European Journal of Obstetrics & Gynecology and Reproductive Biology 181 (2014) 2027

Contents lists available at ScienceDirect

European Journal of Obstetrics & Gynecology and

Reproductive Biology
journal homepage: www.elsevier.com/locate/ejogrb

Review

A review of stroke and pregnancy: incidence, management and

prevention
Zoe Moatti a,*, Manish Gupta b, Rajendra Yadava c, Sujatha Thamban d
a
Specialist Registrar Obstetrics and Gynaecology, Whipps Cross University Hospital, Whipps Cross Road, London E11 1NR, United Kingdom
b
Consultant Obstetrician and Gynaecologist and Subspecialist in Maternal and Fetal Medicine, Barts and The Royal London NHS Trust,
Whipps Cross University Hospital, Whipps Cross Road, London E11 1NR, United Kingdom
c
Consultant Physician, Stroke Specialist, Barts and The Royal London NHS Trust, Whipps Cross University Hospital, Whipps Cross Road,
London E11 1NR, United Kingdom
d
Consultant Obstetrician and Gynaecologist at The Royal London Hospital, Barts and The Royal London NHS Trust, Whipps Cross University Hospital, Whipps
Cross Road, London E11 1NR, United Kingdom

A R T I C L E I N F O A B S T R A C T

Article history: Stroke, dened as a focal or global disturbance of cerebral function lasting over 24 h resulting from
Received 14 May 2014 disruption of its blood supply, is a devastating event for a pregnant woman. This can result in long-term
Accepted 20 July 2014 disability or death, and impact on her family and unborn child.
In addition to pre-existing patient risk factors, the hypercoagulable state and pre-eclampsia need to
Keywords: be taken into account. The patterns and types of stroke affect pregnant women differ from the non-
Stroke pregnant female population of child-bearing age. Like other thrombo-embolic diseases in pregnancy,
High-risk pregnancy
stroke is essentially a disease of the puerperium.
Pre-eclampsia
Population studies have estimated the risk of stroke at between 21.2 and 46.2 per 100,000. The US
Thrombolysis
Nationwide Inpatient Sample, identied 2850 pregnancies complicated by stroke in the United States in
20002001, for a rate of 34.2 per 100,000 deliveries. There were 117 deaths, a mortality rate of 1.4 per
100,000. Both the mortality and disability rates were higher than previously reported, with 1013% of
women dying.
With the increasing prevalence of obesity, hypertension and cardiac disease amongst women of child-
bearing age, so is the incidence of stroke during pregnancy and the puerperium. In the United States, an
alarming trend toward higher numbers of stroke hospitalizations during the last decade was
demonstrated in studies from 1995 to 1996 and 2006 to 2007. The rate of all types of stroke increased
by 47% among antenatal hospitalizations, and by 83% among post-partum hospitalizations. Hypertensive
disorders, obesity and heart disease complicated 32% of antenatal admissions and 53% of post-partum
admissions.
In addition to pre-existing patient risk factors, the hypercoagulable state and pre-eclampsia need to
be taken into account. The patterns and types of stroke affect pregnant women differ from the non-
pregnant female population of child-bearing age. Like other thrombo-embolic diseases in pregnancy,
stroke is essentially a disease of the puerperium.
2014 Elsevier Ireland Ltd. All rights reserved.

Contents

Ischemic stroke . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 21
Hemorrhagic stroke . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 23
Pre-eclampsia. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 24
Challenges of diagnosis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 24
Thrombolysis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 25
Thromboprophylaxis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 25

* Corresponding author. Tel.: +44 7834 550 206.

E-mail address: zmoatti@gmail.com (Z. Moatti).

http://dx.doi.org/10.1016/j.ejogrb.2014.07.024
0301-2115/ 2014 Elsevier Ireland Ltd. All rights reserved.
 Z. Moatti et al. / European Journal of Obstetrics & Gynecology and Reproductive Biology 181 (2014) 2027 21

Psychosocial care and counseling . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 25

Conclusion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 26
Conict of interest statement . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 26
Funding . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 26
Authors contribution. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 26
Ethical approval . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 26
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 26

