Fetal programming

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From a pathophysiological perspective, 'fetal programming' 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, lasting adaptations that determine the structural, metabolic and physiological characteristics of the individual throughout the developmental stages of postnatal life, characteristics that 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.[1] [Note 1] 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':[2]

  • 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.[Note 2]
  • 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.

Examples of fetal programming in humans

In 1986, David Barker and C 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”.[3]

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.[4] 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.

References cited in text

  1. Godfrey KM, Barker DJP. (2001) Fetal programming and adult health. Public Health Nutrition 4(2B):611-624. | Read Abstract in 'Notes' section.
  2. Cite error: Invalid <ref> tag; no text was provided for refs named barker2004
  3. Barker DJ, Osmond C. (1986) Infant mortality, childhood nutrition, and ischaemic heart disease in England and Wales. Lancet 10;1(8489):1077-81.
  4. Katri Raikkonen, Eero Kajantie, Anu-Katriina Pesonen, Kati Heinonen, Hanna Alastalo, Jukka T. Leskinen, Kai Nyman, Markus Henriksson, Jari Lahti, Marius Lahti, Riikka Pyhälä, Soile Tuovinen, Clive Osmond, David J. P. Barker,Johan G. Eriksson. (2013) Early Life Origins Cognitive Decline: Findings in Elderly Men in the Helsinki Birth Cohort Study. PLoS ONE 8(1): e54707.

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Notes

  1. Abstract of article by Godfrey KM, Barker DJP. (2001): Low birthweight is now known to be associated with increased rates of coronary heart disease and the related disorders stroke, hypertension and non-insulin dependent diabetes. These associations have been extensively replicated in studies in different countries and are not the result of confounding variables. They extend across the normal range of birthweight and depend on lower birthweights in relation to the duration of gestation rather than the effects of premature birth. The associations are thought to be consequences of `programming', whereby a stimulus or insult at a critical, sensitive period of early life has permanent effects on structure, physiology and metabolism. Programming of the fetus may result from adaptations invoked when the materno-placental nutrient supply fails to match the fetal nutrient demand. Although the influences that impair fetal development and programme adult cardiovascular disease remain to be defined, there are strong pointers to the importance of maternal body composition and dietary balance during pregnancy.
  2. Cite error: Invalid <ref> tag; no text was provided for refs named barker2004