Increased Stroke Risk For Younger Pregnant Women
Younger pregnant women, including the postpartum period up to six weeks after delivery, appeared to be at increased risk of stroke compared with their nonpregnant counterparts, and that increased stroke risk was not associated with older pregnant women, according to a new article published online by JAMA Neurology.
Eliza C. Miller, M.D., of Columbia University, New York, and coauthors used data on all stroke admissions in the state of New York from 2003 to 2012 to determine age-specific incidence risk ratios for pregnancy-associated stroke (PAS) compared with nonpregnancy-associated stroke (NPAS).
There were 19,146 women hospitalized with stroke during the study period and 797 (4.2 percent) of the women were pregnant or postpartum.
The authors report the incidence of PAS in women 12 to 24 years old was 14 events per 100,000 pregnant/postpartum women compared with a NPAS incidence of 6.4 per 100,000 nonpregnant women. In women 25 to 34, the PAS incidence was 21.2 per 100,000 pregnant women and NPAS incidence was 13.5 per 100,000 nonpregnant women.
In older women 35 to 44, PAS incidence was 33 per 100,000 pregnant women and NPAS incidence was 31 per 100,000 nonpregnant women. In women 45 to 55, PAS incidence was 46.9 per 100,000 pregnant women compared with NPAS incidence of 73.7 per 100,000 nonpregnant women.
Although older pregnant women had higher rates of stroke in pregnancy than younger pregnant women, their risk of stroke was similar to women of their own age who were not pregnant. But in women under 35, pregnancy increased the risk of stroke, more than doubling it in the youngest group, the authors report.
Although
older pregnant women had higher rates of stroke in pregnancy than
younger pregnant women, their risk of stroke was similar to women of
their own age who were not pregnant. But in women under 35, pregnancy
increased the risk of stroke, more than doubling it in the youngest
group, the authors report. NeuroscienceNews.com image is for
illustrative purposes only.
Women with PAS were less likely than women with NPAS to have vascular risk factors, diabetes and active smoking. Death was also lower among women with PAS compared with NPAS. The authors note different underlying stroke mechanisms may factor into why younger women had higher stroke risk during pregnancy.
Study limitations include billing data that lack specificity, especially in regard to PAS.
“In our sample of all women aged 12 to 55 years hospitalized with stroke in New York State from 2003 to 2012, younger pregnant and postpartum women – but not older women – were at increased risk of stroke compared with their nonpregnant contemporaries. These results have potential implications for research aimed at better characterizing and preventing PAS and clinically in terms of counseling patients. Although older women have an increased risk of many pregnancy complications, a higher risk of stroke may not be one of them. Our results should be interpreted with caution and regarded primarily as hypothesis generating; more research is needed to investigate why younger women may have an increased risk of PAS,” the study concludes.
About this neurology research article
Source: Karin Eskenazi – JAMA Image Source: NeuroscienceNews.com image is in the public domain.
Original Research: Full open access research for “Risk of Pregnancy-Associated Stroke Across Age Groups in New York State” by Eliza C. Miller, MD; Hajere J. Gatollari, MPH; Gloria Too, MD; Amelia K. Boehme, PhD, MSPH; Lisa Leffert, MD; Mitchell S. V. Elkind, MD, MS; and Joshua Z. Willey, MD, MS in JAMA Neurology. Published online October 24 2016 doi:10.1001/jamaneurol.2016.3774
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Abstract
Risk of Pregnancy-Associated Stroke Across Age Groups in New York State
Importance Older age is associated with increased risk of pregnancy-associated stroke (PAS). Data are limited on age-specific incidence ratios of PAS compared with stroke risk in nonpregnant women.
Objectives To assess the risk of stroke by age group in pregnant and postpartum women compared with their nonpregnant contemporaries and to compare risk factors across age groups in the exposed (pregnant/postpartum) and unexposed (nonpregnant) populations.
Design, Setting, and Participants International Classification of Diseases, Ninth Revision, billing codes from the calendar year 2003-2012 New York State Department of Health inpatient database and population data were used to identify all women aged 12 to 55 years with cerebrovascular events, including transient ischemic attack, ischemic and hemorrhagic stroke, cerebral venous thrombosis, and nonspecified PAS. The cumulative incidence of PAS per 100 000 pregnant/postpartum women vs nonpregnancy-associated stroke (NPAS) per 100 000 women in age cohorts of 24 years or younger, 25 to 34, 35 to 44, and 45 years or older was calculated. Risk factors between groups were compared using logistic regression models. The study included data from calendar years 2003 through 2012. Data analysis was performed from July 11, 2015, to July 16, 2016.
Exposures Pregnancy, including the postpartum period up to 6 weeks after delivery.
Main Outcomes and Measures Incidence risk ratios (IRRs) for stroke per age cohort, defined as cumulative risk of stroke in the exposed population divided by cumulative risk of stroke in the unexposed population, were determined, and stroke risk factors and mortality were compared between populations.
