The NCS presents previously unrealized opportunities for the identification of risk factors for childhood obesity, and for their subsequent elimination through prevention. Just as the Framingham Heart Study provided health care providers with hitherto novel information on risk factors for cardiovascular disease that enabled them to offer evidence-based advice to limit smoking, reduce the intake of fatty foods, and control hypertension, the NCS will suggest interventions that can be used to prevent obesity by communities, policy makers, and child health providers. A major strength of the study is that it will be representative of American children. It is anticipated, for example, that > 20,000 children in the cohort will be Hispanic, permitting examination of unique risk factors among a subgroup that has been disproportionately affected by the epidemic.
The hypotheses presented in this review cover only a small percentage of the findings likely to emerge from the NCS. The core NCS hypotheses are dynamic, and as the study is implemented, new questions will emerge and result in modifications to the study protocol. Others may be clearly answered through the NCS or other studies, or become outdated as the whole body of knowledge adjusts the direction of inquiry. For some areas of inquiry where the science is in relatively nascent stages, the major benefits to be gained from the study derive from its hypothesis-generating nature. The NCS will provide a major opportunity to confirm putative genetic links identified in other studies through the study of genetic sequences of children and their families (Landrigan et al. 2008
). As new putative EDs are identified, subsamples of biospecimens stored at the NCS Specimen Repository can be rapidly analyzed to test for associations in a large-scale cohort that represents the population of U.S. children.
Of course, no observational study by itself can demonstrate causality. The NCS will identify risk factors for which causality may be suggested on the basis of strength, consistency, temporality, biological gradient, and plausibility. Findings from the NCS will prompt further interventions such as randomized controlled trials, policy interventions, and other initiatives that will confirm or refute the role of identified risk factors in the development of obesity and its associated comorbidities.
The life-course approach underlying the design of the NCS may very well lead to delineating the duration and impact of environmental, behavioral, and social exposures on risk for obesity. No study will have followed women from preconception and subsequently followed their children at such frequent intervals early in childhood and then through adolescence and young adulthood. The NCS will collect an array of biospecimens, dietary and physical activity data, and social and chemical environmental factors on all 100,000 children for all proposed data collection time points, whereas other cohorts have collected more limited data at each time point or collected complete data on a smaller sample.
A major challenge of the NCS will be to overcome the difficulties in measuring physical activity, diet, and anthropometry in children that have bedeviled past studies. Limitations of reliability and validity do exist with food-frequency questionnaires (Coates and Monteilh 1997
; Teufel 1997
) and other instruments commonly used to measure dietary intake, although promising alternatives have been developed for populations in which past instruments have not proven reliable (Yaroch et al. 2000
). The vagaries of collecting information on physical activity by questionnaire are well documented (Kohl et al. 2000
), but accelerometry and other measuring techniques are increasingly promising in their precision and application (Ekelund et al. 2001
; Janz et al. 2002
). BMI is not a perfect measure of adiposity (Pietrobelli et al. 1998
), and dual-absorption X-ray absorptiometry has been strongly correlated with cardiovascular disease factors in children (Lindsay et al. 2001
). Bioimpedance analysis and skinfold thickness are increasingly used to measure adiposity (Gutin et al. 1996
; Kettaneh et al. 2005
These challenges will not be easily dismissed, and the opportunity is ripe for contributions from the obesity research community to ensure that the best questionnaires and measurement approaches are utilized in an efficient and cost-effective way. At this time, the protocol has been finalized only for the seven Vanguard (pilot) locations, and even for those locations only through birth. The NCS also offers major opportunities to study the validity and reliability of alterative measurement approaches through adjunct studies in collaboration with existing study centers. These studies may use the full or a subsample of the study cohort, with the caveat that proposed new data collection not impose undue additional burden on study participants or additional financial burden on the study.
The NCS will also trigger ancillary and follow-up studies and provide the next generation of obesity researchers opportunities to apply for funding (Lyman et al. 2005
). The NCS will make public use, deidentified data sets available in accordance with federal privacy regulations.
Previous cohort studies of cardiovascular risk have plowed the terrain to identify major risk factors and allow the NCS to close in on solutions to the epidemic of childhood obesity. However, they have also demonstrated that these relationships are complex and temporally dependent, making a large longitudinal cohort study beginning in the prenatal period essential. The NCS thus offers us great hope in combating the obesity epidemic among America’s children.