Stroke is dened as a focal or global disturbance of cerebral protein S, increased plasminogen activator inhibitors 1 and 2 and
function lasting over 24 hours resulting from disruption of its down-regulation of brinolysis.
blood supply. It is a devastating event for a pregnant woman, Physiological changes are most marked during the puerperium,
which can result in long-term disability or death, and impact on accounting for the dramatic increase in cardiovascular events, by a
her family and unborn child. factor of 712 [6,7,9].
In addition to pre-existing patient risk factors, the hypercoagu- The Saving Mothers Lives enquiry 20062008 reported 18
lable state and pre-eclampsia need to be taken into account. The maternal deaths from thrombosis and/or thromboembolism, a rate
patterns and types of stroke affect pregnant women differ from the of 0.79 per 100,000 pregnancies (95% CI 0.491.25). Two of the 18
non-pregnant female population of child-bearing age. Like other deaths were attributed to cerebral vein thrombosis and the
thrombo-embolic diseases in pregnancy, stroke is essentially a remainder to pulmonary embolus [10]. Almost all occurred during
disease of the puerperium [17]. the puerperium [10].
Population studies have estimated the risk of stroke at between A nationwide Swedish cohort study found that cerebral
21.2 and 46.2 per 100,000 [15]. The Nationwide Inpatient Sample, infarction (ICD-10, cerebral infarction, unspecied) is 33.8 times
identied 2850 pregnancies complicated by stroke in the United (95% CI 10.584.0) more likely to develop in the three days
States in 20002001, for a rate of 34.2 per 100,000 deliveries. There surrounding delivery (dened as 1 days preceding delivery to 2
were 117 deaths, a mortality rate of 1.4 per 100,000 [1]. Both the days following delivery), and 8.3 (95% CI 4.414.8) times more
mortality and disability rates were higher than previously likely in the subsequent 6 weeks after delivery [6]. Antenatally the
reported, with 1013% of women dying [1]. risk was negligible (OR 2.2, 95% CI 0.84.8) (Fig. 1).
With the increasing prevalence of obesity, hypertension and Western population studies have concluded that ischemic
cardiac disease amongst women of child-bearing age, so is the cerebral events in the pregnant population are more frequent than
incidence of stroke during pregnancy and the puerperium. In the hemorrhagic ones [1,5]. In her study of a Toronto hospital, Jaigobin
United States, an alarming trend towards higher numbers of stroke identied 34 cases of stroke in pregnancy, of which 21 were
hospitalisations during the last decade was demonstrated in infarctions, comprising of 13 arterial and 8 venous infarctions [5].
studies from 1995 to 1996 and 2006 to 2007. The rate of all types of Ischemic strokes were associated with pre-existing factors such as
stroke increased by 47% among antenatal hospitalizations, and by cardiac emboli, coagulopathies and carotid dissection [5].
83% among post-partum hospitalisations [8]. Hypertensive dis- Cerebral sinus thrombosis (CVT) is predominantly an event of
orders, obesity and heart disease complicated 32% of antenatal the puerperium. Indeed, seven out of eight venous thromboses
admissions and 53% of post-partum admissions. identied by Jaigobin occurred after post-partum.
A clinician working in a unit of 3300 deliveries per year is likely Venous thrombosis is more likely to occur in the pregnant
to encounter such a case every 9 months to 2 years. This review population compared to the non-pregnant female population of
seeks a balanced overview of the present knowledge and highlights similar reproductive age [11], an association attributed to the pro-
the importance of prompt diagnosis and treatment. For ease of thrombotic state of the pregnancy and the puerperium. Contrib-
discussion, ischemic and hemorrhagic strokes will be reviewed uting risk factors include hypertension, advanced maternal age,
separately. caesarean delivery, dehydration, infection and excess vomiting
[11,12].
Ischemic stroke CVT remains rare, with an incidence 11.6 per 100,000 deliveries
[11,13]. Its clinical presentation depends on the site involved.
Pregnancy is a hypercoagulable state, resulting from increased Occlusion of the cerebral cortical veins results in focal neurological
production of coagulation factors (Von Willebrand factor, Factor signs and symptoms. Occlusion of the major venous sinuses can
VIII, brinogen), protein C resistance, reduced concentration of result in intra-cranial hypertension and impaired cerebrospinal

