Pregnancy Complications and Risk of Cardiovascular Disease Later in Life: A Nationwide Cohort Study

Abstract

Background The aim of this study was to investigate the associations between pregnancy complications and cardiovascular mortality and hospitalizations of cardiovascular disease (CVD) after adjustment for major confounding. Methods and Results In a nationwide register-based cohort study, women with singleton births between 1973 and 2014 were included from the Swedish Medical Birth Register. Outcomes of mortality and hospitalizations of CVD were collected from the Cause of Death Register and the National Inpatient Register. The cohort was followed from the date of the first delivery until death or end of follow-up, whichever occurred first. The pregnancy complications studied were preeclampsia or eclampsia, gestational hypertension, gestational diabetes, preterm birth, small for gestational age, and stillbirth. Among the 2 134 239 women (mean age at first pregnancy, 27.0 [SD, 5.1] and mean parity 1.96 [SD, 0.9]), 19.1% (N=407 597) had 1 of the studied pregnancy complications. All pregnancy complications were associated with all-cause and cardiovascular mortality and hospitalization for CVD (ischemic heart disease, ischemic stroke, and peripheral artery disease) after adjustment for major confounding in a Cox proportional hazard regression model. The adjusted hazard ratio for cardiovascular mortality was 1.84 (95% CI, 1.38-2.44) for preterm birth and 3.14 (95% CI, 1.81-5.44) for stillbirth. Conclusions In this large cohort study, pregnancy complications were associated with all-cause mortality, cardiovascular mortality, and hospitalizations for CVD, also after adjusting for confounding, including overweight, smoking, and comorbidities. The study highlights that less established pregnancy complications such as preterm birth and stillbirth are also associated with cardiovascular mortality and CVD.

Keywords: cardiovascular disease; ischemic heart disease; ischemic stroke; peripheral artery disease; pregnancy complications.

FIGURE 1. Flowchart of the study population with births in Sweden 1973 to 2014.

FIGURE 2. Unadjusted cumulative incidence plots for all‐cause and cardiovascular mortality in women unexposed and exposed to pregnancy complications in any pregnancy 1973 to 2014.

Women aged ≤75 years at the end of 2014 were included.

FIGURE 3. Unadjusted cumulative incidence plots for all‐cause and cardiovascular mortality stratified into 3 age categories in women unexposed and exposed to pregnancy complications in any pregnancy.

Women aged ≤75 years at the end of 2014 were included.

FIGURE 4. Forest plots for first‐time hospitalization of ischemic heart disease, ischemic stroke/transient ischemic attack, peripheral artery disease, and pregnancy complications.

Data are described as hazard ratios (HRs) calculated by Cox proportional hazard regression by and 95% CI. Adjusted for maternal age, maternal age², BMI, BMI², smoking status, family situation, comorbidities associated with pregnancy and at first‐time hospitalization for cardiovascular disease (diabetes, hypertension, chronic kidney failure, and venous thrombosis), parity, and decade at first pregnancy. Beyond this, we also adjusted for preeclampsia or eclampsia in any pregnancy for the fetal complications. BMI indicates body mass index; GDM, gestational diabetes mellitus; GHT, gestational hypertension; PE or E, preeclampsia or eclampsia; PTB, preterm birth (<37 weeks); SGA, small for gestational age; VPTB, very preterm birth (<32 weeks).

FIGURE 5. Unadjusted cumulative incidence plots for first‐time hospitalizations of ischemic heart disease (IHD) and all‐cause mortality, ischemic stroke/transient ischemic attack (TIA) and all‐cause mortality and peripheral artery disease (PAD) and all‐cause mortality in women unexposed and exposed to pregnancy complications in any pregnancy.

Women aged ≤75 years at the end of 2014 were included.