Stress during the first 1,000 days of life in humans, when everything begins.

Brain development from fetal life to early childhood occurs in highly sensitive periods, during which stress exposure-adaptive or toxic, prenatal or postnatal-can shape neural circuits involved in emotional regulation, particularly amygdala-centered networks. This review synthesizes current evidence on the biological mechanisms of early-life stress and protective interventions. It is based on a narrative review integrating original research, review articles, and international guidelines selected for relevance. Severe or prolonged early-life stress, including prenatal adversity, maternal anxiety, or environmental challenges, can disrupt body-brain interactions, alter hypothalamic-pituitary-adrenal axis activity, reduce vagal tone, and impair connectivity in the amygdala, hippocampus, and salience network. Epigenetic modifications in genes link early adversity to altered stress reactivity and emotional regulation. Functional MRI and physiological assessments indicate these changes are detectable before birth and during the first 1,000 days of life. Supportive caregiver interactions-through polyvagal-mediated synchrony, attachment, and social engagement-promote physiological regulation and healthy neural development. Interventions such as skin-to-skin contact reduce cortisol levels, enhance vagal activity, and increase oxytocin release. Traumatic early life stress can profoundly influence neural, hormonal, and epigenetic pathways, but positive caregiving and interventions can foster resilience and optimize neurodevelopment. These findings highlight the critical need to monitor and support stress regulation during the first 1,000 days of life.