Metabolic consequences of prematurity

A considerable body of scientific evidence now links major diseases of middle-older age, such as the metabolic syndrome, diabetes mellitus and atherosclerotic heart disease, to in utero and perinatal events. Based on replicated epidemiological observations in humans, and experimental evidence in animal models, the data suggest that a period of plasticity during development imposes permanent influences on the way that the organism adapts to the surrounding environment many years later, perhaps via epigenetic and other post-translational modifications of genetic programming, such as regulation of the cell cycle and hormonal programming of metabolic pathways. A critical period appears to be the third trimester, hitherto considered as deprivation of nutrition or other essential factors in utero. Here this review discusses the recent evidence that the critical period also involves the third trimester ex utero, as occurs in prematurity. Data are provided demonstrating insulin resistance compensated by hyperinsulinemia in children born prematurely, whether born appropriate for gestational age or small for gestational age, and comparable in degree with that seen in those born at term with intrauterine growth retardation. Potential mechanisms and implications for treatment of the metabolic consequences of prematurity are discussed within the framework of the fetal salvage hypothesis.