The combination of malnutrition and infection is the leading cause of death among young children in developing countries. Malnutrition alone is estimated to account for more than half of childhood deaths annually.1 In developing countries, approximately 1 83 million children are underweight for their age, 67 million are underweight for their height (wasted), and 226 million are low heightfor-age (stunted).46 Other leading causes of deaths are malaria, acute respiratory infections, diarrheal disease, tuberculosis, and HIV/AIDS, all frequently complicated by varying degrees of malnutrition.2
Protein-energy malnutrition (PEM) represents a spectrum, with kwashiorkor and marasmus at one extreme and stunting and underweight representing the more chronic and mild to moderate forms.3 Micronutrient malnutrition frequently is superimposed on the above forms of malnutrition, rarely occurring in isolation and reflecting poor diet quality, particularly lack of animal-source foods (ASF) in the diet. This silent form of malnutrition can have devastating impacts on fetal growth and on the health, growth, and development of children of all ages, particularly young children.4
The functional consequences of malnutrition range from mild to severe lifetime impairments. The child survival revolution has accomplished much in saving lives of the "under fives" population but until recently has done little to enhance the quality of the surviving child. Improved nutrition, bom of macronutrients and micronutrients, supplied by a diverse diet has much to offer in die promotion of health, growth, development, and productivity of the surviving child.5
FRAMEWORK FOR NUTRITIONAL STATUS
Malnutrition must be viewed in a broad, ecologie context. Describing nutritional status, even in great detail, does not shed light on the distal and proximal causes of the problem, nor does it give an understanding of prevention, as in how and where to direct interventions. Only through analysis and understanding of the contributory factors can sound and effective programs be designed and implemented.
Figure 1. Strategy for improving nutrition for women and children. (Source; UNICEF.)
The Community Nutrition Level Equation, as conceptualized by me late Dr. Derrick B. Jelliffe, provides such a functional framework.3 He incorporated physical, biological, sociocultural, environmental, economic, and geographic considerations, political status and conflict, and infection burden as determinants of the nutrition level of a community. Family size, parental educational level, and literacy also play a large role. The main causal factors, especially those amenable to practical action, need to be identified. Cultural beliefs and practices concerning nutrition cannot be emphasized enough. Some are helpful and supportive of positive nutrition and health, but some can be detrimental to nutritional status.3 A United Nations Children Fund (UNICEF) model, presented in Figure 1, is based on the above framework by Jelliffe.3·6
DEVELOPMENTALVIEW OF NUTRITIONAL PROBLEMS
The pre-conception nutritional status of a young woman, often adolescent and not yet fully grown, sets the stage for her future offspring. In developing countries, pregnant women with a history of poor diet, anemia, short stature (less than 5 feet) and low body weight (less than 100 pounds) are at risk for giving birth to low-birth- weight, intrauterine-growthretarded (IUGR) infants.7 Such infants are at risk for cognitive deficits and never reach their full growth potential postnatally, especially for height, head circumference, and pelvic size. At birth, IUGR infants may have impaired cell-mediated immunity (CMI), which takes several years to recover from, with increased susceptibility to serious infections and poor response to bacille Calmette-Guerin (BCG) vaccine for tuberculosis.8
Infants born to malnourished women often have poor stores of iron, zinc, vitamin A, and vitamin B12. Iron, zinc, and iodine deficiencies in the motfier contribute to retarded fetal growth. Iodine, folate, and vitamin B1, are essential for normal brain and central nervous system (CNS) development and growth.7 Devastating outcomes for the CNS are particularly due to maternal iodine deficiency. In die past decade, increasing attention has been called to the increased risk of IUGR infants for developing type ? diabetes, obesity, cardiovascular disease, and hypertension as adults. Barker9 first recognized this association through epidemiological studies. The origins of adult morbidity are postulated to stem from in utero metabolic aberrations caused by intrauterine malnutrition.
Figure 2. Moderate PEM in a child in Ghana.
The infant from birth to 6 months has been regarded as an "extra-gestate" fetus whose total nutritional requirements optimally are met by exclusive biologic breastfeeding, assuming an adequate diet in the lactating woman.3 There is vast literature on the fine-tuned nutrient content regulation and the antiinfective properties of breast milk and Colostrums. Secretory IgA (slgA), lysozyme, biologically active macrophages, and lactose, which maintains an acidic pH, suppress pathogenic Escherichia coli and other pathogens to help resist infection.10 Breastfeeding, of course, bypasses the exposure to contaminated, often diluted, milk or formula and water. Breast milk substitutes, which are very expensive, often motivate mothers to dilute formula and save the leftovers without refrigeration.
Infants weaned at younger than 6 months are at high risk for diarrheal disease and other infections. In developing countries, although mothers tend to breastfeed their infants well into the second year, exclusive breastfeeding beyond age 4 to 6 months is rare. Nutrient concentrations in breast milk reflect those of the maternal diet, which may be low or deficient in folate, iodine, and vitamins A, B12, and D. Because breast milk is the infant's sole food for the first few months of life, it is important to evaluate the maternal diet. Maternal dietary improvement and added supplementation improve not only the mother's nutritional status but also the nutritional quality of her breast milk and the health of her infant.3·10
Figure 4. Full-blown marasmus in a child in Ghana.
Figure 3. Full-blown kwashiorkor in a child in Uganda.
HIV Risks from Breastfeeding
Because HIV transmission can occur via breast milk of HIV-positive mothers, a debate exists concerning the recommendation that HIV-positive mothers not breastfeed their infants. The transmission risk via breast milk is estimated to be approximately 15%, depending on the timing and viral load in the mother.11 This risk has to be balanced against the greater than 30% risk to her infant of death in circumstances of poverty, poor sanitation, and lack of affordable breast milk substitutes in developing countries if the infant is not breastfed.1'12 Observational studies show infants exclusively breastfed for at least 4 months have greater protection against HTV infection than those who are partially breastfed and receive breast milk substitutes.
