Developmental programming of health and disease - PubMed (original) (raw)

Developmental programming of health and disease

Simon C Langley-Evans. Proc Nutr Soc. 2006 Feb.

Abstract

The environment encountered in fetal and neonatal life exerts a profound influence on physiological function and risk of disease in adult life. Epidemiological evidence suggests that impaired fetal growth followed by rapid catch-up in infancy is a strong predictor of obesity, hypertension, non-insulin-dependent diabetes and CHD. Whilst these associations have been widely accepted to be the product of nutritional factors operating in pregnancy, evidence from human populations to support this assertion is scarce. Animal studies clearly demonstrate that there is a direct association between nutrient imbalance in fetal life and later disease states, including hypertension, diabetes, obesity and renal disease. These associations are independent of changes in fetal growth rates. Experimental studies examining the impact of micro- or macronutrient restriction and excess in rodent pregnancy provide clues to the mechanisms that link fetal nutrition to permanent physiological changes that promote disease. Exposure to glucocorticoids in early life appears to be an important consequence of nutrient imbalance and may lead to alterations in gene expression that have major effects on tissue development and function. Epigenetic mechanisms, including DNA methylation, may also be important processes in early-life programming.

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Figures

Fig. 1

Schematic representation of the Barker hypothesis (Langley-Evans, 2004_b_). The simplest form of the hypothesis is that undernutrition impairs fetal growth. The association between fetal growth and long-term disease outcomes is likely to be confounded by a direct association between undernutrition and disease.

Fig. 2

The thrifty phenotype hypothesis (Hales & Barker, 2001; Gluckman & Hanson, 2004). Exposure of the developing organism to a low plane of nutrition promotes metabolic thrift in order to ensure survival. In a postnatal environment in which nutrients are in short supply this metabolic thrift continues to be a survival trait, but if nutrients are present in excess the thrifty trait will promote the metabolic syndrome.

References

1. Barker DJ. The developmental origins of chronic adult disease. Acta Paediatrica. 2004;93(Suppl):26–33. - PubMed
1. Barker DJ, Bull AR, Osmond C, Simmonds SJ. Fetal and placental size and risk of hypertension in adult life. British Medical Journal. 1990;301:259–262. - PMC - PubMed
1. Barker DJ, Hales CN, Fall CH, Osmond C, Phipps K, Clark PM. Type 2 (non-insulin-dependent) diabetes mellitus, hypertension and hyperlipidaemia (syndrome X): relation to reduced fetal growth. Diabetologia. 1993a;36:62–67. - PubMed
1. Barker DJ, Osmond C. Infant mortality, childhood nutrition, and ischaemic heart disease in England and Wales. Lancet. 1986;i:1077–1081. - PubMed
1. Barker DJ, Osmond C, Simmonds SJ, Wield GA. The relation of small head circumference and thinness at birth to death from cardiovascular disease in adult life. British Medical Journal. 1993b;306:422–426. - PMC - PubMed

Developmental programming of health and disease - PubMed (original) (raw)