Interpretation
Our results show that a history of pre-eclampsia/eclampsia in pregnancy significantly increased the future occurrence rate of stroke, both ischemic and hemorrhagic stroke, even after 10 to 15 years. In this study, after adjusting for potential confounding variables, women with history of pre-eclampsia/eclampsia still had a 2-fold higher long-term stroke risk. Nearly 2-fold higher ischemic stroke risk and up to 3-fold higher hemorrhagic stroke risk were observed.
Reviewing the literature, it has been often reported that pre-eclampsia/eclampsia would increase stroke risk during the pregnancy process, both ischemic and hemorrhagic stroke, a dangerous complication of pregnancy11,25-30. In those studies, pre-eclampsia/eclampsia generally increased a woman’s stroke risk and hypertension between 2~4-fold during pregnancy, respectively14,30-33, and also leads to higher mortality of pregnancy and delivery2,34,35. In a case-control stroke study, Kittner and colleagues found that the adjusted relative risk (aRR) of stroke (both cerebral infarction and intracerebral hemorrhage) during pregnancy and the 6-week postpartum period was 2.4 (95 % CI, 1.6 to 3.6)36. The aRR during pregnancy was 1.1 (95 % CI, 0.6 to 2.0), while for risk during the 6-week postpartum period alone the aRR increased to 7.9 (95 % CI, 5.0–12.7). Compared to our cohort study, our study showed aHR was 1.65 during 0− 1 years after childbirth, 3.20 during 1− 3 years, and 1.80 during 10− 15 years.
In the literature, another case-control study with follow-up time prolonging to one year after childbirth, Tang et al. evaluated the aRRs of ischemic and hemorrhagic stroke during pregnancy and the first postpartum year 14. In that study, they found a U-shape trend of hemorrhagic stroke risk from antepartum to 1-year postpartum (aRR 10.68, to 6.45, to 5.61, to 11.76, to 19.90 for 3 months antepartum, and 3 days, 6 weeks, 6 months, 12 months postpartum, respectively). Compared to that U shape of that short postpartum case-control study, our long-term cohort study showed a reverse-U shape in decade follow-up for hemorrhagic stroke with a peak of aHR 7.49 during 3−5 years after childbirth. .
For the ischemic stroke risk, Tang’s study showed aRR as high as 40.86 within 3 months antepartum, then decrease to 11.23 from 3 days to 6 weeks postpartum, and further decreased to 4.35 from 6 months to 12 months postpartum. In our cohort study, the aHR for ischemic stroke increased from 1.82 during the first year after childbirth, with peak 3.09 during 1−3 years, and then decreased to 1.58 after 10 years.
In the literature, it has been reported that ischemic stroke had two peaks of occurrence, in the first and third trimesters of pregnancy: 24/27 (89%), while intracerebral hemorrhage was more frequently observed during the third trimester: 15/23 (65%)37. Different from previous studies, in our long-term follow-up study, we noted that stroke risk would reach peak during 1−3 years after childbirth for ischemic stroke and during 3−5 years for hemorrhagic stroke. Based on short-term follow-up studies in the past and this long-term study, it is found consistently that ischemic stroke occurs faster and earlier than hemorrhagic stroke.
The role of hypertension in women with pre-eclampsia/eclampsia is also worth to note in this study. In previous studies, compared to patients without pre-existing hypertension those with higher blood pressure have smaller amount of salvageable tissue and obvious intracranial occlusion and thus worsen stroke outcome38-41. Both of the elevation of systolic and diastolic blood pressure increase stroke risk of 2.9-fold for women42,43. In addition, recent study further identifies related genes of predisposing to hypertension may associate with pre-eclampsia/eclampsia in Asian women44. Our study confirm the role of hypertension on stroke in women with history of pre-eclampsia/eclampsia with aHR 3.35 (95% CI 1.99-5.63). For women with pre-eclampsia/eclampsia, the role of hypertension is a red flag in aggravating probability of future stroke occurrence.
Age may also have significant influence on stroke. Previous studies ever discussed the impact of maternal age on stroke risk13,45,46. For example, women aged >39 years and those aged >29 years are significant hemorrhagic and ischemic stroke factors associated with increased risk, respectively46. This is consistent with our results, which showed women with an age at delivery >35 years had a significantly high aHR of hemorrhagic stroke risk.
For socioeconomic status, previous studies suggest that socioeconomic deficiency is associated with increased stroke severity and incidence at young age population47, and stroke mortality47,48. This influence of socioeconomic deficiency may have a greater impact on pregnant women, which may cause pregnant women to have a higher stroke risk than other groups49. Our long-term study also showed that women with lowest family income had elevated stroke risk than women with other family income levels.