DOI: 10.1111/tog.

12413
The Obstetrician & Gynaecologist
Review
http://onlinetog.org

The management of pregnant women with epilepsy:

a multidisciplinary collaborative approach to care
a, b c
Meena Bhatia MBBS MSc MRCOG, * Jane E Adcock BMed MD FRCP FRCAP, Lucy Mackillop BM BCh MA FRCP
a
Specialist Registrar (ST7) in Obstetrics and Gynaecology, Buckinghamshire Healthcare NHS Trust, Stoke Mandeville HP21 8AL, UK
b
Consultant Neurologist, Oxford Epilepsy and Epilepsy Surgery Programme, Oxford University Hospitals NHS Trust, John Radcliffe Hospital,
Headley Way, Headington, Oxford OX3 9DU, UK
c
Consultant Obstetric Physician, High Risk Maternity Services, Oxford University Hospitals NHS Trust, John Radcliffe Hospital, Headley Way,
Headington, Oxford OX3 9DU, UK
*Correspondence: Meena Bhatia. Email: meenab21@aol.com

Accepted on 31 December 2016

Key content
 Epilepsy is the most common serious neurological problem
encountered in pregnancy; however, women with epilepsy are
often not referred to high-risk pregnancy services.
 The 2015 Mothers and Babies: Reducing Risk through Audits and
Confidential Enquiries across the UK (MBRRACE-UK) report on
maternal mortality highlights that the care of pregnant women
with epilepsy requires urgent improvement.
 The two most recently available guidelines (Scottish Intercollegiate
Guidelines Network and Royal College of Obstetricians and
Gynaecologists guidelines) require comparative critical appraisal.
 Collaboration between general practitioners, specialist epilepsy
nurses/midwives, obstetricians, obstetric physicians, neurologists
and anaesthetists is vital to ensure optimal
standardised management.
Learning objectives

To understand the role of pre-conception counselling: to include
advice on seizure control, anti-epileptic drugs (AEDs) and
pre-conception folic acid.
 To understand the risk factors associated with poor outcomes in
pregnant women with epilepsy.
 To understand the risks associated with specific types of AEDs:
mono- and polytherapy.
 To understand the issues regarding the titration of AEDs during
pregnancy, postnatal and breastfeeding periods.
 To understand the importance of a multidisciplinary antenatal,
intrapartum and postnatal schedule of care and
special considerations.
Ethical issues

When should we advise women to avoid pregnancy?
 When, how and by whom should AEDs be modified?
 Are women with epilepsy aware of the risk of sudden unexpected
death in epilepsy in pregnancy?
Keywords: anti-epileptic drugs / epilepsy / sudden unexpected
death in epilepsy in pregnancy

Please cite this paper as: Bhatia M, Adcock JE, Mackillop L. The management of pregnant women with epilepsy: a multidisciplinary collaborative approach to care.
The Obstetrician & Gynaecologist 2017; DOI: 10.1111/tog.12413.

Introduction Why is improved care in women with

Epilepsy is characterised by recurrent, unprovoked seizures
resulting from excessive neuronal discharge.1 Epilepsy affects
approximately 0.5–1.0% of women of childbearing age and it
is the most common serious neurological condition in
pregnancy.2 Anti-epileptic drugs (AEDs) are the mainstay of
treatment and are given in approximately 1 out of every
200 pregnancies in the UK.3 Fortunately, almost two-thirds
of women with epilepsy will remain stable during pregnancy
and 96% will deliver a healthy baby.4,5 However, for some
women with epilepsy, pregnancy may be associated with an
increased risk of significant maternal and perinatal mortality
and morbidity.6
epilepsy in pregnancy important?
The number of new cases of epilepsy per year in young
women is 20–30 per 100 000.2 The risk of mortality for
pregnant women with epilepsy is almost ten times higher
than that of the general population.7 The 2015 Mothers and
Babies: Reducing Risk through Audits and Confidential
Enquiries across the UK (MBRRACE-UK) report found that
epilepsy was not only the most common neurological cause
of death, but was also associated with a mortality rate greater
than any other single pre-existing medical condition.6
Unfortunately, the mortality rate in pregnant women with
epilepsy has remained unchanged since 2006 at 0.4 in