Results There were 19 146 women hospitalized with stroke during the study period; 797 of the women were pregnant/post partum. The overall median (interquartile range) age of the women was 31 (25-35) years in those with PAS and 48 (41-52) years in those with NPAS. The incidence of PAS in women aged 12 to 24 years was 14 events per 100 000 pregnant/postpartum women vs NPAS incidence of 6.4 per 100 000 nonpregnant women (IRR, 2.2; 95% CI, 1.9-2.6); for ages 25 to 34 years, 21.2 per 100 000 vs 13.5 per 100 000 (IRR, 1.6; 95% CI, 1.4-1.7); for ages 35 to 44 years, 33 per 100 000 vs 31 per 100 000 (IRR, 1.1; 95% CI, 0.9-1.2); and for ages 45 to 55 years, 46.9 per 100 000 vs 73.7 per 100 000 (IRR, 0.6; 95% CI, 0.3-1.4). PAS accounted for 18% of strokes in women younger than 35 years vs 1.4% of strokes in women aged 35 to 55 years. Women in the NPAS group vs the PAS group had more vascular risk factors, including chronic hypertension (age <35 years: 437 [15.7%] vs 60 [9.8%], P < .001; age 35-55 years: 7573 [48.6%] vs 36 [19.3%], P < .001), diabetes (age <35 years: 103 [3.7%] vs 9 [1.5%], P = .002; age 35-55 years: 2618 [16.8%] vs 12 [6.4%], P < .001), and active smoking (age <35 years: 315 [11.3%] vs 29 [4.8%], P < .001; age 35-55 years: 2789 [17.9%] vs 10 [5.3%], P < .001); and had higher mortality (age <35 years: 288 [11.3%] vs 37 [6.5%], P < .001; age 35-55 years: 2121 [13.4%] vs 14 [6.1%], P < .001).
Conclusions and Relevance Younger women, but not older women, have an increased stroke risk during pregnancy and post partum compared with their nonpregnant contemporaries. These results suggest that pregnancy does not increase the risk of stroke in older women.
“Risk of Pregnancy-Associated Stroke Across Age Groups in New York State” by Eliza C. Miller, MD; Hajere J. Gatollari, MPH; Gloria Too, MD; Amelia K. Boehme, PhD, MSPH; Lisa Leffert, MD; Mitchell S. V. Elkind, MD, MS; and Joshua Z. Willey, MD, MS in JAMA Neurology. Published online October 24 2016
Researchers find younger women are more than twice as likely to experience stroke during or just after pregnancy than their non-pregnant counterparts.
Lead study author Dr. Eliza C. Miller, of the Department of Neurology at Columbia University Medical Center (CUMC) in New York, and team published their findings in JAMA Neurology.
Each year, around 795,000 people in the United States are affected by stroke, and it is the cause of more than 130,000 deaths.
It is well known that pregnancy can raise stroke risk; gestational diabetes, high blood pressure, and increased bleeding after birth are all factors that can make expectant mothers more susceptible to stroke.
According to Dr. Miller and colleagues, stroke affects around 34 in every 100,000 pregnancies in the United States, and this number is on the increase.
"The incidence of pregnancy-associated strokes is rising, and that could be explained by the fact that more women are delaying childbearing until they are older, when the overall risk of stroke is higher," notes senior study author Dr. Joshua Z. Willey, assistant professor of neurology at CUMC.
"However," he adds. "very few studies have compared the incidence of stroke in pregnant and non-pregnant women who are the same age."
Assessing stroke risk by age at pregnancy
For their study, Dr. Miller and team set out to determine the risk of stroke during pregnancy by age.Using data from the New York State Department of Health Statewide Planning and Research Cooperative System (SPARCS) inpatient database, the researchers were able to pinpoint 19,146 women in New York State aged 12-55 years who had been hospitalized for stroke between 2003-2012.
Of these women, 797 (4.2 percent) were pregnant or had given birth in the last 6 weeks.
The researchers looked at the incidence of stroke for both pregnant and non-pregnant women across four age groups: 12-24 years, 25-34 years, 35-44 years, and 45-55 years.
Overall, the team found that stroke incidence increased with age; there were 14 stroke events per 100,000 pregnant or postpartum women aged 12-24, while the stroke events for pregnant or postpartum women aged 45-55 were 46.9 per 100,000.
Stroke risk doubled for younger expectant mothers
However, when it came to assessing stroke risk relative to non-pregnant women, the team found younger women fared worse.For women aged 12-24, the researchers identified 14 stroke events per 100,000 pregnant or postpartum women, compared with 6.4 per 100,000 for women aged 12-24 who were not pregnant - representing a more than twofold greater risk of stroke for expectant or new mothers.
Among women aged 25-34, pregnant or postpartum women were 1.6 times more likely to have a stroke event than non-pregnant women of the same age, the team reports.
However, among women aged 35-44, stroke incidence among pregnant or postpartum women was comparable to that of non-pregnant women, at 33 per 100,000 and 31 per 100,000, respectively.
Among women aged 45-55, stroke incidence was higher for non-pregnant women, at 73.7 per 100,000, compared with 46.9 per 100,000 for pregnant or postpartum women.
Based on their findings, Dr. Miller and team say it is perhaps time to increase focus on identifying and reducing stroke risk among younger pregnant women.
