Association of spontaneous abortion with all cause and cause specific premature mortality

The British Medical Journal (BMJ):

Increasing evidence suggests that reproductive factors unique to women are associated with a greater risk of death from non-communicable diseases. Even if reproductive events do not increase the risk of death from non-communicable diseases, they could be useful as an early stress test of underlying risk factors that cause adverse reproductive outcomes and death from non-communicable diseases.

Spontaneous abortion is one of the most common adverse outcomes of pregnancy. Substantial evidence indicates that women with a history of spontaneous abortion have a greater risk of non-communicable diseases, including hypertension, cardiovascular diseases, and type 2 diabetes.

What is already known on this topic?

Spontaneous abortion is one of the most common adverse outcomes of pregnancy, with an estimated prevalence of 12-24%.

Whether spontaneous abortion is associated with a long term risk of premature death (before the age of 70) is unclear.

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This study investigated the association of spontaneous abortion with the risk of all cause and cause specific premature mortality (death before the age of 70). It is an ongoing prospective cohort study of women of reproductive age (aged 25-42 at baseline), with continuous follow-up spanning three decades and periodic update of reproductive characteristics and lifestyle and health related factors.

The results from this large longitudinal study, with a 24 year follow-up, indicated that spontaneous abortion was associated with a greater risk of all cause premature death, particularly for recurrent spontaneous abortions and spontaneous abortions occurring early in a woman’s reproductive life.

These associations were primarily because of an increased risk of death from cardiovascular disease, were independent of several shared risk factors (eg, body mass index, smoking, diet, and physical activity), and persisted in a series of sensitivity analyses aimed at isolating the role of spontaneous pregnancy losses from other factors.

The greater risk of all cause premature mortality associated with spontaneous abortion was mainly a result of a higher risk of death from cardiovascular disease.

Study results suggest that spontaneous abortion could be an early marker of future health risk in women, including premature death.

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Abstract

Objective To investigate the association of spontaneous abortion with the risk of all cause and cause specific premature mortality (death before the age of 70).

Design Prospective cohort study.

Setting The Nurses’ Health Study II (1993-2017), United States.

Participants 101 681 ever gravid female nurses participating in the Nurses’ Health Study II.

Main outcomes measures Lifetime occurrence of spontaneous abortion in pregnancies lasting less than 6 months, determined by biennial questionnaires. Hazard ratios and 95% confidence intervals for all cause and cause specific premature death according to the occurrence of spontaneous abortion, estimated with time dependent Cox proportional hazards models.

Results During 24 years of follow-up, 2936 premature deaths were recorded, including 1346 deaths from cancer and 269 from cardiovascular disease. Crude all-cause mortality rates were comparable for women with and without a history of spontaneous abortion (1.24 per 1000 person years in both groups) but were higher for women experiencing three or more spontaneous abortions (1.47 per 1000 person years) and for women reporting their first spontaneous abortion before the age of 24 (1.69 per 1000 person years). The corresponding age adjusted hazard ratios for all cause premature death during follow-up were 1.02, 1.39 and 1.27, respectively. After adjusting for confounding factors and updated dietary and lifestyle factors, the occurrence of spontaneous abortion was associated with a hazard ratio of 1.19 for premature mortality during follow-up. The association was stronger for recurrent spontaneous abortions and for spontaneous abortions occurring early in a woman’s reproductive life. When cause specific mortality was evaluated, the association of spontaneous abortion with premature death was strongest for deaths from cardiovascular disease. Spontaneous abortion was not related to premature death from cancer.

Conclusions Spontaneous abortion was associated with an increased risk of premature mortality, particularly death from cardiovascular disease.

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