ª 2017 Royal College of Obstetricians and Gynaecologists 1

 The multidisciplinary management of pregnant women with epilepsy

100 000 despite urgent calls to improve services and care for
this group.8 It is suggested that the majority of poor
outcomes associated with women with epilepsy could be
prevented by identifying women with epilepsy as high risk
and offering more specialised care.
The management of epilepsy during pregnancy may be
challenging, especially in those taking AEDs, as one balances
potential adverse effects of AEDs on the fetus with seizure
frequency in the mother.9 A number of clinical reviews detail
the maternal and fetal risks associated with pregnancy and
epilepsy; however, this review aims to outline an evidence-
based multidisciplinary pathway of care for women with
epilepsy to optimise outcomes based on the available
literature and guidelines, including the new Royal College
of Obstetricians and Gynaecologists (RCOG) guidelines.10,11
Clinical practice guidelines: a critical
appraisal
There are a number of guidelines on the management of
pregnant women with epilepsy, including the National
Institute for Health and Care Excellence (NICE) guidelines,
the Scottish Intercollegiate Guidelines Network (SIGN) and
the recent RCOG guidance on epilepsy.10,11 The SIGN and
RCOG guidelines cover the subject of pregnancy in women
with epilepsy more extensively than the NICE guidelines and
are more recently published. The authors assessed the quality
of the recommendations by performing a comparative critical
appraisal between the two most recently published guidelines
(Table 1). In addition, the authors have identified differences
in the recommendations between the two guidelines
(presented later in the article), which to the authors’
knowledge is the first such comparative critical appraisal of
these two guidelines. The AGREE II-Global Rating Scale tool
was used, which is a reliable and widely accepted tool for
rapid appraisal of guidelines and can be used by clinicians in
daily practice.12 This tool consists of five domains that assess
guideline reporting, and each domain is scored out of seven.
Why is pre-conception care important and
what elements should be included?
The 2015 MBRRACE-UK report ascertained that 86% of
women with epilepsy who died of sudden unexpected death
in epilepsy (SUDEP) had not received prepregnancy
counselling.6 Moreover, 25% of women with epilepsy who
were members of the British Epilepsy Association said they
had never discussed pregnancy with anyone, and only 38% of
a population-based study of women with epilepsy recalled
any prepregnancy counselling.3,13 Preconception counselling
for women with epilepsy is recommended as routine practice
and is associated with improved epilepsy- and non-epilepsy-

Table 1. Comparison of SIGN and RCOG guidelines and the quality of evidence supporting recommendations regarding pregnancy in women with
epilepsy (AGREE II-GRS Instrument)

Guideline SIGN 2015 RCOG 2016

1. Guideline recommendations and Recommendations: 56 Recommendations: 62

quality of guideline development
2. Quality of presentation
3. Completeness of reporting
4. Overall quality of guideline
5. Recommend this guideline in
practice?
Levels of evidence used
High-quality evidence: 3/56
Moderate-quality evidence: 1/56
Low-quality evidence: 19/56
Practice- and experience-based recommendations:
33/56
6/7 – professional stakeholders involved, no clear
information on patient involvement
Systematic evidence-based approach
6/7 – Well organised
Recommendations easy to locate within text
Could tabulate or represent information in a flow
chart for further ease of use
6/7
Omission of statement on valproate from
European medicines Agency 2014 and MHRA
2015
6/7
Clinically sound recommendations and
appropriate for intended group of patients
Would recommend use in practice and to aid
clinical decision making
See Table 6 for differences
Levels of evidence used
High-quality evidence: 0/62
Moderate-quality evidence: 4/62
Low-quality evidence: 24/62
Practice- and experience-based recommendations:
34/62
7/7 – Stakeholder involvement obvious. Sufficient
professional and patient involvement
Systematic evidence-based approach
6/7 – Well organised
Recommendations easy to locate within text
Could tabulate or represent information in a flow
chart for further ease of use
6/7
Omission of statement on valproate from
European medicines Agency 2014 and MHRA
2015
6/7
Clinically sound recommendations and
appropriate for intended group of patients
Would recommend use in practice and to aid
clinical decision making
See Table 6 for differences

GRS = Global Rating Scale; MHRA = Medicines and Healthcare Products Regulatory Agency; RCOG = Royal College of Obstetricians and
Gynaecologists; SIGN = Scottish Intercollegiate Guidelines Network.

