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.[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]
|
|
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: [3] [4]].[5] |
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.[6] [Note 3]
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”.[7]
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.[8] 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.[9]
References cited in text
- ↑ Godfrey KM, Barker DJP. (2001) Fetal programming and adult health. Public Health Nutrition 4(2B):611-624. | Read Abstract in 'Notes' section.
- ↑ Barker DJ. (2004) The developmental origins of adult disease. J Am Coll.Nutr 23(6 Suppl):5885-5955. | Click title for free access to full text.
- ↑ Entringer S, Buss C, Wadhwa PD. (2010) Prenatal stress and developmental programming of human health and disease risk: concepts and integration of empirical findings. Curr Opin Endocrinol Diabetes Obes 17:507–516.
- ↑ Barouki R, Gluckman PD, Grandjean P, et al. (2012) Developmental origins of noncommunicable disease: implications for research and public health. Environ Health 11:42.
- ↑ Entringer S. (2013) Impact of stress and stress physiology during pregnancy on child metabolic function and obesity risk. Curr Opin Clin Nutr Metab Care 16(3):320-327.
- ↑ Gillman MW. (2005) Developmental Origins of Health and Disease. ‘’N Engl J Med.’’ October 27; 353(17): 1848–1850.
- ↑ Barker DJ, Osmond C. (1986) Infant mortality, childhood nutrition, and ischaemic heart disease in England and Wales. Lancet 10;1(8489):1077-81.
- ↑ 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.
- ↑ Fainberg HP, Sharkey D, Sebert S et al. (2012) Suboptimal maternal nutrition during early fetal kidney development specifically promotes renal lipid accumulation following juvenile obesity in the offspring. Reprod Fertil Dev [Epub ahead of print, Jul 30]
Notes
- ↑ 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.
- ↑ Note...
- ↑ Excerpt of article by Gillman MW. (2005): At first glance, it may seem implausible that your mother’s exposure to stress or toxins while she was pregnant with you, how she fed you when you were an infant, or how fast you grew during childhood can determine your risk for chronic disease as an adult. Mounting evidence, however, indicates that events occurring in the earliest stages of human development — even before birth — may influence the occurrence of diabetes, cardiovascular disease, asthma, cancers, osteoporosis, and neuropsychiatric disorders.