"We have been warning older women that pregnancy may increase their risk of stroke, but this study shows that their stroke risk appears similar to women of the same age who are not pregnant.The researchers stress that their results should be "interpreted with caution regarded and primarily as hypothesis generating."
But in women under 35, pregnancy significantly increased the risk of stroke. In fact, 1 in 5 strokes in women from that age group were related to pregnancy. We need more research to better understand the causes of pregnancy-associated stroke, so that we can identify young women at the highest risk and prevent these devastating events."
Dr. Eliza C. Miller
Still, the team concludes that while older expectant mothers are at greater risk of numerous pregnancy complications, "a higher risk of stroke may not be one of them."
Learn how a woman's pre-pregnancy body mass index (BMI) might influence offspring's lifespan.
Stroke,
the sudden onset of brain dysfunction from a vascular cause, is one of
the most common causes of long-term disability. Although rare during
childbearing years, stroke is even more devastating when it occurs in a
young woman trying to start a family. Pregnancy and the postpartum
period are associated with an increased risk of ischemic stroke and
intracerebral hemorrhage, although the incidence estimates have varied.
There are several causes of stroke that are in fact unique to pregnancy
and the postpartum period, such as preeclampsia and eclampsia, amniotic
fluid embolus, postpartum angiopathy and postpartum cardiomyopathy. Data
regarding these individual entities are scant. Most concerning is the
lack of data regarding both prevention and acute management of
pregnancy-related stroke. The purpose of this article is to summarize
existing data regarding incidence, risk factors and potential
etiologies, as well as treatment strategies for stroke in pregnancy.
Keywords: hemorrhage, pregnancy, stroke, women
Go to:
Epidemiology of stroke in pregnancy
Pregnancy
and the postpartum period are associated with an increased risk of
stroke and cerebral hemorrhage. However, among the small number of
investigations on this topic, estimates of both incidence and risk of
stroke in pregnancy have varied greatly. The data from these studies are
summarized in Table 1.
There have been several population-based studies that have used
variable inclusion criteria. One study using data from 46 hospitals in
the Baltimore–Washington DC (USA) area concluded that the risk of
ischemic stroke and intracerebral hemorrhage (ICH) were increased in the
postpartum period, but not during pregnancy, with a relative risk of
ischemic stroke of 8.7 and 28.3 for ICH [1].
They also found an attributable or excess risk of 8.1 strokes per
100,000 pregnancies. Two subsequent studies utilized data from the
National Hospital Discharge Survey, with the first limiting
cerebrovascular events to the hospitalization of delivery [2], and the second inclusive of antepartum and postpartum events [3].
The study focused on hospitalization found an incidence of 10.3 strokes
(including ICH) and 8.9 cerebral venous thromboses (CVT) per 100,000
deliveries [2].
However, when antepartum and postpartum data were included, the
incidence was 17.7 per 100,000 for strokes and 11.4 per 100,000 for CVT [3].
A third study by the same authors utilized the Nationwide Inpatient
Sample from the years 1993 to 1994 and again restricted events to the
hospitalization of delivery, with an incidence of 13.1 strokes and 11.6
CVT per 100,000 deliveries [4].
All three of these studies were somewhat limited by the use of the
nonspecific ninth edition of the International Classification of
Diseases (ICD-9) code 674.0 for ‘cerebrovascular disorders in the
puerperium’, which includes subarachnoid hemorrhage, ICH and acute but
ill-defined cerebrovascular diseases, as well as occlusions of the
cerebral arteries that may or may not be associated with stroke. Another
study using more recent data from the Nationwide Inpatient Sample from
2000 to 2001 found an overall incidence of 34.2 strokes per 100,000
deliveries, which included both ischemic and hemorrhagic events [5].
Compared with an incidence of 10.7 strokes per 100,000 woman-years
among nonpregnant women of comparable age, this showed a threefold
increase in pregnancy [6].
Finally, a third US study analyzed data from the Nationwide Inpatient
Sample focused specifically on ICH, and found an incidence of 6.1 per
100,000 deliveries or 7.1 per 100,000 at-risk person-years [7].
For all age groups of pregnant women, the rate of hemorrhage was higher
in the postpartum period than antepartum period or the control group.
This corroborated findings from other studies that found the risk of ICH
to be highest in the postpartum period [1,8].
However, it is important to highlight that different etiologies of
hemorrhagic stroke vary in terms of onset. For example, in one study,
92% of hemorrhages due to rupture of a cerebrovascular malformation
occurred antepartum [9].
Table 1
Summary of the published incidence, mortality and morbidity of pregnancy-related stroke.
Several
studies from outside the USA have also utilized population-based or
hospital-based samples to investigate the incidence of pregnancy-related
stroke. In the Ile de France region, the incidence was 4.3 ischemic
strokes and 4.6 ICHs (excluding subarachnoid hemorrhage) per 100,000
deliveries [8].
This study was somewhat limited by the definition of stroke as ‘rapidly
developing clinical symptoms and/or signs of focal, and at times
global, loss of cerebral function with symptoms lasting more than 24 h’,
which included stroke-like deficits from eclampsia. Some of these
events may have been related to a reversible cerebral vasoconstriction
syndrome and not necessarily an ischemic infarct, leading to an
overestimate of stroke incidence [10].