2 ª 2017 Royal College of Obstetricians and Gynaecologists

 Bhatia et al.

related outcomes for both mother and baby.14 This should
involve coordinated interdisciplinary communication
between neurologists, physicians, general practitioners and
obstetricians; however, as up to half of all pregnancies are
unplanned, it is imperative that this discussion forms an
opportunistic part of the consultation for every woman with
epilepsy of childbearing age.2,14
Effective counselling aims to allow for informed decisions
to be made regarding pregnancy, and for pregnancy to be
planned at a time when maternal health is stable and
frequency of seizures is minimal to optimise pregnancy
outcomes (Table 2).14,15 Such counselling should involve
specific goals that include general health promotion.16
Women with epilepsy should be advised on optimisation of

Table 2. Discussion at pre-conception counselling2,9,10,14,20,33,38,42

Reassure women  The majority (96%) of pregnancies have a good outcome

 Women who have been seizure free for >12 months are likely to remain seizure free if they are
compliant with treatment

Inform women  Some may require dose adjustments during pregnancy to maintain seizure control
 Most women with epilepsy can aim for a vaginal birth unless there are obstetric issues
 Epilepsy alone is not an indication for induction of labour or caesarean section

The effect of pregnancy on epilepsy  Seizure free: 64%

 Increased seizure frequency: 17%
 Decreased seizure frequency: 16%
 Intrapartum seizures: 3.5%
 Status epilepticus: <2%

Factors contributing to deterioration of  Poorly controlled epilepsy prior to pregnancy

epilepsy during pregnancy  Seizure frequency of >1 per month
 Multiple seizure types
 Drug-resistant epilepsy
 High-dose polytherapy
 Poor compliance with AEDs
 Reduced drug concentration in pregnancy due to increased renal clearance and metabolism
 Pregnancy specific triggers: nausea and vomiting (reduced AED concentration), sleep deprivation,
labour (pain and hyperventilation)

Risks to the developing fetus  Generally low risk to fetus

 Increased risk of MCMs due to AEDs; however, lamotrigine, levetiracetam and carbamazepine are
commonly used and are considered the safest agents
 Sodium valproate infers the highest risk of MCM (especially neural tube defects), and there is also
evidence of an increased risk of cognitive difficulties/learning disability in children of mothers
taking sodium valproate during pregnancy
 Risks of epilepsy on the fetus: risk of hypoxia and injury from falling during seizures, risk of SUDEP
 The risk is dependent on the dose and number of AEDs (see Table 4)
 Increased risk of intrauterine growth restriction in mothers on polytherapy with AEDs

Risk of developing childhood epilepsy  Increased risk of epilepsy if first-degree relative has epilepsy
 The risk is multifactorial and depends on the type of epilepsy syndrome
 The individual genetic susceptibility should be discussed with the patient’s
neurologist/epileptologist

Medication  5 mg folic acid should be taken preconceptually and throughout pregnancy to reduce the risk of
congenital malformations and long-term cognitive deficits
 Avoid any abrupt withdrawal of AEDs
 Aim for monotherapy with the lowest effective AED dose, if possible
 If taking sodium valproate consider weaning off or an alternative AED on the advice of a
neurologist or obstetric physician
 If sodium valproate needs to be continued, change to the moderate release or increase the daily
frequency to reduce the risk of high peak levels of the drug. Doses >800 mg/day are associated
with greater risks of teratogenicity
 Avoid using sodium valproate as first-line treatment in any women with epilepsy of childbearing
age unless other treatments are ineffective or not tolerated; lamotrigine, levetiracetam and
carbamazepine are suggested

Encourage all women  To register their pregnancy on the national epilepsy and pregnancy database:
http://www.epilepsyandpregnancy.co.uk

AED = anti-epileptic drug; MCM = major congenital malformation; SUDEP = sudden unexpected death in epilepsy.

