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Fetal origins of postnatal health and disease
Early Human Development (2005) 81, 721 — 722
www.elsevier.com/locate/earlhumdev
INTRODUCTION
Fetal origins of postnatal health and disease One of the most remarkable developments in medicine in the last 10—15 years has been the recognition that some serious health problems in later life could have their origins in early life. Large scale epidemiological surveys in several countries have shown significant associations between lower than expected birthweight, a surrogate for fetal exposure to environmental stressors, and late-onset disease states such as coronary heart disease, obesity and type 2 diabetes. These new findings have been interpreted as evidence for the programming of later physiological function by altered early development, a concept that has the potential to explain a number of important adult-onset diseases for which, at present, there is no apparent cause. This has led to a spate of more targeted studies that are starting to unravel the cellular and molecular processes responsible for the developmental programming of later disease risk. It is now apparent that altered structural or functional development of a number of crucial organ systems can bprogramQ or permanently alter organ function and susceptibility to later dysfunction and disease. In essence, developmental programming is due to a change in gene expression pattern that occurs in response to a stressor during development. The physiological adjustments that enable the fetus or neonate to survive exposure to environmental stressors apparently result in later impairments in organ function and a greater vulnerability to disease processes. A key challenge is to identify stressors that are capable of permanently altering organ development and function, and also the stages of development of greatest vulnerability. At present, there is strong evidence that factors leading to lower than expected birthweight (ie intra-uterine growth restriction) such as fetal hypoxia, restricted fetal nutrition, excess exposure to glucocorticoids, and impaired placental function have the potential to
program changes in development. It is also apparent that fetal exposure to commonly used drugs such as alcohol and tobacco can alter organ development and later function. Restricted prenatal growth may not be a requirement for programming to occur: for example early fetal exposure to glucocorticoids does not impair fetal growth but can permanently alter renal development and lead to hypertension in adults. The early postnatal environment is also important as many organ systems continue to develop after birth; it is now recognised that undernutrition, infections and drug exposure during infancy and childhood can adversely affect later health. In this issue of EHD are articles by 5 groups of researchers working at the forefront of attempts to understand the physiological basis and clinical significance of developmental programming. These short reviews are written by authors who are at the cutting edge of research in their field. Each review provides up-to-date information on the potential impact of a sub-optimal intra-uterine or neonatal environment on organ systems and has indicated, in the form of a series of guidelines, how these findings relate to medical practice. They have also presented areas in which further research is needed. In the first article, Prof Abigail Fowden and her colleagues show how restricted fetal growth can alter the development and later functioning of the hypothalamic—pituitary—adrenal axis, leading to an alteration in the endocrine control of metabolism and growth. Their findings explain why infants whose growth was restricted in utero, or who were prenatally exposed to excess glucocorticoids, are at increased risk of adiposity and type 2 diabetes in later life. Dr Avan Sayer and Prof Cyrus Cooper show how body composition, including fat deposition, and musculo-skeletal development, can be permanently altered by factors that restrict fetal growth. Sarcopenia and osteoporosis are major clinical problems
0378-3782/$ - see front matter D 2005 Elsevier Ireland Ltd. All rights reserved. doi:10.1016/j.earlhumdev.2005.08.001
722 of the elderly and with an aging population are likely to increase in prevalence; the recognition that they may have their origins in fetal life provides a means by which they could be prevented. Dr Samantha Louey and Prof Kent Thornburg demonstrate how exposure to stressors during fetal and early postnatal life can alter the development of the heart and blood vessels, increasing later vulnerability to heart and vascular diseases. Therefore, a knowledge of early growth and exposure to stressors could play an important role in the prevention of cardiovascular illness and deaths. The developing central nervous system is particularly vulnerable to early environmental stressors such as those that impair cerebral nutrient and oxygen supply, and the potential exists for alterations induced during early development to cause altered CNS function throughout life. Professors Sandra Rees and Terrie Inder have been at the forefront of studies aimed at understanding how the developing CNS is affected by stressors that are associated with commonly encountered challenges to the developing fetus and infant such as placental insufficiency, infections and preterm birth. The
INTRODUCTION developing lung is one of many organs that can be permanently affected by an adverse intra-uterine or early postnatal environment as the critical functional units of the lungs are formed during fetal life and infancy. Professors Gert Maritz, Colin Morley and Richard Harding review the evidence that the developing lung is vulnerable to the early environment and suggest mechanisms that could form the basis for preventative measures. In presenting these reviews our hope is that an increasing knowledge of the programming of adult health and disease, and its mechanisms, will stimulate efforts aimed at providing each fetus and infant with the most optimal environment in which to develop. In doing so, health outcomes in later life will be improved.
