Stillbirth increase long-term health risks of diabetes, CVD, CVD mortality, and all-cause mortality.

Background: Fewer studies on association of single stillbirth exposure with long-term health outcomes in women. In this study of cohort data from UK Biobank, we aim to explore the association of stillbirth with the risk of diabetes, cardiovascular disease (CVD), all-cause mortality, CVD mortality, ischemic heart disease (IHD), myocardial infarction (MI), heart failure (HF), and stroke.

Methods: We initially included 502,366 participants aged 40-69 years. Multivariate Cox regressions were used to evaluate associations of stillbirths with diabetes, CVD, all-cause mortality, and CVD mortality utilizing hazard ratios (HRs) and 95% confidence intervals (CIs). Moreover, non-linear relationship between stillbirths and four main outcomes above was analyzed by restricted cubic spline (RCS) modeling. Additionally, subgroup analyses and interaction term were performed to explore impact of specific factors on associations of interest. Cumulative incidence rates were calculated to observe time-event changes in target outcomes.

Results: Finally, 248,195 women were included to analyze with 15,128 diabetes cases, 17,834 CVD cases, 15,334 all-cause mortality cases, and 949 CVD mortality cases. Among women who experienced stillbirth, fully adjusted HRs (95% CI) were 1.12 (1.07-1.18) for diabetes, 1.13 (1.08-1.19) for CVD, 1.12 (1.06-1.19) for all-cause mortality, and 1.27 (1.11-1.46) for CVD mortality. No significant associations were observed between stillbirth and all-cause or CVD mortality among women with household income ≥ 31,000 £, or without a history of hypertension. When specific cardiovascular outcomes were considered, the number of stillbirth was significantly associated with increased risk of IHD (HR 1.14; 95% CI 1.08-1.20) and MI (HR 1.14; 95% CI 1.01-1.27), while associations with stroke (HR 1.10; 95% CI 0.99-1.21) and HF (HR 1.12; 95% CI 0.98-1.27) were not statistically significant. Results of RCS plots and cumulative incidence rates show that the risk and incidence rates of diabetes, CVD, all-cause mortality, as well as CVD mortality ovaerall rose with increasing number of stillbirths and time, respectively.

Conclusion: Stillbirth was associated with increased risks of diabetes, CVD, ischemic heart disease, all-cause mortality, and CVD mortality. These associations varied by socioeconomic and clinical factors. Given the observational design, these findings represent associations rather than causal relationships. Further research is needed to clarify underlying mechanisms.