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.