Stroke and Cerebrovascular Disease in Pregnancy

Incidence, Temporal Trends, and Risk Factors

Shiliang Liu, MD, PhD; Wee-Shian Chan, MD, MSc; Joel G. Ray, MD, MSc;
Michael S. Kramer, MD; K.S. Joseph, MD, PhD;
for the Canadian Perinatal Surveillance System (Public Health Agency of Canada)*

Background and Purpose—Few studies have examined the epidemiology of stroke in pregnancy, despite the high associated
burden of death and disability. We aimed to quantify the incidence, temporal trends, risk factors, and case fatality
associated with stroke and cerebrovascular disease in pregnancy.
Methods—All antepartum, peripartum, and postpartum hospitalizations and readmissions within 42 days of delivery in
Canada (except Quebec) were obtained from the Canadian Institute of Health Information for the years 2003 to 2016. We
assessed temporal trends in stroke and quantified associated risk factors using logistic regression.
Results—Five hundred twenty-four stroke cases were identified among 3 907 262 deliveries (13.4 per 100 000). The majority
of cases were hemorrhagic strokes (307 cases, 58.6%) and most occurred in the postpartum period (270 cases, 51.5%).
The case fatality rate was 7.4%. Stroke incidence rose from 10.8 per 100 000 in 2003 to 2004 to 16.6 per 100 000 deliveries
in 2015 to 2016 (P=0.002). Risk factors for stroke included older maternal (age ≥40 years; adjusted odds ratio [AOR],
1.7; 95% CI, 1.1–2.6), preeclampsia (AOR, 7.1; 95% CI, 5.3–9.6), eclampsia (AOR, 65.9; 95% CI, 43.6–99.6), maternal
congenital heart disease (AOR, 38.1; 95% CI, 22.1–65.8), connective tissue disorders (AOR, 12.6; 95% CI, 6.1–26.9),
sepsis (AOR, 7.6; 95% CI, 3.6–16.2), severe postpartum hemorrhage (AOR, 4.7; 95% CI, 2.8–8.0), and thrombophilia
(AOR, 4.2; 95% CI, 1.5–12.1).
Conclusions—The rising incidence of stroke in pregnancy, especially during the postpartum period, and its strong association
with hypertensive disorders of pregnancy (especially preeclampsia) suggest that follow-up of severe hypertensive patients
is required after delivery.   (Stroke. 2019;50:13-20. DOI: 10.1161/STROKEAHA.118.023118.)
Key Words: epidemiology ◼ hypertension ◼ incidence ◼ pregnancy ◼ stroke
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S troke is a neurological emergency and a major cause of

disability and death around the world.1 It is the third lead-
ing cause of death among Canadians,2 and the age-adjusted
occurrence of stroke in Canada increased from 2.3% in 2003
to 2.6% in 2012.1,3 Stroke in pregnancy is of particular impor-
tance not just because it affects women of reproductive age,
but because it is often a result of specific pregnancy-associ-
ated conditions and is potentially preventable.4–8 Pregnancy-
associated strokes are also the most common cause of serious
long-term disability after pregnancy.7,8 Risk factors for stroke
include hypertensive disorders of pregnancy, such as pree-
clampsia and eclampsia, and a prothrombotic state, which
increases the risk of arterial and venous thrombosis.4–8
Canadian studies have reported an incidence of cerebrovas-
cular diseases during hospitalization for childbirth of 4.8 per
100 000 deliveries in 2003 to 20079,10; 45% of affected women
had a prolonged hospital stay, and the associated case fatality
was 9.4%.10 Many other studies have found an increased risk
of stroke in pregnancy, especially in the puerperium.11–14 Jeng
et al11 reported an incidence of stroke during pregnancy and
puerperium among Chinese women in Taiwan of 46.2 per
100 000 pregnancies. A more recent study by Ban et al12 from
United Kingdom reported a 9-fold increased risk of ischemic
or hemorrhagic stroke during the peripartum period and a
3-fold increased risk during the early postpartum period. In
the United States, the rate of stroke (including subarachnoid
hemorrhage, intracerebral hemorrhage, ischemic stroke, tran-
sient ischemic attack, cerebral venous thrombosis, or unspeci-
fied stroke) among antepartum hospitalizations increased from
15 to 22 per 100 000 deliveries from 1994 to 1995 to 2006 to

