Risk of diabetes and cardiovascular diseases in women with vaginal bleeding before 20 gestational weeks: Danish population-based cohort study

Importance The risk of cardiovascular outcomes following a pregnancy complicated by vaginal bleeding (VB) not ending in a miscarriage is not fully understood. Objective To study an association between pregnancy affected by VB and women’s subsequent risks of diabetes and cardiovascular outcomes. Design, Setting and Participants We conducted a population-based cohort study set in Denmark, 1994-2018. Using Danish nationwide registries, we identified 1,901,725 pregnancies among 903,327 women. Of these, 39,265 were affected by VB and ended in childbirth; 1,389,285 were unaffected by VB and ended in childbirth; 333,785 ended in termination, and 139,390 ended in a miscarriage. Exposure(s) Pregnancy affected by vaginal bleeding before 20 gestational weeks. 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. We computed absolute risks and hazard ratios (aHRs) with robust 95% confidence intervals (CIs) adjusted for age, calendar year, reproductive history, comorbidities, and socioeconomic factors using Cox proportional hazards regression. Results At the end of the follow-up, among women with VB-affected vs VB-unaffected pregnancies, the cumulative risks of the outcome events were 1.7% vs 1.4% for diabetes type 1; 6.9% vs 5.6% for diabetes type 2; 11.1% vs 9.0% for hypertension; 3.6% vs 2.7% for ischaemic heart disease, including 1.1% vs 0.8% for myocardial infarction; 1.3% vs 1.0% for atrial fibrillation or flutter; 0.5% vs 0.5% for heart failure; 2.0% vs 1.3% for ischaemic stroke; and 0.8% vs 0.6% for haemorrhagic stroke and aHRs were 1.2 to 1.3-fold increased for diabetes types 1 and 2, hypertension, ischaemic heart disease, myocardial infarction, atrial fibrillation or flutter, and heart failure. The aHRs were 1.4 and 1.5-fold increased for ischaemic and haemorrhagic stroke, respectively. For comparisons of women with VB-affected pregnancy vs termination, aHRs were up to 1.3-fold increased for diabetes and hypertension. Analyses contrasting VB-affected pregnancy with miscarriage resulted in aHRs below or close to the null value. Conclusions Women’s risks of diabetes and cardiovascular outcomes were increased following VB-affected pregnancy when compared with VB-unaffected pregnancy or termination, but not when compared with miscarriage. Key points Question Is having a pregnancy affected by vaginal bleeding and not ending in miscarriage associated with the increased risk of diabetes and cardiovascular outcomes in women? Findings This nationwide registry-based cohort study of 1,901,725 pregnancies among 903,327 women showed that in contrast with having a pregnancy without vaginal bleeding, having a pregnancy with vaginal bleeding before 20 gestational weeks was associated with woman’s increased risks of diabetes types 1 and 2, hypertension, ischaemic heart disease, including myocardial infarction, atrial fibrillation or flutter, heart failure, ischaemic and haemorrhagic stroke. The cardiovascular risks were increased when investigating a woman’s first pregnancy with vaginal bleeding before 20 gestational vs without vaginal bleeding during pregnancy; the associations remained when we additionally adjusted for smoking and body-mass index in a sensitivity analysis. Meaning The results of this study support current clinical practice on cardiovascular prevention in women with pregnancy complications and add to the body of evidence on a common pregnancy complication, vaginal bleeding, and its association with long-term risks of diabetes and cardiovascular conditions.