Women with spontaneous abortion at higher risk of premature death

Spontaneous abortion appears to increase the risk of premature mortality, particularly from cardiovascular disease (CVD), suggests a study.

“Our results suggest that spontaneous abortion could be an early marker of future health risk in women, including premature death,” the researchers said.

This prospective cohort study included 101,681 ever gravid female nurses participating in the Nurses’ Health Study II (1993–2017). Biennial questionnaires were used to determine the lifetime occurrence of spontaneous abortion in pregnancies lasting less than 6 months.

The researchers used time-dependent Cox proportional hazards models to estimate hazard ratios (HRs) and 95 percent confidence intervals (CIs) for all-cause and cause-specific premature death according to the occurrence of spontaneous abortion.

A total of 2,936 premature deaths, including 1,346 from cancer and 269 from CVD, occurred during 24 years of follow-up. Crude all-cause mortality rates were similar between women with and without a history of spontaneous abortion, at 1.24 per 1,000 person-years in both groups. However, such rates were higher for those with three or more spontaneous abortion before the age of 24 (1.69 per 1,000 person-years. [BMJ 2021;372:n530]

The age-adjusted HRs for all-cause premature death during follow-up were 1.02 (95 percent CI, 0.94–1.11), 1.39 (95 percent CI, 1.03–1.86), and 1.27 (95 percent CI, 1.11–1.46), respectively. Moreover, the occurrence of spontaneous abortion correlated with a 19-percent (HR, 1.19, 95 percent CI, 1.08–1.30) higher risk of premature death during follow-up after adjusting for confounding factors and updated dietary and lifestyle factors.

This association was more pronounced for recurrent spontaneous abortions (for three or more spontaneous abortions: HR, 1.59, 95 percent CI, 1.17–2.15; for two: HR, 1.23, 95 percent CI, 1.00–1.50; for one: HR, 1.16, 95 percent CI, 1.05–1.28) and for spontaneous abortions occurring early in a woman’s reproductive life (for age ≤23 years: HR, 1.32, 95 percent CI, 1.14–1.53; for ages 24–29 years: HR, 1.16, 95 percent CI, 1.01–1.33; for age ≥30 years: HR, 1.12, 95 percent CI, 0.98–1.28).

Analysis of the cause-specific mortality revealed CVD (HR, 1.48, 95 percent CI, 1.09–1.99) as the most common cause of death for women experiencing spontaneous abortion. Of note, no significant association was observed between spontaneous abortion and premature death from cancer (HR, 1.08, 95 percent CI, 0.94–1.24).

“The association between spontaneous abortion and CVD might reflect shared mechanistic pathways that contribute to spontaneous abortion and to the development of CVD and ultimately premature death,” the researchers said.

“For instance, insulin resistance, chronic kidney disease, and immune disorders have been linked to both spontaneous abortion and the development of clinical risk factors for CVD,” they added. [Gene 2015;569:136-140; Ginekol Pol 2011;82:272-275; Heart 2013;99:1636-1644]

Endothelial dysfunction was also associated with spontaneous abortion by causing defects of the placenta. Furthermore, it was implicated in the pathogenesis of cardiovascular, microvascular, and homeostatic dysfunction. [Fertil Steril 2013;100:1013-1017; Adv Exp Med Biol 2017;956:511-540]

Genetic or epigenetic features could also predispose women to both spontaneous abortion and CVD. This mechanism was supported by a 2011 study, which found that parents of women with recurrent spontaneous abortions had higher incidence of coronary artery disease. [BJOG 2011;118:557-563]

“More research is needed to establish how spontaneous abortion is related to women’s long-term health and the mechanisms underlying these relations,” the researchers said.