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The biological embedding of early life stress exposure may result in life‐long neurodevelopmental impairment in preterm infants. Infants hospitalized in the neonatal intensive care unit are exposed to significant experiential, environmental, and physiologic stressors over the course of their extended hospitalization. Stress exposure during the sensitive period of brain development may alter biological processes, including functioning of the immune system, the autonomic nervous system, and the hypothalamic‐pituitary‐adrenal axis as well as gene expression. These alterations may subsequently affect brain structure and function. Changes to these processes may mediate the relationship between neonatal stress exposure and neurodevelopment in preterm infants and represent potential therapeutic targets to improve long‐term outcomes. The purpose of this paper is to introduce a conceptual model, based on published research, that describes the mechanisms mediating stress exposure and neurodevelopment impairment in preterm infants and to provide the theoretical foundation on which to base future descriptive research, intervention studies, and clinical care. [ABSTRACT FROM AUTHOR]