Early Life Stress and Adversity in Children: Neuroendocrine Mechanisms, Epigenetic Regulation, and Lifespan...

Early life stress (ELS) and adverse childhood experiences are critical determinants of neurodevelopmental trajectories and long-term somatic and psychiatric health outcomes. This narrative review synthesizes current evidence, identified through searches in PubMed, Scopus, and Web of Science, on the neurobiological and epigenetic mechanisms through which early environmental exposures shape developmental programming and stress responsivity across the lifespan. A central framework is the dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis, which mediates adaptive and maladaptive stress responses. During sensitive developmental periods, including prenatal, perinatal, and early postnatal stages, increased neuroplasticity confers heightened vulnerability to environmental influences, resulting in persistent alterations in stress regulation systems, brain circuitry, and endocrine function. The review further examines the role of maternal stress during gestation, with emphasis on placental regulatory mechanisms and fetal programming processes that establish long-term physiological set points. In parallel, emerging evidence on paternal stress is considered, highlighting potential contributions of germline epigenetic modifications and postnatal environmental transmission pathways. At the molecular level, epigenetic mechanisms-including DNA methylation, histone modifications, and non-coding RNA regulation-are discussed as key mediators linking early environmental exposures to stable changes in gene expression without alterations in DNA sequence. Collectively, the evidence supports ELS as a fundamental biological embedding process with enduring consequences for health across the lifespan. A deeper understanding of these mechanisms, alongside the identification of reliable biomarkers, is essential for early detection and the development of targeted preventive and intervention strategies in pediatric populations.