ª 2017 Royal College of Obstetricians and Gynaecologists 3

 The multidisciplinary management of pregnant women with epilepsy
health before pregnancy (Table 3) and when to delay
pregnancy and continue contraception.
Women with unstable epilepsy or who are in poor health
have a higher incidence of maternal mortality and perinatal
morbidity and mortality.6 Table 4 outlines when women
with epilepsy should be advised to delay or avoid pregnancy.
Anti-epileptic drugs and pregnancy
Pregnant women with epilepsy taking AEDs will require
input from both an obstetrician and a neurologist or
obstetric physician about their recommended regimen
during pregnancy. They will be advised to continue on
their regimen until a medical review, and any women with
epilepsy who are on AEDs and have an unplanned pregnancy
should have an urgent review of their condition with a
neurologist. Common concerns regarding AEDs in
pregnancy are the risk of major congenital malformation
(MCM) and the risk of fetal growth restriction; these are
outlined below (Table 5). In addition, there are concerns
regarding the side-effect profile of certain AEDs, including
mood disturbance, poor concentration, irritability and
tiredness in some women with epilepsy.17,18
Risk of major congenital malformations due to anti-
epileptic drugs
The majority of AEDs cross the placenta and are potentially
teratogenic.2 The incidence of MCMs in women with
epilepsy who are not exposed to AEDs is similar to that of
Table 3. How to optimise health pre-conceptually
Seizure  Remain compliant with AED medication
frequency  Close contact with neurology team to enable
titration of medication
 Avoid seizure triggers
AEDs  Aim to manage seizures effectively with lowest
dose of AED
 Aim for low-dose monotherapy if appropriate
 Avoid changing medication if a women is seizure
free unless on the advice of a neurologist and after
close discussion with the patient
 Consider changing to less teratogenic AEDs where
possible (lamotrigine, levetiracetam
and carbamazepine)
 Avoid sodium valproate if other AEDs
are appropriate
 Note the optimal serum
concentration preconceptually
General  Optimise health (optimise BMI, reduction of
health alcohol consumption, regular exercise)
 Stop smoking (smokers have a higher risk of
preterm labour)
 Start 5 mg folic acid several months pre-conception
AED = anti-epileptic drug; BMI = body mass index.
4 ª 2017 Royal College of Obstetricians and Gynaecologists
the general population (1–3%), indicating that epilepsy itself
does not significantly increase the risk of MCM.19 Children of
mothers taking AEDs have up to a 10% risk of MCMs
compared with the general population.20,21 Potential
fetotoxicity associated with AED use can occur in any
trimester.20 Risk of fetal harm is highest during
organogenesis in the first trimester and the risk of cognitive
impairment typically occurs in the third trimester and is
associated with polytherapy.1 The extent of fetal risk is
influenced by type and dose of AED, maternal age and
parental history of malformation.22
The MCMs associated with AED use include oral clefts,
cardiovascular defects, urogenital defects and neural tube
defects.2 Minor malformations include fetal anticonvulsant
syndrome, which include dysmorphic features, hypertelorism,
and hypoplasia of the nails, digits and midface.2
Small-for-gestational-age fetus and anti-epileptic
drugs
Offspring of women with epilepsy taking AEDs may have an
increased risk of being small for gestational age (SGA).1
There is evidence suggesting that there is a two-fold increased
risk of a baby being SGA in women with epilepsy taking
AEDs compared with women not taking AEDs.23 A recent
systematic review corroborates these findings.24 In addition,
evidence has shown no increased risk in offspring being SGA
in women with epilepsy who were not taking AEDs.25
Therefore, surveillance ultrasound scans for fetal growth may
be considered in women who are on moderate dose
polytherapy with AEDs, although the RCOG recommends
that serial scans should be performed from 28 weeks of
gestation for all pregnant women with epilepsy taking AEDs.
Other obstetric risks from anti-epileptic drugs
A recent systematic review on outcomes in pregnant women
with epilepsy demonstrated an increased risk of miscarriage,
antepartum haemorrhage, hypertensive disorders, induction
of labour, caesarean section, preterm delivery and
postpartum haemorrhage compared with the
background population.24
What is safe anti-epileptic drug practice in
pregnancy?
The choice of AEDs in women of childbearing age is
predominantly determined by the epilepsy type. However,
there is compelling evidence to recommend avoiding sodium
valproate in all women with epilepsy of childbearing age, if
possible. The developing fetus is at high risk (up to 10%) of
MCMs, particularly neural tube defects, when exposed to
sodium valproate monotherapy and even more so with
polytherapy.1,19,22,26,27 There is also evidence that children
exposed in utero to sodium valproate are at a higher risk of
learning difficulties and autistic spectrum disorders.28–30
 Bhatia et al.

