Life Cycle Nutrition

Definition

Life cycle nutrition, which is sometimes called maternal-fetal nutrition, refers to several interrelated concepts. The first is that poor nutrition during fetal development has negative effects that carry into the person's adult life, including such diseases of maturity as cardiovascular disorders, stroke, type 2 (adult-onset) diabetes, and cancer. The second is that a dysfunctional nutrition pattern characterized by fetal undernutrition followed by rapid weight gain after age two negatively impacts the development of adult-onset diseases.

Description

The concept that poor nutrition during fetal development has negative effects that carry into the person's adult life is associated with the work of Dr. David Barker of the University of Southampton in England. This concept is known as the fetal origins of adult disease or the FOAD hypothesis. In Dr. Barker's own words, "Genes provide a general recipe for making a human being, but the human being is determined by the ingredients provided by the mother."

The fetal origins hypothesis is related to the finding of the United Nations Sub-Committee on Nutrition that undernutrition is an intergenerational problem as well as a societal issue. The committee has described a cycle of malnutrition in developing countries in which malnourished women give birth to low-birth weight babies whose growth is stunted in their early years by due to inadequate food and health care. Girls have a brief "window of opportunity" in adolescence to catch up on their physical growth, but the effects of childhood undernutrition on their intellectual and psychological development are difficult to overcome, particularly if they continue to receive poor-quality food and medical attention. These stunted adolescents grow into women who do not gain enough weight during pregnancy to nourish their babies adequately, and the cycle continues into the next generation.

Life cycle nutrition studies have also indicated a clear connection between a dysfunctional nutrition pattern characterized by fetal undernutrition followed by rapid weight gain after the age of two, and such medical problems as obesity and type 2 (adult-onset) diabetes. This finding indicates that the populations of countries undergoing rapid economic development and increased prosperity are likely to see rising rates of metabolic disorders as well. One important implication of recent research in life cycle nutrition is that public health strategies intended to reduce the incidence of noncommunicable lifestyle diseases through modifying food intake, substance abuse, and other behaviors of adults are found to be insufficient. For many people, diseases that become apparent in adult life are the end product of prenatal and early childhood factors that neither they nor their doctors could control. Some researchers have begun to use the acronym DOHAD, which stands for developmental origins of adult health and disease, instead of FOAD to emphasize the fact that prevention of excessive weight gain after early childhood is as important as preventing fetal undernutrition.

Historical background

The notion that poor diet in childhood might be a risk factor for heart disease and other health problems in later life was first expressed in 1964 by Rose, a British doctor who reported that persons who had had siblings who were stillborn or had died in early infancy had twice the risk of heart disease as people whose siblings survived into adulthood. Rose's work was followed in 1967 by a Norwegian physician named Forsdahl, who found that the risk of death from heart disease was highest among people from parts of Norway that had recorded a high rate of infant mortality in the same generation.

The idea that fetal health affected the individual's adult health gained widespread currency in the 1990s, as the result of the work of David Barker, a British doctor who investigated the reasons for the rising rate of coronary heart disease among men in developed countries. In the course of analyzing the British data, Barker was struck by an apparent paradox: heart disease is associated with improvements in nutrition and living standards, yet the highest rates of heart disease in Britain were recorded for areas that had been economically depressed in the early twentieth century. He noticed that these areas also had the highest rates of infant mortality at that time, together with the highest rates of low-birth weight children. He then hypothesized that impaired fetal growth might have predisposed the children who survived infancy to an increased risk of heart disease as adults.

Barker and his research group made a detailed study of mortality from heart disease in men born in Hertfordshire, England, between 1911 and 1939. He chose the area because good records had been kept of children's size at birth and growth in infancy. Barker found that men who had been small at birth and at one year of age had the highest rates of death from heart disease. Other studies showed that low birth weight was also correlated with higher rates of hypertension and impaired glucose tolerance—which are part of the symptom cluster first identified by Dr. Gerald Reaven in 1988 as syndrome X, a precursor of type 2 diabetes. Syndrome X is now generally known as insulin resistance syndrome, metabolic syndrome, or Reaven's syndrome, after its discoverer.