Received August 2, 2018; final revision received September 28, 2018; accepted October 8, 2018.
From the Maternal, Child and Youth Health Division, Centre for Surveillance and Applied Research, Public Health Agency of Canada, Ottawa, ON
(S.L.); Departments of Medicine and Obstetrics and Gynaecology, University of British Columbia, the Children’s and Women’s Hospital of British
Columbia, Vancouver, BC (W.-S.C.); Departments of Medicine, Health Policy Management and Evaluation and Obstetrics and Gynecology, St Michael’s
Hospital, University of Toronto, ON (J.G.R.); Departments of Pediatrics and of Epidemiology, Biostatistics and Occupational Health, McGill University,
Montreal, QC (M.S.K.); and Department of Obstetrics and Gynaecology, the School of Population and Public Health, University of British Columbia and
the Children’s and Women’s Hospital of British Columbia, Vancouver, BC, Canada (K.S.J.).
*A list of all Canadian Perinatal Surveillance System (Public Health Agency of Canada) study participants is given in the Appendix.
The online-only Data Supplement is available with this article at https://www.ahajournals.org/doi/suppl/10.1161/STROKEAHA.118.023118.
Correspondence to Shiliang Liu, MD, PhD, Maternal, Child and Youth Health Division, Centre for Surveillance and Applied Research, HPCDP Branch,
Public Health Agency of Canada, 785 Carling Ave, AL 6804A, Ottawa, ON K1A 0K9, Canada. Email shiliang.liu@canada.ca
© 2018 American Heart Association, Inc.
Stroke is available at https://www.ahajournals.org/journal/str DOI: 10.1161/STROKEAHA.118.023118

13
 14  Stroke  January 2019
2007, whereas rates of stroke were stable at 27 per 100 000
deliveries among delivery hospitalizations and increased from
12 in 1994 to 1995 to 22 per 100 000 deliveries in 2006 to 2007
among postpartum hospitalizations.14 In addition, previous
studies suggest that Asians have an increased risk of hemor-
rhagic stroke compared with whites and blacks.11,13,14
Risk factors for cerebrovascular disease and stroke, such
as older maternal age and hypertension, have increased sig-
nificantly in high-income countries in recent years.15–17 We
performed a study to quantify the incidence, temporal trends,
regional variations, risk factors, and case fatality associated
with cerebrovascular disease and stroke in pregnancy in
Canada.
Methods
The data used for this study are available from the Canadian Institute
for Health Information.
Study Population, Case Ascertainment,
and Stroke Subtypes
This retrospective population-based cohort study included all ante-
natal admissions, delivery hospitalizations, and postpartum hospital
readmissions within 42 days of delivery in Canada (except Quebec)
for the fiscal years 2003 to 2004 to 2016 to 2017. Information on
pregnant women was obtained from the Canadian Institute for Health
Information’s Discharge Abstract Database (DAD), which contained
the abstracted and collated information from medical records of all
hospitalizations in Canada. Data from Quebec are not available in
the DAD.
Hospitalization data were extracted by trained medical archivists
in each hospital and coded according to a standardized protocol18
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and included demographic and residence information, date of ad-
mission, date and status at discharge, principal diagnosis, and up
to 25 secondary diagnoses (coded using the International Statistical
Classification of Diseases and Related Health Problems, Tenth
Revision, Canadian version). Validation and data quality studies have
shown this information to be complete and accurate,19,20 and informa-
tion on pregnancy conditions and obstetric complications in the DAD
is routinely used for perinatal research.19–23
First-ever cases of stroke and cerebrovascular disease in preg-
nancy during the index delivery were identified using International
Statistical Classification of Diseases and Related Health Problems,
Tenth Revision, Canadian version diagnostic codes and categorized
as follows: (1) hemorrhagic stroke (I60-I62); (2) ischemic stroke
(I63 except I63.6); (3) cerebral venous thrombosis (I63.6, I67.6);
(4) stroke not specified (I64); (5) any stroke (including hemorrhagic
stroke, ischemic stroke, cerebral venous thrombosis, and stroke un-
specified); (6) occlusion or stenosis of precerebral or cerebral arter-
ies, transient cerebral ischemic attack (TIA) and related syndromes,
and vascular syndromes of the brain not resulting in stroke (I65, I66,
G45, and G46); and (7) other cerebrovascular diseases not result-
ing in stroke (I67 except I67.6). However, we were unable to verify
whether the identified strokes were first-time events or complications
of a condition that preceded the index pregnancy/delivery. Nor were
we able to follow-up the women with recorded strokes.
Maternal Characteristics and Conditions
Maternal characteristics such as age, parity, gestational age at de-
livery, and province of occurrence were obtained from all delivery
hospitalizations with a gestational age ≥20 weeks, as was informa-
tion on multifetal gestation, chronic hypertension, gestational hyper-
tension, preeclampsia or eclampsia, preexisting diabetes mellitus,
connective tissue disorders, sepsis, HIV infection/disease, migraine,
anemia, obesity, congenital heart disease, postpartum hemorrhage,
and blood transfusion. Other clinical conditions explored as potential
risk factors included renal failure (acute, chronic, and unspecified),
superficial thrombophlebitis, and deep venous thrombosis but these
were not retained in the final analysis because of small numbers of
associated stroke cases. Supplementary analyses were also performed
on a subset of the data including hospital admissions between 2009
and 2016 to examine associations between thrombophilia and stroke
and between use of assisted reproductive technology and stroke
(because these conditions were only coded in the DAD from 2009
onwards).
Hospital length of stay was calculated as the number of days be-
tween admission and discharge. Health insurance numbers (scram-
bled by a systematic algorithm) were used to link antenatal, delivery,
and postpartum admissions for the same woman using deterministic
record linkage (ie, delivery records were linked to any preceding an-
tenatal admission and subsequent postpartum readmissions).
Statistical Analysis
Incidence rates of stroke by 2-year period and province of delivery
hospitalization were calculated, with rates expressed per 100 000
deliveries. The Cochran-Armitage test for trend in proportions was
used to examine biennial trends in the occurrence of stroke. The
burden of illness because of cerebrovascular disease and stroke was
estimated by calculating average length of hospital stay, proportion
of women with prolonged length of stay (ie, >7 days of hospitaliza-
tion), and case fatality rates. Multivariate logistic regression analysis
was used to estimate adjusted odds ratios (AOR) and corresponding
95% CIs for the association between maternal risk factors and stroke
and cerebrovascular diseases. We also estimated the proportion
of stroke cases that would be eliminated if a particular risk factor
(assumed to be causally associated with stroke) were removed from
the population using the adjusted effect measure in the following
equation: Pe(RR-1)/Pe(RR-1)+1 where Pe=proportion of the popu-
lation exposed to the risk factor and RR=relative risk (OR given rare
disease) associated with the risk factor.24 This study was performed
by the Canadian Perinatal Surveillance System of the Public Health
Agency of Canada under its health surveillance and applied research
mandate using publicly accessible anonymized data, hence, ethics re-
view board approval was not required. Statistical analyses were car-
ried out using SAS version 9.2 (SAS Institute, Cary, NC).
Results
A total of 524 stroke cases were identified among 3 907 262
hospital deliveries, yielding an overall incidence of 13.4 cases
per 100 000 deliveries from 2003 to 2016. More than half
(51.7%) of the recorded strokes occurred postpartum, and
the overall case fatality rate was 7.4%. Hemorrhagic stroke
accounted for almost 60% of all strokes, while ischemic
stroke constituted nearly 30% of strokes (Table 1). The rate of
occlusion, stenosis of precerebral or cerebral arteries, or TIAs
or other vascular syndromes not resulting in stroke was 3.5
per 100 000 deliveries, while the frequency of other cerebro-
vascular diseases not resulting in stroke was 6.4 per 100 000
deliveries (Table 1).
Despite substantial fluctuation, the rate of stroke during
pregnancy increased significantly from 10.8 cases per 100 000
deliveries in 2003 to 2004, to 13.8 in 2009 to 2010, and 16.6
per 100 000 deliveries in 2015 to 2016 (P=0.002 for increas-
ing linear trend; Table I in the online-only Data Supplement).
This temporal increase remained significant after adjustment
for maternal age (P=0.005). Women with nonfatal stroke re-
quired longer hospital stays compared with women without
stroke (mean 11.6 versus 2.5 days, respectively; Table 2). The
proportion of women with a nonfatal stroke whose hospital
stay exceeded 7 days was 43.7%, compared with 1.7% among
women without stroke. The frequency of stroke by gestational
 Liu et al   Risk of Stroke in Pregnancy   15