A single-center Canadian study found an incidence of 18 strokes and
eight cerebral hemorrhages per 100,000 deliveries, with most ischemic
strokes occurring in the postpartum period [11]. Studies in Asian populations suggest that ICH may be more common compared with Western populations. Liang et al.
found an incidence of 13.5 strokes and 25.4 hemorrhages per 100,000
deliveries in a Taiwanese hospital, and also summarized data from a
total of nine recent studies, which yielded an average incidence of 21.3
strokes per 100,000 deliveries [12].
Cerebral
venous thrombosis represents approximately only 2% of all
pregnancy-related strokes. The incidence is similar to ischemic stroke,
at approximately 12 per 100,000 deliveries [13].
The highest risk period for CVT is third trimester and postpartum,
similar to the time frame for risk of venous thromboembolic events [13].
The data from the Baltimore–Washington DC population-based study [1] and the Canadian study [11]
both suggested that the highest risk period for stroke is postpartum.
However, a detailed study of the timing of several different circulatory
diseases (including ischemic stroke, hemorrhagic stroke and
subarachnoid hemorrhage) associated with pregnancy showed that the
majority of events occur at the delivery period, and the frequency of
events decrease in the postpartum period [14].
This was also shown in a smaller case series, where the frequency of
stroke decreased substantially 7 days or more after delivery [15]. These differences may be based on the cutoff at delivery (Ros et al. included the 2 days after delivery in the delivery category [14]). Based on the available evidence, the highest risk periods appear to be the delivery period and up to 2 weeks postpartum.
Only
a few of the studies previously cited reported mortality associated
with pregnancy-related strokes. The three investigations by Lanska and
Kryscio found no fatalities attributed to CVT, but stroke fatality rates
of 2.2, 2, 3.3, 3 and 14.7 per 100,000 deliveries [4]
in chronological order of analysis in the Nationwide Inpatient Sample
database. The death rate from CVT is thought to be lower in pregnant
than in nonpregnant women of comparable age [16].
The most recent Nationwide Inpatient Sample analysis reported a 4.1%
case fatality rate associated with pregnancy-related stroke, and a
mortality rate of 1.4 per 100,000 deliveries [5].
This was low compared with the average case fatality rate for stroke at
any age (24%), and even compared with the range of case fatality rates
for stroke in young adults (4.5–24%) [5].
The authors speculated that this could be due to missed deaths
occurring weeks or months after discharge from the hospital, or better
access to treatment if the patient is already hospitalized around the
time of delivery. Liang et al. summarized mortality data from
nine recent studies and found an average mortality rate of 13.8% for ICH
and 3.9% for ischemic stroke [12].
Of
all stroke types, pregnancy-related ICH leads to the highest risk of
mortality. In the Nationwide Inpatient Sample, the in-hospital mortality
rate for pregnancy-related ICH was 20.3%, although this was lower than
previously reported mortality rates ranging from 25 to 40% [7]. However, ICH accounted for 7.1% of all pregnancy-related mortality in the Nationwide Inpatient Sample database [7]. This is comparable to previous studies suggesting that ICH is r esponsible for 5–12% of all maternal deaths [9].
Even
fewer studies have examined poststroke morbidity in young women with
pregnancy-related stroke. In the Ile de France population, 33% of women
with ischemic stroke had mild-to-moderate residual deficits based on a
modified Rankin score of 1–2 (minimal residual stroke disability for
both scores), while one woman developed epilepsy. Conversely, 50% of
women with ICH had mild-to-moderate deficits with Rankin scores of 1–3
(moderate disability and mobility impairment) [8]. The percentage of women discharged to facilities other than home ranged from 9 to 22% [4,5]. Another French study followed young women after a first stroke to determine the impact on subsequent pregnancies [17].
In total, 34% of the women followed in this study stated that they
would have desired more pregnancies, and the most popular reasons for
avoiding pregnancy were fear of recurrent stroke, medical advice against
pregnancy and residual handicap from their initial stroke [17].
However, of these 441 women, there were 13 recurrent strokes. Only two
of these strokes occurred in pregnancy, both in the setting of known
underlying causes (antiphospholipid syndrome and thrombocythemia) [17].
In addition, of the 37 women whose initial stroke occurred during
pregnancy, there were no recurrent strokes in a total of 24 subsequent
pregnancies [17].
This suggests that a history of stroke should not be an automatic
contraindication for subsequent pregnancy, but instead women should
receive counseling regarding their specific underlying risk factors.
There is also a need for additional research focused on
pregnancy-related stroke outcomes.
Go to:
Risk factors for pregnancy-related stroke & CVT
Young
pregnant women may have risk factors that are typically associated with
stroke in the general population, especially with the increasing
prevalence of obesity at younger ages. Some of these risk factors
associated with pregnancy-related stroke include hypertension, diabetes,
valvular heart disease, hypercoagulable disorders, sickle cell disease,
lupus, abuse of tobacco and other substances, and migraines [4,5].