their use, and due to the lower risk of subsequent cognitive

Table 4. When to avoid/postpone pregnancy
Seizure  Uncontrolled seizures (particularly tonic clonic)
frequency
AEDs  Taking high doses of AEDs
 Polytherapy: multiple AEDs
 Drug resistant epilepsy/uncontrolled epilepsy
 Non-compliance with medication
General health  Poor general health or other
medical comorbidities
AED = anti-epileptic drug.
However, there may be some women with epilepsy for whom
the only effective AED is valproate, and in these
circumstances the benefits of valproate for seizure control
may outweigh the potential risks to the fetus. It should only
be used after careful discussion with the woman.31
Lamotrigine and levetiracetam are recommended as first-
line agents in patients who would otherwise be considered for
sodium valproate therapy (women with generalised epilepsy
syndromes) due to the lower rate of MCM associated with
and neurodevelopmental problems.32 It must be noted that
the levels of these drugs may fall with advancing gestation,
and therefore dose titration may be required to prevent
seizures effectively.33 Clobazam is also used for exacerbation
of seizures during pregnancy or in the postnatal period, and
is considered relatively safe.34
Monitoring plasma levels of anti-epileptic drugs
during pregnancy
The physiological adaptations of pregnancy, including
increased AED distribution, enhanced hepatic enzyme-
induced metabolism and increased renal clearance, may
contribute to decreased AED concentration with advancing
gestation.2 The AEDs most likely to be affected in this
manner are lamotrigine, levetiracetam, carbamazepine and
oxcarbazepine; however, the true clinical implications of this
are uncertain.35,36
Plasma levels of AEDs may be misleading and should be
interpreted by specialists.37 With the exception of lamotrigine,
levetiracetam, carbamazepine and oxcarbazepine, plasma level

Table 5. The AED-specific congenital malformation frequency rate

Possible congenital Risk of congenital

AED malformations malformation Safety in pregnancy and breastfeeding

No AED34,43,44 2.0–2.3%
Carbamazepine1,22,26,34,43,45 Cardiac defects 2–5% Pregnancy: Considered safest
Facial clefts Dose-dependent risk Breastfeeding: Safe
Lamotrigine1,5,22,34,43 Cardiac defects 2–5% Pregnancy: Considered safest; may need
Facial clefts Dose-dependent risk dose adjustment in third trimester (check
plasma levels)
Breastfeeding: Safe
Levetiracetam22,34,43 Cardiac defects 1–2% Pregnancy: Considered safest
Neural tube defects Breastfeeding: Safe
Further studies needed
Oxcarbazepine21,22,46 Cardiac defects 1–3% Pregnancy: Relatively safe
Facial clefts Breastfeeding: Safe
Phenobarbital1,22,45 Cardiac defects 2% Pregnancy: Relatively safe
Breastfeeding: Avoid (drowsiness)
1,5
Phenytoin Facial clefts 1–2% Pregnancy: Relatively safe
Poor cognition and Breastfeeding: Safe
neurodevelopment
Sodium Neural tube defects 6–10% Pregnancy: Avoid if possible
valproate1,19,22,26,27,47 Facial clefts Dose-dependent risk Breastfeeding: Safe
Hypospadias
Poor cognition and
neurodevelopment
Topiramate34 Cardiac defects 4–6% Pregnancy: Less safe, avoid if possible
Facial clefts Breastfeeding: Safe
Hypospadias
Monotherapy1,22 3–5%
Polytherapy1,22 6–8%
Polytherapy with Up to 10%
valproate1,25

The evidence for the safety profile in breastfeeding1,21,48–50

AED = anti-epileptic drug.