Table 1.  Number and Rate of Stroke Subtypes and Related Conditions by Period of the Pregnancy, Canada (Excluding Quebec), 2003 to 2016

No. of Cerebrovascular Events by Timing of

Occurrence in Pregnancy or Postpartum Periods
Index Delivery Postpartum Rate per
Stroke Subtypes and Other Related ICD-10CA Diagnostic Antenatal Hospitalization Readmission Total Strokes, 100 000 Case Fatality,
Conditions Codes (n=377 370) (n=3 907 262) (n=67 438) Number (%) Deliveries Number (%)
Hemorrhagic stroke I60, I61, I62 12 131 164 307 (58.6) 7.9 25 (8.1)
Ischemic stroke I63 (except I63.6) 15 52 82 149 (28.4) 3.8 11 (7.4)
Cerebral venous thrombosis I63.6, I67.6 1 6 15 22 (4.2) 0.6 2 (9.1)
Stroke not specified I64 2 38 10 50 (9.4) 1.3 1 (2.3)
Any stroke* I60-I64, I67.6 29 224 271 524 (100.0) 13.4 39 (7.4)
Occlusion, stenosis of precerebral I65, I66, G45,G46 2 97 30 137 3.5 0 (0.0)
and cerebral arteries, TIAs, vascular
syndromes (not resulting in stroke)
Other cerebrovascular diseases (not I67 (except I67.6) 6 78 53 252 6.4 2 (0.8)
resulting in stroke)
Puerperal readmission refers to admission within 42 days after termination of pregnancy. ICD-10 indicates International Classification of Diseases and Related Health
Problems; and TIA, transient ischemic attack.
*More than one stroke subtype may be coded.

