Pregnancy and Stroke Risk in Women

Jessica Tate; Cheryl Bushnell

Disclosures

Women's Health. 2011;7(3):363-374. 

In This Article

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]

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 responsible 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.

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