Miscarriage associated with increased risk for premature death
Women with previous pregnancy losses had an increased risk for premature death from all causes and cardiovascular mortality, according to results of a prospective cohort study.
“From this study alone, we cannot discern what are the underlying biologic links of this relation,” Jorge Chavarro, MD, ScD, associate professor of medicine at Harvard Medical School and associate epidemiologist at Brigham and Women’s Hospital, told Healio Primary Care. “We can, however, be fairly certain that the relation we observed is not due to shared risk factors such as smoking, diet quality or obesity.”
Chavarro and colleagues used data from the Nurses’ Health Study II, an ongoing prospective cohort study that first began recruiting participants in 1989. The current analysis is based on data collected from 1993 to 2017. The study population included 101,681 female nurses who completed questionnaires biennially.
The researchers compared outcomes between participants who had a spontaneous abortion (mean age, 38.32 years; non-Hispanic and white, 92.49%) with those who did not have a spontaneous abortion (mean age, 38.85 years; non-Hispanic and white, 91.44%). Overall, 25.6% (n=26,102) of women in the study had at least one pregnancy that ended in a spontaneous abortion.
The researchers reported 2,936 premature deaths, including 269 from CVD and 1,346 from cancer. After adjusting for confounding factors as well as updated dietary and lifestyle factors, the data showed that women who had a spontaneous abortion had an increased risk for premature mortality (HR = 1.19; 95% CI, 1.08-1.3). The link was stronger among women who had recurrent spontaneous abortions. Compared with those who did not have a spontaneous abortion, the hazard ratio for premature mortality was 1.59 (95% CI, 1.17-2.15) among women with three or more spontaneous abortions, 1.23 (95% CI, 1-1.5) for those with two spontaneous abortions, and 1.16 (95% CI, 1.05-1.28) for those with one spontaneous abortion.
The researchers also found that women who had a spontaneous abortion earlier in life had a greater risk for premature mortality than those who had one later in life. The hazard ratio was 1.32 (95% CI, 1.14-1.53) for those aged 23 years or younger, 1.16 (95% CI, 1.01-1.33) for those aged 24 to 29 years, and 1.12 (95% CI, .98-1.28) for those aged 30 years or older compared with women who did not have a spontaneous abortion.
When evaluating cause-specific mortality, the researchers found the strongest association was for deaths related to CVD (HR = 1.48; 95% CI, 1.09-1.99). There was no significant relationship between spontaneous abortion and cancer mortality, they wrote.
“The main take-home message of our study is that women who have experienced miscarriages are at a higher risk of premature mortality, particularly for deaths due to CVD and for women who have either had multiple miscarriages throughout their life or have experienced miscarriages in their 20s or earlier,” Chavarro said.
He said that future research should consider “whether and to what extent shared biological factors, such as genetic predisposition, insulin resistance or endothelial dysfunction, may explain this relation.”
“A crucial question will be to understand whether this elevated risk can be explained by known risk factors for CVD such as elevated BP, in which long-term risk management could be essentially an extension of what is already done, or if this elevated risk is also present in women without traditional risk factors for CVD, which may necessitate discovery of risk biomarkers and a better understanding of the biological pathways linking miscarriage to premature cardiovascular mortality,” Chavarro said.
Perspective
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This is an important study because it’s been looked at before, but this is unique because of the data set. Nurses’ health studies are a well-known, well-run, very large data set that allows us to make longitudinal observations that are hard to do otherwise. And while there has been some studies in other countries that have suggested this, this [current study] is in the U.S. and most relevant to our practices here. With this, clinical implications are twofold. One is for people who take care of women to keep this on their radar for their risk for cardiovascular morbidity and death because it becomes a risk factor, similar to family history. For people who take care of women, especially in their 40s, 50s, 60s, it’s important to keep in mind. Second, it’s also intriguing because we don’t really understand what’s going on. There are different causes of miscarriages. Some are chromosomal, some are medical and some are mysterious — up to half of them we aren’t able to explain. This would suggest there is possibly some connection, especially between how early miscarriages early in a woman’s life either increases the risk for later death or there is some underlying cause we have not yet identified that makes her at risk for both miscarriages and early death.
This study answers a question and asks a number of questions, which is typical for good research. It is important to note that people shouldn’t panic from reading this because miscarriages happen to a lot of people, up to 15% to 25% of pregnancies. I would not want everyone thinking they’re at terrible risk, but they should always have a conversation with their provider about their global risks, family risks, medical risks, activity risk, and we have to keep in mind cardiovascular causes are the No. 1 killer of women. We always should be looking for ways to reduce their risk of a cardiac morbidity or mortality. It’s important [to note], heart attack and stroke often times will manifest differently in men and women, so it’s important their caregivers are in tune with what those risks are and how to diffuse those risks.
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