mental data from randomized controlled trials in humans, however, impedes efforts to determine how much of any observed association is causal. In the following discussions, inferences regarding causality were made using the best data available in consideration of plausible biologic mechanisms, susceptibility to confounding and other aspects of the study methodology, and patterns of results.

When considering potential causal relationships between GWG and the various child outcomes reviewed, the committee relied on the same conceptual model that it utilized when evaluating the determinants of GWG (see Figure 6-1). This model fits well with two paradigms that offer useful conceptual frameworks for considering long-term effects on the offspring. The first—the “life course approach to chronic disease”—invokes two axes (Kuh and Ben-Shlomo, 2004): time, with temporal factors acting in the pre-conceptional through the prenatal period, into infancy, childhood, and beyond to determine risk of chronic disease; and hierarchy, with hierarchical

FIGURE 6-1 Schematic summary of neonatal, infant, and child consequences of GWG.