The Obstetrician & Gynaecologist / Volume 22, Issue 1 / p.

21-33

Review Free Access

A review of stroke in pregnancy: incidence, investigations and

management

Azriny S Khalid MRCPI MRCOG , Adriana Hadbavna MRCPI, David Williams PhD FRCPI FRCPE,
Bridgette Byrne MD FRCOG

First published: 14 November 2019

https://doi.org/10.1111/tog.12624
Citations: 6

Abstract

Key content
The incidence of stroke in young and middle-aged adults is increasing, with
pregnancy-related strokes occurring in 30 in 100 000 pregnancies; strokes are
three times more common among pregnant than among nonpregnant
individuals aged 15–44 years.
The investigation and management of stroke is changing because of the time-
sensitive bene"ts of thrombolysis and thrombectomy in the acute
management of ischaemic stroke.

The approach to clinical assessment and investigation of a pregnant woman

presenting with suspected stroke is not di#erent from that of a nonpregnant
patient: timely brain imaging and intervention is important to optimise long-
term outcome, and further investigations should be directed towards
determining the aetiology and risk factors of stroke.

The ‘time is brain’ approach to treatment is imperative: thrombolysis with

recombinant tissue plasminogen activator administered within 4.5 hours of
stroke onset signi"cantly improves overall outcome.
:
 Mechanical thrombectomy is appropriate in only 10% of patients with acute
ischaemic stroke, but has been shown to improve outcome if performed within
6 hours of onset and can be performed up to 24 hours in highly selected cases.
Trials have largely excluded pregnant women, although thrombolysis can be
performed to treat moderate to severe stroke in pregnancy if the bene"ts
outweigh the risk of uterine bleeding.

As recurrent strokes occur in 25–30% of cases, identi"cation of risk factors for

stroke in a young woman is important as this will direct the approach to
secondary prevention and management in future pregnancies.

Learning objectives
To understand the clinical presentation, aetiology and di#erential diagnosis of
stroke in pregnancy.

To know the current recommendations for investigation and management of

acute stroke and how they apply to pregnancy.
To understand the secondary prevention of stroke and the safety of these
strategies in pregnancy.

To recognise of the importance of multidisciplinary input in the management

of pregnancy and delivery in women with stroke.

Ethical issues
There have been no published trials in pregnant women.
How should the maternal and fetal risks be balanced while investigating and
treating acute stroke?

Introduction
Stroke is de"ned as a neurological de"cit attributed to acute focal injury of the central
nervous system by a vascular cause, including cerebral infarction, cerebral vein
thrombosis (CVT), intracranial haemorrhage (ICH) and subarachnoid haemorrhage.1 It
is the second leading cause of death and third leading cause of adult disability, with
one in six people at risk of experiencing a stroke in their lifetime.1, 2 The proportion of
people under the age of 20 years and young and middle-aged adults (20–64 years)
a#ected by stroke is increasing, suggesting that it should no longer be regarded as a
:
 disease of old age.3, 4 A systematic review and meta-analysis of stroke in pregnancy,5
which included 11 studies (out of 111 potentially relevant papers) published between
1990 and January 2017, reported an incidence of 30 per 100 000 pregnancies, which is
three times the incidence in nonpregnant female individuals aged 15–44 years.5 Most
strokes (90%) occur peripartum or in the 6 weeks following delivery.5 United Kingdom
Obstetrics Surveillance System (UKOSS) data from 2007 to 2010 show that strokes
during the antenatal period are rare, citing an incidence of 1.5 per 100 000 deliveries.
This report, however, did not include strokes occurring postpartum.6, 7 The
independent risk factors for stroke in this study included maternal age >35 years
(odds ratio [OR] 2.3), migraine (OR 8.5), gestational diabetes (OR 26.8), pre-eclampsia
or eclampsia (OR 7.7) and pre-existing hypertension (OR 8.5), with a case fatality rate
ranging from 8.8% to 20.0%. Fatality in haemorrhagic stroke of pregnancy is 13.9%,
compared with 3.4% in ischaemic stroke in pregnancy. Likewise, residual disability is
higher in haemorrhagic stroke (50%) compared with ischaemic stroke (33%) events in
pregnancy, with ICH being the single greatest cause of maternal death from stroke.6-8
A more recent study in Japan9 reported an estimated incidence of pregnancy-
associated stroke to be 10.2 per 100 000 deliveries. This was a retrospective analysis in
736 hospitals recognised by the Japan Stroke Society between 2012 and 2013.9

Most strokes in the general population are ischaemic (80–85%), but in pregnancy,
ischaemia, haemorrhage and venous thrombosis have a similar contribution to
aetiology.5, 10 The pooled crude rate per 100 000 pregnancies was 19.9 (95%
con"dence interval [CI] 10.7–36.9) from non-haemorrhagic stroke (both arterial and
venous thrombosis) and 12.2 (95% CI 6.4–23.2) from haemorrhagic stroke.5 In studies
reporting cerebral venous thrombosis as a separate entity, the rate was 12.2 (95% CI
6.7–22.2) in ischaemic stroke, 9.1 (95% CI 4.3–18.9) in cerebral venous thrombosis and
12.2 (95% CI 6.4–23.2) in haemorrhagic stroke per 100 000 pregnancies.5 This
di#erence is attributable to the younger age pro"le, with a greater incidence of CVT
and ICH, and relatively fewer ischaemic strokes compared with the general
population.10 Vascular dissections, aneurysms, arteriovenous malformations and
congenital cardiac conditions are also more common aetiologies in the younger
population.10

