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The current review addresses the importance of the prospective cohort design in large, unselected populations starting early in life for understanding the origins of childhood health disorders.Cohort studies originating in healthy populations have contributed to great advances in health, especially in cardiovascular diseases, but have only recently been applied systematically to study the origins of childhood disorders. Several large population-based pregnancy and/or birth cohorts have been developed in different parts of the world, and these are beginning to contribute to better understanding of the underlying causes of rare but important childhood disorders, such as autism. The environmental influences on child health outcomes (ECHO) Program is distinct in leveraging and building upon 84 existing cohorts to prospectively investigate the role of early-life exposures and underlying biological mechanisms in childhood health and disease, specifically perinatal conditions, obesity, neurodevelopmental disorders, asthma and related pulmonary disorders as well as optimum child health. ECHO is expected to comprise approximately 50 000 children. It is the first US study of this size and scope since the US Collaborative Perinatal Project of 1959–1966.The ECHO project represents a new approach to cohort studies in childhood, efficiently making use of extant cohorts while adding new data collection elements that should permit novel insights into the underlying causes of several important pediatric conditions.