Premature mortality after pregnancy loss: Trends at 1, 5, 10 years, and beyond

https://doi.org/10.1016/j.ejogrb.2021.10.033Get rights and content

Highlights

  • We studied how pregnancy loss including miscarriage, induced abortion, ectopic or molar pregnancy, and stillbirth relate to premature mortality.

  • We found that nearly all forms of pregnancy loss are associated with premature mortality.

  • Risk is greatest in first 5 years after pregnancy loss but persists up to 30 years later.

  • Associations are strongest with cardiovascular, cancer, and suicide mortality.

Abstract

Objective

Little is known on the long-term risk of mortality following pregnancy loss. We assessed risks of premature mortality up to three decades after miscarriage, induced abortion, ectopic or molar pregnancy, and stillbirth relative to live birth.

Study design

We carried out a longitudinal cohort study of 1,293,640 pregnant women with 18,896,737 person-years of follow-up in Quebec, Canada, from 1989 to 2018. We followed the women up to 29 years after their last pregnancy event to determine the time and cause of future in-hospital deaths before age 75 years. We used adjusted Cox regression models to estimate hazard ratios (HR) and 95% confidence intervals (CI) for the association of miscarriage, induced abortion, ectopic pregnancy, molar pregnancy, and stillbirth with premature mortality, compared with live birth.

Results

Premature mortality rates were higher for most types of pregnancy loss than live birth. Compared with live birth, pregnancy loss was associated with an elevated risk of premature mortality (HRmiscarriage 1.48, 95% CI 1.33, 1.65; HRinduced abortion 1.50, 95% CI 1.39, 1.62; HRectopic 1.55, 95% CI 1.35, 1.79; and HRstillbirth 1.68, 95%. CI 1.17, 2.41). Molar pregnancy was not associated with premature mortality (HR 0.87, 95% CI 0.33, 2.32). Miscarriage and induced abortion were associated with most causes of death, whereas ectopic pregnancy was associated with cardiovascular (HR 2.18, 95 % CI 1.39, 3.42), cancer (HR 1.38, 95 % CI 1.11, 1.73), and suicide-related mortality (HR 4.94, 95 % CI 2.29, 10.68). Stillbirth was associated with cardiovascular mortality (HR 4.91, 95 % CI 2.33, 10.36).

Conclusion

Pregnancy loss is associated with an elevated risk of premature mortality up to three decades later, particularly cardiovascular, cancer, and suicide-related deaths.

Introduction

Little is known on the relationship between reproductive history and premature mortality. Premature mortality has decreased for women in most countries, but a high burden remains [1], [2]. There is some evidence that reproductive factors such as irregular menstrual cycles and age at menopause are associated with an increased risk of premature death [3]. Pregnancy outcomes such as preeclampsia and gestational diabetes are associated with an accelerated risk of mortality over the long-term [4], [5]. However, attention to pregnancy outcomes such as miscarriage, induced abortion, ectopic pregnancy, or molar pregnancy is limited [4].

Pregnancy loss is common [6], [7], [8], and has been associated with adverse sequelae that may increase the risk of premature mortality [4], [9], [10], [11]. Women with a history of miscarriage have a greater risk of cardiovascular disease and mortality [4], [9], [10]. Women with molar pregnancies are at risk of metastatic cancer [11], and women with ectopic pregnancies are at risk of maternal mortality [12]. Certain types of pregnancy loss may be associated with a greater risk of premature death. Pregnancy loss could be used to identify women in need of preventative care, particularly to prevent premature mortality before 75 years or deaths from cardiovascular disease, cancer, and suicide. We sought to determine the risk of premature mortality during 29 years of follow-up for women with miscarriage, induced abortion, ectopic pregnancy, molar pregnancy, stillbirth, and live birth.

Section snippets

Study design and population

We carried out a longitudinal cohort study of 1,293,640 women admitted for pregnancy events between 1989 and 2016 in Quebec, Canada. We obtained the data from the Maintenance and Use of Data for the Study of Hospital Clientele registry [13], which includes discharge records from all hospitals in the province. Discharge records allow us to identify admissions for miscarriage, induced abortion, ectopic pregnancy, molar pregnancy, and delivery of a live or stillborn infant. In Quebec, 99% of

Results

The cohort included 1,293,640 pregnant women with 18,896,737 person-years of follow-up (Table 1). A total of 8,549 women died during 29 years of follow-up for an overall incidence of 45.2 per 100,000 person-years. The median age of death was 46.4 years, and 99.1% of deaths occurred at age 65 years or less. 2.4% of women had miscarriage, 4.1% induced abortion, 1.2% unspecified abortion, 1.1% ectopic pregnancy, 0.1% molar pregnancy, and 0.2% stillbirth as the final pregnancy event. Mortality

Discussion

In this study of 1,293,640 women with nearly 19 million person-years of follow-up, miscarriage, induced abortion, ectopic pregnancy, and stillbirth were associated with an elevated risk of premature mortality up to three decades later compared with live birth. Mortality risk for these types of pregnancy loss was greatest within the first five years of pregnancy. Miscarriage, induced abortion, and ectopic pregnancy were strongly associated with cancer and suicide deaths, whereas induced

Conclusion

In this study of 1.3 million pregnant women, most types of pregnancy loss were associated with an elevated risk of mortality up to three decades after pregnancy, with associations strongest for cardiovascular, cancer, and suicide mortality. Molar pregnancy was not associated with an increased risk of premature death. Women with pregnancy loss may benefit from closer clinical follow-up to reduce the risk of premature mortality due to cardiovascular disease, cancer, suicide, and other causes.

Declaration of Competing Interest

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Acknowledgements

The authors thank Siyi He for statistical analysis and assistance with a preliminary version of the manuscript.

Funding information

This study was supported by the Heart & Stroke Foundation of Canada (G-18-0021776) and Fonds de recherche du Québec-Santé (296785). The sponsors were not involved in study design; in the collection, analysis and interpretation of data; in the writing of the report; and in the decision to submit the article for publication.

References (26)

  • S.M. Grandi et al.

    Cardiovascular disease-related morbidity and mortality in women with a history of pregnancy complications

    Circulation

    (2019)
  • Ø. Lidegaard et al.

    Pregnancy loss: A 40-year nationwide assessment

    Acta Obstet Gynecol Scand

    (2020)
  • J. Horn et al.

    Early or late pregnancy loss and development of clinical cardiovascular disease risk factors: A prospective cohort study

    BJOG

    (2019)
  • View full text