Association of adverse pregnancy outcomes history and lifestyle factors with cardio-renal-metabolic multimorbidity: a prospective cohort study

The impact of adverse pregnancy outcomes (APOs) and their interaction with modifiable lifestyle factors on the overall occurrence and long-term progression of Cardio-Renal-Metabolic Diseases (CRMDs) in women remains unclear. This prospective cohort study included 165,684 women from the UK Biobank. Cardio-Renal-Metabolic Multimorbidity (CRMM) was defined as the concurrent presence of two or more conditions: cardiovascular disease, type 2 diabetes, and chronic kidney disease. Multi-state models were used to evaluate the interaction and predictive probability of APOs and lifestyle factors (diet, smoking, alcohol consumption, physical activity, and body shape) on the occurrence and progression of CRMDs. During a median follow-up of 44 years after the initial state (first live birth or diagnostic of APOs), women with a history of APOs showed higher progression percentages than those without APOs history at almost all stages: initial state to first CRMD [FCRMD, 19.84% vs. 15.56%; adjusted hazards ratio (aHR) = 3.32, 95% confidence interval (CI) = 3.07–3.58], FCRMD to CRMM (24.27% vs. 19.86%; aHR = 1.41, 95%CI = 1.20–1.66), CRMM to death (26.95% vs. 19.04%; aHR = 1.65, 95%CI = 1.20–2.25), initial state to death (1.41% vs. 3.04%; aHR = 1.46, 95%CI = 1.10–1.94), and FCRMD to death (5.81% vs. 8.37%; aHR = 1.28, 95%CI = 0.93–1.76). A significant interaction between APOs and high-risk lifestyle factors, especially alcohol consumption, insufficient physical activity, and unhealthy body shape, plays a pivotal role in the transition from APOs to FCRMD. In addition, the multi-state prediction model showed that the combination of APO status and number of lifestyle risk factors increased the probability of disease progression. Women with a history of APOs exhibited higher transition hazards to CRMDs. Significant interactions were observed for alcohol consumption, physical activity, and body shape during the transition from the initial state to FCRMD.