Hypertension in pregnancy may be pre-existing, gestational, or
associated with preeclampsia or eclampsia. Compared with women without
hypertension, women with hypertension complicating pregnancy are six- to
nine-fold more likely to have stroke [3,5].
Complications of pregnancy, labor and delivery have also been
associated with increased risk of stroke, including hyperemesis
gravidarum, anemia, thrombocytopenia, postpartum hemorrhage,
transfusion, fluid, electrolyte and acid-base disorders, and infection [4,5]. Cesarean delivery has been associated with peripartum stroke, although a causal relationship has not been well established [2,4].
The association may reflect a higher likelihood for physicians to
recommend cesarean delivery in women who suffer strokes during
pregnancy. Historically, cesarean delivery has been advocated for women
with ICH, particularly recent subarachnoid hemorrhage, untreated
ruptured arteriovenous malformation (AVM) or unclipped ruptured
aneurysm, to avoid potential risks during labor and delivery [2]. However, studies suggest that outcomes of vaginal and cesarean delivery are probably equivalent after ICH [18,19].
On the other hand, cesarean delivery may actually be a risk factor for
postpartum stroke due to CVT. Normal physiologic changes during
pregnancy, including resistance to activated Protein C and a decrease in
functional Protein S, compounded by the transient hypercoagulability
associated with surgery, may lead to clot formation [4].
Finally, age greater than 35 years increased the odds of stroke
twofold, and African–American race-ethnicity increased the odds of
stroke by 1.5-fold [5]. Similar results were reported in an analysis of pregnancy-related ICH alone [7].
Potential
causes of stroke identified in the literature include those that can
occur in the young nonpregnant population, and those that are exclusive
to pregnancy. Diagnoses that are not specific to pregnancy include
venous sinus thrombosis, cardioembolism, CNS or systemic vasculitis.
Those that are more specific complications of pregnancy include
preeclampsia/eclampsia, amniotic fluid embolism and postpartum
angiopathy [1,8,11,12,20]. Postpartum cardiomyopathy can result in cardioembolism, or less commonly, watershed infarction from hypotension.
Although
CVT occurs due to thrombosis of the sinuses, cerebral veins or jugular
veins, and ischemic stroke occurs as a result of an arterial thrombosis
or hemodynamic cause, there is quite a bit of overlap in the risk
factors for both types of strokes during pregnancy. The primary causes
for both types of strokes are thought to be influenced by the
prothrombotic state of pregnancy itself, often in the setting of
dehydration or an underlying predisposition for thrombophilia [13]. The causes and risk factors for CVT and thrombophilias have been extensively reviewed and published recently [13].
The physiologic changes during pregnancy that may lead to arterial or
venous thrombo embolism include decreases in circulating antithrombotic
factors, venous stasis or sudden reduction in blood volume after
delivery [18]. Identifiable etiologies of stroke in the population-based studies previously cited are summarized in Table 2.
Table 2
Published causes of ischemic stroke during pregnancy.
Several
studies have found that preeclampsia/eclampsia and underlying
cerebrovascular malformations were the most common identifiable causes
of pregnancy-related ICH (Table 3) [1,7,8,11,12,20].
Preeclampsia/eclampsia is a cause of reversible posterior
leukoencephalopathy syndrome, which can be associated with reversible
vasogenic edema, typically in the posterior portion of the brain, as
well as ICH, presumably due to the abnormalities in autoregulation [21].
In addition, preeclampsia/eclampsia has been associated with the
spectrum of reversible cerebral vasoconstriction syndromes, which is a
clinical syndrome consisting of thunderclap headache with or without
focal neurologic deficits, and reversible arterial segmental
vasoconstriction [10].
These two reversible syndromes are most likely under-recognized and
under-diagnosed because the primary manifestation may be headache plus
visual scotomata, representing severe preeclampsia, and the most
important priority is delivery of the infant, rather than diagnostic
imaging [22].
Table 3
Published causes of pregnancy-related intracerebral hemorrhage.
There
are several factors that may increase the risk of AVM or aneurysmal
rupture during pregnancy, such as increased blood volume and cardiac
output, and structural changes in the vascular wall [18]. However, whether pregnancy truly increases risk of rupture is a topic of ongoing debate. Bateman et al.
found that the rate of hemorrhage attributable to cerebrovascular
malformations was similar in pregnant and nonpregnant women, at 0.50 and
0.33 per 100,00 person-years, respectively [7].
Additional etiologies in pregnancy include metastatic choriocarcinoma,
and abuse of other substances, including alcohol and methamphetamines [19,23].
Go to:
Diagnosis of pregnancy-related stroke & CVT
Diagnosis
of stroke in pregnancy may be hindered by fear of adverse fetal
outcomes from specific diagnostic tests. For example, physicians may be
hesitant to obtain an MRI because of the effects of the magnetic field
on the fetus, especially in the first trimester. However, the American
College of Radiology guidelines state that pregnant patients can undergo
MRI if warranted by the risk–benefit ratio, although administration of
gadolinium contrast should probably be avoided in most cases because it
does cross the placenta and its effects on the fetus have not been
studied [24].
