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Leonardo Trasande,^1,2 Chris Cronk,³ Maureen Durkin,⁴ Marianne Weiss,⁵ Dale A. Schoeller,⁶ Elizabeth A. Gall,⁴ Jeanne B. Hewitt,⁷ Aaron L. Carrel,⁸ Philip J. Landrigan,^1,2 and Matthew W. Gillman⁹

¹Department of Community and Preventive Medicine, and ²Department of Pediatrics, Mount Sinai School of Medicine, New York, New York, USA; ³Medical College of Wisconsin and Children's Hospital of Wisconsin, Milwaukee, Wisconsin, USA; ⁴Department of Population Health Sciences, University of Wisconsin, Madison, Wisconsin, USA; ⁵College of Nursing, Marquette University, Milwaukee, Wisconsin, USA; ⁶Interdepartmental Program in Nutritional Sciences, University of Wisconsin, Madison, Wisconsin, USA; ⁷Marine and Freshwater Biomedical Sciences Center, University of Wisconsin-Milwaukee, Milwaukee, Wisconsin, USA; ⁸Department of Pediatrics, University of Wisconsin, Madison, Wisconsin, USA; ⁹Obesity Prevention Program, Department of Ambulatory Care and Prevention, Harvard Medical School and Harvard Pilgrim Health Care, Boston, Massachusetts, USA

Abstract
Objective: In this review we describe the approach taken by the National Children's Study (NCS) , a 21-year prospective study of 100,000 American children, to understanding the role of environmental factors in the development of obesity.

Data sources and extraction: We review the literature with regard to the two core hypotheses in the NCS that relate to environmental origins of obesity and describe strategies that will be used to test each hypothesis.

Data synthesis: Although it is clear that obesity in an individual results from an imbalance between energy intake and expenditure, control of the obesity epidemic will require understanding of factors in the modern built environment and chemical exposures that may have the capacity to disrupt the link between energy intake and expenditure. The NCS is the largest prospective birth cohort study ever undertaken in the United States that is explicitly designed to seek information on the environmental causes of pediatric disease.

Conclusions: Through its embrace of the life-course approach to epidemiology, the NCS will be able to study the origins of obesity from preconception through late adolescence, including factors ranging from genetic inheritance to individual behaviors to the social, built, and natural environment and chemical exposures. It will have sufficient statistical power to examine interactions among these multiple influences, including gene–environment and gene–obesity interactions. A major secondary benefit will derive from the banking of specimens for future analysis.

Key words: bisphenol A, built environment, endocrine disruptors, diet, National Children's Study, obesity, phthalates, physical activity. Environ Health Perspect 117:159–166 (2009) . doi:10.1289/ehp.11839 available via http://dx.doi.org/ [Online 12 September 2008]

Address correspondence to L. Trasande, Department of Community and Preventive Medicine, Mount Sinai School of Medicine, One Gustave L. Levy Place, Box 1043, New York, NY 10029 USA. Telephone: (212) 241-8029. Fax: (212) 996-0407. E-mail: leo.trasande@mssm.edu

The authors are investigators in the Queens, New York, and Waukesha County, Wisconsin, Vanguard Centers and the Coordinating Center of the National Children's Study. This project has been funded in whole or in part with federal funds from the National Institute of Child Health and Human Development, National Institutes of Health, under contracts NICHD HHSN275200503411C/N01-HD-5-3411.

The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products, or organizations imply endorsement by the U.S. Government.

The authors declare they have no competing financial interests.

Received 21 June 2008 ; accepted 11 September 2008.