There are three major types of evidence supporting Barker's theory that there is a connection between fetal nutrition and susceptibility to disease in adult life:

• Nutritional experiments with animals. Experimental reduction of the amount of protein in the diet of pregnant mammals (mice, sheep, rats, and guinea pigs) has shown that the offspring are reduced in size at birth and that they tend to develop hypertension and impaired glucose tolerance.
• Experiments with cross-breeding and embryo transplantation in animals. These experiments have demonstrated that the supply of nutrients to the fetus is a more important determinant of size at birth than genetic makeup.
• Analysis of medical data from historical episodes of semi-starvation. Since deliberate starvation of human subjects would violate contemporary codes of ethics for researchers, nutritionists often turn to instances of food shortages from the recent past to obtain their data. The most frequently studied example of such an occurrence is the so-called Dutch Hunger Winter of 1944–1945, when the average food ration in the western part of the Netherlands dropped to 400-800 Calories per day. (For purposes of comparison, a daily intake of 1,200-1,500 calories per day is recommended for adult women in developed countries seeking to lose weight safely.) The famine resulted from a combination of several factors: the embargo placed on food transportation by the occupying German army; the ruin of agricultural land by the retreating Germans; and an unusually cold and snowy winter. About 30,000 people died from starvation during the famine. Women who became pregnant during the Hunger Winter gave birth to infants with reduced birth size and an increased risk of glucose intolerance and obesity in adult life, with the risk highest in those who were born in the third trimester of pregnancy.

The "thrifty phenotype" hypothesis

The findings of a connection between low birth weight and glucose intolerance as well as heart disease led Barker to propose what he has called the "thrifty phenotype" hypothesis. Phenotype refers to the sum total of an organism's observable physical appearance and functioning as determined by the interaction of environmental and genetic factors. In contrast genotype refers to the specific genetic makeup or genome of an individual organism. Barker hypothesized that the fetus in an undernourished mother makes the best of a bad situation, so to speak, by allocating its limited nutritional resources to protect the development of its brain and its overall chances of survival. It also reduces its secretion of and sensitivity to insulin and other growth hormones. In Barker's terms, the fetus becomes nutritionally thrifty. This part of the theory is supported by the fact that men born just after the Dutch Hunger Winter have unusually large heads compared with their overall body weights.

The problem with the fetus's thrifty "solution" to its prenatal undernourishment is twofold. On the one hand, the fetus is well adapted to a low-calorie and low-fat environment. However, its "prediction" may well turn out to be wrong, and it may find itself in a high-calorie, high-fat dietary environment in which its thrifty metabolism leads to faulty appetite regulation, obesity, and insulin resistance. The other problem is the long-term consequences of the developmental compromises the fetus must make. In particular, the development of the brain may be protected at the expense of the digestive tract, the kidneys, and other internal organs. A team of researchers in Boston found that fetuses whose growth was restricted are born with fewer nephrons, the structures in the kidneys that form urine. Since each nephron must work harder, it is likely to wear out and die relatively early in the person's life. The eventual result is high blood pressure.

The thrifty phenotype hypothesis suggests that low weight at birth combined with an unfavorable pattern of growth after birth leads to an increased risk of adult health problems. Dr. Barker's most recent findings, published in the New England Journal of Medicine in October 2005, identify this unfavorable pattern as low birth weight coupled with thinness at two years of age followed by a rapid weight gain up to age 11. It is thought that a rapid increase in weight between two and eleven years of age leads to a high proportion of body fat in relation to muscle. Barker concludes that prevention of coronary heart disease in adult life depends on three factors: the mother's consumption of a balanced and varied diet before and during pregnancy; maintaining a healthy rate of growth after birth; and avoiding rapid weight gain in children who were small at birth or thin at age two.