Anthropometric Cutoffs for Stunting, Underweight, and Wasting*
Women who are HIV positive must be counseled about the risks of HIV transmission to the infant with exclusive breastfeeding for the first 4 months, versus the risk of infant death from diarrhea and other infections with the use of breast milk substitutes from birth. The risk of an infant dying if not exclusively breastfed for at least 4 months is considerably greater than the risk of the infant dying from HTV infection.12 Thus, the current World Health Organization (WHO) recommendation for women who cannot readily obtain and afford safe breast milk substitutes, nor have access to safe water and refrigeration, is to exclusively breastfeed the infant for 4 months and then abruptly wean the infant to locally available animal milk or formula. Abundant instruction is needed about the sanitary and correct preparation and storage of such milk feedings.
Effects of Micronutrient Deficiencies
Creative and promising work is in progress in East Africa. Relactation of HIV-negative grandmothers is being implemented so their expressed breast milk may be used to feed grandchildren bom to their HIV-positive daughters.13 Also, maternal milk of HIV-positive mothers is being home pasteurized to kill the virus. Virologie testing of such treated breast milk is showing the milk to be infection-free. 14
The Weanling or Transitional Child
The weaning period is a time fraught with danger for the 1- to 3-year-old child living in food-insecure households with unsanitary surroundings and unsafe water. Typically, children in their second year of life are at maximum risk for malnutrition and infection.312 Weaning may be abrupt or gradual, often occurring when the mother becomes pregnant again.
The child is usually weaned onto a bulky, high-carbohydrate, low-protein, and energy-dilute diet. The diet usually is devoid of animal foods and contains high fiber and phytate, a substance in whole grains and cereals that binds certain nutrients such as iron, calcium, and zinc, making them nonabsorbable. Thus, bioavailability of micronutrients is very limited, especially for iron and zinc. Such a child is in need of a diverse diet that includes plant staples of cereal or tubers, legumes, vegetables, fruits, and animal foods, especially meat of any type, in small, frequent feedings. Feedings must be maintained during bouts of illness, if at all possible. Animal milk is also important for its calcium and protein content (see discussion of rickets later in this article).
The pathogenesis of protein-energy malnutrition (PEM) is complex, and there is a wide spectrum of predisposing and precipitating factors, as well as clinical manifestations (Figure 2, see page 661). It is the most prevalent form of malnutrition in young children in developing countries and a major factor in at least 50% of deaths among young children.3 Although difficult to estimate, taking into account the range of syndromes encompassed by PEM, the WHO suggests that, globally, at least a half-billion children have PEM.15 Inadequate intakes of energy and protein to near starvation during times of famine are seen, and multiple micronutrient deficiencies coexist. Protein deficiency with near-adequate to adequate energy intakes tends to lead to kwashiorkor (Figure 3, see page 661), while severe lack of macronutrients and micronutrients, or "balanced starvation," leads to marasmus (Figure 4, see page 661). Marasmic kwashiorkor is the usual syndrome.
Severe PEM encompasses the syndromes of kwashiorkor, marasmus, or both, with high case fatality. These conditions are also seen in adults during famine or starvation conditions, or in those who have AIDS or other severe infections. In historical perspective, the severe form of PEM, with low serum albumin, edema, muscle wasting, skin lesions, lightened hair color and increased pluckability, enlarged fatty liver, extreme apathy, and muscle wasting, was first described in Ghana by Dr. Cecily Williams. She named the above condition "kwashiorkor," meaning displaced child, from the local Ga language.3 The toddler typically was displaced from being breastfed and in close physical contact with the mother and the newborn sibling, and thus, abruptly weaned on to a starchy, bulky, energypoor and protein-poor diet. Typically, kwashiorkor is preceded by measles or another significant infection as the precipitating factor. In light of the low albumin, the etiology of kwashiorkor was viewed mainly as protein malnutrition due to deficient protein intake. Treatment emphasized the need for proteinrich foods, neglecting the need for adequate overall energy intake and micronutrients as well.3·16
Figure 5. Severe vitamin A deficiency can result in ocular consequenses such as keratomalacia and blindness.
The new term of PEM was coined to cover the full range of syndromes from kwashiorkor and marasmus to wasting, underweight, and stunting. In children younger than 5 in developing countries, rates of the severe forms of PEM range from 1% to 5%, except in times of famine, when prevalence rates increase to 10% to 20%. 15 Mild to moderate forms of PEM with no specific physical signs range from 30% to 70% in the 1to 5-year-old population. The role of infection in both precipitating kwashiorkor and complicating severe forms of PEM has been appreciated for the past 4 decades, with abundant research supporting this interaction.
Mild to moderate malnutrition is detected in children only by serial weight measurements with comparison to weight and height reference growth data, as there are no pathognomonic signs of mild to moderate PEM.3 Mid-upper arm circumference is used in children ages 1 to 5 to triage them for PEM. The cutoff of 13.0 cm is indicative of PEM and correlates highly with weight-for-age (Table 1, see page 662).3
Stunting or linear growth retardation is a form of chronic PEM and represents the lifetime nutritional history of the child. Approximately 40% of the world's children are stunted, with the highest rates up to 60% in sub-Saharan Africa and southeast Asia.15·16 The major period for onset of stunting is between ages 6 months and 18 months, but onset can occur before age 6 months. The short stature is due primarily to chronic deficiency of energy, protein, and micronutrients, particularly of iodine or zinc. Vitamin D or calcium deficiency with rickets can also cause stunting. A heavy burden of multiple infections also affects linear growth negatively.17·18 Genetics and high altitude are suggested as etiologies of stunting, but these are minor and secondary to the above nutrition and infection experiences of a child.
Stunting is associated with adverse functional outcomes. In stunted children, concurrent or late mental and motor retardation are seen, and school performance is jeopardized. Among stunted adults, work capacity and cognitive function are reduced compared with normalheight peers.16 Obstetric risks such as difficult and obstructed labors and deliveries and risk of fetal growth retardation are seen in stunted women.7 Catch-up growth to some degree may be possible throughout childhood and in early adolescence but may not be complete. Therefore, stunting carries serious physical, cognitive, and economic consequences.
