Infertility and pregnancy loss may increase stroke risk in women later in life

Overview: A new study reports that female infertility and miscarriage increase the risks of both fatal and nonfatal strokes later in life.

Source: BMJ

Infertility and pregnancy loss are associated with an increased risk of nonfatal and fatal stroke later in life, finds an analysis of observational studies, published in The BMJ.

Early monitoring of women who have had a miscarriage or stillbirth, along with healthy lifestyle changes, could lower their risk of stroke, the researchers suggest.

Stroke is one of the leading causes of death and disability in women worldwide. In 2019, about 3 million women died from a stroke. In addition, women lost a total of 10 million years of healthy life due to disability after stroke – 44% more years than men.

Known stroke risks such as obesity, high blood pressure, hypertension and diabetes do not fully explain the higher risk of stroke in women. Previous studies of the association between infertility, miscarriage, and stillbirth with long-term stroke risk have been inconclusive.

To fill in the gaps, this study aimed to assess the association between infertility, miscarriage and stillbirth with the risk of fatal and non-fatal stroke and a specific type of stroke.

The researchers analyzed data from the InterLACE consortium, which pools data on reproductive health and chronic disease, from a total of 27 studies. Data from eight studies from seven countries (Australia, China, Japan, Netherlands, Sweden, UK and US) were included in the analysis.

Questionnaires were used to find information about infertility, miscarriage and stillbirth. Data for non-fatal stroke was also found using self-reported questionnaires or hospital records. Hospital data was used to identify fatal stroke cases and stroke subtypes (hemorrhagic or ischemic).

In total, about 620,000 women were enrolled in the study, ages 32 to 73 at baseline.

Of these, 275,863 women had nonfatal and fatal stroke data, 54,716 women had nonfatal stroke data only, and 288,272 had fatal stroke data only. Of these women, 9,265 (2.8%) had a first non-fatal stroke at a median age of 62 years, and 4003 (0.7%) had a fatal stroke at a median age of 71 years.

Women who had a nonfatal stroke before age 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 had a 14% higher risk of nonfatal stroke than women without infertility.

Miscarriage was also associated with an 11% higher risk of non-fatal stroke compared to women who had not miscarried. 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 the risk of stroke, respectively.

For women who had three or more miscarriages, the increased risk of nonfatal ischemic and hemorrhagic stroke was 37% and 41%, respectively. Similarly, for fatal ischemic and hemorrhagic stroke, three or more miscarriages were linked to a risk increase of 83% and 84%, respectively.

A history of stillbirth was associated with a greater than 30% higher risk of nonfatal stroke, and women who had multiple stillbirths (two or more) were nearly 80% more likely to have a nonfatal ischemic stroke.

The study also found that repeated stillbirths were associated with a more than 40% higher risk of fatal stroke.

The researchers say the link between infertility and an increased risk of stroke may be due to conditions such as polycystic ovary syndrome (PCOS) and premature ovarian insufficiency (POI), while endothelial dysfunction (narrowing of the arteries of the heart) increases the risk of stroke. for women with a history of repeated stillbirth or miscarriage.

Early monitoring of women who have had a miscarriage or stillbirth, along with healthy lifestyle changes, could lower their risk of stroke, the researchers suggest. Image is in the public domain

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 increased risk of stroke.

This is an observational study and as such cannot determine a cause. The study has other limitations, for example information was collected from questionnaires; the effects of other treatments were not studied due to limited data; and definitions of infertility, stillbirth, and miscarriage may differ in the studies.

Nevertheless, this was a large, well-designed study and the results were largely unchanged after further analyses, suggesting that the findings are robust.

According to the researchers, “a history of repeated pregnancy loss may be considered 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 lower the risk of stroke later in life.

About this news about stroke and fertility research

Author: press office
Source: BMJ
Contact: Press agency – BMJ
Image: The image is in the public domain

Original research: Open access.
“Infertility, recurrent pregnancy loss and risk of stroke: pooled analysis of individual patient data from 618 851 women” by Chen Liang et al. BMJ


Abstract

Infertility, recurrent pregnancy loss and risk of stroke: pooled analysis of individual patient data from 618 851 women

Objective

Exploring the associations of infertility, recurrent miscarriage and stillbirth with the risk of first nonfatal and fatal stroke, further stratified by stroke subtypes.

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Design

Individual participant pooled analysis of eight prospective cohort studies.

Institution

Cohort studies in seven countries (Australia, China, Japan, Netherlands, Sweden, United Kingdom and United States) participating in the InterLACE (International Collaboration for a Life Course Approach to Reproductive Health and Chronic Disease Events) consortium, which was established in June 2012.

Attendees

618 851 women aged 32.0-73.0 years at baseline with data on infertility, miscarriage or stillbirth, at least one outcome event (non-fatal or fatal stroke), and information on covariates were included; 93 119 women were excluded. Of the participants, 275 863 had nonfatal and fatal stroke data, 54 716 had nonfatal stroke data only, and 288 272 had fatal stroke data only.

Main outcome and measures

Non-fatal strokes were identified through self-reported questionnaires, linked hospital records, or national patient registries. Fatal strokes were identified through death registry data.

Results

The median follow-up for nonfatal stroke and fatal stroke was 13.0 years (interquartile range 12.0-14.0) and 9.4 years (7.6-13.0), respectively. A first non-fatal stroke was experienced by 9265 (2.8%) women and 4003 (0.7%) had a fatal stroke.

Hazard ratios for nonfatal or fatal stroke were stratified by hypertension and adjusted for race or ethnicity, body mass index, smoking status, education level, and study. Infertility was associated with an increased risk of non-fatal stroke (hazard ratio 1.14, 95% confidence interval 1.08 to 1.20). Recurrent miscarriage (at least three) was associated with a higher risk of nonfatal and fatal stroke (1.35, 1.27 to 1.44, and 1.82, 1.58 to 2.10, respectively).

Women with stillbirth had a 31% higher risk of nonfatal stroke (1.31, 1.10 to 1.57) and women with recurrent stillbirth had a 26% higher risk of fatal stroke (1,26, 1 .15 to 1.39).

The increased risk of stroke (nonfatal or fatal) associated with infertility or recurrent stillbirths was primarily caused by a single stroke subtype (nonfatal ischemic stroke and fatal hemorrhagic stroke), while the increased risk of stroke (nonfatal or fatal) associated with recurrent miscarriages was driven by both subtypes.

Conclusion

A history of recurrent miscarriage and death or loss of a baby before or during birth may be considered a female-specific risk factor for stroke, with risk differing by stroke subtype. These findings may contribute to better monitoring and stroke prevention for women with such a history.

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