Physiological changes in pregnancy and pregnancy-speci"c diseases also contribute to

di#erences in aetiology. The risk of CVT is increased by the physiological upregulation
:
 of clotting factors in pregnancy.4, 6, 8 Pregnancy-speci"c conditions that further
increase the hypercoagulability state include ovarian hyperstimulation syndrome,
hyperemesis gravidarum and pre-eclampsia. Pro-thrombotic medical conditions in
pregnancy, such as antiphospholipid syndrome, sickle cell disease, thrombotic
thrombocytopenic purpura, haemolytic uraemic syndrome, mechanical heart valves
and cardiomyopathies, also increase the risk of ischaemic stroke.11.12 Hypertensive
disorders of pregnancy, including pre-eclampsia and eclampsia, increase the risk of
haemorrhagic or ischaemic stroke and can be associated with posterior reversible
encephalopathy syndrome and reversible cerebral vasoconstriction syndrome.
Amniotic $uid embolism is a rare, pregnancy-speci"c condition that has been
associated with stroke.7, 8

The approach to the investigation and management of acute stroke has changed
dramatically, moving towards one of potentially curable disease with improved
outcomes when treated early and in the appropriate setting. In ischaemic stroke, time-
sensitive thrombolysis and thrombectomy improves outcomes.13-16 Recent studies
have further advanced the care of stroke in pregnancy, with increasing evidence on
the safety of vital imaging and the application of revolutionary treatment options in
pregnancy.17 Stroke in young, pregnant women has a profound e#ect on their lives,
their families and the healthcare system. Prompt investigation, timely treatment and a
standardised approach to secondary prevention and rehabilitation are imperative to
prevent signi"cant disability and death.

This article provides a comprehensive review on the clinical assessment, investigations

and treatment options for women presenting with stroke in pregnancy.

Clinical presentation, symptoms and signs of

stroke
Stroke is a clinical syndrome characterised by rapidly developing symptoms, with signs
of focal cerebral loss of function and no cause other than that of a vascular origin. The
symptoms and signs relate to the a#ected area of the brain (Figure 1). It is vital to
obtain a good history from the patient or witness to identify the timing and sudden
nature of symptom onset. Examples of speci"c questions to ask are listed in Box 1.
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 Figure 1 Open in !gure viewer PowerPoint

Brain anatomy and functions. Symptoms and signs of stroke relate to the a#ected area of the brain.

Box 1. Speci"c questions to ask when taking a history

Where were you when you experienced the symptoms of stroke?

What were you doing at the time?

What did you "rst notice was wrong?

When were you last free of symptoms?
Then what happened?
:
 The onset of stroke is typically sudden, with focal symptoms and clinical de"cits
conforming to a vascular territory. Symptoms include: unilateral numbness or
weakness of the face, arm or leg; dysphasia; hemianopia; and cerebellar features,
such as dysarthria and ataxia. Nonfocal symptoms – such as generalised weakness
and/or sensory disturbance, light-headedness, brief loss of consciousness, urinary or
faecal incontinence, confusion and tinnitus – are less likely to be caused by a stroke.
However, CVT can be variable in its clinical presentation, with only 40% of patients
presenting with typical stroke symptoms and signs. It is often associated with a
headache; drowsiness or confusion can also occur with deep vein occlusion of the
thalamus.18 The FAST campaign (Box 2) was created to promote public awareness of
the symptoms and signs of stroke and to encourage rapid response.

Box 2. The FAST campaign, outlining how to recognise symptoms of stroke

F – Face drooping

A – Arm weakness

S – Speech di%culty

T – Time to call

Subarachnoid haemorrhage is not uncommonly associated with hypertension as a

consequence of the bleed, rather than being caused by hypertension itself. Severe
intracranial bleeds can also be associated with a relative bradycardia. Therefore, when
presented with a patient who is hypertensive and relatively bradycardic, this may lead
to suspicion of an intracranial bleed, rather than a stroke.19 It is clinically di%cult to
distinguish an intracerebral haemorrhage from an ischaemic stroke at the bedside,
but headache, nausea, vomiting and a depressed level of consciousness are more
common in haemorrhagic strokes. Systemic blood pressure tends to be higher in ICH
than in acute ischaemic stroke (AIS); a relative bradycardia may also be seen in severe
intracranial haemorrhages with associated raised intracranial pressure.19

Seizures can occur following a stroke – although these are not typical during an acute
presentation. In pregnancy, it is a rule of thumb that most new-onset seizures after
:
 20 weeks of gestation and up to 2 weeks postnatally are caused by eclampsia unless
proven otherwise. Importantly, note that focal neurological de"cits are not typical of
eclampsia. Visual symptoms are, however. These include blurring of vision, diplopia,
amaurosis fugax, photopsia, scotomata and homonymous hemianopia.20 These
symptoms could be caused by cortical blindness, serous retinal detachment,
Purtscher-like retinopathy, central retinal vein occlusions and retinal or vitreous
haemorrhages, which may occur as a complication of pre-eclampsia.20 Imaging is
necessary if there are focal neurological symptoms and signs or visual symptoms
persist despite optimisation of blood pressure control.