The role of micronutrient nutrition on the health and function of human beings is now well documented. Widespread multiple micronutrient deficiencies are due to a number of factors. When diet quantity or energy is deficient, so are multiple micronutrients. When the diet is monotonous, lacks diversity, and is largely cereal, legume, or tuber-based, the inherent micronutrient content may be low. Even if the micronutrients are present in substantial quantities, as in some cereals or legumes, uieir bioavailability may be curtailed due to the high fiber and phytate content of traditional staples, which form insoluble complexes. Poverty, lack of availability, accessibility, and affordability of animal foods, lack of knowledge about me importance of animal foods for the health and growth of young children, and cultural beliefs and practices limit the inclusion of micronutrient-rich and energy-dense meat in the diet.18 In affluent countries, strict vegetarian diets and fear of "red meat" consumption dictated by philosophical, spiritual, and health beliefs contribute to micronutrient deficiencies, which adversely affect a considerable number of children and women with devastating and adverse societal and individual effects.
The micronutrient deficiencies of major concern (Table 2, see page 662), particularly in children, are iron, iodine, zinc, and vitamins A and B12. Individual micronutrient deficiencies are described briefly.
Iron deficiency is one of the most common global nutrition disorders, in both developed and developing countries. Estimates are that at least 50% of children and women of reproductive age and about 25% to 30% of men are iron deficient in developing countries.19 Because iron deficiency can be present witìi only depleted stores (mild to moderate deficiency) without anemia, the true degree of iron deficiency is far greater than just those with iron deficiency anemia (IDA). Decrease in hemoglobin production and anemia is an indication that all stores of iron are exhausted, which represents severe depletion. For every person with IDA, at least 2 to 3 times more have iron deficiency without anemia.
Iron is part of many metallic enzyme systems and a number of neurotransmitters, as well as part of hemoglobin, myoglobin, and heme protein. Iron deficiency even in the absence of anemia can have adverse functional consequences, particularly for cognitive development and behavior in children. Even with moderate anemia (8 to 9.9 g/dL) and severe anemia (8 g/dL or less), serious interference with the oxygen carrying capacity of hemoglobin and myoglobin can occur. Increased mortality with severe anemia is seen during pregnancy. Increased mortality may occur in young children with severe anemia and infection.19
Evidence has been mounting for a causal association between iron deficiency, with or without anemia, and psychomotor development, behavior, and activity.20 Children with iron deficiency score significantly worse than children with no deficiency on cognitive tests. Although some degree of reversibility of the deficits is seen with correction of IDA, long-term follow-up studies show some irreversible cognitive deficits. In the longest follow-up to date, Lozoff et al.21 reported persistence of cognitive deficits in young adults despite the treatment of IDA when they were young children. Physical activity in children and work productivity in adults are impaired in those who have IDA. Increased infection, anorexia, poor growth, reduced physical activity, apathy, and lack of perseverance in completion of tasks also have been noted.
Much is known about the pathophysiology and the detection of iron status and anemia, but the challenge is to identify risk factors that are amenable to change. Such known risk factors are the prevention of low birth weight, promotion of breastfeeding, diet modification to increase the bioavailability of iron absorption otherwise limited by high phytate and fiber in the diet, the need for heme protein from meat to increase the absorption of iron from plant-based foods, and the use of enhancers of iron absorption, such as citrus witfi meals. Meat is also intrinsically rich in vitamin B 12, iron, and zinc.'8 Control of helminths by periodic deworming - especially hookworm, which can cause IDA in 40% of children - also is an important step.19
Traditional technologies such as soaking and fermentation of cereals, grains, and starch to reduce phytate content have been shown to improve iron and zinc bioavailability.22 Simpler methods of enriching the diet with iron seen mainly in Africa include cooking in iron pots or drinking "iron water," dilute vinegar or citrus juice in which iron nails or ingots are immersed for several days. In both Chile and Kenya, bovine blood clots are dried into powder and added to stews or porridges. Blood-enriched biscuits also are widely used in Chile. Fortification of commonly used foodstuffs and condiments is increasing year by year but these often are unavailable to subsistence farming families in rural areas.19 Flour products, salt, soy sauce, and sugar have been used as vehicles for iron fortification.
Treatment with iron preparations for children and pregnant women and other deficient individuals also is indicated. Preparations are relatively inexpensive, and even biweekly and weekly dosing have been effective. Pre-term infants, toddlers, and pregnant women represent the highest-risk groups and would benefit most from treatment, which is generally available and affordable.
Vitamin A Deficiency
Vitamin A deficiency (VAD) is a major public health nutrition problem in the developing world, with high-risk regions being south and southeast Asia, Africa, the eastern Mediterranean, the western Pacific, and some areas in Central and South America. The age groups most affected are preschool children and women of reproductive age. Approximately 127.2 million and 4.4 million preschool-aged children were reported as havingh VAD and xerophthalmia, respectively.23
The ocular consequences of VAD are characterized by poor dark adaptation, conjunctival and corneal xerosis, and eventual corneal ulceration, lens destruction, and necrosis known as keratomalacia (Figure 5, see page 663). Irreversible blindness ensues rapidly. Of the 131.6 million children worldwide with VAD, 44% live in south and southeast Asia, 26% in Africa and 10% in the eastern Mediterranean region. Approximately 19.8 million pregnant women in the highrisk regions have low to deficient vitamin A status reported annually, with a third of these women reporting night blindness.24 Vitamin A deficiency also is described among school-age children and adolescents in different parts of the world, with the prevalence up to 70% in Kenya and 40% in adolescents in Nigeria.
Vitamin A deficiency is attributed to low dietary intakes of plant and animal sources of vitamin A and fat. The resulting disorders include severe infections, increased mortality risk, xerophthalmia and blindness, anemia, and poor physical growth. Vitamin A supplementation reduces mortality from respiratory and diarrheal diseases among children and reduces illnesses among pregnant and lactating women.25 Increased infection in VAD is attributed to the cornification of protective mucous membranes, loss of anti-infective function, and impaired CMI.
