Pregnancy and Stroke Risk in Women

Jessica Tate; Cheryl Bushnell

Disclosures

Women's Health. 2011;7(3):363-374. 

In This Article

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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