Investigations and management of stroke

A brief history of time of onset, symptoms and premorbid status, along with potential
contraindications to thrombolysis, is taken. Scores on the National Institutes of Health
Stroke Scale (NIHSS; Table 1) and modi"ed Rankin Scale (mRS; Table 2) should be
recorded.

Table 1. National Institutes of Health Stroke Scale (NIHSS) scores

:
 Category Score/ Description Date/time/ Date/time/ Date/time/ Date/time/ Date/time/
Initials Initials Initials Initials Initials

1a. Level of 0 = Alert

consciousness
1 = Drowsy
(LOC)

2 = Stuporous

3 = Coma

1b. LOC 0 = Answers both

questions correctly
(month, age)
1 = Answers one
correctly

2 = Incorrect

1c. LOC 0 = Obeys both

commands correctly
(open/close
1 = Obeys one
eyes, make
correctly
"st/let go)

2 = Incorrect

Table 2. Modi"ed Rankin Scale

:
 Score Score description

0 No symptoms at all

1 No signi"cant disability despite symptoms; able to perform all usual duties and activities

2 Slight disability; unable to perform all previous activities, but able to look after own a#airs without

assistance

3 Moderate disability; requiring some help, but able to walk without assistance

4 Moderately severe disability; unable to walk without assistance and unable to attend to own bodily
needs without assistance

5 Severe disability; bedridden, incontinent and requiring constant nursing care and attention

6 Dead

Imaging
All patients with suspected AIS should have brain imaging on arrival to hospital. In
most cases, non-contrast computed tomography (CT; Figure 2, Figure 3) will provide
the necessary information to make decisions about acute management, such as
intravenous thrombolysis.20, 21 ICH is a contraindication to thrombolysis, with
management directed towards haemostasis and correction of coagulopathy with
surgical intervention if appropriate. CVT is treated with full anticoagulation with
heparin, although, in some instances, thrombectomy and local intravenous
thrombolysis may be required.
:
 Figure 2 Open in !gure viewer PowerPoint

Non-contrast computed tomography of a brain with normal brain parenchyma.

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 Figure 3 Open in !gure viewer PowerPoint

Non contrast computed tomography of a brain showing acute ischaemia in the territory of the left

middle cerebral artery.

CT angiogram (Figure 4) should be performed for all potential candidates for

mechanical thrombectomy to evaluate for large vessel occlusion.21, 22 The most
accurate assessment of the site of occlusion, infarct core, salvageable brain tissue and
collateral circulation in patients suspected of acute stroke is a#orded by a
combination of CT perfusion and CT angiogram.22 CT angiogram has high diagnostic
value in detecting high degrees of cerebral arterial stenosis, whereas CT perfusion
provides high speci"city in detecting infarction and ischaemia of brain tissue.22
:
 Patients with a small infarct core and a large penumbra are most likely to bene"t from
reperfusion therapies.

Figure 4 Open in !gure viewer PowerPoint

Computed tomography angiogram of a brain showing an occlusion of the left middle cerebral artery.

Other investigations include magnetic resonance imaging (MRI) of the brain (Figure 5),
which may further distinguish between stroke subtypes and vascular imaging, either
with carotid Doppler or magnetic resonance angiogram. Magnetic resonance
angiogram of extracranial and intracranial vessels may be particularly helpful for
further evaluation of posterior circulation strokes if CT angiography is unavailable. For
patients with non-disabling stroke (mRS score 0–2) in the carotid territory who are
:
 candidates for carotid endarterectomy or stenting, noninvasive imaging of the cervical
vessels should be performed routinely within 24 hours of admission.22

Figure 5 Open in !gure viewer PowerPoint

Magnetic resonance imaging of a brain (di#usion weighted imaging sequence) showing an acute

infarct of the left middle cerebral artery.

In eclampsia, posterior reversible encephalopathy syndrome (PRES) is demonstrable

on CT. While PRES can be associated with stroke concurrently, it is not in itself a stroke
disorder. The presentation of PRES can be very similar to a stroke; however, the signs
and symptoms of neurological de"cit may not be unilateral. The commonest areas
involved are parieto-occipital, followed by frontal, temporal and – more rarely –
:
 cerebellar regions, basal ganglia, thalamus and the brainstem.23 Ill-de"ned subtle
white matter hypodensities suggestive of vasogenic oedema in frontal, parietal and
occipital regions with variable levels of lobar involvement can be seen, with atypical
features that may include the thalamic and cerebellar hemispheres.23 On MRI, white
matter lesions are hyperintense on T2 and hypointense on T1, and demonstrate free
di#usion on di#usion-weighted imaging.23

In pregnancy, imaging should be done promptly to allow early treatment and optimise
outcomes. MRI is the preferred "rst-line imaging modality in pregnancy because it
does not expose the pregnant woman to radiation. Potential hazards include:
theoretical biological damage related to cell migration, proliferation and
di#erentiation; tissue heating; and potential damage to the fetal ear caused by the
high acoustic noise level.24 No harmful short- or long-term e#ects have been shown
following MRI in pregnancy on the fetus at T1.5 or less.24

