Pregnancy and Stroke Risk in Women

Table 1.  Summary of the published incidence, mortality and morbidity of pregnancy-related stroke.

Study (year)	Population sampled (years)	Inclusion	Incidence (per 100,000 deliveries)	Mortality/morbidity (%)	Ref.
Cross et al. (1968)	Killearn Hospital, Glasgow, Scotland, UK (1956–1967)	Carotid artery distribution infarcts in pregnancy plus up to 16 days PP	5	Mortality 26	[25]
Wiebers et al. (1985)	Rochester, MN, USA (1955–1979)		3.8		[49]
Simolke et al. (1991)	Parkland Memorial Hospital, Dallas, TX, USA (1984–1990)	Stroke: included CVT ICH: included SAH	Stroke: 10 ICH: 6.7	Overall: morbidity 40, mortality 20	[50]
Sharshar et al. (1995)	Hospitals in region of Ile de France (1989–1992)	Stroke: 'stroke-like deficits', excluded CVT ICH: excluded SAH Pregnancy plus 2 weeks PP	Stroke: 4.3 ICH: 4.6	Stroke: morbidity 33, mortality 0 ICH: morbidity 50, mortality 25	[8]
Kittner et al. (1996)	Hospitals in Baltimore–Washington DC, USA (1988–1991)	Stroke: included CVT ICH: excluded SAH Pregnancy plus 6 weeks PP Women aged 15–44 years	Stroke: 11 ICH: 9		[1]
Lanska and Kryscio (1997)	National Hospital Discharge Survey (1979–1991)	Diagnosis codes 674.0† or 671.5‡ from hospitalization of delivery	Stroke: 10.3† CVT: 8.9	Stroke: mortality 2.2 CVT: mortality 0	[2]
Lanska and Kryscio (1998)	National Hospital Discharge Survey (1979–1991)	Diagnosis codes 674.0 or 671.5, not restricted to hospitalization of delivery Women aged 15–44 years	Stroke: 17.7† CVT: 11.4	Stroke: mortality 3.3 CVT: mortality 0	[3]
Lanska and Kryscio (2000)	Nationwide Inpatient Sample (1993–1994)	Diagnosis codes 674.0 or 671.5 from hospitalization of delivery Women aged 15–44 years	Stroke: 13.1† CVT: 11.6	Stroke: mortality†14.7 CVT: mortality 0 9.3 of those discharged had postacute care needs	[4]
Jaigobin and Silver (2000)	Toronto Hospital, Canada (1980–1997)	Stroke: included CVT ICH: included SAH	Stroke: 18 ICH: 8	Stroke: mortality 0 ICH: mortality 23	[11]
James et al. (2005)	Nationwide Inpatient Sample (2000–2001)	Included hemorrhage, arterial stroke, CVT or diagnosis code 674.0	34.2	Mortality 4.1 22 discharged to facility other than home	[5]
Bateman et al. (2006)	Nationwide Inpatient Sample (1993–2002)	ICH: diagnosis code 431 Women aged 15–44 years	ICH: 6.1	Mortality 20.3	[7]
Liang et al. (2006)	Chang Gung Memorial Hospital, Taiwan (1992–2004)	Stroke: included CVT ICH: included SAH	Stroke: 13.5 ICH: 25.4		[12]

^†The ninth edition of the International Classification of Diseases (ICD-9) 674.0 includes the following ICD-9 codes, occurring during pregnancy, childbirth or the puerperium: 430 SAH; 431 ICH; 432 other and unspecified intracranial hemorrhage; 433 occlusion and stenosis of precerebral arteries; 434 occlusion of cerebral arteries; 436 acute, but ill-defined cerebrovascular disease (which includes apoplectic apoplexy and cerebral seizure); 437 other and ill-defined cerebrovascular disease (which includes cerebral atherosclerosis, hypertensive encephalopathy, cerebral aneurysm unruptured, cerebral arteritis, Moyamoya disease, nonpyogenic thrombosis of the intracranial venous sinus and transient global amnesia).
^‡ICD-9 671.5: CVT.
CVT: Cerebral venous thrombosis; ICH: Intracerebral hemorrhage; PP: Postpartum; SAH: Subarachnoid hemorrhage.

DIC: Disseminated intravascular coagulation; TTP: Thrombotic thrombocytopenic purpura.

DIC: Disseminated intravascular coagulation; ICH: Intracerebral hemorrhage.