Many attempts are being made to control VAD in different parts of the world, with provision of high-dose vitamin A capsules as the most common form of supplementation. These capsules are provided in different doses: 50,000, 100,000, and 200,000 International Units (IU) for toddlers, schoolchildren, and women, respectively. Postpartum mothers are being given a larger dose of vitamin A to improve breast milk content.
The United Nations Children's Fund (UNICEF) and Helen Keller International have taken leading roles in working with different agencies to implement and maintain vitamin A supplementation programs in various countries.24 However, coverage rates still vary across the different world regions, with mean coverage rates among children age 6 months to 59 months being 46% to 75%. Wide variations in coverage rates within the regions exist, with rates in India and Bangladesh at 25% and 90% coverage, respectively; while Ethiopia and Kenya, both from sub-Saharan Africa, show 16% and 90% coverage, respectively. Vitamin A capsule administration strategies include distribution through well-child clinics and immunization campaigns.24 Although identified as an effective way to control VAD, vitamin A capsule supplementation programs suffer lack of sustainability, mainly due to the reliance on importation of capsules from other countries, poor field logistics such as inadequate capsule supplies, unreliable transportation, poor storage facilities, and occasional reports of vitamin A toxicity from accidental overly frequent capsule administration.
Efforts to increase dietary vitamin A intake include nutrition education, breastfeeding encouragement, and inclusion of vitamin ?-rich foods in the diets of both nursing mothers and children. Most of the dietary diversification efforts have consisted of small study trials, targeted to specific groups within populations. Different approaches, through home gardening and consumption of vitamin ?-rich foods, showed the positive association with improved vitamin A status among different populations, especially preschool children and pregnant women.24 Common dietary sources of provitamin A carotenoids are plant-based foods such as dark green leafy vegetables, including spinach, kale, and amaranth; and orange-colored fruits and vegetables, such as mangoes, papaya, carrots, tomatoes, squash, and pumpkin. The orange sweet potato and finger-size pond and lake fish are promising foodstuffs high in vitamin A that are found in Africa and Bangladesh.
The conversion rate of beta carotene to retinol is now known to be one-third as efficient as once thought. Instead of die ratio 6:1, it is now known that the ratio may be 20: 1 .26 Diets in developing countries generally are low in fat, which impairs the absorption of preformed vitamin A and carotenoids and consequently lowers plasma retinol concentrations. Therefore, added fat to the diet enhances vitamin A absorption, both from plant and animal sources. Common dietary sources of preformed vitamin A are animal source foods such as liver, egg yolk, and dairy products. Animal foods with preformed vitamin A have been associated with a stronger and higher improvement in vitamin A status, compared with plant-source foods.
Countries such as Brazil, Peru, Mexico, Indonesia, India, and the Philippines successfully have implemented large-scale vitamin A fortification programs using foods such as cooking oils, margarines, cereal flours, biscuits, and beverages. However, there is still need to improve the monitoring and evaluation of these programs to ensure adequate vitamin A at the intake level. The International Vitamin A Consultative Group has provided recommendations on how to maintain successful vitamin A fortification programs.27 The Philippines has bred yellow rice with high beta carotene content successfully, and it is now being grown there.
Other efforts to control VAD are through prevention of infections such as diarrhea, respiratory diseases, and measles. Infection and VAD interact in a vicious cycle whereby one exacerbates and increases vulnerability to the other. Studies in Africa and Asia have shown that preschoolers with either diarrhea or acute respiratory disease were twice as likely as healthier children to have developed xerophthalmia in a subsequent 3-month period.28 Decreased vitamin A absorption due to diarrhea or intestinal parasites may depress serum retinol.23 Many hospitals now administer 200,000 IU of retinol to children admitted with measles, pneumonia, diarrhea, or other serious infections to prevent severe VAD and blindness. With this treatment, fatality rates for the above illnesses decrease dramatically.25
An estimated 1.6 million people worldwide may consume inadequate amounts of iodine.29 Iodine is essential for the synthesis of thyroid hormones and critical for the growth and development of the fetus, infant, and child. Although small amounts of iodine are naturally present in soil, water, plants, and animals, most of the iodine in soil has been lost through erosion, runoff, and vaporization, leading to insufficient dietary intake of naturally occurring iodine. This is particularly true of water supplies derived from melted mountain snow, which leaches out the iodine as it flows down the mountains. Fresh water river deltas also leach iodine out from the soil. Goitrogens in me diet, such as cyanides in cassava and other compounds in maize, millet, cabbage, and other root crops block the uptake of iodine by the thyroid, and mus produce goiter. A good source of iodine is sea life, including sea plants, animals, and salt.
The consequences of inadequate iodine intake are known as iodine deficiency disorders (IDD), a wide spectrum of effects of iodine deficiency on human growth and development. These disorders include cretinism, mental retardation, impaired physical development, increased perinatal and infant mortality, hypothyroidism, and goiter. The outcome of severe iodine deficiency during fetal life is endemic cretinism characterized by mental retardation, deaf-mutism, and spastic diplegia. Goiter is the most visible sign of IDD and is most common among schoolchildren, adolescents, and adults, especially pregnant mothers. Serious iodine deficiency in the mother during pregnancy may result in stillbirths, abortions, and cretinism.
Of far greater global and economic significance is IDD's less visible, yet more pervasive, level of mental impairment that lowers economic development and intellectual ability at home, at school, and at work. WHO estimates indicate iodine-deficient people may forfeit 15 IQ points, and that even marginal deficiency may reduce a child's mental development by about 10%.29 Iodine deficiency remains the single greatest cause of preventable brain damage, mental retardation, and stunting worldwide. Estimates based on urinary iodine levels indicate 35% of the world's population is affected by IDD, with 10% to 57% of those in Europe, the eastern Mediterranean, Africa, and southeast Asia affected.
The main strategy for preventing IDD worldwide is iodine supplementation, using a variety of methods. These include commercial iodinization of salt, iodized oil (administered orally or by injection every 1 to 2 years), and iodized bread and water. Of all mese, iodized salt has been the most widely used because of its availability, rate of consumption, and comparatively lower overall costs. At the 1990 World Summit for Children at the United Nations, universal salt iodinization was recommended as the main strategy in eliminating IDD as a public health problem.30 According to UNICEF, only 52% of households in the leastdeveloped countries consume iodized salt, indicating the need for more work focused on increasing knowledge about and access to such salt in mese communities. UNICEF and WHO continue to work withvarious governments and communities worldwide to increase access to iodized salt.
