History of recurrent spontaneous abortions linked to increased risk of premature mortality

1. Spontaneous abortion could potentially serve as a marker for future health risk in women, particularly death from cardiovascular disease.

2. Association of risk is particularly strong with women who experience three or more recurrent spontaneous abortions and those reporting spontaneous abortions occurring before age 24.

Evidence Rating Level: 2 (Good)

Study Rundown: Pregnancy is thought to be the ultimate stress test on the body, as a woman’s body must work overtime to support the needs of the fetus. Underlying risk factors for premature mortality, such as poor cardiovascular health or gestational diabetes, may arise for the first-time during pregnancy and return later in life. Additionally, spontaneous abortions are a common adverse outcome of pregnancy that may have implications for maternal health. Using the Nurses’ Health Study II (1993), this publication compares the reported reproductive history of spontaneous abortions and risk of premature death of women throughout 24 years of follow-up. Women who have had self-reported spontaneous abortions were seen to be at a higher risk for premature death, notability death from cardiovascular disease. This association strengthens for women who have had multiple spontaneous abortions or those would had spontaneous abortions before age 24. Strengths of this study over similar include the large sample size, thorough follow-up, prospective nature, and ability to adjust and modify for many variables, such as lifestyle, reproductive, and health factors. As an RCT is not possible with spontaneous abortions, this study cannot demonstrate causality; however, causality is not required to rationalize that spontaneous abortion is a marker, rather than a cause, of premature death. This study further supports that pregnancy is a physiological stress test and reproductive events can indicate health later in a woman’s life.

Click to read the study in the BMJ

Relevant Reading: Spontaneous loss of early pregnancy and risk of ischaemic heart disease in later life: retrospective cohort study

In-Depth [prospective cohort]: The Nurses’ Health Study II is a currently ongoing prospective cohort study of 116 429 nurses (aged 25-42) with continuous follow-up spanning three decades. Inclusion criteria was based on non-zero gravida (n=101 681) and exclusion criteria included death before 1993 and missing history data. History was taken through questionnaires every two years on pregnancies, spontaneous and induced abortions. Cause of death was determined by autopsy reports, medical records, and death certificates. Many other variables were reported: gestational diabetes and hypertensive disorders of pregnancy were self-reported; body weight, height, race, and ethnicity were collected at baseline in follow-ups; family history and social history were updated every two to four years. Overall, there were 2936 premature deaths (1346 from cancer and 269 from cardiovascular disease) in the study cohort. Cause-specific analysis showed spontaneous abortion was not associated with death from cancer (hazard ratio 1.08, 95% CI 0.94 to 1.24), but was associated with greater risk of death from cardiovascular disease (1.48, 95% CI 1.09 to 1.99). The final multivariable adjusted hazard ratios for all cause premature death were 1.59 (95% CI 1.17 to 2.15) for three or more spontaneous abortions, 1.23 (95% CI 1.00 to 1.50) for two spontaneous abortions, and 1.16 (95% CI 1.05 to 1.28) for one spontaneous abortion. Additionally, multivariable adjusted hazard ratio was 1.32 (95% CI 1.14 to 1.53) for a first spontaneous abortion occurring in women aged 23 or younger relative to no spontaneous abortion. Compared to gravid women who never had a spontaneous abortion, hazard ratios for premature mortality from cardiovascular disease were 1.59 (95% CI 1.15 to 2.20) for women who had a spontaneous abortion and 1.06 (95% CI 0.70 to 1.62) for women who had an induced abortion, but no spontaneous abortion.

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