ª 2017 Royal College of Obstetricians and Gynaecologists 5

 The multidisciplinary management of pregnant women with epilepsy

Table 6. Differences in recommendations between SIGN and RCOG guidelines

Recommendation SIGN 2015 RCOG 2016

Folic acid dose 400 micrograms: not on AEDs 5 mg prior to conception until at least end of first
5 mg: if on AEDs or if not on AEDs, but high risk (family trimester
history of neural tube defects or BMI >30 kg/m2)

AEDs Consider increasing dose of lamotrigine in pregnancy and Routine monitoring not recommended (individualise)
reducing postnatally
Consider dose adjustment of levetiracetam and other AEDs if
there is a change in seizure frequency or if suspecting toxicity

Antenatal corticosteroid Women with epilepsy on enzyme-inducing AEDs who require Routine doubling of the dose is not recommended
dose antenatal corticosteroids should receive double the dose of
betamethasone/dexamethasone (48 mg over 12–24 hours)

Oral maternal Consider 10 mg oral maternal vitamin K if there are additional There is insufficient evidence for routine maternal
vitamin K in the third risk factors for haemorrhagic disease of the newborn vitamin K to prevent haemorrhagic disease of the
trimester (maternal liver disease or anticipated preterm delivery) newborn or postpartum haemorrhage

Ultrasound scanning in There is insufficient evidence to support the use of routine Serial growth scans from 28 weeks in women with
third trimester to detect ultrasound scanning in the third trimester unless an SGA fetus epilepsy on AEDs as the odds ratio is 3.5
a SGA fetus is clinically suspected

Analgesia during labour Low threshold for epidural anaesthesia Pain relief options include: TENS, entonox, regional
anaesthesia
Avoid the use of pethidine during labour as it may be
epileptogenic

AED = anti-epileptic drug; RCOG = Royal College of Obstetricians and Gynaecologists; SGA = small for gestational age; SIGN = Scottish
Intercollegiate Guidelines Network; TENS = transcutaneous electrical nerve stimulation.

monitoring is not required unless there is a change in seizure Multidisciplinary team

frequency, poor compliance is suspected or there are concerns
regarding toxicity.10,11,38 If there is an increase in seizure
frequency, other factors affecting plasma AED levels (i.e.
vomiting, poor compliance or medication interactions) should
be considered. In some units, serum levels of AEDS may not be
able to be processed promptly. Given that the evidence for
testing plasma drug levels is currently inconclusive it is
reasonable to titrate AEDs in response to the clinical
symptoms and seizure control.
Antenatal care
A multidisciplinary approach
There is a lack of robust evidence on which to base
recommendations for care of women with epilepsy in
pregnancy. Despite a number of confidential enquiries and
guidance outlining the need for individualised
multidisciplinary care for women with epilepsy, care in
pregnancy remains varied and in many cases
suboptimal.24,38,39 Pregnancy in women with epilepsy
requires collaborative multidisciplinary planning and
management.8 Recent confidential enquiries highlight that
women with epilepsy are often not seen by an appropriately
trained obstetrician or neurologist during the course of
their pregnancy.6,8
To ensure a safe and collaborative approach to the care
received by women with epilepsy during pregnancy, each
healthcare unit should develop a designated pathway based
on the availability of local resources. This should include a
dedicated team with the ability to appropriately manage these
pregnancies safely; Box 1 outlines the team members who
should be involved.
Schedule of care
Care of pregnant women with epilepsy should be shared and
involve a joint obstetric and neurology clinic or a pathway
Box 1. Multidisciplinary team required for care of pregnant women
with epilepsy
 Obstetrician (specialist interest in epilepsy and/or maternal
medicine trained)
 Neurologist (with working knowledge of the care and management
of pregnant women with epilepsy)
 Obstetric physician where available
 General practitioner
 Anaesthetist
 Midwife
 Epilepsy nurse specialist – should integrate into routine
antenatal service

6 ª 2017 Royal College of Obstetricians and Gynaecologists

 Bhatia et al.