For hard-to-reach populations living in remote areas such as the Andes, the Himalayas, and remote areas of Africa and Asia, iodized oil is administered orally or by injection every 1 to 2 years. For creative approaches, the French purify water with iodine instead of chloride, and the Chinese have had success irrigating crops with iodized water. Iodine drops are used for home or school iodinization of drinking water where iodized salt is not available.31
Health education and social marketing programs to develop awareness of and motivation to use iodized salt have been intensified on community and nationwide targets, using television, radio, and print media such as picture discs, flip charts, posters, and public service announcements. Additionally, songs, drama, puppetry, and oral stories are being used.
To maintain adequate levels of iodine in fortified salt, WHO, UNICEF and the International Council for Control of Iodine Deficiency Disorders recommend ongoing monitoring and evaluation of salt iodine content at the production, retail, and household levels, and several types of rapid iodine testing kits are available for use in the field, because iodine losses from salt occur through vaporization when exposed to moisture and heat.32 Campaigns also should include messages on preventing salt iodine losses at the household and market level by proper storage techniques. Much is known about the causes and consequences, treatment, and prevention of IDD, but the political will of governments must exist to eradicate this serious and devastating deficiency.
Given the vital role of zinc in human health, growth, and development, this widespread deficiency has public health implications. Zinc is a critical component in more than 200 enzyme systems in the body and is involved with RNA and DNA synthesis, critical to cellular growth and differentiation. Zinc is particularly important in periods of rapid growth, which require nucleic acid synthesis and protein metabolism. Only a small percent of zinc is in the rapidly exchangeable plasma pool, with a small amount of total body zinc (approximately 1 .5 g) in children. Sixty percent of the body's zinc is in the muscle, 20% in the bone, 5% in the blood and liver, and 3% in the gastrointestinal tract and the brain.33 Zinc deficiency interacts with thyroid deficiency and goiter in that iodine uptake by the thyroid is diminished with zinc deficiency.34
Zinc deficiency is difficult to assess, as the signs and symptoms of deficiency are nonspecific; therefore, a high index of suspicion is needed. Early growth failure and stunting are common. Decreased cell-mediated immunity with increased morbidity has been well documented. Persistent diarrhea (lasting longer man 2 weeks) and increase in other infections are commonly seen with zinc deficiency. These illnesses are reduced significantly in prevalence with zinc merapy.
Lack of meat in the diet, combined with the high phytate and fiber content of dietary staples, limit zinc's absorption and bioavailability. Zinc also shows a number of interactions with other micronutrients. Vitamin A status improves with zinc treatment of vitamin A-deficient children, and vitamin A mobilization from hepatic stores and the synthesis of retinol-binding protein (RBP) increases. With zinc treatment of vitamin ?-deficient children, zinc promotes the synthesis of RBP, essential for retinol transport from hepatic cells to the blood.35
Disappointingly, zinc does not improve linear growth consistently in intervention studies of toddlers and children. This has been attributed to the fact that zinc intervention may occur at the wrong ages, missing the 6- to 18-month age interval in which postnatal cell division and growth are most rapid; thus, zinc is given too late. Zinc plays a role in increase of muscle mass in children.36
Food-based approaches to zinc deficiency have consisted of encouraging increased intake of meat from any source. As with iron, small amounts of meat added to plant foods increase the bioavailability and absorption of zinc. Traditional methods of fermentation and soaking have been used to lower the high phytate content from cereals and legumes to improve the zinc bioavailability.
Food fortification has not included zinc to any great extent in developing countries.22 The agricultural sector has been carrying out breeding research and development and has produced high-zinc maize, as well as low-phytate maize. To date, the adoption and dissemination of these maize varieties have been limited.
In summary, zinc is an essential micronutrient for promoting health, growth, development, and pregnancy outcome. It serves an important role in combating infection through cell-mediated immune system and wound healing. The main challenge is to have a high index of suspicion about me presence of zinc deficiency, then treat in a timely manner. The most critical periods appear to be in pregnancy and in young children during the first 18 months of life.
Nutritional rickets is re-emerging as a problem both in developing countries and in the United States and Europe. It is a condition of young children caused by a deficiency of vitamin D, calcium, or bom, associated with low intake of dairy products and liver. Ultraviolet rays in sunlight convert 7-dehydrocholesterol in the skin to vitamin D3. In the absence of this exposure, the process does not take place, resulting in vitamin D3 deficiency. Rickets can also result from inadequate intake of calcium, as well as phosphorus, both present in dairy products. Infants who are solely breastfed for prolonged periods of time with no vitamin supplementation and young children who are weaned early are particularly at risk of developing calcium deficiency rickets if little or no milk products are included in weaning foods.
Nutritional rickets is characterized by multiple bony deformities, which include bossing of the skull and delayed closure of the anterior fontanel, delayed dentition, and chest deformities with ribs deformed by the rachitic rosary and Harrison's groove. Deformities of the long bone shaft results from weight bearing, with bowing of the lower limbs if the child is walking and upper arms if the child is crawling due to uncalcified osteoid bone. Knock-knees and enlarged epiphyses at the wrists and ankles are seen. Affected children commonly have repeated pneumonia and hypotonia.37
Rickets attributed to deficiency of vitamin D commonly is observed in the winter months in the temperate climates, with little or no exposure to sunlight and when there is inadequate intake of vitamin D. With the discovery of vitamin D, nutritional rickets largely was eliminated through preventive measures, including fortification of cow's milk and infant formulas and supplementation with vitamin D in breastfed infants. However, during the past 2 decades, cases have appeared among refugees living in the northern industrialized cities of England and now in the United States and Canada. The increase of vegetarianism, fear of sun exposure, and use of sunscreen to prevent skin cancer contribute to these cases of rickets.37
Rickets also is re-emerging in subsanaran Africa. It would seem that, with abundant sunshine in the tropics, rickets would not appear. However, cases of fullblown rickets have been reported in several African countries. Diet assessment points to low calcium intake as an important cause.38,39 The dark skin of African children and women, coupled with the wrapping of babies and women, who are nearly totally covered for religious reasons, means they are inadequately exposed to sunlight. Thus, vitamin D3 also may be low.
