Stillbirths and miscarriages increase risk of stroke later in life

Women with a history of stillbirth and miscarriage may be at increased risk of stroke and cardiovascular events. GPs have an important role to play in mitigating those risks.

IN 2018, 18 400 females and 20 200 males experienced stroke events in Australia. Previous research has shown that there is sex difference in the strength of association between modifiable risk factors and outcomes of stroke (here, and here).

Recent research, has demonstrated that women who have had a stillbirth or miscarriage have an increased risk of stroke in later life, and that the risk increases with each stillbirth or miscarriage.

The latest study from our group, published in June 2022 by the BMJ, pooled data from eight cohort studies of women conducted in Australia, China, Japan, Netherlands, Sweden, the UK, and the US. In total, 618 851 women were included in the study. The women were aged between 32 and 73 years when they were first recruited into each of the studies and followed for an average of 11 years.

Over that time, information on whether a woman had experienced non-fatal stroke was available for 330 579 women, out of whom 9265 had one or more non-fatal strokes (2.8%). Of the 564 135 women with information on fatal stroke, 4003 women had a fatal stroke (0.7%).

Women also provided data on history of pregnancy loss; 24 873 (4.6%) reported at least one stillbirth with 4924 (0.9%) who had two or more stillbirths; 91 569 (16.2%) reported at least one miscarriage with 8064 (1.5%) who had three or more miscarriages.

What did we find?

Among women who had been pregnant at least once, women who had a stillbirth had a 31% increased risk of a non-fatal stroke and a 7% increased risk of a fatal stroke compared with women who had not had a stillbirth. Women who had two or more stillbirths had a 23% higher risk of a fatal stroke in later life.

Women who reported a miscarriage also had a higher risk of stroke, with the risk increasing with each miscarriage. Women who reported three or more miscarriages had a 35% increase in non-fatal stroke, and an 82% increase in fatal strokes.

Looking at the types of stroke, women who had a stillbirth had an increased risk of non-fatal ischaemic strokes and of fatal haemorrhagic strokes. Women who had a history of miscarriage had an increased risk of both ischaemic and haemorrhagic strokes.

The study adjusted for whether the women smoked or not, had high blood pressure or diabetes, body mass index, ethnicity (defined as white, Asian or other), and education level.

What do these findings means?

This study is, we believe, the first to conclusively show a link between pregnancy loss and stroke.

Compared with the overall incidence of non-fatal and fatal stroke (2.8% and 0.7%), the incidence among women with stillbirths (two or more) or recurrent miscarriages (three or more) increased up to five times: recurrent stillbirth 5.1% and 3.6%; and recurrent miscarriage 4.1% and 1.2%.

Previous research has also shown an association between pregnancy loss and coronary heart disease.

It is not yet known whether adding these risk factors to a traditional cardiovascular risk calculator (such as the calculators used in Australian general practice software) increases the accuracy of the calculator. Liang and colleagues adjusted for the other potential variables, such as smoking status, high blood pressure, diabetes, body mass index, ethnicity and education level, as measured at baseline when women entered the study. It may be that if these variables were measured at the time of doing a cardiovascular risk assessment (which is done between the ages of 45 and 75 years), pregnancy loss would not add to the ability of the calculator to predict cardiovascular disease. However, pregnancy loss may occur some time before a standard cardiovascular risk assessment, and so it may represent an opportunity to identify women at higher risk and to implement measures to try to prevent later cardiovascular disease.

Other reproductive factors which increase the risk of cardiovascular disease are gestational diabetes, pregnancy-induced hypertension/pre-eclampsia and early menopause (here, and here).

What should be done in the clinic?

It is important that GPs take a thorough reproductive history from their patients. If women have had any of these conditions, they should be aware that these women are at an increased risk of cardiovascular disease and to monitor them for other changes, such as the development of high blood pressure, diabetes, and high cholesterol.

Professor Gita D Mishra is an NHMRC Leadership Fellow at, and Director of the Australian Women’s and Girls Health Research Centre at the University of Queensland.

Professor Jenny Doust is a Clinical Professorial Research Fellow, and Lead of the Clinical Practice and Policy Theme at the Australian Women’s and Girls’ Health Research Centre at the University of Queensland.

The statements or opinions expressed in this article reflect the views of the authors and do not necessarily represent the official policy of the AMA, the MJA or InSight+ unless so stated.

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