Commentary: The impact of fetal and infant exposures along the life course.

What happens in the womb sets the stage for development of the child and influences the health of offspring throughout their life course. Until recently, however, most epidemiologists focusing on adult diseases paid little attention to fetal origins of health. Due in part to tantalizing reports that birthweight is associated with health outcomes in both children and adults, that has changed. In this recent surge of interest, the best documented finding for adults is that lower birthweight predicts higher risk of cardiovascular disease. 1,2 A smaller but growing literature reports intriguing findings for numerous other domains of child and adult health, for example, higher birthweight has been related to an increased risk of breast and other cancers. 1 Especially relevant to the papers in this issue of the Journal are recent findings suggesting that the relation of neurocognitive development to birthweight goes beyond low birthweight and well into the normal birthweight range. The few available reports on birthweight and health in developing countries, including two in this issue, find similar relationships. The accumulating evidence for associations between birth-weight and health posed three central challenges from the start: refining the measure of early experience, tracing the causal pathway that connects early experience with later health, and ruling out confounding by social class. As yet, none has been fully met. Nonetheless, progress has been made, and the studies in this issue are noteworthy for pursuing these lines of questioning. In early reports, maternal nutrition was sometimes assumed to be the operative factor. A common view was that poor maternal nutrition led to low birthweight as well as to intrauterine 'pro-gramming', i.e. a long-term alteration in genetically programmed development induced by in utero experience. This hypothesis was a useful starting point but could not explain the complex findings from human studies. Studies of the Dutch Hunger Winter, for example, reported that severe maternal under-nutrition in late gestation led to reduced weight, length and head size at birth. 3 With respect to later health outcomes, however, early gestation undernutrition was related to increased obesity, 4 and increased risk of schizophrenia. Neither early nor late gestation undernutrition was related to IQ at age 18. 3,5 More refined hypotheses are needed to explain these results along with the associations noted earlier for birthweight and health. As underscored in the accompanying review paper in this issue, 6 many investigators have taken up this challenge and now advance …