In most cases, a complete stroke work-up, including brain CT scan
and/or MRI, transthoracic echocardiogram and vascular ultrasound, should
be completed in pregnant women. Echocardiography is a standard test in
stroke patients to evaluate for sources of cardiac emboli, but this may
be especially important in Asian populations. Two studies in Taiwan
identified cardioembolism as the most common etiology of
pregnancy-related stroke, possibly due to the persistent presence of
rheumatic heart disease in some Asian countries [12,20].
In
the past, prior to the advent of modern imaging techniques such as
magnetic resonance venogram, the majority of pregnancy-related strokes
were attributed to ‘cerebral thrombophlebitis’ [25]. Cross et al.
challenged this idea in 1968 by demonstrating with carotid angiography
that 70% of women with strokes (n = 31) were due to arterial occlusion [25].
Today, it is well documented that the majority of cerebral infarcts in
pregnancy are related to arterial causes. However, CVT is an important
diagnosis because it can lead to infarction or hemorrhage or both. The
diagnosis of CVT can still be challenging, despite modern imaging
capabilities, since it may present primarily as a severe headache with
other signs of increased intracranial pressure, such as vomiting or
papilledema, with or without subtle focal neurologic deficits due to
venous infarction [26].
The best imaging modality for diagnosis is most likely MRI, with
magnetic resonance venogram if possible, to evaluate for both thrombosis
and acute stroke. The risk factors for CVT are classically related to
dehydration, postpartum infection and thrombophilia, but also include
those that overlap those for arterial stroke, including hypertension,
older age and excessive vomiting [4,5].
One review of 67 cases of CVT suggested that morbidity and mortality is
reduced in pregnancy-related CVT compared with those that occur outside
pregnancy [16].
Postpartum
angiopathy is a unique condition associated with pregnancy, and it
falls within the spectrum of disorders known as reversible cerebral
vasoconstriction syndromes [10].
Although the pathophysiology may be similar, postpartum angiopathy is
not confined to patients with history of preeclampsia or eclampsia and
frequently occurs in patients who had uncomplicated pregnancies and
deliveries. Patients classically present within days of delivery with
thunderclap headache, vomiting, altered mental status and/or focal
neurologic deficits. Such deficits may be transient or may be a result
of ischemic stroke or cerebral hemorrhage [10].
Diagnosis is made with angiography, which demonstrates multifocal
segmental narrowing in the large and medium-sized cerebral arteries,
with a similar appearance to vasculitis. The cerebrospinal fluid is
typically normal. By definition, the process is generally self-limited,
with resolution of angiographic abnormalities within 4–6 weeks and
typically complete resolution of symptoms [10].
However, owing to its association with both infarction and hemorrhage,
postpartum angiopathy does carry a risk of morbidity and mortality. Some
studies have also suggested an association between postpartum
angiopathy and cervical arterial dissection [27,28].
Subarachnoid
hemorrhage should be considered in pregnant patients with sudden onset
of severe headache, particularly in the setting of neck stiffness,
altered mental status, nausea and vomiting, seizure, focal neurologic
signs and/or hypertension. It is important to note that these symptoms
may be mistaken for preeclampsia/eclampsia, especially when protein-uria
is present [19].
If subarachnoid hemorrhage is suspected, emergent uninfused CT scan
should be performed. If this test is carried out within 24 h, it will
detect subarachnoid blood in approximately 90–95% of cases, although the
sensitivity decreases with time [29].
If angiography is indicated, special modifications, such as shielding
of the fetus, fetal monitoring, and maternal hydration to avoid fetal
dehydration due to contrast, should be made [30].
Go to:
Stroke prevention during pregnancy
Very
minimal data exists on preventative treatment of stroke in pregnancy,
and there are no randomized controlled trials. Use of aspirin, in
particular, has been a source of debate because animal studies have
suggested an increased risk of congenital anomalies. In addition,
several human studies reported increased risks of specific malformations
including heart defects, neural tube defects, hypospadias, cleft
palate, gastroschisis and pyloric stenosis [31].
Other potential risks include maternal or fetal bleeding and premature
closure of the patent ductus arteriosus. A meta-analysis in 2002 showed
no overall increase in risk of congenital malformations associated with
aspirin, but determined that there may be an association between aspirin
use in the first trimester and gastroschisis [31].
However, a subsequent meta-analysis study in 2003 failed to find any
increased risk associated with aspirin, including placental abruption,
fetal intraventricular hemorrhage or congenital malformations [32].
Notably, a recent meta-analysis suggests that aspirin is beneficial in
preventing preeclampsia when started earlier than 16 weeks’ gestation,
but not when initiated after 16 weeks [33]. In that study, early treatment with aspirin also resulted in a decrease in gestational hypertension and preterm birth.
Owing
to the limited data and lack of randomized controlled studies, current
guidelines regarding the recommendations for aspirin in pregnant women
vary. According to the American Heart Association/American Stroke
Association guidelines, women at increased risk of stroke in whom
antiplatelet therapy would likely be considered outside of pregnancy,
may be considered for unfractionated heparin (UFH) or
low-molecular-weight heparin (LMWH) during the first trimester, followed
by low-dose aspirin [34].