However, access to CT may be easier, thus it remains the most appropriate tool for
initial rapid diagnosis of acute neurological conditions in the general population. The
fetal radiation dose in a non-contrast CT of the brain is approximately 5% of the
naturally occurring background radiation dose during a full-term pregnancy (on
average, this is 0.5–1.0 mGy).25 Studies have shown that a fetal radiation dose of less
than 0.1 Gy (100 mGy) is not associated with an increased risk of adverse e#ects in
human beings.25 Fetal exposure will be well below regulatory limits with the use of
standard shielding of 0.5 mm lead equivalent.25

It is possible to perform CT angiogram safely in pregnancy and this causes less

radiation exposure than CT perfusion. No mutagenic or teratogenic e#ects have been
described in human pregnancies after administration of iodinated contrast. There is a
theoretical risk of fetal thyroid suppression; thus, neonatal thyroid function should be
monitored in the initial 2 weeks of life. The American College of Radiology
recommends that iodinated contrast be used in pregnant women only when no
alternative test is available, information from the study is useful to both mother and
fetus and the referring physician considers it imprudent to delay the study until after
delivery.26

Gadolinium chelate can be used to enhance MRI studies. It traverses the placenta and
may accumulate in the amniotic cavity, with contrast medium cycling through the fetal
:
 gastrointestinal and genitourinary tracts. Studies show that only 0.01% of the
gadolinium dose remains present in the fetus after 4 hours and only traces remain
after 24 hours. The American College of Radiology states that gadolinium-based
agents should be used with extreme caution and following well-documented informed
consent.26

Investigations for underlying cause of stroke

Further investigations are directed towards revealing pre-existing risk factors for
stroke in a young woman (Table 3).

Table 3. Investigations for underlying causes of stroke in a young woman

Investigations Risk factors

12-lead electrocardiogram Atrial "brillation, cardiac

ischaemia

24-hour cardiac/Holter monitor Atrial "brillation

Prolonged cardiac monitor/implantable loop recorder Paroxysmal atrial "brillation

Transoesophageal echocardiogram Patent foramen ovale

Transthoracic echocardiogram with ‘bubble test’ Patent foramen ovale

Full blood count, urea and electrolytes, liver function tests, uric acid, Pre-eclampsia

coagulation pro"le

Lipid pro"le Hypercholesterolaemia

Thrombophilia screening Antiphospholipid syndrome

*
Inherited thrombophilias

Carotid and lower limb Dopplers Venous thromboembolism

**

*Limited bene"t of inherited thrombophilia screening in pregnancy. **In presence of patent foramen ovale, to
:
 rule out paroxysmal thromboembolic event.

At the time of presentation, a 12-lead electrocardiogram should be undertaken to

reveal possible underlying arrhythmia, such as atrial "brillation or cardiac ischaemia.
Most patients presenting with a subarachnoid haemorrhage also have ST changes on
a 12-lead electrocardiogram, probably because of myocardial injury secondary to
sympathetic activation.27 All patients with ischaemic stroke should undergo early 24-
hour cardiac/Holter monitoring.21 A prolonged cardiac monitor or implantable loop
recorder should be considered for cryptogenic strokes potentially caused by
paroxysmal atrial "brillation.28 Evidence suggests the event loop recorder is superior
to a Holter monitor for diagnosis in pregnancy.29

Transthoracic echo is the preferred "rst-line investigation. A ‘bubble test’ or contrast

echocardiogram can be performed from the cardiac apex, which involves the use of
agitated saline and a Valsalva manoeuvre to demonstrate an intra-atrial shunt.
Transoesophageal echocardiogram (TOE) can be performed if the transthoracic echo
gives equivocal results.30 TOE remains the optimum investigation to rule out aortic
arch atheroma, left atrial appendage thrombus, patent foramen ovale and other
sources of emboli in young patients without cardiovascular disease, or in patients with
mechanical prosthetic valves.31 It can be performed safely in pregnancy but requires
sedation and therefore has a risk of aspiration.

Internal carotid and vertebral arterial dissections are rare. Doppler imaging of the
extracranial carotid and vertebral arteries is useful to rule out the presence of
extracranial dissections, stenosis and occlusions.21

If pre-eclampsia is suspected, full blood count, liver function tests, urea and
electrolytes and uric acid levels should be checked to rule out HELLP (haemolysis,
elevated liver enzymes, low platelets) syndrome or thrombocytopaenia.

Severe hypoglycaemia and hyperglycaemia may present with focal neurological

de"cits that mimic stroke. These should be identi"ed and treated prior to
thrombolysis. Other blood tests include full blood count, coagulation pro"le, troponin,
urea and electrolytes, liver function tests and lipid pro"ling. The usefulness of
thrombophilia screening in patients with ischaemic stroke is unclear.21 In one Danish
:
 study of young patients,32 thrombophilia did not confer an increased risk of ischaemic
stroke. Factor V Leiden heterozygosity was associated with an increased risk of
transient ischaemic attacks/amaurosis fugax and persistent lupus anticoagulant was
more likely to be associated with ischaemic stroke.32 Testing for inherited
thrombophilia is of limited bene"t in pregnancy because of the physiological fall in
protein S levels and reduced activity of activated protein C. However, testing for
inherited gene mutations, such as prothrombin gene mutations and factor V Leiden,
as well as acquired thrombophilia, such as lupus and anticardiolipin antibodies, can be
tested in pregnancy and this may help to guide the intensity and duration of
treatment.33 A complete thrombophilia screen should be repeated at least 6 weeks
postnatally, as some components may not be accurate in the setting of pregnancy and
early postpartum.

