Pregnancy Complications May Set the Stage for Heart, Kidney and Metabolic Disease Decades Later

A woman’s medical chart often treats pregnancy as a chapter that closes once the baby arrives. A large new study argues that it is better understood as the opening line of a story that can unfold across an entire lifetime. Drawing on more than 165,000 women followed for a median of 44 years, researchers report that a history of adverse pregnancy outcomes — complications such as gestational diabetes and hypertensive disorders of pregnancy — dramatically raises the odds of developing cardio-renal-metabolic multimorbidity, the simultaneous presence of two or more of cardiovascular disease, type 2 diabetes and chronic kidney disease. Just as striking, the study finds that everyday lifestyle choices can either amplify or blunt that inherited risk trajectory.

The research, published in BMC Medicine by a team led by Sixian Liu and Jieyun Yin of Soochow University together with colleagues at Sichuan University, mined the UK Biobank, one of the world’s richest biomedical databases. The team defined the starting point of their disease model as either a first live birth or the diagnosis of an adverse pregnancy outcome, whichever came first. From there, they tracked women through a sequence of health states: the appearance of a first cardio-renal-metabolic disease, the accumulation of a second condition to reach multimorbidity, and ultimately death. This staged framing matters because it treats chronic disease not as a single event but as a process with distinct, measurable transitions.

Statistically, the investigators relied on multi-state models, a class of survival-analysis techniques that estimate the hazard — the instantaneous risk — of moving from one health state to the next, while adjusting for confounders such as age, socioeconomic status and other baseline characteristics. The approach allowed them to quantify not only whether adverse pregnancy outcomes raise risk, but at which point in the disease cascade that risk is concentrated. It also enabled them to test for interaction, asking whether the effect of a complicated pregnancy depends on what a woman does afterwards in terms of diet, smoking, alcohol, physical activity and body shape.

The headline numbers are sobering. Women with a history of adverse pregnancy outcomes progressed from a healthy initial state to a first cardio-renal-metabolic disease at a rate of 19.84 percent, compared with 15.56 percent among women without such a history — and the adjusted hazards ratio of 3.32 means their risk of making that transition was more than three times higher. That first transition proved to be the steepest part of the curve. Once a first disease had appeared, the excess risk of progressing to full multimorbidity persisted but moderated, with a hazards ratio of 1.41, and the risk of dying after multimorbidity was elevated at 1.65.

The mortality findings add a darker dimension. Women with adverse pregnancy outcomes faced a higher hazard of dying even before any cardio-renal-metabolic diagnosis, with an adjusted hazards ratio of 1.46 for the transition from the initial state directly to death, and a ratio of 1.28 for death after a first disease, though the latter estimate carried wider statistical uncertainty. Across nearly every stage of the model, the progression percentages were higher in the adverse-outcomes group, painting a consistent picture of a population whose pregnancies left a durable physiological signature.

What elevates the study beyond a simple risk tally is its treatment of lifestyle as a modifying force rather than a background variable. The researchers found a significant interaction between adverse pregnancy outcomes and high-risk lifestyle factors, with alcohol consumption, insufficient physical activity and unhealthy body shape emerging as the pivotal players during the transition from the initial state to a first cardio-renal-metabolic disease. In other words, the damage associated with a complicated pregnancy was not a fixed sentence; it interacted with behaviors that women and their clinicians can actually change.

The biological plausibility of such a long shadow is grounded in vascular and metabolic physiology. Hypertensive disorders of pregnancy are thought to reveal, and possibly worsen, underlying vulnerabilities in endothelial function — the health of the thin cell layer lining blood vessels — while gestational diabetes signals impaired glucose regulation that may predate the pregnancy itself. Pregnancy thus functions as a natural stress test for the cardiovascular, renal and metabolic systems. A woman who fails that test may carry forward subtle deficits in insulin sensitivity, blood pressure regulation and kidney filtration that silently accumulate until they cross diagnostic thresholds years or decades later.

The multi-state prediction component of the study carries practical weight. By combining adverse pregnancy outcome status with the number of lifestyle risk factors, the model showed that the probability of disease progression increased as risks stacked up. This has direct implications for how medicine organizes care. Obstetric histories are frequently recorded and then forgotten once a patient transitions to primary or specialty adult care, yet the findings argue that a history of gestational diabetes or preeclampsia should function as a lifelong flag — a reason for earlier screening, tighter monitoring of blood pressure and glucose, and more aggressive counseling on alcohol, activity and weight.

There are, of course, limits to what an observational cohort can prove. The UK Biobank population is not fully representative, and lifestyle factors were measured at baseline rather than tracked continuously across four decades, so changes in behavior over time are imperfectly captured. Residual confounding can never be excluded, and the interaction analyses, while statistically significant, describe associations rather than guaranteed causal pathways. Still, the sheer size of the cohort, the length of follow-up and the consistency of the hazard estimates across transitions give the findings considerable weight.

The broader message is one of opportunity. Cardio-renal-metabolic multimorbidity is among the most burdensome and expensive patterns of chronic disease in aging populations, and it rarely arrives unannounced. This study suggests that for millions of women, the first warning sign appears not in middle age but in a delivery room — in a blood pressure reading or a glucose tolerance test. Treating adverse pregnancy outcomes as the beginning of a long-term prevention program, rather than the end of a pregnancy complication, could shift the entire trajectory of women’s cardiovascular, kidney and metabolic health, and the lifestyle levers identified here offer a concrete place to start.

Subject of Research: The association between adverse pregnancy outcomes, lifestyle factors and long-term cardio-renal-metabolic multimorbidity risk in women

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

Article References: Liu, S., Long, L., Peng, Y., Guo, N., Gu, Y., Yang, M., & Yin, J. (2026). Association of adverse pregnancy outcomes history and lifestyle factors with cardio-renal-metabolic multimorbidity: a prospective cohort study. BMC Medicine. https://doi.org/10.1186/s12916-026-05224-w

Image Credits: AI Generated

DOI: 10.1186/s12916-026-05224-w

Keywords: adverse pregnancy outcomes, cardio-renal-metabolic multimorbidity, UK Biobank, gestational diabetes, hypertensive disorders of pregnancy, lifestyle factors, chronic kidney disease, type 2 diabetes, cardiovascular disease, multi-state models, epidemiology, women's health