Third trimester 2 days before to 1 day Day 2 to 6 weeks

after delivery

Sub-Arachnoid OR 0.8 OR 46.9 OR 1.8

haemorrhage 95%CI 0.2-2.5 95%CI 19.3-98.4 95%CI 0.5-4.9

Intra-cerebral OR 1.3 OR 95 OR 11.7

haemorrhage 95%CI 0.3-4.1 95%CI 42.1 194.8 95%CI 6.1-21.6

Cerebral Infarction OR 2.2 OR 33.8 OR 8.3

95%CI 0.8-4.8 95%CI 10.5-84.0 4.4-14.8

Fig. 1. Standardized incidence rate ratios with 95% condence intervals of sub-arachnoid hemorrhage, intra-cerebral hemorrhage and cerebral infarction [6].
22 Z. Moatti et al. / European Journal of Obstetrics & Gynecology and Reproductive Biology 181 (2014) 2027

1 14 7 15
James et al Bushnell Lanska Douglas

OR (95% CI) OR (95% CI) OR (95% CI) (n=1 408 015)

n = 2850 OR (95% CI)

Migraine 16.9, 15.05

9.7-29.5 8.26-27.4

Thompbophilia 16.0

9.4-27.2

Systemic Lupus 15.2

Erythematosus 7.4-31.2

Heart Disease 13.2 Heart Failure

10.2-17.0 3.19

(0.77-13.29)

Rheumatic fever and valvular

heart disease

3.32

(1.83- 6.00)

Hypertension 9.1 peripartum

3.7-22.2 6.08

CI 4.44 to 8.32

postpartum

13.95

8.38 to 23.22

Sickle cell disease 9.1

3.7-22.2

thrombocytopania 6.0

1.5-24.1

Fig. 2. Standardized odds rate ratios with 95% condence intervals for medical comorbidities associated with Stroke.

uid absorption, causing headache, vomiting and papilledema.
Cavernous sinus thrombosis may lead to eye pain and exophthal-
mos.
The mortality rate for CVT is 210%, secondary to intracranial
hemorrhage or trans-tentorial herniation [11,12].
In the clinical setting, stroke should fundamentally be consid-
ered for women with risk factors for atherosclerosis, as well as
conditions tabulated below [1,7,14] (Fig. 2).
Conditions strongly associated with stroke, as part of the US
Nationwide Inpatient Sample, including migraine headache,
systemic lupus erythematosus, heart disease, sickle cell disease,
hypertension, and thrombocytopaenia [1]. African American
women and women aged 35 or older were disproportionately
represented [1].
Migraine headache in pregnancy is common (185 in 100,000).
However, this was found to be linked with a number of rare
cardiovascular events including stroke (OR 15.05, 95% CI 8.26
27.4) [14] as part of a US case-control study.
Anti-phospholipid syndrome (APS) is particularly pro-throm-
botic in pregnancy [15]. Women with APS and previous
cerebrovascular event, were found to experience a 10.7% recur-
rence in pregnancy despite aspirin and low-molecular-weight
heparin thromboprophylaxis.
Peripartum cardiomyopathy [7,16] and patent foramen ovale
[17] are conditions increasing the risk of thrombo-embolic stroke
in pregnancy.
Peripartum cardiomyopathy is a rare dilating cardiomyopathy
affecting women with no pre-existing heart disease. Typical
symptoms include heart failure and atrial brillation with left
ventricular systolic dysfunction [16]. The estimated risk develop-
ing stroke is 5%, with a risk ratio of 107.1 (P < 0.001) [7].
Patent foramen ovale (PFO) is a congenital inter-atrial
communication present in 27% of adults, and a leading cause of
stroke in the young population [17]. The hypercoagulable state of
pregnancy, cardiovascular changes, and susceptibility to arrhyth-
mias can lead to emboli being shunted from right to left atria.
 Z. Moatti et al. / European Journal of Obstetrics & Gynecology and Reproductive Biology 181 (2014) 2027 23

Post-partum Pre-eclampsia/ Blood Post- Caesarean Excess Fluids

haemorrhage Pregnancy- transfusion partum section vomiting electrolytes

induced infection and acid-base

hypertension disorders

James et 1.8 4.4 10.3 25 - - -

1
al 1.2-2.8 3.6-5.4 7.1-15.1 18.3-34.0

OR (95%

CI)