The American College of Chest Physicians (ACCP) has published
guidelines for the management of thromboembolism and thrombophilia in
pregnancy, and although they do not specifically address stroke, they
recommend low-dose aspirin throughout pregnancy for women at high risk
of preeclampsia [35].
This may include women with preexisting hypertension, diabetes, renal
disease, obesity, of age greater than 35 years and prior preeclampsia.
According to the document [35]:
“If the indication for aspirin is clear and there is no satisfactory alternative agent, clinicians should offer first-trimester patients aspirin.”
There
are virtually no data available regarding use of other antiplatelet
agents, such as clopidogrel or aspirin-dipyridamole, in pregnancy. A
2008 survey polled US neurologists regarding which antithrombotic they
would choose for stroke prophylaxis during the first trimester in
pregnant women with and without history of previous stroke [36].
A total of 75% responded that they would use prophylaxis, most commonly
aspirin 81 mg, for women without a history of stroke. In total, 88%
chose prophylactic therapy, most commonly aspirin 81 mg followed by
LMWH, for women with previous stroke. However, this study was
significantly limited in that treatment choice is typically dependent on
the mechanism of stroke, and the physicians surveyed were not provided
with any background information on these hypothetical patients [36].
According
to American Heart Association/American Stroke Association stroke
secondary prevention guidelines, three options may be considered for
pregnant women with ischemic stroke and ‘high-risk thromboembolic
conditions such as hypercoagulable state or mechanical heart valves’:
UFH throughout pregnancy, LMWH throughout pregnancy or UFH/LMWH until
week 13, followed by warfarin until the middle of the third trimester,
then UFH/LMWH up to the time of delivery [34]. The ACCP has identical recommendations for high-risk women with mechanical valves [34,35].
Women with a history of venous thromboembolism plus a known
thrombophilia, particularly antithrombin-III deficiency,
antiphospholipid antibody syndrome, prothrombin gene mutation or Factor V
Leiden, may be treated with prophylactic-dose LMWH or UFH during
pregnancy followed by postpartum anticoagulation with warfarin [34,35].
For women with antiphospholipid antibody syndrome and no history of
venous thromboembolism, but recurrent pregnancy loss, prophylactic UFH
or LMWH plus aspirin throughout pregnancy is recommended [34,35]. Standard management of CVT and arterial dissection during pregnancy also includes anticoagulation [35].
LMWH is the most attractive option owing to more predictable dose
response and ease of use compared with UFH, as well as decreased risk of
osteoporosis and thrombocytopenia. Some authors have suggested a
transition to UFH just prior to delivery to decrease the risk of
epidural hematoma associated with regional anesthesia [37].
AHA/ASA stroke secondary prevention guidelines recommend
anticoagulation for at least 3 months in the setting of CVT, followed by
antiplatelet therapy [34].
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Treatment of acute pregnancy-related stroke
Treatment
of acute arterial stroke in pregnancy is also controversial.
Recombinant tissue plasminogen activator (rtPA) is a drug that lyses
clot when given intravenously or inta-arterially to patients with acute
ischemic stroke. Randomized clinical trial evidence demonstrated that if
rtPA is administered within 3 h of ischemic stroke onset in nonpregnant
patients, this drug decreases the risk of mortality and improves
outcome at 90 days poststroke compared with placebo [38].
However, there is an approximate 6% risk of hemorrhage, and this risk
increases with administration greater than 3 h after onset of the stroke
symptoms [38].
Thrombolytic drugs can be administered intra-arterially for proximal
middle cerebral artery occlusions effectively and relatively safely [39]. In addition, there are devices that have been approved for mechanical thrombectomy, such as the Merci device [40]. or the Penumbra device [41].
In some cases, intra-arterial rtPA can be combined with mechanical
thrombectomy. Patients tend to have optimal outcomes if whatever method
is used leads to partial or complete recanalization of the occluded
artery.
Recombinant tissue plasminogen activator does not
cross the placenta and there has been no evidence of teratogenicity in
animal studies [42].
It is listed as a category C drug and pregnancy is considered a
relative contraindication for administration, but there are multiple
case reports of successful use in pregnant women. In one instance, rtPA
was given intra-arterially in the third trimester, 5 h after onset of
left hemiplegia, with catheter angiogram demonstrating a right middle
cerebral artery trunk occlusion [43].
The infant was delivered without complication 3 days later, and at
2-month follow-up the mother had no residual neurologic deficits.
Several other case reports and case series have reported successful
outcomes after use of thrombolytics for mothers, and in most cases for
infants when mothers did not choose elective termination (Table 4) [44-47].
Risks and benefits should be carefully weighed, but it appears that
thrombolytics can be used both intravenously and intra-arterially in
pregnancy with positive outcomes.
Table 4
Summary of cases of recombinant tissue plasminogen activator for pregnant women with acute ischemic stroke.