duration at delivery increased with advancing gestation (Table
II in the online-only Data Supplement).
Mothers aged 35 to 39 and ≥40 years had a significantly
higher risk of any stroke than younger mothers (ie, women
20–29 years) with an AOR of 1.6; 95% CI, 1.2–2.0 and 1.7;
95% CI, 1.1–2.6, respectively (Table 3). Gestational hyperten-
sion was associated with a 60% higher risk of stroke, while
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was significantly associated with hemorrhagic stroke (AOR,
2.0; 95% CI, 1.4–2.8 for women 35–39 years) but not is-
chemic stroke (AOR, 1.3; 95% CI, 0.8–2.0 for women 35–39
years). Similarly, gestational hypertension was significantly
associated with hemorrhagic stroke but not ischemic stroke.
However, the AOR for multifetal gestation and hemorrhagic
stroke (0.7; 95% CI, 0.3–1.7) was significantly lower than the

the AOR for stroke associated with chronic hypertension was
2.5 (95% CI, 1.3–4.7). Preeclampsia (AOR 7.1), eclampsia
(AOR 65.9), connective tissue disorders (AOR 12.6), sepsis
(AOR 7.6), postpartum hemorrhage with blood transfusion
(AOR 4.7), and congenital heart disease (AOR 38.1) were
all strongly associated with stroke. Approximately 7.9% and
3.8% of the stroke cases could be attributed to preeclampsia
and eclampsia, respectively. Overall, 20.3% of stroke cases
could be prevented if any of hypertensive disorders were elim-
inated from the pregnant women (Table 3).
Table 4 shows the associations between maternal risk fac-
tors for hemorrhagic and ischemic stroke. Older maternal age
AOR for ischemic stroke (3.7; 95% CI, 1.9–7.1). AORs were
also different between parity and hemorrhagic stroke versus
ischemic stroke. Other risk factors, such as preeclampsia,
eclampsia, connective tissue disorders, sepsis, postpartum
hemorrhage with blood transfusion, and congenital heart di-
sease, showed strong associations with both hemorrhagic and
ischemic stroke. HIV infection and migraine were strongly as-
sociated with ischemic stroke (Table 4).
Table 5 shows associations between maternal risk fac-
tors for occlusion, stenosis of precerebral or cerebral arteries,
or TIAs or vascular syndromes not resulting in stroke. Most
associations were similar to those observed with hemorrhagic

Table 2.  Length of Hospital Stay Among Pregnant Women With and Without Nonfatal Stroke, Canada (excluding Quebec), 2003 to 2016

Mean (SD) Length of No. (%, 95% CI) With a

Stroke Subtypes and Other Related Conditions Number Stay in d* Mean (SD) Length of Stay >7 d
Hemorrhagic stroke 282 12.1 (13.2) 124 (44.0, 38.1–50.0)
Ischemic stroke 138 12.9 (12.5) 70 (50.7, 42.1–59.3)
Cerebral venous thrombosis 20 9.6 (11.3) 8 (40.0, 19.1–63.9)
Stroke not specified 48 4.9 (6.8) 7 (14.6, 6.1–27.8)
Any stroke 485 11.6 (12.7) 212 (43.7, 39.2–48.3)
Occlusion, stenosis, TIAs, and vascular syndromes not 137 5.3 (6.2) 23 (16.8, 11.0–24.1)
resulting in stroke
Other cerebrovascular diseases not resulting in stroke 250 5.7 (6.3) 50 (20.0, 15.2–25.5)
Hospitalizations excluding those with stroke and other 4 350 706 2.5 (2.2) 73 917 (1.70, 1.69–1.71)
cerebrovascular conditions
*Mean length of stay (LOS) was calculated as 42 d for women with a LOS >42 d.
 16  Stroke  January 2019

Table 3.  Rates of Stroke and Crude and Adjusted Odds Ratios Showing Associations Between Maternal Characteristics and Conditions and Any Stroke* During
Pregnancy, Childbirth and the Postpartum Period, Canada (Excluding Quebec), 2003 to 2016