Nutrition transition

Statistics collected by the Sub-Committee on Nutrition of the World Health Organization (WHO) lend some support to the thrifty phenotype hypothesis. On the one hand, the prevalence and number of underweight children in most countries have declined steadily since 1980, even in south-central Asia, which is the worst-affected region. In 1980, WHO estimated that 47% of children under the age of five in developing countries had stunted growth due to undernutrition. By 2000, that figure had declined to 32%. Only in Africa are the rates of underweight and stunted children rising in the early 2000s. About 70% of the world's undernourished children live in Asia, while about 24% live in sub-Saharan Africa. By contrast, fewer than 1% of children in the United States suffer from chronic malnutrition.

On the other hand, the so-called nutrition transition—the changes in eating habits and lifestyles associated with urbanization and greater affluence in many developing nations—appears to be accelerating the increased incidence of heart disease, obesity, and type 2 diabetes in such countries as India. The Society for the Natal Effects of Health in Adults (SNEHA) in India reported in 2003 that 20% of Indian women and 16% of Indian men will meet current definitions of obesity by 2020. In addition, evidence is accumulating that persons of either sex from southern Asia have a higher risk of obesity-related disorders than Caucasians of the same weight and body mass index. Another example of health disorders in adults attributed to nutrition transition is the Falashas, a group of African Jews who migrated from Ethiopia, a country stricken by recurrent famine, to Israel, a Westernized nation, in the 1980s. Within five years of the migration, the rate of type 2 diabetes among the Falashas had risen to 18%—30 times the rate among Ethiopians who had remained in Ethiopia and twice as high as the rate among the general Israeli population.

Function

Overview of maternal and fetal nutrition

A summary overview of maternal and fetal nutrition may be helpful as background for the FOAD hypothesis. In a normal human pregnancy, the fetus is nourished by a structure called the placenta, which develops from the outer layer of cells in the blastocyst (an early stage in the development of the embryo). The blastocyst implants itself in the lining of the uterus between 5 and 8 days after fertilization. As the placenta develops, it produces hormones needed to sustain the pregnancy, carries oxygen and nutrients from the mother's circulation to the fetus and transports waste materials from the fetus to the mother. As the placenta grows, it develops tiny projections called villi that extend into the wall of the uterus. The villi serve to increase the area of contact between the placenta and the uterine wall, which in turn increases the efficiency of nutrient and waste product exchange. At the time of delivery, the average human placenta weighs about 1 lb (.5 kg).

It is important to understand the distinction between maternal and fetal nutrition. In humans, the fetus develops at the end of a supply line that begins with the mother's dietary intake, her metabolic and endocrine status, the adequacy of blood flow in the uterus, and the adequacy of the transfer mechanisms in the placenta. It is possible for a fetus to receive insufficient nourishment, not because the mother's diet is inadequate, but because of other factors including:

• high blood pressure interfering with blood flow in the uterus
• diabetes in the mother altering the amount of glucose available to the fetus
• damage to the placenta resulting in lowered transfer capacity
• similar factors impeding blood flow from mother to fetus

From that perspective, fetal nutrition has a greater impact on birth weight and growth after birth than the mother's diet taken by itself.

Fetal programming

The concept of programming as used by nutritionists was first defined by a scientist named Alan Lucas in 1991. He described it as "the permanent response of an organism to a stimulus or insult during a critical period of development." Programming is a phenomenon that has been found in the life cycle of many animals. For example, the sex of crocodiles is determined by programming related to the temperature at which the eggs develop rather than by sex chromosomes. Experiments with rats have shown that newborn female rats given testosterone during the first week of life will be unable to ovulate and reproduce. Testosterone given after this time, however, has no effect. Thus researchers studying programming speak of a "vulnerable" or "sensitive" period.