AA: African–American; AT-III: Antithrombin III; AVR: Aortic valve replacement; CN: Cranial nerve; CVT: Cerebral venous thrombosis; DVT: Deep venous thrombosis; HA: Headache; IA: Intra-arterial; ICH: Intracerebral hemorrhage; IV: Intravenous; L: Left; MVR: Mitral-valve replacement; NIHSS: NIH Stroke Scale; PFO: Patent foramen ovale; R: Right; rtPA: Recombinant tissue plasminogen activator; s/p: Status post; UK: Urokinase.

Authors and Disclosures

Jessica Tate¹ & Cheryl Bushnell<sup>†1

1</sup>Wake Forest University Baptist Medical Center Stroke Center, Women's Health Center of Excellence, Wake Forest University Health Sciences, Medical Center Boulevard, Winston Salem, NC 27157, USA

^†Author for correspondence
Tel.: +1 336 716 9482 Fax: +1 336 716 9810 cbushnel@wfubmc.edu

Sidebar

Executive Summary

Epidemiology of stroke in pregnancy

• The incidence of stroke during pregnancy ranges from approximately 9 to 34 per 100,000 deliveries worldwide.

• Of all stroke types, intracerebral hemorrhage during pregnancy and the puerperium carries the highest morbidity and mortality, with an in-hospital mortality of 20%.

• Although infrequently reported, the morbidity following pregnancy-related stroke is lower than for typical stroke patients, and the risk for recurrent stroke in subsequent pregnancies is very low.

• Causes of pregnancy-related stroke include those that are unique to pregnancy (preeclampsia/eclampsia, postpartum angiopathy, amniotic fluid embolism and postpartum cardiomyopathy) and causes seen in nonpregnant women, including hypertension, diabetes, vasculitis, arteriovenous malformations or aneurysms.

Risk factors for pregnancy-related stroke & cerebral venous thrombosis

• The women who are at the highest risk for pregnancy-related stroke are those who are over the age of 35 years; those who are of African–American race-ethnicity; and those with preeclampsia/eclampsia/gestational hypertension, thrombophilias, migraine headaches, diabetes, prepregnancy hypertension, hyperemesis gravidarum, anemia, thrombocytopenia, postpartum hemorrhage, transfusion, fluid, electrolyte and acid-base disorders and infection.

Diagnosis of pregnancy-related stroke & cerebral venous thrombosis

• Brain imaging is essential in order to determine whether a pregnant woman has suffered an intracerebral hemorrhage. Brain MRI and magnetic resonance venogram are generally considered the gold standard for the diagnosis of ischemic stroke and cerebral venous thrombosis, respectively.

• The timing of scans may depend on the stage of pregnancy and the risk–benefit ratio of performing these scans. The risk from MRI is generally considered lower after the first trimester, and the risks with administration of gadolinium is still under debate.

Stroke prevention during pregnancy

• Strategies to prevent stroke during pregnancy in high-risk women mimic those used for thromboprophylaxis, which include either unfractionated or low-molecular-weight heparin to 13 weeks' gestation, followed by warfarin until the middle of the third trimester, then heparin until delivery and warfarin for 6 weeks postpartum.

• There are no randomized controlled trials of acute stroke treatment with thrombolysis or mechanical thrombectomy to guide decision-making in the pregnant population.

Treatment of acute pregnancy-related stroke

• Treatment of acute stroke in pregnant women is still controversial, but not strictly contraindicated. Several case reports have documented successful reperfusion, in addition to satisfactory maternal and fetal outcomes.

• However, there are no trials of anticoagulation or antiplatelet therapies for stroke prevention in pregnancy.

Future perspective

• There are many gaps in our knowledge about pregnancy-related stroke, including detailed knowledge about mechanism outcomes posthospital discharge, due to the lack of patient-level detail.

• In order to better understand pregnancy-related stroke causes and outcomes, the development of multisite, multidisciplinary registries are needed.

• In the next 5–10 years, it is most likely that an increasing number of pregnant women with acute ischemic stroke will be treated with recombinant tissue plasminogen activator as neurologists and interventional radiologists develop new or improved imaging strategies (e.g., MRI perfusion) to identify women who would clearly benefit from reperfusion while minimizing the risk to the fetus.

• In the next couple of years, new anticoagulants, such as direct thrombin inhibitors (dabigatran), may be used in pregnancy, especially for women who cannot receive heparin or warfarin. Dabigatran is currently US FDA category C for pregnant women, but more testing in humans will be required in order to determine the number of adverse pregnancy outcomes and the risk–benefit ratio for preventing stroke and cerebral venous thrombosis during pregnancy.