Fetal origins of coronary heart disease

BMJ 1995; 311 doi: http://dx.doi.org/10.1136/bmj.311.6998.171 (Published 15 July 1995)
Cite this as: BMJ 1995;311:171

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  1. D J P Barker
  1. MRC Environmental Epidemiology Unit, University of Southampton, Southampton SO16 6YD
  • Accepted 20 June 1995

The fetal origins hypothesis states that fetal undernutrition in middle to late gestation, which leads to disproportionate fetal growth, programmes later coronary heart disease. Animal studies have shown that undernutrition before birth programmes persisting changes in a range of metabolic, physiological, and structural parameters. Studies in humans have shown that men and women whose birth weights were at the lower end of the normal range, who were thin or short at birth, or who were small in relation to placental size have increased rates of coronary heart disease. We are beginning to understand something of the mechanisms underlying these associations. The programming of blood pressure, insulin responses to glucose, cholesterol metabolism, blood coagulation, and hormonal settings are all areas of active research.The BMJ's recent editorial on the fetal origins hypothesis stated that it rests only on the “very general” proposition that fetal undernutrition causes coronary heart disease.1 This is incorrect. The hypothesis states that coronary heart disease is associated with specific patterns of disproportionate fetal growth that result from fetal undernutrition in middle to late gestation.2 3

Disproportionate fetal growth

During embryonic life—that is, during the first eight weeks after conception—the body does not increase greatly in size, but the basic human form is laid down in miniature. The embryo does not contain a description of the person to whom it will give rise,4 rather it contains in its genes a generative programme for making a person. In the fetal period, from nine weeks after conception onwards, there begins the phase of rapid growth that continues until after birth. The main feature of fetal growth is cell division. Different tissues of the body grow during periods of rapid cell division, so called “critical” periods.*RF 5* The timing of these critical periods differs for different tissues. Growth depends on nutrients and …

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