One potential female-specific stroke risk factor is a history of miscarriage or stillbirth
According to an analysis of observational studies published in The BMJ, infertility and miscarriage are linked to a higher risk of non-fatal and fatal stroke in later life. The researchers propose that early surveillance of women who have had a miscarriage or stillbirth, together with healthy lifestyle improvements, might reduce the incidence of stroke.
One of the top causes of mortality and disability for women worldwide is stroke. About 3 million women died from strokes in 2019. Furthermore, women lost 10 million years of healthy living in total due to disability after a stroke, which is 44% longer than males.
Obesity, hypertension, diabetes, and other known stroke hazards may not entirely account for women’s greater risk of stroke. Previous research on the relationship between infertility, miscarriage, and stillbirth and the risk of long-term stroke has come up empty.
This research sought to fill in the gaps by evaluating the relationship between infertility, miscarriage, and stillbirth and the risk of fatal and non-fatal stroke, as well as specific types of stroke
The researchers analyzed data from a total of 27 studies from the InterLACE consortium, which collects information on chronic illness and reproductive health. The analysis also included data from eight studies conducted in seven nations (Australia, China, Japan, Netherlands, Sweden, UK, and the USA).
Information on infertility, miscarriage, and stillbirth was gathered using questionnaires. Self-reported questionnaires or medical records were used to get information on non-fatal strokes. The identification of fatal stroke cases and subtypes of stroke was done using hospital data (hemorrhagic or ischaemic).
In all, 620,000 women who ranged in age from 32 to 73 were included in the study.
Of these, 275,863 women had data on non-fatal and fatal stroke, 54,716 women only had data on non-fatal stroke, and 288,272 only had data on fatal stroke. Among these, 9,265 (2.8%) women experienced a first non-fatal stroke at a median age of 62, and 4,003 (0.7%) had a fatal stroke at a median age of 71.
Women with non-fatal stroke before the age of 40 were excluded, as they may have had a stroke before a history of infertility, pregnancy loss, or stillbirth could be established. Several factors that could have influenced the results were also taken into account, such as ethnicity, weight, lifestyle, and underlying conditions.
Infertility, miscarriage, and stillbirth were all associated with an increased risk of stroke, especially recurrent miscarriages (three or more) and stillbirths, the study finds.
Women with a history of infertility were at a 14% higher risk of non-fatal stroke than women without infertility.
Miscarriage was also associated with an 11% higher risk of non-fatal stroke compared to women who had not had a miscarriage. The risk increased with the number of miscarriages a woman had: one, two, and three miscarriages led to a 7%, 12%, and 35% increase in stroke risk, respectively.
For women who had three or more miscarriages, the increased risk of non-fatal ischaemic and hemorrhagic stroke was 37% and 41% respectively. Similarly, for fatal ischaemic and hemorrhagic stroke, three or more miscarriages were linked to an 83% and 84% risk increase respectively.
History of stillbirth was associated with an over 30% higher risk of non-fatal stroke, and women who had multiple stillbirths (two or more) were almost 80% more likely to experience a non-fatal ischaemic stroke. The study also found that recurrent stillbirth was associated with an over 40% higher risk of fatal stroke.
The researchers say that the link between infertility and increased stroke risk may be due to conditions such as polycystic ovary syndrome (PCOS) and premature ovarian insufficiency (POI), while endothelial dysfunction (narrowing of the heart’s blood vessels) may explain the increased risk of stroke for women with a history of recurrent stillbirth or miscarriage.
But they also suggest that unhealthy lifestyles (such as smoking or obesity) are also associated with pregnancy loss, as well as infertility, which could also contribute to an elevated risk of stroke.
This is an observational study, and as such, can’t establish a cause. The study has other limitations, for example, information was collected from questionnaires; the effects of other treatments were not explored due to limited data; and definitions of infertility, stillbirth, and miscarriage may be different across the studies.
Nevertheless, this was a large, well-designed study and results were largely unchanged after further analyses, suggesting that the findings are robust. According to the researchers, “having a history of recurrent pregnancy loss may be considered as a female-specific risk factor for stroke.”
And they suggest early monitoring of women with a history of pregnancy loss or infertility while promoting healthy habits may help to lower their risk of stroke later in life.
Reference: “Infertility, recurrent pregnancy loss, and risk of stroke: pooled analysis of individual patient data of 618 851 women” by Chen Liang, Ph.D. candidate, Hsin-Fang Chung, research fellow, Annette J Dobson, professor, Kunihiko Hayashi, professor, Yvonne T van der Schouw, professor, Diana Kuh, professor, Rebecca Hardy, professor, Carol A Derby, professor, Samar R El Khoudary, associate professor, Imke Janssen, associate professor, Sven Sandin, statistician, Elisabete Weiderpass, director and Gita D Mishra, professor, 4 May 2022, The BMJ.
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