tracked referrals for high-risk women with epilepsy to

Box 2. Questions to ask at the first antenatal appointment
allow for timely planning and management of
 Who is the neurologist overseeing the care?
their pregnancy.38
 When was epilepsy diagnosed (childhood or teenage onset)? Neither RCOG nor SIGN recommend fetal
 What types of seizures are experienced? echocardiography in pregnant women with epilepsy due
(e.g. a) focal, b) generalised, c) non-convulsive or d) unclassified) to a lack of available evidence. However, it is well
 What is the frequency of seizures?
 When was the last seizure?
established that certain AEDs are associated with cardiac
 What AEDs are taken and at what dose? malformations, particularly polytherapy regimens. Recent
 What other features of seizures (triggers, aura, activity during International Society of Ultrasound in Obstetrics and
seizure) occur? Gynecology practice guidelines consider fetal
 Is there a history of status epilepticus or ITU admission?
echocardiography in high-risk women the gold standard
AED = anti-epileptic drug; ITU = intensive treatment unit. for detecting congenital cardiac malformations.40 These
guidelines state that structural cardiac anomalies, such as
where both specialist fields complement each other at the defects commonly associated with AEDs, are commonly
individualised regular intervals. Continuity of care is key missed with routine anomaly ultrasound, as some
to achieve consistent messages and to optimise outcomes. abnormalities are not evident from the four-chamber view
At the first antenatal appointment a thorough epilepsy alone. Further differences in the national guidelines are
history should be taken (Box 2). There should be fast- highlighted in Table 6.

No AEDs Pregnant WWE: 5 mg folic acid

at least until end of first trimester (RCOG)
Seizure free >10 years Ultrasound scans (USS)
No AEDs ≥5 years Yes, taking AEDs
No, refer
Yes
Manage as high risk with shared specialist care
CONSIDER: USS
(RCOG & SIGN)
Manage as Low Risk (RCOG) (GPs, Obstetricians, Neurologists or Obstetric Physicians,
echocardiography*
Epilepsy Nurse Specialists and Midwives) if high risk (previous
congenital cardiac defect or
polytherapy) 18-24 weeks
Refer
Any further seizures?
Individualise frequency of visits and input of specialists
Based on severity and stability of epilepsy
Serial USS:
for fetal growth from
28 weeks (RCOG)
At each visit discuss and consider:

Involving Avoid seizure Ensure AED Assess seizure Consider AED levels Vitamin K
other specialties: triggers compliance frequency and titrate dose: (10 mg oral)
PAEDIATRICS if on lamotrigine or if on enzyme inducing
if on multiple AEDs levetiracetam or if AEDs if high risk for
or concerns about seizure frequency haemolytic disease of
congenital malformations increased (SIGN) the newborn (liver disease
or preterm delivery
anticipated) (SIGN)
ANAESTHETISTS
if on polytherapy
AEDs or concerns re.
interactions with
anaesthetic agents or
previous issues with
anaesthetics

NEUROPSYCHIATRISTS
if WWE may benefit from
their input
*Based on clinical experience

Figure 1. An evidenced-based multidisciplinary pathway of antenatal care for women with epilepsy
AED = anti-epileptic drug; GP = general practitioner; RCOG = Royal College of Obstetricians and Gynaecologists; SIGN = Scottish Intercollegiate
Guidelines Network; WWE = woman with epilepsy.

