Abstract

Exposure of the fetus to the intrauterine milieu can have profound effects on the health of the offspring in adulthood. These observations are highly reproducible in many populations worldwide although the mechanisms behind them remain elusive.

The ‘thrifty phenotype’ hypothesis proposes that poor fetal nutrition leads to programming of metabolism and an adult phenotype that is adapted to poor but not plentiful nutrition. Results of a series of studies demonstrate the powerful influence of the mother’s metabolic state on whether the emerging adult develops obesity and hyperinsulinemia. Importantly, these attributes can be passed on to the next generation non-genetically and can be reversed and prevented.

Such hypothesis has been expanded on by the “Developmental Origins of Health and Disease” (DOHaD) hypothesis which describes the origin of adult disease in terms of fetal developmental ‘plasticity’ or the ability of the fetus to respond to poor in-utero conditions. A wealth of epidemiological evidence has provided a convincing link between a sub-optimal gestational environment and an increased propensity to develop adult onset metabolic disease.

In this paper the factors that participate in the programming of the fetus and infants that lead to endocrine dysfunction in postnatal life are reviewed.

Keywords: Thrifty phenotype hypothesis, Developmental Origins of Health and Disease hypothesis, Type 2 diabetes, Childhood growth, Programming