Women's Mortality Following Childbirths Affected by Vaginal Bleeding Due to Threatened Miscarriage: A Danish Cohort Study with up to 40 Years of Follow-up

Background: Women whose reproductive history includes only pregnancy terminations or only miscarriages are at up to 3-fold greater risk of death from any cause. Little is known about the association of vaginal bleeding (VB)-affected childbirths and women's mortality.

Objectives: To investigate women's mortality risk following childbirth affected by VB due to threatened miscarriage as compared with that following VB-unaffected childbirths, terminations or miscarriages.

Methods: This was a registry-based cohort study in Denmark. We identified 1,355,935 women and their 3,164,570 pregnancies in 1979-2017, followed through 2018. We ascertained 70,845 VB-affected childbirths and three comparison cohorts: 2,236,360 VB-unaffected childbirths; 591,425 terminations; and 265,940 miscarriages. We computed all-cause and cause-specific mortality rates per 10,000 person-years (PY) and cumulative mortality at 40 years of follow-up. Hazard ratios (HRs) with 95% confidence intervals (CIs) were obtained using Cox proportional hazards regression, adjusting for age, calendar year, comorbidities, comedications, and socioeconomic factors using inverse probability of treatment weighting.

Results: At the end of follow-up, there were 2,320 deaths from any cause among women following VB-affected childbirth (mortality rate: 14.86, 95% CI: 14.26-15.47 per 10,000 PY); 55,030 deaths following VB-unaffected childbirth (12.67, 12.56-12.77); 27,500 deaths following a termination (21.87, 21.61-22.13) and 10,865 deaths following a miscarriage (19.18, 18.83-19.55). An association with all-cause mortality following VB-affected vs VB-unaffected childbirth (HR=1.11, 95% CI: 1.06-1.16) disappeared in a sensitivity analysis of pregnancies recorded in 1994 onwards (HR=1.00, 95% CI: 0.90-1.10). Following VB-affected vs VB-unaffected childbirth, women's mortality from non-natural causes (HR=1.26, 95% CI: 1.11-1.42), including non-motor vehicle accidents or violence (HR=1.41, 95% CI: 1.18-1.69) and suicides (HR=1.22, 95% CI: 1.00-1.50) was increased. Comparisons with terminations and miscarriages showed decreased risks of all-cause mortality (HR=0.84, 95% CI: 0.80-0.89 and HR=0.88, 95% CI: 0.83-0.94, respectively) and mortality from natural causes (HR=0.86, 95% CI: 0.81-0.91 and HR=0.89, 95% CI: 0.83-0.96, respectively).

Conclusions: Following VB-affected vs VB-unaffected childbirths, we found no increased risk of women's all-cause and natural causes mortality; there was an increased risk of non-natural causes mortality including suicides, although the absolute risk was low.