Richard Harding Department of Physiology, Monash University, Melbourne, VIC 3800, Australia E-mail address: [email protected]. Tel.: +61 3 9905 2514; fax: +61 3 9905 2584.
www.elsevier.com/locate/earlhumdev
INTRODUCTION
Fetal origins of postnatal health and disease One of the most remarkable developments in medicine in the last 10—15 years has been the recognition that some serious health problems in later life could have their origins in early life. Large scale epidemiological surveys in several countries have shown significant associations between lower than expected birthweight, a surrogate for fetal exposure to environmental stressors, and late-onset disease states such as coronary heart disease, obesity and type 2 diabetes. These new findings have been interpreted as evidence for the programming of later physiological function by altered early development, a concept that has the potential to explain a number of important adult-onset diseases for which, at present, there is no apparent cause. This has led to a spate of more targeted studies that are starting to unravel the cellular and molecular processes responsible for the developmental programming of later disease risk. It is now apparent that altered structural or functional development of a number of crucial organ systems can bprogramQ or permanently alter organ function and susceptibility to later dysfunction and disease. In essence, developmental programming is due to a change in gene expression pattern that occurs in response to a stressor during development. The physiological adjustments that enable the fetus or neonate to survive exposure to environmental stressors apparently result in later impairments in organ function and a greater vulnerability to disease processes. A key challenge is to identify stressors that are capable of permanently altering organ development and function, and also the stages of development of greatest vulnerability. At present, there is strong evidence that factors leading to lower than expected birthweight (ie intra-uterine growth restriction) such as fetal hypoxia, restricted fetal nutrition, excess exposure to glucocorticoids, and impaired placental function have the potential to
program changes in development. It is also apparent that fetal exposure to commonly used drugs such as alcohol and tobacco can alter organ development and later function. Restricted prenatal growth may not be a requirement for programming to occur: for example early fetal exposure to glucocorticoids does not impair fetal growth but can permanently alter renal development and lead to hypertension in adults. The early postnatal environment is also important as many organ systems continue to develop after birth; it is now recognised that undernutrition, infections and drug exposure during infancy and childhood can adversely affect later health. In this issue of EHD are articles by 5 groups of researchers working at the forefront of attempts to understand the physiological basis and clinical significance of developmental programming. These short reviews are written by authors who are at the cutting edge of research in their field. Each review provides up-to-date information on the potential impact of a sub-optimal intra-uterine or neonatal environment on organ systems and has indicated, in the form of a series of guidelines, how these findings relate to medical practice. They have also presented areas in which further research is needed. In the first article, Prof Abigail Fowden and her colleagues show how restricted fetal growth can alter the development and later functioning of the hypothalamic—pituitary—adrenal axis, leading to an alteration in the endocrine control of metabolism and growth. Their findings explain why infants whose growth was restricted in utero, or who were prenatally exposed to excess glucocorticoids, are at increased risk of adiposity and type 2 diabetes in later life. Dr Avan Sayer and Prof Cyrus Cooper show how body composition, including fat deposition, and musculo-skeletal development, can be permanently altered by factors that restrict fetal growth. Sarcopenia and osteoporosis are major clinical problems
0378-3782/$ - see front matter D 2005 Elsevier Ireland Ltd. All rights reserved. doi:10.1016/j.earlhumdev.2005.08.001
722 of the elderly and with an aging population are likely to increase in prevalence; the recognition that they may have their origins in fetal life provides a means by which they could be prevented. Dr Samantha Louey and Prof Kent Thornburg demonstrate how exposure to stressors during fetal and early postnatal life can alter the development of the heart and blood vessels, increasing later vulnerability to heart and vascular diseases. Therefore, a knowledge of early growth and exposure to stressors could play an important role in the prevention of cardiovascular illness and deaths. The developing central nervous system is particularly vulnerable to early environmental stressors such as those that impair cerebral nutrient and oxygen supply, and the potential exists for alterations induced during early development to cause altered CNS function throughout life. Professors Sandra Rees and Terrie Inder have been at the forefront of studies aimed at understanding how the developing CNS is affected by stressors that are associated with commonly encountered challenges to the developing fetus and infant such as placental insufficiency, infections and preterm birth. The
INTRODUCTION developing lung is one of many organs that can be permanently affected by an adverse intra-uterine or early postnatal environment as the critical functional units of the lungs are formed during fetal life and infancy. Professors Gert Maritz, Colin Morley and Richard Harding review the evidence that the developing lung is vulnerable to the early environment and suggest mechanisms that could form the basis for preventative measures. In presenting these reviews our hope is that an increasing knowledge of the programming of adult health and disease, and its mechanisms, will stimulate efforts aimed at providing each fetus and infant with the most optimal environment in which to develop. In doing so, health outcomes in later life will be improved.
Richard Harding Department of Physiology, Monash University, Melbourne, VIC 3800, Australia E-mail address: [email protected]. Tel.: +61 3 9905 2514; fax: +61 3 9905 2584.