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In 1986, Barker and Osmond published a study that examined patterns of death related to coronary heart disease in England and Wales between 1968 and 1978. These investigators found that the death rates in the northern industrial towns were about 20% above the national average. In contrast, the more affluent areas in the rural south and east had heart disease death rates that were 20% below the national average. The pattern of death rates from coronary heart disease among adults paralleled that for infant mortality a half century earlier. One in 10 newborns died in the first year of life in the industrial north compared with one in 20 in the rural south and east.

This ecological association between infant mortality and adult heart disease led these investigators to conduct a subsequent study of men born between 1911 and 1930 in Hertfordshire, England and followed them for subsequent risk of death from coronary heart disease. They found that low-birth-weight (LBW) infants had a 50% increased death rate from heart disease as adults. The results were even more striking with weight at 1 year of age—those in the lowest weight category (≤18 lb) had a twofold increase in risk of death from adult heart disease.

The observation that events before birth and shortly thereafter could affect the risk of disease five or more decades later became known variously as the “Barker Hypothesis,” “The Thrifty Phenotype Hypothesis,” or the “Fetal Origins Hypothesis.” The basic premise of this theory is that adult heart disease (and related conditions such as diabetes mellitus, obesity, and hypertension) may arise because of the body’s response to undernutrition early in life. A number of mechanisms have been suggested, including metabolic responses to undernutrition in utero leading to decreased insulin secretion from the pancreas, diminished insulin sensitivity in muscles in order to conserve glucose, increased cortisol secretion, reduced number of nephrons, diminished myocytes, and impaired endothelial function.

The association between low birth weight and chronic diseases in adulthood has been demonstrated in many populations for heart disease, diabetes mellitus, hypertension, and obesity. Less clear is whether other chronic conditions, such as renal insufficiency, may have a link to LBW. In this chapter, we will explore how the LBW association with adult renal insufficiency can be explored using the case-control research approach.


Low birth weight is defined as a weight at birth of less than 2500 g (5 lb, 8 oz). Further distinctions, such as very low birth weight (VLBW) at less than 1500 g and extremely low birth weight (ELBW) at less than 1000 g, can be made, but our focus here is on LBW. At present, approximately 1 in 12 newborns in the United States falls with the LBW classification, which represents nearly a quarter of a million affected births in the United States each year. There are two ...

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