A history of infertility, recurrent miscarriage, or stillbirth may be a risk factor for stroke later in life, according to an analysis of eight prospective cohort studies.
Among over 600,000 women, infertility was associated with an increased risk of non-fatal stroke (HR 1.14, 95% CI 1.08-1.20), while a history of at least three miscarriages was associated with higher risks of both non-fatal stroke (HR 1.35, 95% CI 1.27-1.44) and fatal stroke (HR 1.82, 95% CI 1.58-2.10), reported Gita Mishra, PhD, of the University of Queensland in Australia, and colleagues.
Furthermore, those who experienced a stillbirth were at a 31% higher risk of non-fatal stroke, and those who had a history of recurrent stillbirth were at a 26% higher risk of fatal stroke, they noted in The BMJ.
“A history of recurrent miscarriages and death or loss of a baby before or during birth could be considered a female specific risk factor for stroke, with differences in risk according to stroke subtypes,” Mishra and team concluded. “These findings could contribute to improved monitoring and stroke prevention for women with such a history.”
Analyses by subtypes of non-fatal stroke showed infertility was associated with an increased risk of ischemic stroke (HR 1.15, 95% CI 1.07-1.23), while women with recurrent miscarriage were more likely to experience ischemic and hemorrhagic stroke versus women without miscarriage (HR 1.37, 95% CI 1.23-1.53, and HR 1.41, 95% CI 1.08-1.84, respectively).
As for fatal stroke, women with recurrent miscarriages were more likely to experience ischemic and hemorrhagic fatal stroke (HR 1.83, 95% CI 1.39-2.41, and HR 1.84, 95% CI 1.39-2.44, respectively), and those with recurrent stillbirth were more likely to have hemorrhagic fatal stroke (HR 1.44, 95% CI 1.35-1.53).
Mishra and team noted that the link between infertility and increased stroke risk may be due to disorders such as polycystic ovary syndrome and premature ovarian insufficiency, while endothelial dysfunction may explain the increased risk of stroke for women with a history of recurrent stillbirth or miscarriage.
For this analysis, Mishra and colleagues analyzed data on 618,851 women ages 32 to 73 from eight studies from seven countries — China, Sweden, the Netherlands, the U.K., Japan, Australia, and the U.S. — as part of the InterLACE (International Collaboration for a Life Course Approach to Reproductive Health and Chronic Disease Events) consortium. Of the included women, 275,863 had data on fatal and non-fatal stroke: 9,265 (2.8%) experienced a non-fatal stroke and 4,003 (0.7%) experienced a fatal stroke.
Median follow-up was 13 years after a non-fatal stroke and 9.4 years after a fatal stroke. Average ages at the time of first non-fatal stroke and fatal stroke were 62 and 71.
Of the included women, 17.2% experienced infertility, 16.6% experienced miscarriage, and 4.6% experienced stillbirth.
There were several limitations to this analysis, the authors acknowledged. Since data on infertility, miscarriage, and stillbirth were collected from questionnaires, recall bias is possible. Furthermore, while most models adjusted for certain comorbidities, others, such as endometriosis, thyroid disorders, and pelvic inflammatory disease, were not available in all studies.
This study was funded by the Australian National Health and Medical Research Council Centres of Research Excellence.
The study authors reported no conflicts of interest.