Lin23 - - - - 1.67 - -

OR (95% 1.29-2.16

CI)

Witlin28 - - - - 3.2, 95% CI - -

OR (95% 1.2-8.5

CI)

Douglas15 - - - 1.55 3.33 9.55 4.58

(n=1 408 0.98- 2.45 2.67-4.15 3.41- 2.56- 8.18

015) 26.77

OR (95%

CI)

Brown24 - 1.59 - - - - -

OR (95% 1.00-2.62

CI)

(n=2610

Lanska7 - - - - peripartum - -

OR (95% 3.56

CI) 2.62- 4.83

postpartum

2.40

1.45-3.99

Fig. 3. Standardized odds rate ratios with 95% condence intervals for obstetric associated with Stroke.

Straining during delivery may invert the pressure gradient across
the heart [17]. Percutaneous device closure of PFO under
echocardiography guidance is a therapeutic option for pregnant
patients who develop cardio-embolic stroke [18,19].
Obstetric and delivery conditions also confer a number of
signicant risks, in particular postpartum infection and pre-
eclampsia [1,7,2022] (Fig. 3).
Population studies agree that delivery by caesarean section
increases the likelihood of post-partum stroke [11,2022]. A
nationwide study in Taiwan (n = 987,010) found that after delivery
by caesarean section, the odds ratios for a stroke were 1.67 within
the rst 3 months, 1.61 within the rst 6 months, and 1.49 within 1
year [21].
Hemorrhagic stroke
Contrary to western population studies, Taiwanese studies have
claimed hemorrhagic strokes are more prevalent than ischemic
strokes among the Asian population [35]. The incidence in the
Asian population was estimated at 4369% compared to 3352% in
western countries [4].
The etiology for hemorrhagic stroke differs greatly from
ischemic stroke [35]. In Jaigobins study, a third were due to
ruptured aneurysms, half associated with Arterio-venous mal-
formations, and the rest to disseminated intra-vascular coagula-
tion [5].
In Liangs study, of 32 cases of stroke (2006) the most common
causes of intra-cranial hemorrhage were vascular anomaly (29%),
pre-eclampsia/eclampsia (24%), undetermined (24%) and coagulo-
pathy (19%) [4].
Hemorrhagic stroke is associated with the poorest outcomes-
death or neurological decit [4,22]. In the Taiwanese study, the
mortality rate was 17.8%, 77.8% of deaths were due to intracranial
hemorrhage [4].
Subarachnoid 9SAH and intracerebral hemorrhage (ICH), are
most likely to occur in the three days surrounding delivery
24 Z. Moatti et al. / European Journal of Obstetrics & Gynecology and Reproductive Biology 181 (2014) 2027
(dened as 2 days before to 1 day after) and during the puerperium,
compared to the small third trimester risk [6] (see Fig. 1).
The risk of ICH rises sharply in the three days surrounding
delivery (OR 95, 95% CI 42.1194.8), and remains 11.7 times more
likely during the puerperium (95% CI 6.121.6) [6]. ICH accounts
for 27% of cases of stroke in pregnancy [7].
This effect is even more marked for SAH, where the risk peaks at
delivery (OR 46.9, 95% CI 0.54.9) and reduces rapidly thereafter
[6]. SAH, occurring in 2.4 per 100,000 pregnancies, is mostly due to
AV malformations or aneurysms, most likely to rupture around
the time of delivery.
Multiparous women with 2 or more previous pregnancies were
found to be at signicantly increased risk of hemorrhagic stroke
compared to women in their rst or second pregnancies, each
additional parity increasing the risk by 1.27 for ICH, and 1.34 for
SAH [23].
Pre-eclampsia
Pre-eclampsia is a complex multi-system disorder, conferring
risks for both ischemic and hemorrhagic stroke [24]. Indeed, pre-
eclampsia is present as a risk factor in 25 to 45% of cases of stroke in
pregnancy [25,26] and is associated with a 312 fold risk of stroke
[20].
Many factors increase the risk of stroke: raised blood pressure,
endothelial dysfunction, hemolysis, elevated liver enzymes and
low platelets (HELLP syndrome) leading to brin deposition and
platelet aggregation, hemoconcentration and the activation of the
coagulation cascade.
In the United Kingdom (20062008), 14 out of 19 deaths from
severe pre-eclampsia and eclampsia were from cerebral causes.
1.Investigations
a.Emergency CT brain scans
b. MRI Brain and MR angiogram of intracranial and extracranial vessels from aortic arch and
above.
c. continuous cardiac monitoring at least for next 48 hours.
d.12 lead ECG
e.Bubble echocardiogram for assessment of PFO(patent Foramen Ovale) and ASD (Atrial septal
defect).
f. Baseline testing to exclude concurrent illnesses (extensive testing is not required prior to a