Population Rate of Stroke per Rate of Stroke per Odds Ratio (95% CI) Population
Frequency 100 000 When Factor 100 000 When Factor Attributable
Characteristic (n=3 907 262) % Is Present Is Absent Crude Adjusted† Fraction, %
Maternal age, y <20 4.1 16.4 13.3 1.4 (0.9–2.3) 1.3 (0.9–2.1) 1.2
 20–29 43.9 12.4 13.9 1.0 (reference) 1.0 (reference) …
 30–34 32.6 18.7 12.4 1.1 (0.9–1.4) 1.1 (0.9–1.4) 3.2
 35–39 16.0 22.1 13.1 1.7 (1.3–2.1) 1.6 (1.2–2.0) 8.8
 ≥40 3.4 51.2 13.2 2.0 (1.3–3.0) 1.7 (1.1–2.6) 2.3
Parity 0 34.8 8.4 16.1 1.3 (0.9–1.8) 1.1 (0.8–1.6) 3.4
 1 27.0 5.4 5.8 1.0 (reference) 1.0 (reference) …
 2 14.3 5.5 5.4 1.0 (0.7–1.6) 1.0 (0.6–1.5) …
 ≥3 2.6 9.1 5.2 1.7 (0.9–3.4) 1.4 (0.7–2.9) …
 Unknown 21.3 30.2 6.2 5.5 (4.1–7.3) 5.1 (3.8–6.8) …
Multifetal gestation 1.5 35.0 13.1 2.7 (1.6–4.3) 1.5 (0.9–2.4) 0.7
Chronic hypertension 0.6 51.2 13.2 3.8 (2.0–7.1) 2.5 (1.3–4.7) 0.4
Gestational hypertension‡ 4.1 20.5 13.1 1.6 (1.1–2.3) 1.6 (1.1–2.3) 2.4
Preeclampsia 1.4 133.1 117.8 11.4 (8.7–14.9) 7.1 (5.3–9.6) 7.9
Eclampsia 0.06 1313.2 12.6 105.2 (71.5–154.3) 65.9 (43.6–99.6) 3.8
Preexisting diabetes mellitus 0.7 7.7 13.2 0.7 (0.2–2.6) 0.4 (0.1–1.6) 0
Connective tissue disorders 0.08 278.8 13.2 22.1 (11.0–44.5) 12.6 (6.1–26.9) 0.9
Sepsis 0.11 21.9 13.2 17.4 (8.6–35.0) 7.6 (3.6–16.2) 0.7
HIV infection 0.05 50.2 13.4 4.4 (0.6–31.3) 4.3 (0.6–30.6) 0.2
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PPH+blood transfusion 0.5 113.7 12.9 8.8 (8.5–14.2) 4.7 (2.8–8.0) 1.8
Migraine 0.03 81.4 13.4 7.2 (1.01–50.9) 3.6 (0.5–26.8) 0.1
Congenital heart disease 0.1 520.8 13.0 41.3 (24.2–70.4) 38.1 (22.1–65.8) 3.6
Gestational diabetes mellitus 5.6 21.5 12.9 1.7 (1.2–2.3) 1.2 (0.8–1.6) 1.1
Anemia 2.2 42.6 12.8 3.4 (2.3–4.9) 1.3 (0.9–2.0) 0.7
Obesity 1.3 21.9 13.3 1.6 (0.8–3.1) 1.3 (0.7–2.6) 0.4
Any of hypotensive disorders§ 6.1 58.0 10.5 5.5 (4.5–6.8) 5.2 (4.2–6.4) 20.3
ICD-10 indicates International Classification of Diseases and Related Health Problems; and PPH, postpartum hemorrhage.
*Any stroke includes hemorrhagic stroke, ischemic stroke, cerebral venous thrombosis, and stroke not specified.
†All the variables listed in the first column are included in the adjusted modeling.
‡Defined using ICD-10 code O13 which included mild preeclampsia.
§Hypertensive disorders during pregnancy include chronic hypertension, gestational hypertension, preeclampsia, and eclampsia.

and ischemic stroke, except for a strong association with pre-
existing diabetes mellitus (AOR, 5.5; 95% CI, 2.5–12.3) and
a nonsignificant association with preeclampsia (AOR, 1.8;
95% CI, 0.6–4.8). Table 5 also shows associations between
maternal risk factors and other cerebrovascular diseases not
resulting in stroke. These associations were generally similar
to those with hemorrhagic and ischemic stroke.
Supplementary analyses based on hospital admissions be-
tween 2009 and 2016 showed that thrombophilia was strongly
associated with stroke (AOR, 4.2; 95% CI, 1.5–12.1). The
crude association between assisted reproductive technology
and stroke was not statistically significant (AOR, 0.5; 95%
CI, 0.2–1.3), although the adjusted association showed use
of assisted reproductive technologies was associated with a
significantly lower rate of stroke (AOR, 0.3; 95% CI, 0.1–0.7;
Table III in the online-only Data Supplement).
Discussion
We observed a temporal rise in the age-adjusted incidence
of stroke during pregnancy in Canada over the past 14 years.
Strokes occurring in the postpartum period and resulting in
rehospitalization accounted for the majority of cases. The
case fatality rate following stroke was substantial, with 7.4%
of women dying during hospitalization. Risk factors for stroke
included older maternal age, hypertensive disorders, especially
preeclampsia and eclampsia, connective tissue disorders,
sepsis, severe postpartum hemorrhage, and congenital heart
disease. Risk factors for the subtypes of stroke were generally
 Liu et al   Risk of Stroke in Pregnancy   17

Table 4.  Crude and Adjusted Odds Ratios Showing Associations Between Maternal Characteristics and Conditions and Hemorrhagic and
Ischemic Subtypes of Stroke During Pregnancy, Childbirth and the Postpartum Period, Canada (Excluding Quebec), 2003 to 2016

Hemorrhagic Stroke (n=250) Ischemic Stroke (n=132)