Management of stroke
It is imperative that a ‘time is brain’ approach is adopted in the management of acute
stroke. Time-sensitive and reperfusion therapies are associated with improved
functional outcomes.

Intravenous thrombolysis
Irrespective of age or stroke severity and despite a risk of haemorrhagic
transformation of 2–6% in the "rst few days after treatment, recombinant tissue
plasminogen activator (rt-PA) signi"cantly improves the overall odds of good stroke
outcome when administered within 4.5 hours of stroke onset. The earlier the
treatment, the bigger the proportional bene"t.13 Patients presenting with stroke
symptoms should be assessed rapidly, as per local hospital protocols. In patients
eligible for thrombolysis, the bene"t of therapy is time-dependent and treatment
should be initiated as quickly as possible.21 Contraindications to thrombolysis are
summarised in Box 3. Pregnancy is a relative contraindication. Complications include
ICH, systemic bleeding and anaphylaxis. General post-thrombolysis management is
summarised in Box 4.

Box 3. Contraindications to thrombolysis

Absolute contraindications
:
 Intracerebral haemorrhage

Suspected subarachnoid haemorrhage, even if normal computed tomography

(CT)

Neurosurgery, head trauma within the last 3 months

Systolic blood pressure >185 mmHg, diastolic blood pressure >105 mmHg
History of intracerebral haemorrhage

Known intracerebral arteriovenous malformation, neoplasm or aneurysm

Active internal bleeding

Suspected/con"rmed endocarditis

Known bleeding diathesis

○ Platelets <100 000

○ Heparin within 48 hours

○ Current use of warfarin with international normalised ratio (INR) >1.7

○ Direct thrombin inhibitors or factor Xa inhibitors

Blood glucose <2.8 or >22.2 mmol/L, with resolution of symptoms when

corrected

Relative contraindications

Age >80 years

National Institutes of Health Stroke Scale >25 and coma

Multilobar infarction on CT
Previous stroke within the last 3 months

Diabetes mellitus and previous stroke

Minor or rapidly improving stroke

Major surgery or serious non-head trauma within 14 days

Gastrointestinal or urinary tract haemorrhage within 21 days

Seizure at stroke onset

Recent arterial puncture at non-compressible site

:
 Recent lumbar puncture

Post myocardial infarction pericarditis

Pregnancy

Box 4. Post-stroke thrombolysis care

24 hours of bedrest (may not be essential if very stable)

Maintain O2 saturations above 95%

Maintain normal temperature; use paracetamol if >37.5°C

Maintain blood glucose <10 mmol/l

Deep vein thrombosis prophylaxis with intermittent pneumatic compression

devices (as per the CLOTS-3 study)

No arterial lines, nasogastric tubes or central lines for 24 hours

No urinary catheter until at least 1 hour after infusion ends

Avoid suctioning and careful mouth care

No aspirin, clopidogrel, dipyridamole or anticoagulants for 24 hours

Repeat computed tomography in 24–36 hours

Hydration and nutrition

Fall risk assessment and prevention

Stop rt-PA if neurological deterioration of 2 points on Glasgow eye/motor scale

Observe for signs of systemic bleeding – stop rt-PA

Blood pressure – stop rt-PA if systolic blood pressure <100 or >180 mmHg and
diastolic blood pressure >105 mmHg if sustained for more than 5 minutes
Observe for signs of anaphylaxis – stop rt-PA

rt-PA = recombinant tissue plasminogen activator.

The use of thrombolysis in pregnancy and postpartum has been reported in over 200
:
 cases. However, pregnant women have generally been excluded from all randomised
controlled trials (RCTs). As per current American Heart Association/American Stroke
Association guidelines, intravenous administration of rt-PA may be considered in
pregnancy when the bene"ts of treating moderate or severe stroke outweigh the
increased risks of uterine bleeding. Although rt-PA does not cross the placenta, there
is a theoretical risk of placental bleeding and intrauterine fetal death.34

A review of 65 articles describing studies of thrombolysis in 141 pregnant women with

serious thrombotic events was recently published.17 Only one prospective study was
identi"ed and, not surprisingly, there has been no RCT of thrombolysis in pregnancy.
The review included thrombolysis for deep vein thrombosis, pulmonary embolism,
stroke and mechanical prosthetic valve thrombosis. There were four maternal deaths
(2.8%), 12 major bleeding episodes (8.5%), 13 mild/moderate bleeding episodes (9.2%),
two fetal deaths (1.4%), one neonatal death (0.7%), nine miscarriages (6.4%) and 14
preterm deliveries (9.9%).17 The maternal deaths reported occurred antenatally, but
were attributed to underlying pathologies, not thrombolytic therapy.17, 34 The data
suggest that complication rates are comparable to those of the general population.