ª 2017 Royal College of Obstetricians and Gynaecologists 7

 The multidisciplinary management of pregnant women with epilepsy
Recommendations for an antenatal pathway of care
Figure 1 depicts a suggested pathway for antenatal care for
pregnant women with epilepsy based on the available
evidence and critical appraisal of the two national guidelines.
Intrapartum care
Women with epilepsy can be reassured that the risk of
intrapartum seizures is low (3.5%); however, for all women on
the high-risk care pathway, delivery in a consultant-led unit is
advised.10,11 Women with epilepsy should be admitted in early
stages of labour and will require intravenous access and one-to-
one midwifery care. It is important to have adequate analgesia,
be well hydrated, be compliant with AEDs, and avoid stress,
hyperventilation and sleep deprivation, so as to reduce the risk
of seizures. In women with epilepsy, the use of pethidine during
labour should be avoided due to the increased risk of seizures
associated with its use. An epidural is considered safe in women
with epilepsy. Seizures in labour should be treated promptly to
reduce the risk of maternal and fetal hypoxia and fetal acidosis.
A seizure in labour should be treated with benzodiazepines
(intravenous lorazepam 2–4 mg bolus doses repeated every
10–20 minutes, or intravenous diazepam 5–10 mg in slow
bolus dose if lorazepam is unavailable), and a left lateral tilt (or
manual displacement of the uterus), oxygenation and
continuous electronic fetal monitoring should commence.11
In refractory cases, intravenous phenytoin can be used; a
loading dose of 18 mg/kg can be increased by 5 mg/kg to a
maximum rate of 50 mg/minute.
Postnatal care and breastfeeding
The absolute risk of postnatal seizures in women with epilepsy
is low, but higher than the risk of seizures during pregnancy.
The risk is associated with increased stress, sleep deprivation
and reduced AED compliance. If the AED dose was modified
during pregnancy it will require a review to ensure it is effective
postnatally. Ideally, any woman taking AEDs should have an
epilepsy review within the first month of delivery. There may
be a need for a dose reduction to avoid AED toxicity, as the
pregnancy-related physiological changes will now be reversed.
The alteration of AED dose should be planned by neurology
and communicated effectively to the obstetric team for action
in the immediate postnatal period.
Breastfeeding is actively encouraged in the term infant of
women with epilepsy, as the concentration of most AEDs in
breast milk is minimal (see Table 4 for the AED-specific
safety profile in breastfeeding). Caution is advised in women
who are taking polytherapy, phenobarbitone or benzo-
diazepines, or in preterm infants, who should be closely
monitored. Women with epilepsy and their families should
be advised about safety measures for mother and baby, for
8 ª 2017 Royal College of Obstetricians and Gynaecologists
example, avoiding co-bedding and minimising excessive
tiredness. Practical measures include: placing the baby in a
cot or play pen if mother feels unwell; feeding the baby while
sitting on the floor; changing and bathing the baby on the
floor; and not bathing the baby alone.
All women with epilepsy should be counselled about
contraception and avoiding unplanned pregnancies in the
future. The recommended contraceptive preparations are
levonorgestrel-releasing intrauterine systems, copper
intrauterine devices and medroxyprogesterone injections,
as these are not affected by enzyme-inducing AEDs.11
Those women on non-enzyme-inducing AEDs (lamotrigine
and levetiracetam) can consider estrogen-based preparations.
Sudden unexpected death in epilepsy in
pregnancy
SUDEP is death that is unrelated to trauma, drowning or
status epilepticus. Unfortunately, it remains the
predominant cause of death in women with epilepsy.6 The
MBRRACE-UK report highlights that the risk of SUDEP is
higher than expected in women with epilepsy. Modifying
risk factors such as AED compliance, first aid training of
family members and avoiding sleeping alone may reduce the
risk.6 There are concerns regarding the use of lamotrigine,
as the incidence of SUDEP in women with epilepsy taking
lamotrigine is higher (2.5 per 1000 patient years) than in
those taking other AEDS (0.5–1.0 per 1000 patient years).41
Explanations for this higher risk include the relative
common usage of lamotrigine and the reduced serum
drug levels with advancing gestations potentially resulting in
an increased seizure frequency.
Conclusion
There is scope to improve the general care provided to all
women with epilepsy. Pregnancy is an excellent opportunity
to promote seizure control and good health in women with
epilepsy, the effects of which may confer long-term benefits
both at a patient level and from a global health perspective.
There is sufficient evidence to suggest that the reorganisation
of care and services should be a multidisciplinary priority in
the immediate future to prevent further avoidable mortality
and morbidity.
Disclosure of interests
The authors report no conflicts of interest.
Author contributions
MB instigated, researched and drafted the article. LM and
JEA made critical revisions to the manuscript and all authors
approved the final version for publication.
 Bhatia et al.

21 Hernandez-Dıaz S, Smith CR, Shen A, Mittendorf R, Hauser WA, Yerby M,

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