Spontaneous miscarriage and later lifestyle in predicting hazard of premature mortality: a cohort study in UK Biobank

OBJECTIVE: To prospectively assess the association of spontaneous miscarriage with the hazard of premature mortality and to examine the interaction between spontaneous miscarriage and lifestyle in relation to premature mortality. METHODS: A total of 231,148 participants from the UK Biobank were included. The unhealthy lifestyle was defined as an unhealthy diet, smoking, irregular physical activity, and an abnormal body mass index. Cox proportional hazards models were used to evaluate the associations. RESULTS: During a median follow-up time of 12.3 years, 11,672 premature mortalities were documented. Compared to women who did not have a spontaneous miscarriage, the multivariable-adjusted hazard ratios (aHRs) for all-cause premature mortality according to the number of spontaneous miscarriages were 0.98 (95% confidence interval [CI] 0.93-1.04) for one, 1.16 (1.06-1.27) for two, and 1.24 (1.10-1.39) for three or more, respectively (P-trend < 0.001). In contrast, the ever-versus-never comparison (any miscarriage) was not significant after adjustment for lifestyle factors. We found a significant interaction on an additive scale between a greater number of spontaneous miscarriages and the unhealthy lifestyle score (P for additive interaction = 0.03) on the risk of premature mortality. CONCLUSIONS: Our findings indicate that recurrent spontaneous miscarriage (≥ 2 events) serves as a risk marker for higher hazard of all-cause premature mortality, particularly death from cardiovascular disease, whereas a single miscarriage and the ever-versus-never comparison showed no significant association after full adjustment. A postnatal unhealthy lifestyle may partly account for the observed association, suggesting that lifestyle modification could be a focus for future preventive strategies in this high-risk population.