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 Health impact in later years It should be kept in mind that nutrition is not the only environmental factor that can affect the growth of the developing fetus. Low oxygen, radiation exposure, and exposure to various chemicals, both natural and therapeutic, may also cause changes in the growth patterns that affect health in later life. Genetics & environment in development Human development is the result of the interaction of genetic and environmental factors. The genes that a fetus inherits from the parents represent a range of developmental possibilities, while the prevailing environmental conditions during development channel development into certain possible outcomes. A dramatic example of such geneticenvironmental interaction is illustrated in the development of a turtle. Unlike mammal eggs, a fertilized turtle egg has the genetic potential to develop into either a male or a female. Fertilized turtle eggs are buried in sand to hatch; whether an egg develops as a male or female depends on the temperature of the sand. If the temperature is below 30°C, the eggs will develop into males; above 30°C, females are produced. The activity of specific genes that control the formation of male sex hormones and hormone receptors are activated at low temperature, while at higher temperature, the activity of a different set of genes responsible for female sex hormones and receptor production are activated. Once triggered, the sex of the turtle is determined and will remain unchanged throughout the life of the turtle. Role of nutritional environment of the fetus in future health Epidemiological studies from different parts of the world show that there is an association between low birth weight of the human fetus and coronary heart disease and type II diabetes in later life. The range of the studies extends from less than 2500 grams, or 5.5 lbs, to more than 4300 grams, or 9.5 lbs. (A full-sized infant weighs 2500 grams or more; low birth weight is less than 2500 grams, and very low birth rate is less than 1500 grams, or 3.3 lbs. Less than 1000 grams, or 2.2 lbs, is considered extremely low) While coronary heart disease and type II diabetes can occur in individuals whatever their birth weight, individuals born at the lower end of the birth weight range have a higher risk. This increased risk appears to be independent of some environmental influences in later life, such as smoking, but is accentuated by other factors. For example, those with low birth weight who become obese later in life have a greater risk for diabetes than those wwho are not obese. Ultimately, the nutritional environment may work by directly acting on genes that have a crucial role in early development, enhancing the activity of some and inhibiting the activity of others. Fetal programming hypothesis It has been proposed that a low birth weight is not in itself the cause of adult diseases; rather, it is an indicator of some other aspects of fetal growth that are responsible. During the development of the fetus, the organs and systems of the body have "developmental plasticity," that is, their structures and metabolism can develop in a number of different ways within the limits of their genetic makeup. The fetus is sensitive to its nutritional environment and which ways its developments take depend on this environment. Main reasons for low birth weight can be poor nutrition of the mother during pregnancy, or a failure of transmission to the fetus because of placental or other problems in well-nourished mothers. When there is a nutrition deficit, fetal development responds to this deficit by adapting the development of organs and systems for survival to the low nutrition environment. The environment is said to have "programmed" the fetus, that is, caused permanent changes in structure and physiology, which may trigger long-term health consequences for the individual. The adaptations can include smaller body size and reduction of metabolic rate as a means of conserving limited nutrition and energy resources. These permanent structural and metabolic adaptations of the fetus may be optimal and necessary for fetal development under low nutrient levels, but will likely have adverse effects later in life when the individual encounters a rich nutritional environment. Because fetal growth and early childhood both affect the health status of an individual later in life, it has been suggested that the "fetal origins hypothesis" may be more appropriately referred to as the "developmental origins hypothesis". Both terms are used. Health effects of fetal programming in later life How does fetal response to undernutrition lead to disease later in life? Some studies have shown that the structures of organs are affected by fetal growth under less than optimum nutrient conditions. The kidney and liver are significantly smaller in low weight newborns than those in the normal weight range. In the case of the kidney, all the kidney cells (nephrons) are formed by 32 to 34 weeks of gestation, and no additional cells are added to the kidney after. Thus, a deficit of nephrons in a newborn will persist throughout life. In growth restricted human fetuses, the number of nephrons is significantly less than in fetuses with normal growth, with the number of nephrons increasing with birth weight. Studies on rats subjected to a poor fetal environment have shown a reduction in the number of cells in the heart and pancreas besides in the kidneys, leading