decision regarding thombolysis) FBC, CRP, ESR, LFT, U&Es, coagulation screen, calcium, glucose,
Magnesium, fasting lipid profile, homocysteine, arterial blood gases including lactate levels, serum
protein electrophoresis.
g.Thrombophilia screen including lupus anticoagulant, anti-cardiolipin antibodies, anti- beta 2
glycoprotein, antithrombin, protein C, Factor V Leiden mutation and APC Resistance Assay,
Prothrombin Gene Mutation (G-20210-A)
h.Vasculitic screen including ANA, ENA, ANCA, Rh factor, cryoglobulin, complement levels
i. HIV, hepatitis and VDRL (to exclude secondary causes).
j. toxicology screen (if indicated, from symptoms or behaviour)
i.Diagnostic lumbar puncture, especially when small subarachnoid haemorrhage is to be
excluded.
Fig. 4. Matrix for management of stroke in pregnancy.
Nine of the fourteen were from intracranial hemorrhage, and ve
from anoxia during eclamptic seizure [27].
Women with pre-eclampsia complicated by intra-cerebral
hemorrhage are at signicantly higher risk of death (11%)
compared to women with pre-eclampsia or eclampsia without a
stroke (1.9%) [28]. The gure has remained between 33 and 45% as
outlined in CEMACH reports since 1997 [27,29].
An eclamptic seizure may present with headache, coma or
confusion. Sudden-onset or persistent neurological decits should
be further investigated.
Women with a history of pre-eclampsia are 60% more likely to
have a non-pregnancy-related ischemic stroke than those without
a history of pre-eclampsia [22]. However, for pre-eclampsia not
complicated by a myocardial infarction or stroke, the life-long risk
of stroke remained small in comparison to other known risk factors
[26].
Challenges of diagnosis
Stroke in pregnancy remains rare, therefore patients are
optimally investigated and managed as part of a multi-disciplinary
team, including stroke physicians, obstetricians and radiologists.
Patients with persistent neurological decit or other clinical
features should undergo urgent imaging. CT scanning should
balance the risk of ionizing radiation to the mother and fetus.
Diagnostic lumbar puncture may be indicated for suspected
subarachnoid hemorrhage (Fig. 4).
2.Management of Acute stroke in pregnancy.-Multidisciplinary
a. HASU(Hyperacute stroke unit)
b.Thrombolysis rtPA
c. Antiplatelet Therapy
d. Possible role of anticoalulant Therapy (stroke physician input) +/ -Pneumatic Intermittent
compression devices
e.Percuataneous device closures
f.Psycho-social care and Neuro Rehabilation
3.Management of pregnancy with previous history of stroke
a.Preconception counseling- Need to change medications like antihypetensives
b.Aspirin prophylaxis
c.Uterine artery dopplers.
d.Pscyhological support .
e.Anaesthetic Involvement regarding Safety of Regional anaesthesia for labour or CS.
f. Mode of delivery to be considered depending on the History.
g.postnatal thromborohylaxis
h.Perinatal Mental health Team and social services to be involved to provide support
i.6 weeks postnatal check debrief and counsel about contraception and risk of recurrence.
Fig. 4. (Continued ).
 Z. Moatti et al. / European Journal of Obstetrics & Gynecology and Reproductive Biology 181 (2014) 2027
Every effort should be made to investigate the underlying cause
of stroke.
In particular for cerebral venous thrombosis, a full thrombo-
philia and vasculitis screen is required [1113]. Thrombophilia
screening should be repeated 6 weeks postnatally, due to the
effects on protein S levels, and 1 month after stopping anti-
coagulants [7].
In cases of suspected embolic stroke, vascular studies, MRI Brain
and MR angiogram of intracranial and extracranial vessels is
indicated. Investigations for cardio-embolism should include a 12-
lead ECG on arrival, to check for cardiomyopathy or acute cardiac
event, followed by continuous cardiac monitoring for at least 48 h.
A bubble echocardiogram is useful to exclude patent foramen ovale
(PFO) and atrial septal defect [17,18].
Presenting features of post-partum stroke were difcult to
characterize as part of a 20-year retrospective review [26]. The
median time of onset was 8 days, but ranged from 8 to 35 days [26].
Common features included headache, visual change, seizure or
hemiparesis. However, none of the symptoms were specic to that
particular type of stroke, nor were they predictive of the severity of
