What is the clinical evidence from this study?

Study design: Cohort. Population: Cardiovascular disease risk in postmenopausal women (n=77701). Intervention: History of stillbirth (1 or more) vs. No history of stillbirth. Primary outcome: Coronary heart disease (CHD) (OR 1.27, 95% CI 1.07-1.51).

July 1, 2014Open Access

Risk of Cardiovascular Disease Among Postmenopausal Women with Prior Pregnancy Loss: The Women's Health Initiative

Key Result

A history of one or more stillbirths increased the risk of coronary heart disease (OR 1.27) compared to no stillbirth in postmenopausal women.

Study Design

Type

Cohort (n=77,701)

Multicenter

Yes

Structured PICO

Does a history of pregnancy loss increase the risk of cardiovascular disease in postmenopausal women?

Population

77,701 postmenopausal women evaluated from 1993-1998

Intervention

History of pregnancy loss (1 or 2 or more miscarriages, and 1 or more stillbirths)

Comparator

No history of miscarriage or stillbirth

Outcome

Occurrence of cardiovascular disease (coronary heart disease and ischemic stroke)hard clinical

Pregnancy loss, including miscarriages and stillbirths, is associated with an increased risk of future coronary heart disease in postmenopausal women, suggesting a need for closer surveillance.

Main Result

Effect estimate: OR 1.27 (95% CI 1.07-1.51)

Limitations

Pregnancy loss was based on self-report and subject to misclassification bias
Self-reports of miscarriage may be underestimated
Lack of biomarker data such as high-sensitivity C-reactive protein
Information on weeks of gestation and age at pregnancy loss was not available
Observational nature of the study cannot prove causality

Abstract

PURPOSE: Metabolic, hormonal, and hemostatic changes associated with pregnancy loss (stillbirth and miscarriage) may contribute to the development of cardiovascular disease (CVD) in adulthood. This study evaluated prospectively the association between a history of pregnancy loss and CVD in a cohort of postmenopausal women. METHODS: Postmenopausal women (77,701) were evaluated from 1993-1998. Information on baseline reproductive history, sociodemographic, and CVD risk factors were collected. The associations between 1 or 2 or more miscarriages and 1 or more stillbirths with occurrence of CVD were evaluated using multiple logistic regression. RESULTS: Among 77,701 women in the study sample, 23,538 (30.3%) reported a history of miscarriage; 1,670 (2.2%) reported a history of stillbirth; and 1,673 (2.2%) reported a history of both miscarriage and stillbirth. Multivariable-adjusted odds ratio (OR) for coronary heart disease (CHD) for 1 or more stillbirths was 1.27 (95% CI, 1.07-1.51) compared with no stillbirth; for women with a history of 1 miscarriage, the OR=1.19 (95% CI, 1.08-1.32); and for 2 or more miscarriages the OR=1.18 (95% CI, 1.04-1.34) compared with no miscarriage. For ischemic stroke, the multivariable odds ratio for stillbirths and miscarriages was not significant. CONCLUSIONS: Pregnancy loss was associated with CHD but not ischemic stroke. Women with a history of 1 or more stillbirths or 1 or more miscarriages appear to be at increased risk of future CVD and should be considered candidates for closer surveillance and/or early intervention; research is needed into better understanding the pathophysiologic mechanisms behind the increased risk of CVD associated with pregnancy loss.

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