Three interpretations of the association between birth weight and cardiovascular disease

Abstract

Most epidemiological studies of cardiovascular disease have had a focus on smoking, blood pressure, diet, physical activity and obesity in adulthood as determinants of cardiovascular disease. A few studies from the 1970s and onwards attempted to shed light on the early origins of this disease, and it is now established through cohort studies that there is a fairly strong and consistent relationship between low birth weight and increased risk of later cardiovascular disease. However, the interpretation of this relationship is under discussion. Three alternative interpretations of the association are discussed. The first interpretation, the environmental causal model, claims that the external influences on the growth of fetal organ systems have detrimental biological consequences that predispose the child for cardiovascular disease as an adult. This is the fetal programming hypothesis, which presently more often is called the theory of developmental plasticity, integrating environmental events before and after birth. The second interpretation, the genetic confounding model, says that the association between low birth weight and later cardiovascular disease is not causal. The association is due to confounding by pleiotropic genes, i.e. genes that influence more than one phenotype. The third interpretation, the environmental confounding model, says that lifestyles and general socioeconomic conditions that correlate across generations cause both low birth weight and predisposes for cardiovascular disease, and thereby leads to a spurious association. The conclusion is that, with the studies reported up to now, one cannot dismiss any of these interpretations. By utilizing the large pregnancy cohorts set up in Norway and other countries, these models can be put to critical tests.