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Risk of diabetes and cardiovascular diseases in women with pregnancies complicated by vaginal bleeding: Danish population-based cohort study

Objective: To investigate an association between childbirths affected by vaginal bleeding within 20 gestational weeks and women's subsequent risks of diabetes and cardiovascular diseases. Design: Cohort study in Denmark, 1979-2018. Setting: Danish nationwide registries. Participants: Between 1979 and 2017, we identified 3,085,955 pregnancies among 1,329,331 women. Of these pregnancies, 69,230 ended in childbirth affected by vaginal bleeding (VB) within 20 gestational weeks; 2,180,855 ended in VB-unaffected childbirth; 578,355 ended in termination, and 258,430 ended in a miscarriage. Main outcome measures: The outcomes were diabetes types 1 and 2, hypertension, ischaemic heart disease, including myocardial infarction, atrial fibrillation or flutter, heart failure, ischaemic and haemorrhagic stroke, coronary artery bypass grafting, and percutaneous coronary intervention. We computed the incidence rates per 10,000 person-years and cumulative incidences of cardiovascular outcomes at up to 40 years of follow-up. Hazard ratios (HRs) with 95% confidence intervals adjusted for age, calendar year, reproductive history, baseline comorbidities, and socioeconomic factors were computed using conventionally and inverse probability of treatment weighted Cox proportional hazards regression. Results: At the end of the follow-up, among women with VB-affected vs VB-unaffected childbirths, the cumulative risks of the outcome events were 4.5% vs 3.5% for diabetes type 1; 13.8% vs 11.1% for diabetes type 2; 25.1% vs 21.4% for hypertension; 10.6% vs 8.2% for ischaemic heart disease, including 2.9% vs 2.6% for myocardial infarction; 5.3% vs 4.4% for atrial fibrillation or flutter; 2.3% vs 2.0% for heart failure; 5.1% vs 4.0% for ischaemic stroke; 1.8% vs 1.4% for haemorrhagic stroke; 0.5% vs 0.4% for coronary artery bypass graft; and 2.4% vs 1.9% for percutaneous coronary intervention. Adjusted HRs were 1.2 to 1.3-fold increased for diabetes types 1 and 2, hypertension, ischaemic heart disease, atrial fibrillation or flutter, heart failure, ischaemic and haemorrhagic stroke as well as a coronary artery bypass grafting. Following women's first pregnancies and in sensitivity analyses, the HRs remained increased. For comparisons of VB-affected childbirths with terminations, HRs were up to 1.3-fold increased for diabetes and 1.1-fold increased for hypertension, ischaemic heart disease, atrial fibrillation or flutter, and haemorrhagic stroke. HRs were unity when we compared having VB-affected childbirth with having a miscarriage. Conclusions: Women's risks of diabetes types 1 and 2 and multiple cardiovascular outcomes were increased on the relative scale following childbirths affected by VB within 20 gestational weeks when compared with VB-unaffected childbirths and terminations, but not when compared with miscarriages.