Monitoring post thrombolysis should be initiated as described in Box 4. Antenatal

patients should be observed for vaginal or intra-abdominal bleeding, pain and further
neurological signs. Ultrasound can be useful to observe for retroplacental haematoma
formation and to assess fetal wellbeing.

The safety and e%cacy of thrombolysis in the early postpartum period (<14 days after
delivery) are not well established. A history of major surgery within the preceding
2 weeks is a relative contraindication for systemic thrombolytic therapy. This curtails
its use after a caesarean section or a di%cult vaginal delivery. Levels of thrombolytic
agents in milk are highest in colostrum and decrease rapidly during the "rst week. No
information is available, however, on its safety during breastfeeding.35 Women
receiving thrombolytic therapy in the postpartum period should be monitored as
described in Box 4 and observed for bleeding and haematoma formation, particularly
at wound sites.

Mechanical thrombectomy
In 2015, "ve RCTs showed that mechanical thrombectomy with stent retriever devices
:
 was superior to intravenous rt-PA alone in acute anterior circulation ischaemic
stroke.36-40 The HERMES meta-analysis of these "ve trials con"rmed bene"t for up to
6 hours.15 All eligible patients with a large vessel occlusion on CT angiogram should
be considered for clot retrieval and urgently referred to a neurointerventional centre.
In highly selected cases, this can be performed up to 24 hours after stroke onset.

Among patients with AIS who had last been known to be well 6–24 hours earlier with a
mismatch between clinical de"cit and infarct, outcomes for disability at 90 days were
better with thrombectomy plus standard care than with standard care alone.14, 16 To
date, two publications41, 42 have reported four antenatal cases of severe stroke
treated with thrombectomy with good outcomes, both short-term and long-term. Only
one received thrombolysis prior to thrombectomy.41, 42 All four women continued
their pregnancies to term with no fetal complications. The cerebral vessels were
accessed via the femoral artery with a microcatheter guided by angiography. The
duration of the interventional procedure varied between 2 hours 30 minutes to just
over 6 hours.41, 42 Fetal radiation exposure was minimised by limiting the number of
angiographic exposures performed intraoperatively, using low-dose, pulsed
$uoroscopy and radiation shields.42 Women undergoing thrombectomy should be
monitored in an intensive care setting until stable, with fetal wellbeing assessed with
ultrasound before and after the procedure. Thrombectomy can only be performed in
specialised centres and is only appropriate in 10% of cases of AIS.11

Management of intracerebral haemorrhage

Immediate treatment is directed towards haemostasis, correction of coagulopathy and
hyper/hypoglycaemia, blood pressure control and venous thromboembolism
prophylaxis. Coagulopathy and thrombocytopenia should be corrected. Patients on
warfarin with a prolonged international normalised ratio for prothrombin time should
have their warfarin withheld and receive intravenous vitamin K and prothombin
complex. Aggressive blood pressure control with an aim to lower systolic blood
pressure to 140 mmHg is safe unless contraindicated and can be e#ective in
improving functional outcome. All patients with ICH should have intermittent
pneumatic compression from the day of admission. Antiepileptic medications should
be used to treat patients with clinical seizures or with electroencephalogram changes.
Surgical decompression (with or without external ventricular drain insertion) should
be considered in patients with cerebellar haemorrhage with deteriorating neurological
:
 function, or in patients with brainstem compression and/or hydrocephalus from
ventricular obstruction.43

Management of cerebral venous thrombosis

The treatment of CVT is predominantly anticoagulation with either low molecular
weight heparin (LMWH) or unfractionated heparin to prevent propagation of the
thrombus and emboli. If anticoagulation is contraindicated, or if the patient does not
respond to anticoagulation, thrombolysis or thrombectomy can be considered,
although evidence for this is lacking. Patients with signs of increased intracranial
pressure can be treated with intravenous mannitol and should be considered for
decompressive craniectomy in cases of impending herniation.18

Management of pre-eclampsia/eclampsia and posterior

reversible encephalopathy syndrome
The role of magnesium sulphate in the treatment and prevention of eclampsia is well
documented.44 Augmented seizure susceptibility caused by increased blood–brain-
barrier permeability and neuroin$ammation has been demonstrated in animal
studies.45 Magnesium sulphate treatment has been shown to increase seizure
threshold and decrease neuroin$ammation without a#ecting blood–brain-barrier
permeability, thus preventing eclamptic seizures during severe pre-eclampsia.45

Posterior reversible encephalopathy syndrome (PRES) in pregnancy is typically

associated with pre-eclampsia and eclampsia. Other clinical conditions associated with
PRES include hypertension, infection/sepsis, shock, autoimmune disease, drugs,
chemotherapy and massive transfusion. The treatment of PRES is directed towards
optimising blood pressure control, removal or treatment of suspected causative
factors and, in the case of pre-eclampsia and eclampsia, delivery of the fetus. In most
cases, PRES resolves spontaneously, with recovery within days to weeks.46

Stroke unit care

All patients should be managed in a multidisciplinary stroke unit that provides focused
expert nursing care, specialist medical treatment, optimised treatment protocols,
coordination of rehabilitation services and patient education. Stroke patients receiving
organised inpatient care in a stroke unit are more likely to be alive, independent and
:
 living at home 1 year after the stroke.47 Unfortunately, admission to a stroke unit
usually means separation of mother and baby, and may a#ect bonding and feeding.