Calcium and phosphorus are the main essential minerals required for bone calcification and are the principal organic constituents of the bone, dentin, and tooth enamel. Only 1% of calcium is in serum, where it strictly maintains homeostasis; the remaining 99% is in the bones and teeth. Phosphorus, too, is largely in the bones and teeth, with a calcium to phosphorus ratio of 2: 1. Calcium and phosphorus are the building materials on which the rigidity and strength of the bones depend. No amount of vitamin D will promote normal bone development unless the mineral elements necessary for building bones are provided in the diet in adequate quantities.37
Rickets due to calcium deficiency has been described in Nigeria38 and recently in Kenya.39 In both countries, those affected responded well to calcium supplements of 500 mg per day. After 12 weeks of treatment, most cases showed radiological evidence of healing, with calcium concentrations returning to normal levels. In Kenya, 25 of 324 children studied (7.8%) developed rickets between ages 1 and 5, after they were weaned to low-calcium diets of cerealbased foods with little or no animalsource milk or dairy products. The children were consuming 100 to 300 mg per day of calcium, which is low. In addition, the cereals they were consuming, such as millet and sorghum, contain high levels of phytates and oxalates, which bind calcium and other essential nutrients, causing decreased bioavailability. The children with rickets shared several risk factors: short duration of breastfeeding, weaning to cereal-based unfortified complementary foods with negligible cow or goat milk, and being kept indoors while their mothers cultivated fields.
In summary, health care providers need to be alert to the re-emergence of nutritional rickets in young children. The residual bony deformities in untreated children can result in stunting, impaired mobility, and increased pneumonia prevalence. In girls, pelvic deformities may result in obstructed labors and deliveries during childbirth.
Vitamin B12 Deficiency
There is increasing evidence that vitamin B12 deficiency is relatively common in developing countries such as India, Mexico, and eastern African nations. Particularly affected are women of reproductive age, nursing mothers, young children, and schoolchildren. Vitamin B12 is supplied mainly by animal foods, particularly milk and meat. A very small percentage can be supplied through products of fermentation, but this is a minor source. Malabsorption of vitamin B12 may be due to gastrointestinal infection, both parasitic and bacterial, as well as Tropical "Sprue."40
Vitamin B12 deficiency was documented in adults and children in Nutrition Collaborative Research Support Program studies in Kenya and Mexico. In Kenya, pregnant and lactating women consumed deficient levels of vitamin B12, and deficient levels of vitamin B12 were found in the breast milk of lactating women.41 Plasma levels of less than 300 mg/dL are indicative of vitamin B1, deficiency. Intakes in Mexican children and adults were in the deficient range, and macrocytic anemia, an important cause of nutritional anemia, was associated with anemia in pregnant women and children. Also, elevated concentrations of methylmalonic acid were found; this is a precursor in a metabolic reaction for which vitamin B12 is a co-factor. Macrocytic anemia and an elevated percent of hypersegmented neutrophil nuclei were noted both in women and in schoolchildren.40
In a recently completed feeding intervention study in approximately 1,000 Kenyan schoolchildren, a high percentage were found to have vitamin B12 deficiency at baseline.42 Macrocytic anemia was also found in these children. Vitamin B12 concentrations improved and even normalized when meat and milk groups were supplemented for 2 years.
Vitamin B12 deficiency has been found to be associated with impaired brain activity,47 neurologic consequences,48 and decreased cognitive function in Dutch49 and Guatemalan50 children. Vitamin B12 deficiency also has been linked to impaired CMI and low birth weight.51
A food-based approach is being promoted to treat this deficiency by incorporating the consumption of meat (of any variety) and milk by weaning children and by women, particularly during pregnancy and lactation. Nutrition education, small animal husbandry, and milk and meat production should be a goal of livestock extension education and nongovernmental organizations. Because men tend to eat more meat both in the household and in "eating out," the deficiency is less widespread among men.
Anemia due to folate deficiency may also be widespread and needs to be distinguished from B12 deficiency. Both deficiencies produce macrocytic anemia, but if vitamin B12 deficiency is not corrected, central nervous system damage may result.
INTERACTION OF NUTRITION AND INFECTION
As stated above, the interaction of malnutrition and infection is the leading cause of morbidity and mortality in developing countries. The frequency, chronicity, and complications of infections in malnourished individuals have long been appreciated. Ordinarily, mild infections often follow more severe courses in the malnourished. In developing countries, the death rates in children ages 1 to 4 are 30 to 40 times those in industrialized nations, with 30% to 50% dying before their fifth birthday.43 Because of their increased nutritional requirements, pregnant and lactating women, young children, and the adolescents (particularly if pregnant) are the most vulnerable to malnutrition and infection. Other vulnerable groups are those with chronic debilitating diseases, particularly AIDS and tuberculosis (see also the article by Dr. Adams, page 685).
A synergistic relationship between nutrition and infection is well established in animal studies and well-controlled human field studies. Infection adversely affects nutritional status, and malnutrition adversely affects die ability of the host to resist infection. Antagonism to infection, particularly with viral infections in animals, can occur when a nutritional deficiency or a metabolic disturbance produced by a deficiency has a greater effect on the agent than on me host. However, the overwhelming number of interactions tends to be synergistic and harmful to human hosts. In a vicious downward cycle, infection causes a worsening of malnutrition, thereby making the host more vulnerable to infection and further deteriorating nutritional status.43
The Effects of Infection on Nutritional Status
Almost all infections have a nutritional cost to the host and are readily understandable through their signs and symptoms. Fever increases metabolic and energy needs. Anorexia during an infection causes reduced food intake - as do cough, rapid breathing, and congested nasal passages - interfering with a child's ability to nurse or eat. Abnormal losses of nutrients accompany perspiration, diarrhea, and vomiting. Diarrheal disease interferes with absorption of foodstuffs because of rapid transit time and transient enzyme defects. Parasitic infestations such as hookworm, ascaris, or lake whitefish tapeworm may contribute to malabsorption or loss of blood.
