Fetal programming

From a pathophysiological perspective, 'fetal programming' —a.k.a., the fetal origins of adult disease— refers to adaptations made by a fetus in response to adverse intrauterine environments, adaptations targeting the fetus’s survival, adaptations that alter fetal structure and function during the highly plastic period of embryonic/fetal development, adaptations that persist after birth and that determine the structural, metabolic and physiological characteristics of the individual throughout the developmental stages of postnatal life and throughout adult life, which system characteristics can predispose the individual in later life to maladaptations in response to environmental conditions differing from those that the individual adapted to during fetal development. The adaptations 'program' the newborn infant for the the responses it makes to its environment throughout its lifetime.

In a 2004 review, pioneer of fetal programming phenomena, David Barker, summarized the following as 'key teaching points':

Studies have shown an association between low birthweight and risk for cardiovascular diseases and other chronic conditions [e.g., hypertension, stroke, metabolic syndrome, type 2 diabetes] later in life. Developmental plasticity describes the fetuses ability to respond to their mother’s diet in utero. Low birthweight and inadequate nutrition early in life may lead to lifelong alterations in the body’s setting of metabolism and hormones as well as the number of cells in key organs. Low birthweight followed by rapid weight gain during infancy has been shown to further increase risk for disease.

In a more recent review, psychoneuroendocrinologist Sonja Entringer describes fetal programming this way:

Substantial evidence in humans and animals suggests that conditions during intrauterine life play a major role in shaping not only all aspects of fetal development and birth outcomes but also subsequent newborn, child, and adult health outcomes and susceptibility for many of the complex, common disorders that confer the major burden of disease in society (i.e., the concept of fetal, or developmental, origins of health and disease risk) [cites: ].

Focusing on pathophysiology, fetal programming also goes by the name, 'fetal origins of adult disease'. From a broader perspective than the pathophysiological, however, the fetus also responds to beneficial intrauterine environments, adapting its metabolism, physiology, and structure to health and lower susceptibility to disease in later life. For one example, in the studies of Barker mentioned above, the babies born with higher birth-weight due to more optimal maternal nutrition had significantly lower risk of developing coronary heart disease than did the lower birth-weight babies.<barker 2004/>

Recognition of fetal programming led to recognition that the earliest stages of development, including infancy, could respond to environmental conditions in ways that influenced health status in later life, which, in turn, led to a new discipline, The Developmental Origins of Health and Disease.

Examples of fetal programming in humans

In 1986, David Barker and Clive Osmond reported on their studies of the relationships among infant mortality, childhood nutrition, and adult ischemic heart disease in England and Wales. By geographical regions, past infant mortality rates, highest where poverty was greatest, associated positively with present occurrences of ischemic heart disease, whereas increasing heart disease presently associated with increasing prosperity. From their analysis the investigators suggested that “poor nutrition in early life increases susceptibility to the effects of an affluent diet”.

Fetal programming applies also to age-related cognitive decline. A long term follow-up study in men by Katri Raikkonen and colleagues showed that lower cognitive ability at mean age 67.9 years associated with lower birth-weight, birth-length, and birth-head-circumference. Similarly, cognitive decline after age 20 years associated with those lower measures of intrauterine physical growth. The investigator found that in "predicting resilience to age related cognitive decline, the period before birth seems to be more critical" compared to the period of infancy.

Examples of fetal programming in non-human animals

In sheep, suboptimal maternal nutrition coincident with early fetal kidney development results in enhanced renal lipid deposition following juvenile obesity and could accelerate the onset of the adverse metabolic, rather than cardiovascular, symptoms accompanying the metabolic syndrome.

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