disease or eventual maternal outcome [26].
Subtler complaints include confusion, photosensitivity, vomit-
ing, altered consciousness, painful eye and exophthalmos.
Certain rare stroke sub-types, such as postpartum cerebral
angiopathy (PCA) are particularly difcult to differentiate from
pre-eclampsia or eclampsia. PCA is an extremely rare type of
stroke, part of the reversible cerebral artery vasoconstriction
syndromes [3032]. These syndromes causes reversible vasocon-
striction of cerebral arteries, and other causes include drug
exposure, migraine, mechanical trauma or hypercalcemia.
Presenting features of PCA include sudden thunderclap
headache, photosensitivity, vomiting, altered consciousness, sei-
zure and transient or permanent focal neurological decits [30
32]. Median time of onset is 5 days post-partum, but most cases
present in the rst 2 weeks [32].
Unlike eclampsia, PCA is limited to the nervous system, and
most patients have a history of an uncomplicated pregnancy and
delivery. Radiological diagnostic signs include segmental narrow-
ing of the cerebral arteries, which resolve completely after 46
weeks [30,32]. Treatment is observational because the condition is
considered self-limiting. However mortality is 22% and residual
weakness affects 28% [30,31].
Thrombolysis
The pharmaceutical prescription guidelines for alteplase state
that pregnancy and the rst week post-partum are not contra-
indications for treatment. However pregnant women were not
included in phase-II and phase-III trials, therefore a thorough risk
assessment of bleeding risks for that patient is recommended.
The clinical overview must encompass risks posed to the
mother or fetus from ante-partum or post-partum hemorrhage
[33,34]. Evidence for the safe use of anti-thrombolytic issues from
a number of case reports and series, both for ischemic [3538] and
thromboembolic stroke [39,40].
Recombinant tissue plasminogen activator (rt-PA) Alteplase is
the current licensed UK medication for ischemic stroke thrombol-
ysis. The drug rt-PA is not known to be teratogenic, and the
molecule is too large (72 000 kD) to cross the placenta. Streptoki-
nase and urokinase are rarely used for thrombolysis in the Western
world.
Cases amenable to hyper-acute stroke thrombolysis must be
managed by a full multi-disciplinary team, taking into account
clinical and radiological factors, age, stroke severity and the arterial
occlusion site.
25
After thrombolysis all patients should be closely monitored in a
hyper-acute stroke unit (HASU) for 4872 h. Further radiological
imaging, preferably MRI, is recommended in order to map the
occlusion site. Patients with middle cerebral artery territory or
posterior circulation territory stroke should be closely monitored
for raised intracranial tension from secondary cytotoxic edema, a
preventable cause of death. Drowsy patients with acute stroke
should be reviewed by the specialist stroke team on the day of
admission to consider prophylactic decompressive craniectomy to
avoid tentorial herniation, and death from rising intracranial
pressure.
Intra-arterial thrombolysis or mechanical thrombectomy is an
option for patients in whom Thrombolysis is contra-indicated, or
for patients with a large-vessel occlusion who would not benet
from the intended recanalization of thrombolysis. Such cases need
urgent joint discussion with a stroke specialist and an interven-
tional neuro-radiologist.
Leonhardt, reported on 28 cases of systemic thrombolysis in
pregnancy using tissue plasminogen activator (Rt-PA) for various
indications, including 10 cases for stroke [34]. Thrombolysis failed
in 3 cases (11%), two patients died (7%), and three suffered
complications managed conservatively (11%) [34]. Complication
rates were similar to the non-pregnant population.
Failure and complication rates for stroke thrombolysis also
reected those in the non-pregnant population [34], with optimal
outcomes in 7 of the 10 cases. One patient suffered a dense
hemiparesis, another died from ischemic infarction due to arterial
dissection. In a third case, the patient showed signs of delayed
deterioration, successfully treated by a second thrombolytic
treatment [34]. Among surviving mothers, three pregnancies were
lost, however causation to prior thrombolysis could only be
established in two cases (8%). None of the live-born children
