Title: The "foetal origins" hypothesis

Key words: Intrauterine malnutrition, low birthweight, CHD, diabetes, hyperlipidaemia, foetal origins, epidemiological studies, hypertension

Date: July 2000

Category: 10. Reproduction

Type: Article

Author: Dr Van Rhijn

The "foetal origins" hypothesis

How it could influence our approach to public health and preventative medicine



The foetal origins hypothesis suggests that an adverse environment, ie undernutrition in utero, cause retardation or disproportional intrauterine growth1, programming for several chronic, degenerative2 diseases and thereby heightening the risk of adult morbidity and mortality3. Understanding of the mechanisms involved is crucial in advising early and preventative treatment strategies.


Animal studies have shown that undernutrition in foetal life, permanently alters the structure or function of an individual and leads to persisting changes in a range of metabolic, physiological and structural parameters. This programmed susceptibility interacts later with diet and environmental stresses to cause overt disease many decades after the original insult4, 5. Human epidemiological studies, strongly supported by animal data, associate low birth weight6 with hypertension in childhood7 and adult life8, glucose intolerance, non-insulin dependent diabetes mellitus and increased rates of coronary heart disease9 in adult life. Hyperlipidemia, alteration in clotting factors, stroke, syndrome X and mortality from chronic obstructive airways disease has also been associated. It has been suggested that the inverse relationship between adult height and coronary heart disease (CHD) risk could be attributable to the foetal origins of CHD10, but inconsistencies between and within the studies exist11.


Although the mechanisms are unknown, recent findings suggest that many human foetuses have to adapt to a limited supply of nutrients12, probably due to maternal under nutrition, resulting in altered programming of cardiovascular, neuro-endocrine and metabolic regulatory systems. Subsequent pineal gland hypoplasia is suggested as a foetal contribution to sudden infant death syndrome, coronary artery disease and ischaemic stroke and the loss of melatonin's antioxidant activity is proposed as an additional factor to consider in atherosclerotic vascular disease13. Experimental models are suggestive of an excess of glucocorticoid hormones14, via the hypothalamo-pituitary-adrenal (HPA) axis, in the intrauterine programming of atherosclerosis15, cardiovascular function16, hypertension17 and glucose intolerance in later life18. Polycystic ovary syndromes have either higher androgen secretion (obese), or altered hypothalamic control of LH release resulting from prolonged gestation19. Although twins, and in particular monozygotic twins, experience growth retardation in utero, the foetal origins hypothesis is not true for the retardation in intrauterine growth experienced by twins20.


Coronary heart disease and stroke are the commonest causes of illness and death for people living in the UK. In fact, all the above mentioned diseases are areas of active research aimed at improving our understanding of their aetiology and associations with the uterine nutritional environment. Until individual nutrients are identified, general improvement in maternal and infant health by proper prenatal nutritional care may be a start to effective prevention of the numerous chronic diseases of adult life.




There is enough observational evidence to link early life events to the risk of subsequent disease. Understanding of the relationships between maternal diet and the development and maturation of foetal tissues may enable prevention of these diseases by intervention in early life. Further research is required before specific advice can be issued to the public at large to achieve this. The implementations of folic acid supplementation in the prevention of neural tube defects, or screening for inborn errors of metabolism are examples of successful intervention at present.



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