There
are no clear guidelines for medical management of subarachnoid or ICH
in pregnancy. Drugs used on a routine basis in nonpregnant patients,
such as mannitol for elevated intracranial pressure, antiepileptics for
prevention or management of seizures, and nimodipine for vasospasm, must
be utilized with caution in pregnant women. Mannitol may result in
fetal hypoxia and acid-base shifts, antiepileptic drugs are associated
with varying degrees of teratogenic risk, and nimodipine has been linked
with teratogenicity in some animal experiments, but there is minimal
data in humans [19,29].
However, ultimately, the use of these agents in critically ill pregnant
patients may outweigh the potential risks. Obviously, careful
monitoring of hemodynamic parameters in both the mother and fetus are a
priority. Some authors advocate emergent cesarean delivery, if near
term, prior to attempting surgical management of vascular malformations [29].
However, studies have suggested that surgical management of ruptured
aneurysms during pregnancy is associated with significantly lower
maternal and fetal mortality [9].
This did not hold true for surgical excision of arteriovenous
malformations, despite a high risk of rebleeding (up to 30%) within the
same pregnancy [9,19].
Since AVMs are now frequently repaired endovascularly, benefits may
still outweigh the risks. Studies have suggested that route of delivery,
cesarean versus vaginal, does not affect outcome in patients with a v
ascular anomaly [18].
Stroke
Pregnancy Complications May Increase Stroke Risk
Many women encounter complications during pregnancy. Two of the most common ones, elevated blood sugars (gestational diabetes) and elevated blood pressure (preeclampsia) have emerged as possible indicators of increased risk of stroke.Pregnancy Complications
Elevated Blood Sugars (Gestational Diabetes)
Gestational Diabetes is the inability of the body to process carbohydrates during pregnancy. Often there are no symptoms of the condition. It is recommended that all pregnant women be screened for gestational diabetes during their pregnancy.The symptoms are usually mild and not life-threatening to the pregnant woman. However, the increased blood sugar levels in the mother are associated with an increased rate of complications in the baby, including:
- Large size at birth
- Birth trauma, especially of the shoulders
- Hypoglycemia (low blood sugar)
- Jaundice (yellowing of the skin)
- Older age when pregnant
- African or Hispanic ancestry
- Obesity
- Gestational diabetes in a previous pregnancy
- Having a previous baby weighing over 9 pounds
Elevated Blood Pressure (Preeclampsia)
Preeclampsia is the development of elevated blood pressure about mid-way through pregnancy. Common symptoms may include swelling of the face and hands. The exact cause of preeclampsia is not known. Preeclampsia occurs in approximately 8% of all pregnancies.Increased risk is associated with:
- First pregnancies
- Advanced maternal age
- African-American heritage
- Multiple pregnancies
- Past history of diabetes, high blood pressure, or kidney disease
- Bed rest
- Close monitoring
- Delivery as soon as the fetus is able to survive outside the womb
Long-Term Effects: New Information on Stroke Risk
Recent results from two research groups show that there can be consequences of pregnancy complications extending beyond the delivery date. Dr. Cheryl Bushnell and her colleagues at Duke University Medical Center looked at medical records and found:Women who experienced preeclampsia and gestational diabetes during their pregnancy were twice as likely or more to have a stroke, on average, 13.5 years after the pregnancy.
Dr. David Brown and colleagues conducting the Stroke Prevention in Young Women Study in Baltimore, Maryland came up with similar results. They found that:
Women with preeclampsia were 60% more likely to have a stroke in the months and years that followed their pregnancy.
While these results need to be confirmed with additional study they highlight the importance of the need for regular pre-natal visits to identify preeclampsia and gestational diabetes, as well as other problems. The results also show the need to identify ways to prevent these problems, so that the secondary consequence of stroke later in life can be avoided.
What You Can Do
Reducing Your Risk of Pregnancy Complications
It is important for all pregnant women to obtain early and ongoing prenatal care. This allows for the early recognition and treatment of these and other pregnancy-related conditions. As with any condition or disease, some risk factors are controllable, or treatable, which means you can take action to reduce that risk. Other factors are beyond your control. Risk of these complications can be reduced through:- Maintaining a healthy weight
- Eating a balanced diet that keeps blood sugars level
- Exercising regularly
Reducing your Risk of Stroke After Pregnancy
Stroke is the nation's third leading killer and the leading cause of adult disability. The ailment strikes as many as 750,000 Americans a year, killing over 150,000 and permanently impairing hundreds of thousands more.To learn more about stroke NetWellness has developed a complete Stroke health topic area featuring information on:
- Understanding Stroke
- Triggers and warning signs of a stroke
- How to assess your risk
- James AH, Bushnell CD, Jamison MG, and Myers ER. Incidence and Risk Factors for Stroke in Pregnancy and the Puerperium. Obstetrics and Gynecology 2005;106:509-516
- David W. Brown, Nicole Dueker, Denise J. Jamieson, John W. Cole, Marcella A. Wozniak, Barney J. Stern, Wayne H. Giles and Steven J. Kittner, From the Stroke Prevention in Young Women Study Preeclampsia and the Risk of Ischemic Stroke Among Young Women. Results. published online Feb 16, 2006; Stroke
For more information:
Go to the Stroke health topic, where you can:- Read articles on this topic
- Browse commonly asked questions
- Learn about health research and how to participate
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