Crude Odds Ratio Adjusted Odds Ratio Crude Odds Ratio Adjusted Odds Ratio
Characteristic/Condition (95% CI) (95% CI)* (95% CI) (95% CI)*
Maternal age, y <20 1.5 (0.8–2.8) 1.3 (0.7–2.5) 1.5 (0.7–3.3) 1.7 (0.8–3.7)
 20–29 1.0 (reference) 1.0 (reference) 1.0 (reference) 1.0 (reference)
 30–34 1.2 (0.9–1.6) 1.2 (0.9–1.7) 1.1 (0.7–1.6) 1.0 (0.6–1.5)
 35–39 2.0 (1.4–2.7) 2.0 (1.4–2.8) 1.6 (0.9–2.5) 1.3 (0.8–2.0)
 ≥40 2.8 (1.7–4.6) 2.6 (1.5–4.3) 1.5 (0.7–3.6) 1.1 (0.5–2.6)
Parity 0 1.3 (0.8–1.9) 1.1 (0.7–1.7) 0.7 (0.3–1.5) 0.6 (0.3–1.3)
 1 1.0 (reference) 1.0 (reference) 1.0 (reference) 1.0 (reference)
 2 0.6 (0.3–1.1) 0.5 (0.3–1.0) 2.0 (1.0–4.2) 2.0 (1.0–4.2)
 ≥ 3 0.9 (0.3–2.9) 0.7 (0.2–2.3) 4.6 (1.8–12.0) 4.2 (1.6–11.0)
 Unknown 5.0 (3.5–7.2) 4.6 (3.2–6.7) 7.6 (4.3–13.4) 7.0 (3.9–12.3)
Multifetal gestation 1.4 (0.6–3.4) 0.7 (0.3–1.7) 6.1 (3.3–11.4) 3.7 (1.9–7.1)
Chronic hypertension 2.7 (1.1–7.2) 1.9 (0.7–5.2) 5.2 (1.9–14.0) 2.8 (0.9–7.9)
Gestational hypertension† 1.7 (1.1–2.8) 1.7 (1.1–2.9) 1.1 (0.5–2.5) 1.1 (0.5–2.5)
Preeclampsia 14.0 (10.0–19.6) 9.2 (6.4–13.2) 9.4 (5.5–16.1) 5.1 (2.8–9.1)
Eclampsia 128.8 (80.5–205.9) 74.8 (45.1–124.0) 61.3 (25.1–149.9) 38.0 (14.8–97.3)
Preexisting diabetes mellitus 0.6 (0.1–4.1) 0.3 (0.1–2.4) 1.1 (0.2–7.8) 0.7 (0.1–4.7)
Connective tissue disorders 9.8 (2.4–39.3) 5.0 (1.2–20.4) 37.8 (14.0–102.4) 21.2 (7.3–61.5)
Sepsis 11.6 (3.7–36.1) 4.6 (1.4–15.2) 37.5 (15.3–91.6) 15.3 (5.9–40.0)
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HIV infection ... ... 14.9 (2.1–107.1) 11.8 (1.6–85.7)

 PPH and blood transfusion 8.8 (4.7–16.5) 5.4 (2.7–10.7) 11.8 (5.5–25.3) 5.2 (2.2–12.2)
Migraine ... ... 24.3 (3.4–174.1) 10.1 (1.3–77.3)
 Congenital heart disease 26.0 (10.7–63.0) 25.4 (10.4–62.2) 50.1 (20.5–122.6) 43.2 (17.1–109.3)
 Gestational diabetes mellitus 1.8 (1.2–2.7) 1.2 (0.8–1.9) 1.5 (0.8–2.9) 1.1 (0.6–2.0)
 Anemia 2.7 (1.6–4.6) 1.1 (0.6–1.9) 5.4 (3.1–9.3) 1.8 (0.9–3.4)
 Obesity 1.4 (0.5–3.4) 1.0 (0.4–2.9) 2.4 (0.9–6.5) 2.1 (0.8–5.9)
ICD-10 indicates International Classification of Diseases and Related Health Problems; and PPH, postpartum hemorrhage.
*All variables listed in the first column are included in the adjusted modeling.
†Defined using ICD-10 code O13 which included mild preeclampsia.

similar to those for occlusion, stenosis of precerebral or cere-
bral arteries, and TIAs, vascular syndromes or other cerebro-
vascular diseases not resulting in stroke. Exceptions included
preexisting diabetes mellitus, which was not a risk factor for
stroke in pregnancy but was strongly associated with occlu-
sion, stenosis of precerebral and cerebral arteries, TIAs, and
vascular syndromes not resulting in stroke.
Rates of stroke observed in our study differed from
those reported elsewhere. The rate of stroke reported in the
United States was considerably higher (22 per 100 000 dur-
ing antepartum hospitalizations, 27 per 100  000 during
childbirth hospitalizations, and 22 per 100 000 during post-
partum hospitalizations in 2006–2007) than the 13.4 per
100 000 deliveries observed in our study for the entire preg-
nancy and postpartum period. The higher rate reported in
the United States may be explained by differences in cod-
ing systems used (International Classification of Diseases,
Ninth Revision, Clinical Modification [ICD-9-CM] in the
US versus International Statistical Classification of Diseases
and Related Health Problems, Tenth Revision, Canadian ver-
sion in this study) and differences in the conditions included
in the stroke definition (eg, TIAs were included in the US
study). Population differences in maternal age distributions
and race (the United States has a much larger proportion of
black women, who are at high risk for stroke) may also have
contributed to the reported differences.25 A different US study
also reported a pregnancy-related stroke incidence of 34.2 per
100 000 deliveries but acknowledged that the incidence may
have been overestimated.26
The higher risk of stroke we observed in the postpartum
period8 and the temporal age-adjusted increase in incidence
have both been reported previously.10,25 Previous studies have
attributed the temporal increase to a rise in prevalence of hyper-
tensive disorders and heart disease in pregnancy.8,14,26 A recent
 18  Stroke  January 2019