Interleukin- 1 (IL-I), produced by infection-activated monocytes, has been identified as a potent mediator of metabolic, immunologic, and nutritional alterations in animal models and humans. The acute phase reactants and lymphokines, whose production is activated by IL- 1 , stimulate skeletal muscle catabolism supplying amino acids for the production of acute phase reactants. The infection-induced stress reaction mediated through adrenal corticoids further depletes muscle tissue and can depress immune function.44
The feeding of sick individuals, particularly during childhood and pregnancy, may be curtailed by cultural beliefs. Often certain foods and multiple nutrients are withheld and dilute fluids, low in energy and protein, are provided during acute illness. Infections can cause anorexia, and treatment with purges may add to further nutritional difficulties. The net result is deterioration in nutritional status.43
Adverse Effects of Malnutrition and Resistance to Infection
Among the body's mechanical barriers against infection mat depend on adequate nutrition are the connective tissue, skin, mucosal surfaces of the eye, respiratory tract, and gastrointestinal tract. Any break in the integrity of these tissues provides a portal of entry for microorganisms. Some cells have a specialized structure and function, such as me respiratory epithelial cells, which secrete protective anti-infective substances such as mucous and have cilia that sweep away bacteria and other foreign materials. Vitamins A and C, the B vitamins, protein, and zinc play major roles in maintaining the integrity of these barriers.
In people with PEM, antibody response to several pathogenic organisms in vaccines and natural infection may be reduced; these include typhoid, diphtheria, and yellow fever. Reponses to measles and certain other infections appear to be normal or near normal. Granulocyte functions such as Chemotaxis, phagocytosis, and killing of microorganisms are diminished. The ability to ward off infection through an inflammatory response also may be impaired. Vitamin A, zinc, and iron deficiencies, as well as PEM, all play a role in the above defenses.
CMI is involved in combating many viral and bacterial infections. Tuberculosis and HIV are particular challenges. CMI is impaired in PEM; degree of impairment is directly related to the degree of malnutrition and is readily reversed by nutritional rehabilitation. Depressed CMI also prevents an adequate response to certain immunizations in the malnourished, such as BCG against tuberculosis. Small-for-date infants malnourished in utero may be born with impaired CMI, which is not readily reversible until at least age 6 to 12 months, or even years longer. These infants are especially vulnerable to infection.8 In addition to PEM, deficiencies in iron, zinc, folate, and vitamins A and B12 impair CMI but largely are reversible with treatment.
Production of slgA, found in respiratory epithelium, tears and saliva, and mucosal antibody responses, may be decreased in subjects with moderate or severe PEM. The slgA response to liveattenuated measles and poliomyelitis immunizations was found to be greatly decreased or absent in malnourished children. This reduced secretory and mucosal binding of pathogens and increased shedding and colonization of pathogens are seen in the malnourished children.44
Some serum proteins that participate in combating infection are reduced drastically in malnutrition. One such protein, transferrin, binds iron and free serum iron, which can promote bacterial growth, resulting in sepsis. The complement system, which enhances certain antigen and antibody reactions, is decreased as well.43
Measles. Measles is one of the most serious infectious diseases among children in developing areas. Death rates exceed those in affluent industrialized nations by 200 to 400 times, and casefatality rates range from 20% to 40%, compared with less than 1 % in the United States. The pneumonia complication rate is exceedingly high, particularly during the first year of life and in malnourished children. Reduced host resistance caused by malnutrition rather than increased virulence of the virus is the problem.
Conversely, measles can have devastating effects on nutritional status. In populations in which nutritional status is marginally adequate, measles may precipitate weight loss, a fall in serum albumin level, and kwashiorkor within weeks. Universal measles immunization would accomplish much in reduction of PEM among young children.3,43
Weaning. This period is fraught with danger because the anti-infective protection from placentally transferred antibody has waned and the protective effects of breast milk are being lost. In Africa, the child literally leaves the safety of the mother's back and is put down on the ground to toddle and crawl in an unsanitary environment, while it is deprived of the anti-infection protection from milk. The infant tends to be weaned onto lowprotein and often contaminated and indigestible starchy feedings. Nonhuman milk, if available, may be contaminated or diluted. There is a striking increase in incidence of "weanling diarrhea" and pneumonia during the weaning period, with high death rates. This is also the age period (18 to 24 months) of maximum risk for PEM.3,43
AIDS. A dramatic example of the interaction of nutrition and infection is exemplified by people with AIDS. Marasmus is a common presenting condition for infants with HIV/AIDS infection and tuberculosis. Almost continuous bouts of malabsorption, severe diarrhea, and marked unrelenting weight loss occur secondary to opportunistic enteric and generalized infections (eg, cytomegalovirus, tuberculosis, Pneumocystis carinii). Severe suppression of CMI, loss of integrity of mucosal barriers, thinning of the villi, and infiltration of the mucosal layers by microorganisms is seen. Improving the nutritional status of those with ALDS with macro and micronutrients, especially vitamin A and zinc, improves immune function and well-being.
Intestinal parasites. Ascaris infects perhaps 1 .2 million people in the world, hookworm about 800 million, whipworm around 600 million, and schistosomiasis about 250 million, most in Africa, Asia, and Latin America.2 All of these parasites contribute to malnutrition, IDA, and poor growth. Omnipresent Giardia causes fatty malabsorption, which may reduce absorption of vitamins A, D, and E.
Now that highly effective, relatively inexpensive, and safe broad-spectrum anthelminthics such as mebendazole are available, periodic mass deworming through clinics and schools has been introduced in areas where parasitic infections are prevalent. Schistosomiasis can now be treated with metrifonate or praziquantel to prevent serious pathology and anemia.