suffered a permanent decit. One pregnancy was terminated, the
other nine were healthy [34].
In conclusion, thrombolysis during pregnancy and the puerpe-
rium has similar levels of safety and efcacy to the pregnant
population, and as such should not be withheld [3340].
Thromboprophylaxis
Patients with a history of stroke should be managed with joint
neurological input. Aspirin is recommended for patients with a
history of ischemic stroke, and low-molecular heparin (LMWH)
should be considered in certain cases.
For patient with no prior history of stroke, anticoagulation with
LMWH is required in certain circumstances, e.g. thrombophilia
disorders or prosthetic heart valve. Heparin is safe during the
pregnancy and breastfeeding. Unfractionated low-molecular
weight heparin can induce thrombocytopaenia and this complica-
tion should be monitored for.
As part of the treatment of an acute stroke, aspirin 300 mg, then
75 mg once a day is recommended. However further neuro-
imaging is required after thrombolysis to exclude hemorrhagic
transformation, before antiplatelet therapy is commenced.
The use of low-molecular weight heparin (LMWH) after an
acute ischemic stroke is subject to the clinical situation and
requires stroke physician input. In certain cases it is not advised on
account of the risk of inducing hemorrhagic transformation.
Intracranial hemorrhage related to cerebral venous thrombosis,
present in 40% of patients before treatment, is not a contra-
indication to heparin treatment [41,42].
Psychosocial care and counseling
Stroke can have severe effects on a mothers physical, cognitive
and psychological health. Compared to men, women fare worse in
26 Z. Moatti et al. / European Journal of Obstetrics & Gynecology and Reproductive Biology 181 (2014) 2027
terms of quality of life after an ischemic stroke or TIA in terms of
mobility, pain/discomfort, and anxiety/depression [43].
Multi-disciplinary neuro-rehabilitation and referral to special-
ist perinatal mental health services is essential for her capacity to
care for her newborn child. Social interventions such as daily
support and home adaptations may be appropriate.
When debrieng a patient and her partner after an acute event,
or counseling pre-conceptually, the evidence is that stroke
recurrence is low, between 1.8 and 2.7% [4446].
A study of 9 neurological centers identied 441 women with
early-onset ischemic stroke, gathering information on stroke
recurrence and reproductive history [45].
One hundred and eighty seven women had subsequent
pregnancies, three of which were complicated by stroke
recurrence, a recurrence risk 1.8%. The overall risk of recurrence
outside pregnancy, was 1% within 1 year, and 2.3% within 5
years, and noted to be higher for patients with a known cause of
stroke.
After the initial stroke, 34% of women indicated that they would
have wanted more pregnancies, but had avoided these as they
were concerned about recurrence, had received medical advice
against pregnancy, or had residual handicap [45].
Conclusion
Stroke during pregnancy has signicant maternal morbidity
and mortality, and a profound impact on the patient and her
family. The etiology differs to the non-pregnant population: the
hypercoagulable state of the pregnancy and the puerperium, and
pre-eclampsia come into effect.
Clinical presentations vary considerably, and early recourse to
radiological investigation and neurology input is required for
suspected cases. Thrombolysis has a safe and successful record,
and as such should not be withheld for cases of severe ischemic
stroke.
Despite a rising incidence, stroke in pregnancy remain rare.
Patients with acute stroke are optimally managed by multi-
disciplinary teams in centers of expertise. They can be reassured
that the recurrence risk in pregnancy is low.
Conict of interest statement
None.
Funding
This research received no specic grant from any funding
agency in the public, commercial, or not-for-prot sectors.
Authors contribution
Zoe Moatti is the corresponding and guaranteeing author for
this article, as such she guarantees the manuscripts accuracy and
contributorship of all co-authors. The contributing authors Manish
Gupta, Rajendra Yadava and Sujatha Thamban have approved the
version to be published.
Ethical approval
Not applicable.
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