Secondary prevention strategies

Recurrent strokes account for 25–30% of all strokes.48 Identi"cation and treatment of
the underlying cause and secondary prevention strategies are critical. Blood pressure
management is one of the key elements of secondary prevention. In patients with a
blood pressure of <220/120 mmHg who did not receive thrombolysis or mechanical
thrombectomy and do not have a comorbid condition requiring acute
antihypertensive treatment, initiating or reinitiating treatment of hypertension within
the "rst 48–72 hours after an AIS has not been shown to be e#ective in preventing
death or dependency, even though it is safe to do so.21 Gradual, sustained lowering of
blood pressure is recommended for all stroke patients – but care is needed,
particularly in patients with carotid or vertebrobasilar occlusive disease.49 However,
maternal mortality has been shown to be increased with systolic blood pressure
>160 mmHg and diastolic blood pressure >100 mmHg, primarily because of ICH.50
Therefore, blood pressure control should be more aggressive in the context of
pregnancy.

Administration of aspirin is recommended in AIS within 24–48 hours of onset. For

patients receiving thrombolysis, aspirin is delayed until 24 hours later, when ICH is
excluded.21 In patients presenting with minor stroke or transient ischaemic attacks,
treatment with dual antiplatelet therapy (aspirin and clopidogrel), begun within 24
hours and continued for 21 days, can be bene"cial for early secondary stroke
prevention.21, 51 A careful risk–bene"t assessment is needed; however, a recent trial
of dual therapy demonstrated a lower risk of major ischaemic events but a higher risk
of major haemorrhage at 90 days compared with patients who received aspirin
alone.52

The safety of aspirin in pregnancy is well documented, but there are limited human
data on the use of clopidogrel in pregnancy.53 It is unknown whether or not it crosses
the human placenta. Animal studies, however, have shown that it is not teratogenic
and case studies have shown low complication rates. Considering use in pregnancy,
clopidogrel is classed by the US Food and Drug Administration as category B
(Table 4).54 It is recommended that treatment with clopidogrel should not be withheld
:
 because of pregnancy, if deemed necessary.55 A study in nonpregnant patients
demonstrated an increased risk of signi"cant bleeding if used within 7 days of
surgery.56 Hence, clopidogrel should be stopped 7–10 days before a scheduled
delivery.11, 56 If spontaneous labour occurs or delivery is expedited while on
clopidogrel, neuroaxial anaesthesia is not recommended because of the potential
increased risk of spinal or epidural haematomas.53

Table 4. US Food and Drug Administration classi"cations for drugs in pregnancy

Category Evidence

A Adequate and well-controlled studies have failed to demonstrate a risk to the fetus in the "rst

trimester of pregnancy (and there is no evidence of risk in later trimesters)

B Animal reproduction studies have failed to demonstrate a risk to the fetus and there are no

adequate and well-controlled studies in pregnant women

C Animal reproduction studies have shown an adverse e#ect on the fetus and there are no

adequate and well-controlled studies in humans, but potential bene"ts may warrant use of drug
in pregnant women despite potential risks

D There is positive evidence of human fetal risk based on adverse reaction data from
investigational or marketing experience or studies in humans, but potential bene"ts may warrant

use of the drug in pregnant women despite the risks

X Studies in animals and humans have demonstrated fetal abnormalities and there is positive

evidence of human fetal risk based on adverse reaction data from investigational or marketing
experience, and the risks involved in use of the drug in pregnant women clearly outweigh

potential bene"ts

For most patients with AIS in the setting of atrial "brillation, it is reasonable to initiate
oral anticoagulation within 4–14 days of the onset of neurological symptoms.21
Warfarin is a vitamin K antagonist that crosses the placenta. Exposure in the "rst
trimester is associated with warfarin embyropathy and second- and third-trimester
exposure is associated with possible neurological sequelae, including seizures,
developmental delay, hypotonia and intracranial microhaemorrhage.53 Warfarin
:
 during pregnancy is categorised by the US Food and Drug Administration as category
X (Table 4).53, 54 The anticoagulant of choice in pregnancy is either LMWH or
unfractionated heparin. LMWH does not cross the placenta and is not teratogenic.53
There are also no reports of neonatal bleeding.53 LMWH o#ers several advantages
over unfractionated heparin, including a longer half-life, e%cacy with weight-based
dosing and once-daily dosing.53 Antenatal CVT is treated with LMWH.

