Joint Association of Parity and Spontaneous Miscarriage with Incident Cardiovascular Diseases

Background: To prospectively investigate the combined association of parity and spontaneous miscarriage in relation to cardiovascular diseases (CVD) risks. Methods: In this prospective UK Biobank cohort analysis, multivariable Cox proportional hazards models were used in outcome-specific analytic cohorts: 219,422 participants free of prevalent CHD or stroke (CHD and stroke analyses) and 230,231, 230,589, and 229,123 participants free of the respective prevalent condition (PAD, HF, and AF analyses). Results: During a median follow-up of 12.2 years, parity exhibited a significant positive linear association with CHD risk. Nonlinear U-shaped associations were observed with HF and AF risks, with two live births representing the lowest risk. Importantly, a history of spontaneous miscarriage did not modify these associations. Compared to participants with two live births and no history of spontaneous miscarriage, individuals without any live births and no history of spontaneous miscarriage had the lowest point estimate for CHD (hazard ratio [HR] = 0.81, 95% confidence interval [CI] = 0.68– 0.95), whereas those with four or more live births and a history of spontaneous miscarriage exhibited the highest point estimate (HR = 1.43, 95% CI = 1.28– 1.60). Participants with four or more live births and a history of spontaneous miscarriage had the highest point estimate for HF and AF. Conclusion: The combined association of parity and spontaneous miscarriage and the risk for various CVDs exhibits outcome-specific patterns. Keywords: parity, spontaneous miscarriage, cardiovascular diseases