Prenatal factors shaping adolescent cardiovascular function and cardiometabolic risk trajectories

Abstract

Cardiovascular disease remains the leading cause of mortality worldwide, with early risk markers, including elevated blood pressure, arterial stiffness, and adverse lipid profiles, often emerging during adolescence. These phenotypes are clinically important, as adolescent cardiovascular risk strongly predicts adult subclinical atherosclerosis and future cardiovascular events. Increasing evidence from developmental origins of health and disease (DOHaD) research suggests that cardiovascular outcomes in adolescence are associated, in part, with prenatal exposures. This review synthesizes current evidence linking prenatal factors to cardiovascular outcomes in adolescence and examines the biological mechanisms that may mediate these associations. A structured literature search of PubMed from database inception through March 14, 2026 was conducted, including peer-reviewed studies published in English that examined associations between prenatal exposures and cardiovascular outcomes in adolescent populations. Growth-related metrics, particularly low birth weight and preterm birth, emerged as the most consistent correlates of elevated blood pressure and adverse structural phenotypes. Maternal preeclampsia and gestational hypertension were associated with altered offspring cardiac structure and endocrine regulation. Maternal obesity and diabetes were correlated with adverse cardiometabolic outcomes, though these associations were largely mediated by offspring adiposity, suggesting a prominent role for shared genetic and postnatal environmental factors. Prenatal nutritional interventions showed limited effects on cardiovascular outcomes, while environmental exposures such as maternal smoking and chemical pollutants were associated with increased risk, potentially through oxidative stress and disrupted organogenesis. Common mechanistic pathways across exposure categories included impaired nephrogenesis, hypothalamic-pituitary-adrenal axis dysregulation, and disrupted autonomic regulation. Despite these advances, significant knowledge gaps remain in fully understanding the contribution of prenatal factors to cardiovascular health during adolescence. Further studies utilizing state-of-the-art technologies to better characterize prenatal exposures, including metabolomic, exposomic, and other omics-based approaches, are needed to clarify the biological pathways linking the prenatal environment to adolescent cardiovascular risk and to inform earlier risk identification and preventive strategies.