In mammals, the sensitive or critical period is usually a phase of rapid cell division. Unlike some other mammals, humans undergo most of their phases of rapid cell division prior to birth; there are 42 rounds of cell division in the human infant, most of them occurring before delivery. This means that the timing of the fetus's exposure to famine or other adverse conditions determines which organs will be affected. Undernutrition in early pregnancy appears to increase the risk of cardiovascular disease and slow cognitive development, while undernutrition late in pregnancy increases the risk of kidney damage. It is thought that programming affects the general level of functioning of fetal tissues, as well as the total number of cells in the developing body. It is not yet known, however, precisely how the fetus's genetic makeup interacts with its prenatal environment.

Other agents that have been implicated in fetal programming include fungicides and other chemicals that oppose the effects of androgens (male hormones), birth control pills and other synthetic estrogens (female hormones); and smoking, which lowers the amount of oxygen available to the fetus.

Role in human health

Intrauterine growth retardation (IUGR)

Intrauterine growth retardation (IUGR) refers to fetal growth that has been retarded by inadequate prenatal nutrition. It is usually defined as growth that falls below the 10th percentile for a reference population, taking gestational age into account. WHO estimated in 2004 that as many as 24%, or 30 million infants, in the developing countries are affected by IUGR.

The primary cause of IUGR in developing countries is nutritional: poor maternal nutritional status before pregnancy; short stature of the mother due to illness and undernutrition in childhood; and low weight gain during pregnancy resulting from inadequate food intake. In addition, intestinal parasites, diarrheal diseases, malaria, and respiratory infections often contribute to IUGR in these countries. By contrast, the most important single cause of IUGR in the developed countries is tobacco smoking, followed by compulsive dieting and eating disorders, alcohol, and drug abuse.

In addition to increasing the individual's risk of heart disease and insulin resistance syndrome in adult life, IUGR is associated with a higher risk of neurological disorders, slowed cognitive development, and an impaired immune system.

Childhood illnesses and disorders

Undernutrition in children of preschool age is associated with underweight (low body mass relative to age); stunting (shortness of height relative to age); and wasting (severe weight loss as the end result of famine, chronic dietary insufficiency, or disease). The number of underweight children in the world has decreased steadily since 1990. Wasting is less common than either stunting or underweight, and is thought to affect about 9% of the world's children as of 2004. The incidence of wasting can change rapidly, however, particularly during disease epidemics and in refugee situations.

Other adult diseases and disorders

The possibility that life cycle nutrition issues may be associated with other diseases and disorders has stimulated research around the world. Disorders related to high blood pressure during pregnancy, for example, appear to be related to the pregnant woman's having been a low-birth weight infant. International congresses on the fetal origins of adult disease were held at Mumbai, India, in 2001 and at Brighton, England, in 2003. The National Institute of Child Health and Human Development (NICHD) has been funding research on the issue since 2000. In January 2005, the endocrinology, nutrition, and growth branch of the NICHD reported on the six studies of fetal programming of adult disease and two studies of maternal-fetal nutrition that were funded in 2004. One study found that children born to women who had been asked to eat a pound of meat per day and avoid foods high in carbohydrates during the last three months of pregnancy had very high levels of cortisol, a glucocorticoid that regulates the metabolism of glucose, protein, and fats. High levels of cortisol contribute to insulin resistance, thus increasing a person's risk of developing type 2 diabetes.

KEY TERMS

Insulin resistance syndrome— A group of symptoms and metabolic disorders associated with an increased risk of type 2 diabetes. The symptoms include impaired glucose tolerance, obesity, high blood pressure, and high triglyceride levels.

Insult— In medicine, an injury or hurt, usually physical or developmental.

Malnutrition— A general term for any disorder of nutrition.

Nutrition transition— A term used to describe the changes in eating patterns that take place in countries undergoing rapid economic development and improved standards of living.

Phenotype— The entire observable physical and biochemical constitution of an organism as determined by its environment as well as its genetic makeup.

Placenta— The organ in pregnant mammals formed by the joining of the mucous membrane in the lining of the uterus with the membranes surrounding the fetus. The placenta serves to convey nourishment to the fetus and carry away its waste products.

