Confidential enquiry into maternal deaths (2017).
4. Winterbottom, J. B. et al. (2009) Preconception counselling for women with epilepsy to reduce adverse pregnancy outcome. Cochrane Database of Systematic Reviews, Issue 3.
5. Ernst, L. et al. (2016) Medication adherence in women with epilepsy who are planning pregnancy. Epilepsia, 57, pp
6. Williams, J. et al. (2002) Self-discontinuation of antiepileptic medication in pregnancy: Detection by hair analysis. Epilepsia, 43, pp
7. Stepanova, D. & Beran, R. G. (2015) The benefits of antiepileptic drug (AED) blood level monitoring to compliment clinical management of people with epilepsy. Epilepsy & Behaviour, 42, pp. 7-9.
8. Epilepsy in Pregnancy –Green-top guideline No. 68 (2016) Royal College of Obstetricians and Gynaecologists.