Table 5.  Crude and Adjusted Odds Ratios Showing Associations Between Maternal Characteristics and Conditions and
Cerebrovascular Disease Subtypes During Pregnancy, Childbirth and the Postpartum Period, Canada (Excluding Quebec), 2003 to 2016

Occlusion, Stenosis of Precerebral and

Cerebral Arteries, TIAs and Vascular Other Cerebrovascular Diseases Not Resulting
Syndromes (n=129) in Stroke (n=238)
Characteristic/Condition Crude OR Adjusted OR* Crude OR Adjusted OR*
Maternal age, y <20 0.5 (0.3–0.9) 0.5 (0.3–1.01) 1.2 (0.6–2.3) 1.0 (0.5–1.9)
 20–29 1.0 (reference) 1.0 (reference) 1.0 (reference) 1.0 (reference)
 30–34 0.7 (0.5–1.2) 0.7 (0.5–1.2) 1.1 (0.8–1.5) 1.2 (0.9–1.6)
 35–39 1.2 (0.7–1.9) 1.1 (0.7–1.8) 1.2 (0.8–1.8) 1.3 (0.9–1.9)
 ≥ 40 2.1 (1.0–4.1) 1.8 (0.8–3.6) 2.7 (1.7–4.4) 2.5 (1.5–4.1)
 Parity 0 1.0 (0.6–1.6) 0.9 (0.6–1.6) 1.8 (1.2–2.5) 1.5 (1.1–2.2)
 1 1.0 (reference) 1.0 (reference) 1.0 (reference) 1.0 (reference)
 2 1.4 (0.8–2.5) 1.3 (0.8–2.3) 0.8 (0.5–1.4) 0.8 (0.5–1.3)
 ≥ 3 1.5 (0.5–4.4) 1.3 (0.4–3.7) 1.8 (0.8–3.9) 1.4 (0.6–3.1)
 Unknown 1.9 (1.2–3.0) 1.8 (1.1–3.0) 2.1 (1.5–3.1) 2.0 (1.4–2.9)
Multifetal gestation 0.5 (0.1–3.8) 0.3 (0.1–2.4) 2.3 (1.2–4.8) 1.4 (0.7–3.0)
Chronic hypertension 6.7 (2.7–16.3) 3.4 (1.3–8.7) 7.3 (3.9–13.7) 4.2 (2.2–8.3)
Gestational hypertension† 2.6 (1.5–4.6) 2.5 (1.4–4.4) 2.5 (1.6–3.8) 2.2 (1.4–3.4)
Preeclampsia 2.3 (0.9–6.3) 1.8 (0.6–4.8) 7.4 (4.8–11.6) 4.1 (2.6–6.5)
Eclampsia 24.5 (6.1–99.0) 19.1 (4.6–79.8) 159.7 (102.8–248.1) 103.8 (65.1–165.5)
Preexisting diabetes mellitus 8.2 (3.8–17.6) 5.5 (2.5–12.3) 3.7 (1.6–8.3) 1.8 (0.8–4.2)
Connective tissue disorders 9.5 (1.3–67.6) 3.2 (0.4–25.3) 20.7 (7.7–55.6) 9.7 (3.4–27.4)
Sepsis 15.0 (3.7–60.5) 10.0 (2.4–41.6) 4.0 (0.6–28.6) 1.8 (0.2–13.0)
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PPH and blood transfusion 5.0 (1.6–15.8) 2.8 (0.8–9.5) 5.5 (2.4–12.3) 2.4 (0.9–5.7)
Migraine 102.2 (37.7–277.0) 55.4 (19.3–158.8) 13.4 (1.9–95.9) 6.6 (0.9–48.3)
Congenital heart disease 107.2 (56.2–204.5) 94.6 (48.6–184.0) 32.9 (14.6–74.1) 25.7 (11.2–58.9)
Gestational diabetes mellitus 0.8 (0.4–1.9) 0.6 (0.3–1.5) 1.3 (0.8–2.1) 1.0 (0.6–1.6)
Anemia 3.0 (1.5–6.1) 1.8 (0.8–3.9) 3.5 (2.1–5.7) 1.9 (1.1–3.3)
Obesity 1.2 (0.3–4.9) 0.7 (0.2–2.9) 4.1 (2.3–7.3) 2.8 (1.5–5.0)
ICD-10 indicates International Classification of Diseases and Related Health Problems; and PPH, postpartum hemorrhage.
*All variables listed in the first column are included in the adjusted modeling. OR denotes odds ratio and TIA denotes transient
ischemic attacks.
†Defined using ICD-10 code O13 which includes mild preeclampsia.