High-intensity statin therapy should be initiated or continued as a "rst-line therapy in

all patients who have clinical atherosclerotic cardiovascular disease, unless
contraindicated. While earlier reports suggested that exposure to statins in pregnancy
was associated with an increased incidence of central nervous system and cardiac
anomalies, these "ndings have recently been challenged. A systematic review of 16
clinical studies found no clear relationship between congenital anomalies and statin
use in pregnancy.57 This is supported by a cohort study of more than 800 000 women.
When pre-existing diabetes and other potential confounders were controlled for, the
apparent increased risk of congenital malformations with statins was no longer
present.58 The current consensus, however, is to temporarily interrupt statin therapy
pre-conceptually and throughout pregnancy. The timing of starting or restarting statin
therapy postnatally should be based on individual circumstances with regard to
speci"c risk factors and breastfeeding intentions.59

Smoking cessation is an important part of secondary prevention. Healthcare providers

should strongly advise patients with AIS who have smoked in the past year to quit.21
The incidence of patent foramen ovale (PFO) in the general population is
approximately 20%. However, the presence of a high-risk PFO, such as a PFO with an
atrial septal aneurysm, or a substantial shunt size, should be considered for closure.60
This can be done postnatally if diagnosed in pregnancy.

Mode of delivery
To date, no studies have suggested that a caesarean delivery is safer than a vaginal
delivery following stroke; therefore, the decision as to the mode of delivery requires
multidisciplinary input and should be individualised. Case studies have reported the
safety of vaginal delivery in women with prior ischaemic stroke and treated
arteriovenous malformations or aneurysms.11, 61 In most cases, an early epidural
was planned to reduce $uctuation in maternal blood pressure, as well as a shortened
:
 second stage with an elective operative vaginal delivery to prevent prolonged Valsalva
and increased intracranial pressure. However, it remains unclear as to which is the
safest mode of delivery in women with ruptured aneurysms, untreated or partially
treated arteriovenous malformations and very recent neurosurgery.11

Postpartum management and contraception

The postpartum period is the highest risk period for venous thromboembolism and
stroke. Anticoagulation should be continued for at least 6 weeks postpartum,
depending on the timing and aetiology of stroke. A multidisciplinary approach to
postnatal care is as important as during the acute phase to ensure implementation of
secondary prevention strategies, rehabilitation and further investigations if indicated.

Although the role of routine post-stroke thrombophilia screening in the general

population is unclear, factor V Leiden heterozygosity and persistent lupus
anticoagulant is associated with increased risks of transient ischaemic attacks,
amaurosis fugax and ischaemic stroke.32 The presence of thrombophilia also has
signi"cant implications for future pregnancies.64 A complete thrombophilia screen
should be arranged 6 weeks postnatally to ensure optimal anticoagulation in future
pregnancies.

Warfarin, LMWH and aspirin are safe to take while breastfeeding; clopidogrel is
classed as category B based on limited animal data. Therefore, breastfeeding should
be encouraged.53, 54

Advice on postpartum and long-term contraception must be considered carefully.

Combined hormonal contraception is contraindicated and non-hormonal forms of
contraception are recommended. For women taking progesterone-only contraception,
the risk of recurrent venous thromboembolism has been a subject of debate. Evidence
is limited and this contraception can therefore be considered. Cohort studies have
shown no increased risk in stroke in women taking progesterone-only contraception.
However, the duration of use in relation to the onset of the stroke should be carefully
considered when deciding whether continuation of the method is appropriate.65

Pre-conceptual care
Pre-conceptual counselling in women with a prior stroke should be individualised,
:
 depending on the aetiology of stroke. There is no consensus on the best protocol for
secondary prevention of stroke in pregnancy. Statins, clopidogrel and vitamin K
antagonists are usually discontinued. Blood pressure control is optimised using
pregnancy-safe medications pre-conceptually. Aspirin is safe and has been shown to
prevent or delay pre-eclampsia and growth restriction in high-risk women, so should
therefore be continued in future pregnancies. In women with a high thrombotic risk,
LMWH is also commenced.

Pregnancy complications are reportedly higher in women with prior stroke – probably
secondary to underlying cardiovascular pathophysiology. The overall risk of stroke
recurrence is reported to be 0–1.8% in a subsequent pregnancy and 0.5% outside of
pregnancy.62, 63 In women with concurrent thrombophilia, the risk has been quoted
as being up to 20%.64

Future pregnancies should be closely monitored for complications. The pregnancy

care plan for women with prior stroke should be individualised on the aetiology of
stroke and individualised risk of each woman.

Multidisciplinary care
When a pregnant or recently pregnant woman presents with a stroke, the
multidisciplinary input of obstetrics, neurology, radiology, neurosurgery, cardiology,
anaesthesiology and haematology is imperative. Imaging should be done
appropriately, with reassurance about fetal safety. Pre-eclampsia-related central
nervous system manifestations should be identi"ed and managed appropriately. In
AIS, the choice of therapeutic interventions depends on the severity of the stroke, the
woman's pregnancy status and anticipated risk of bleeding. Identi"cation of the
underlying cause and secondary prevention strategies needs careful evaluation. The
importance of the many disciplines represented in a stroke team cannot be
underestimated in the recovery phase.

Patient education is vital. Patients should be provided with information, advice and the
opportunity to talk about the impact of the illness on their lives.16 Stroke in pregnancy
presents unique challenges and emphasises the need for a multidisciplinary approach
to this uncommon complication of pregnancy.
:
 Disclosure of interests
There are no con$icts of interest.

Contribution to authorship
AK and AH wrote the article. BB initiated and edited the article. DW edited the article.
The "nal version was approved by all the authors.

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