Abstract
<title>Abstract</title> <p>Background The cardio-kidney-metabolic (CKM) syndrome, recently conceptualized by the American Heart Association (AHA) in 2023, integrates cardiovascular, renal, and metabolic dysfunction into a unified staging framework. To date, no study worldwide has examined the association between parity and CKM syndrome stages. Fertility history may influence long-term metabolic health through hormonal fluctuations, inflammatory responses, and cumulative physiological stress. This cross-sectional design cannot support causal inference. Methods We analyzed 4,814 women aged 45 years and older with complete blood biomarker data from the China Health and Retirement Longitudinal Study (CHARLS, 2011–2018). CKM stages were classified using objective biomarkers including cystatin C-based estimated glomerular filtration rate (eGFR). Parity was categorized as 0, 1, 2 (reference), 3, 4–5, and 6 or more. Poisson regression with robust standard errors estimated adjusted prevalence ratios (aPR). Restricted cubic splines (RCS) assessed dose-response relationships. Exploratory factor analysis identified multimorbidity patterns. Multiple imputation by chained equations (MICE) addressed missing data. Results The prevalence of CKM Stage 2 or higher was 53.2%. Parity demonstrated a U-shaped association with CKM syndrome. Compared with parity = 2, aPRs were: parity = 1: 0.88 (95% CI: 0.75–1.02, P = 0.078); parity 6 or more: 0.87 (95% CI: 0.74–1.03, P = 0.110). RCS analysis confirmed a nonlinear dose-response with the nadir at parity = 2–3 (Wald P = 0.042). Factor analysis revealed three multimorbidity patterns: respiratory-cardio-arthritic (beta = + 0.026, P = 0.001), cardio-metabolic (beta approximately 0, P = 0.98), and digestive-arthritic-renal (beta = + 0.014, P = 0.020). MICE analysis (n = 7,236) confirmed directionally consistent findings. Conclusions Parity exhibits a U-shaped association with CKM syndrome in Chinese middle-aged and older women, suggesting a "healthy mother effect" with dual protective pathways. These findings support integrating fertility history into sex-specific CKM risk assessment.</p>