to modified functions of these organs and an increase in the risk for diseases such as hypertension and diabetes. Does fetal sensitivity to nutritional deficit differ at different times during the pregnancy? Attempts to identify the time in pregnancy when the fetus is most sensitive to programming by nutrition included a study of individuals who were conceived during a wartime famine in Holland from November 1944 to May 1945. During this period, official food rations ranged from 400 to 800 calories per day. It was found that the famine only slightly reduced body size at birth. However, tests for glucose tolerance on the subjects indicated that those who had been exposed to the famine during late gestation had a lower tolerance than those exposed at other stages of gestation or individuals born the year before or conceived the year after the famine. Results of this study suggest that fetal nutritional deficiency has a significant impact on the insulinglucose metabolism of the individual later in life. Furthermore, the results indicate that nutritional deficit can affect the fetus without necessarily reducing birth weight. In addition, the highest level of glucose intolerance was found in those individuals who were exposed to the famine and had low birth weights or became obese in later life, suggesting that the effects of fetal programming can be enhanced later in life by lifestyle. Childhood growth affects adult health Not only is growth during the fetal stage related to later health, butthere is evidence that growth during early childhood can also be important. A study in Finland of a birth cohort of 4630 men included 357 who suffered from coronary heart disease. Data on their birth weights, and their weights and heights for the first 12 years of life were available for analysis. Researchers found that those who later developed heart disease had a low birth weight, and their weights remained lower than average for the first 2 years of life, followed by a period of accelerated growth in weight and body mass index. At age 12, their body weights almost reached the average weight of those who did not develop heart disease as adults. However, those with heart disease had remained significantly shorter than average at age 12. Women who developed heart disease also showed a similar weight change pattern. Type II diabetes and high blood pressure in both males and females show a similar association with growth: The risk of disease decreases with increasing birth weight, and rises when there is rapid weight gain during early childhood. It is suggested that reducing the BMI (Body mass index, see p.39) of susceptible children between the ages of 3 to 11 may reduce the risk of cardiovascular disease in their later years. Another study also shows an association between growth changes during childhood and type II diabetes using BMI to map early growth. At the age of 2, children's BMI begin to decrease as they lose fat; it reaches a minimum by about age 6, and then begins to increase again. This increase is referred to as the "adiposity rebound". Adiposity rebound can start from about 3 years to 8 years of age or older. Data shows that an early age of rebound is associated with a high BMI later in childhood, and an increased risk of type II diabetes later in life. For children whose rebound began at age 4, the incidence of type II diabetes later in life was 8.6%, whereas children who began the rebound at around 8 years had an incidence of 1.8%. Of significance is the finding that early adiposity rebound is related to thinness at birth and at 1 year of age. Apparently, a young child who is thin at birth and gains weight rapidly thereafter is at greater risk for type II diabetes than a young child who is overweight. Additional findings Epidemiological studies of two conditions of old age, osteoporosis and sarcopenia (loss of muscle mass and strength), indicate that fetal programming is involved. The data for osteoporosis in both men and women shows an association of bone mineral content with weight at 1 year of age even after adjustments for differences in lifestyle. In the case of sarcopenia, there is a strong relationship between small size at birth and reduced muscle mass and strength in elderly men and women. This suggests fetal programming, but it is not yet clear whether the programming is a result of prenatal undernutrition. However, in studies on sheep, prenatal undernutrition was found to reduce muscle mass in the newborn, and this reduction persists into later life. Some investigators question the statistical analyses of the data used to formulate the fetal origins hypothesis. But it is generally accepted that low fetal growth is associated with future health, and that fetal growth is dependent on maternal nutrition and the mother's delivery system (e.g. placenta and uterine blood supply) for getting nutrients to her fetus. Exactly how the fetus responds to its nutritional environment and how this response can increase the risk for disease has yet to be determined. It is becoming clear that fetal hormonal systems and the number of cells in fetal organs are factors. It should be kept in mind that nutrition is not the only environmental factor that can affect the growth of the developing fetus. Low oxygen, radiation exposure, and exposure to various chemicals, both natural and therapeutic, may also cause changes in the growth patterns that affect health in later life. |
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