study reported an increased risk of stroke during pregnancy
among younger women (compared with their nonpregnant
contemporaries) but not among older pregnant women.14,26,27
However, some of the temporal increase in stroke may be the
product of improved ascertainment. Thus, the very high OR
associated with eclampsia (versus the high OR associated
with preeclampsia) may be partly attributable to the imaging
and other testing routinely used for women with eclampsia in
recent years.28
In addition to hypertensive and connective tissue disor-
ders,7,29,30 congenital heart disease has been reported as a
significant risk factor for pregnancy-related stroke.25,31 With
advances in cardiac surgery and improved survival among
affected children over the past few decades, a growing pop-
ulation of women with congenital heart disease is choos-
ing to experience pregnancy. In this study, we examined
congenital heart disease as a single entity and observed
a 40-fold higher risk of pregnancy-associated stroke
among such women. Whether this association results from
decreased cardiac output from inadequate hemodynamic
adaption to pregnancy, intracardiac shunts, or thrombi for-
mation, requires further study.31,32 Women with congenital
heart diseases are also at increased risk of a number of ad-
verse pregnancy outcomes,31,33 including maternal placental
syndrome.34
We also observed a higher risk of both hemorrhagic and
ischemic stroke associated with postpartum hemorrhage
requiring blood transfusion. We speculate that massive trans-
fusion for postpartum hemorrhage, which has been linked to
a higher rate of maternal morbidity,35 may also be responsible
for increasing stroke risk. Use of assisted reproductive tech-
nologies for conception was not associated with an increased
risk of stroke after adjusting for other potential confounding
factors, such as age and hypertensive disorders.

Limitations of our study include use of a large perinatal
database that likely included transcription and other errors.18,19
However, data in the DAD have been validated in several stud-
ies,19–21 and the information is considered accurate, especially
for highly morbid conditions, such as stroke and eclampsia.
Stroke events in the antepartum and postpartum periods were
identified after linking childbirth and other hospitalizations
using scrambled health insurance numbers, which could have
introduced some errors. Additionally, information on some
important confounders, such as maternal smoking, body mass
index, ethnicity, and socio-economic status, was not available
in the database used for our analysis. Finally, the data source
did not include home deliveries, although the latter constitute
a small fraction of deliveries in Canada (≈2%).18
Our study details the changing epidemiology of stroke
and cerebrovascular disease in pregnancy in Canada. Age-
adjusted incidence has increased over the past 14 years, and
the case fatality from stroke and cerebrovascular disease re-
mains high, even relative to other subtypes of severe mor-
bidity.9,10,36 Risk factors for stroke and cerebrovascular disease
include older maternal age, hypertensive disorders, connec-
tive tissue disorders, severe postpartum hemorrhage, HIV in-
fection, sepsis, thrombophilia, and congenital heart disease.
The higher risk of stroke in the postpartum period and strong
association between hypertensive disorders of pregnancy (es-
pecially preeclampsia) and stroke suggest that follow-up of
severe hypertensive patients is required after delivery. The
high case fatality rate associated with the development of
stroke and cerebrovascular disease in pregnancy emphasizes
Downloaded from http://ahajournals.org by on July 23, 2019
the need for clinical vigilance, prompt diagnosis, and manage-
ment of the factors leading to the development of this maternal
complication.
Appendix
Canadian Perinatal Surveillance System External Advisory
Committee Members: Laura Arbour (University of British Columbia,
Vancouver), Nathalie Auger (University of Montreal, Montreal),
Liz Darling (Midwifery Group of Ottawa, Ottawa), Jane Evans
(University of Manitoba, Winnipeg), K.S. Joseph (University of
British Columbia, Vancouver), Julian Little (University of Ottawa,
Ottawa), Michael S. Kramer (McGill University, Montreal), Lily Lee
(Perinatal Services BC, Vancouver), Sarah McDonald (McMaster
University, Hamilton), Aideen Moore (The Hospital for Sick Children,
Toronto), Phil Murphy (Perinatal Program of Newfoundland and
Labrador, St. John’s), Joel G. Ray (St. Michael’s Hospital, Toronto),
Reginald Sauve (University of Calgary), Heather Scott (Dalhousie
University, Halifax), Prakesh Shah (University of Toronto, Toronto),
Mike Van den Hof (Dalhousie University, Halifax).
Acknowledgments
We thank the Canadian Institute for Health Information for providing
access to the Discharge Abstract Database (DAD). We thank Susie
Dzakpasu, Emily Hollink, Wei Luo, Howard Morrison, Anne-Marie
Ugnat (all with the Public Health Agency of Canada) for their review
of the previous version of article.
Sources of Funding
This study was performed by the Public Health Agency of Canada.
Disclosures
None.
Liu et al   Risk of Stroke in Pregnancy   19
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