Programming— The notion that the intrauterine environment can influence fetal metabolism at a critical point in pregnancy in such a way as to predispose the child to disease in adult life.

Retrospective study— A research study that analyzes medical records or other data recorded in the past. The Hertfordshire Cohort Study is a retrospective study.

Syndrome X— An early name for insulin resistance syndrome.

Undernutrition— Malnutrition caused by an inadequate food supply or by the body's inability to use or absorb necessary nutrients from the food that is consumed.

Resources

BOOKS

Langley-Evans, Simon C. "Fetal Programming of Adult Disease: An Overview." In S. C. Langley-Evans, ed., Fetal Nutrition and Adult Disease: Programming of Chronic Disease through Fetal Exposure to Under nutrition. Cambridge, MA: CABI Publishing, 2004.

United Nations Sub-Committee on Nutrition (SCN). Fourth Report on the World Nutrition Situation. New York: United Nations Development Programme, 2004.

PERIODICALS

Barker, D. J., and S. P. Bagby. "Developmental Antecedents of Cardiovascular Disease: A Historical Perspective." Journal of the American Society of Nephrology 16 (September 2005): 2537-2544.

Barker, D. J., C. Osmond, T. J. Forsen, et al. "Trajectories of Growth among Children Who Have Coronary Events as Adults." New England Journal of Medicine 353 (October 27, 2005): 1802-1809.

Bhagarva, S. K., H. S. Sachdev, C. H. Fall, et al. "Relation of Serial Changes in Childhood Body-Mass Index to Impaired Glucose Tolerance in Young Adulthood." New England Journal of Medicine 350 (February 26, 2004): 865-875.

Editorial. "The Child Is Father to the Patient: Fetal Origins of Adult Disease." Economist, 12 June 2003.

Fall, Caroline H. D. "The Early Life Origins of Adult Disease." Indian Pediatrics 40 (2003): 480-502.

Harding, J. E. "Review: The Nutritional Basis of the Fetal Origins of Adult Disease." International Journal of Epidemiology 30 (2001): 15-23.

Kim, Sue Y. S., MD. "Fetal Origins of Adult Disease: The Barker Hypothesis Revisited—2004." Current Opinion in Endocrinology and Diabetes 11 (2004): 192-196.

Ravelli, A. C., J. H. van der Meulen, R. P. Michels, et al. "Glucose Tolerance in Adults after Prenatal Exposure to Famine." Lancet 351 (January 17, 1998): 173-177.

Syddall, H. E., A. A. Sayer, S. J. Simmonds, et al. "Birth Weight, Infant Weight Gain, and Cause-Specific Mortality: The Hertfordshire Cohort Study." American Journal of Epidemiology 161 (June 1, 2005): 1074-1080.

ORGANIZATIONS

International Food Policy Research Institute (IFPRI). 2033 K Street, NW, Washington, DC 20006-1002. (202) 862-5600. Fax: (202) 467-4439. http://www.ifpri.org.

National Institute of Child Health and Human Development (NICHD). Information Resource Center, P. O. Box 3006, Rockville, MD 20847. (800) 370-2943. Fax: (301) 984-1473.

Society for the Natal Effects on Health in Adults (SNEHA)-India. c/o Centre for the Study of Social Change, Plot No. 6, Block F, opposite Government Colony Building No. 326, Bandra East, Mumbai, India 400-051. (91-022) 2657-0924. Fax: (91-022) 2657-0980. http://www.sneha-india.org.

United Nations Development Programme, One United Nations Plaza, New York, NY 10017. (212) 906-5764. Fax: (212) 906-6661. http://www.unsystem.org.

OTHER

Dr. David Barker's web site: http://www.barkertheory.com.

Grigsby, Donna G., MD. "Malnutrition." eMedicine, 18 December 2003. http://www.emedicine.com/ped/topic1360.htm.

National Institute of Child Health and Human Development (NICHD), Endocrinology, Nutrition, and Growth Branch. Report to the NACHHD Council: January 2005. Rockville, MD: NICHD, 2005.