Comprehensive approaches for improving the nutritional status of children must be directed toward infection prevention and reduction, environmental sanitation, immunization programs, early treatment of infections and feeding of sick children. To control infections optimally and maximize protection by immunizations, nutritional status must be improved simultaneously. Breastfeeding, with its excellent nutritional value and anti-infective properties, should be promoted aggressively. Just as there is a synergism of malnutrition and infection, so must there be a "synergism of services."
Malnutrition permeates all aspects of health, growth, cognition, motor and social development of young children in developing countries. More than 50% of deaths in these children can be attributed to malnutrition, most often in conjunction with serious infection. Irreversible and lifelong sequelae prevent children from reaching their full potential.
Child survival initiatives and programs have accomplished much to save the lives of children from common and preventable illnesses, but the quality of the survivors' health needs to be improved, with much more attention paid to nutrition of die preschool and school child. Promotion of nutritional health must become an integral part of primary health services, especially for infants, preschoolers, schoolchildren, and women. Promotion of exclusive breastfeeding and appropriate complementary feeding and weaning are essential inputs.
A daunting challenge is to improve diet quality through the raising and consumption of small animals by rural subsistence households to enhance maternal and child nutrition. School feeding from preschool onward must be an integral part of education so children are in a condition to learn. An excellent example of such programs is the WHO initiated Integrated Management of Childhood Illness, which integrates nutrition into the care of both sick and well children. The Early Child Development Program initiated by the World Bank and UNICEF has taken hold in many countries. Nutrition outcomes are closely linked with health and education activities starting in the preconception period through pregnancy, lactation, and childhood. Investment in human capital early in life will optimize the growth and social and economic development of children, families, and communities.
1. Pelletier DL, Frongillo EA. Changes in child survival are strongly associated with changes in malnutrition in developing countries. JNutr. 2003;133(1):107-119.
2. Jones G, Steketee RW, Black RE, Bhutta ZA, Morris SS; Bellagio Child Survival Study Group. How many child deaths can we prevent this year? Lancet. 2003;362(9377):65-71.
3. Jelliffe DB, Jelliffe EFP. Community Nutritional Assessment: With Special Reference to Less Technically Developed Countries. New York, NY: Oxford University Press; 1989.
4. Scrimshaw NS. The consequences of hidden hunger for individuals and societies. Food Nutr Bull. 1994;15:2-23.
5. Lee JW. Child survival: a global health challenge. Lancet. 2003: 362(9380):262.
6. United Nations Children's Fund (UNICEF). Strategy for Improved Nutrition of Children and Women in Developing Countries. New York. NY: UNICEF; 1990.
7. Institute of Medicine. Nutrition During Pregnancy. Washington, DC: National Academies Press; 1990.
8. Neumann CG, Stiehm ER, Zahradnick J,e t al. Immune function in intrauterine growth retardation. Nutr Res. 1998: 18(2):20 1-224.
9. Barker DJP. Growth in utero and coronary heart disease. Nutr Rev. 1996;54(2 Suppl 2):1S-7S.
10. Lawrence RA. Breastfeeding: A Guide for the Medical Profession. 5th ed. St. Louis, MO: Mosby; 1999.
11. Thome C, Newell ML. Epidemiology of HIV infection in the newborn. Early Hum Dev. 2000.580): 1-16.
12. World Health Organization Collaborative Study Team on the Role of Breastfeeding on the Prevention of Infant Mortality. Effect of breastfeeding on infant and child mortality due to infectious diseases in less developed countries: a pooled analysis. Lancet. 2000; 355(9202):45 1-455.
13. Covington C, Abdullah M, Omar A, Nduati R, Roberts A. Surrogate grandmother lactation to prevent mother-to-child breast milk HIV transmission in coastal Kenya. Presented at: XV International AIDS Conference; July 1114, 2004; Bangkok, Thailand.
14. Jeffrey BS, Webber L, Mokhondo KR, Erasmus D. Determination of the effectiveness of inactivation of human immunodeficiency virus by pretoria pasteurization. J Trop Pediatr. 2001 ;47(6):345-349.
15. World Health Organization Department of Nutrition for Health and Development. WHO Global Database on Child Growth and Malnutrition. Available at: http://who.int. nutgrowthdb. Accessed July 8, 2004.
16. Martorell R. The nature of child malnutrition and its long-term implications. Food Nutr Bull. 1999;20(3):288-92.
17. Neumann CG, Harrison GG. Onset and evolution of stunting in infants and children. Examples from the Human Nutrition Collaborative Research Support Program. Kenya and Egypt studies. Eur J Clin Nutr. 1994; 48(Suppl 1):90S-102S.
18. Bwibo NO, Neumann CG. The need for animal source foods by Kenyan children. J Nutr. 2003; 133(11 Suppl 2):3936S-3940S.
19. Yip R, Iron deficiency: contemporary scientific issues and international programmatic approaches. J Nutr. 1994; 124(8 Suppl): 1479S-1490S.
20. Grantham-McGregor S, Ani C. A review of studies on the effect of iron deficiency on cognitive development in children. J Nutr. 2001:131(2 Suppl 2):649S-666S.
21. Lozoff B, Smith J, Liberzon T, et al. Longitudinal analysis of cognitive and motor effects of iron deficiency in infancy. Abstract #128. Pediatric Research. 2004.
22. Ferguson EL, Gibson RS, Opare-Obisaw C, et al. The zinc nutriture of preschool children living in two African countries. J Nutr. 1993; 123(9): 1487- 14%.
23. West KP, Jr.. Damton-Hill I. Vitamin A deficiency. In: Semba RD, Bloem MW, eds. Nutrition and Health in Developing Countries. Totowa, NJ: Humana Press; 2001:267-306.
24. Allen LH and Gillespie SR. What Works? A Re\'iew of the Efficacy and Effectiveness of Nutrition Interventions. Manila. Phillipines: Asian Development Bank; 2001:61-68. United Nations Administrative Committee on Coordination, Sub-Committee on Nutrition, Nutrition Policy Paper No. 19.
25. West KP, Jr., Pokhrel RP, Katz J, et al. Efficacy of vitamin A in reducing preschool child mortality in Nepal. Lancet. I991;338(8759): 67-71.
26. West CE, Castenmiller JJ. Quantification of the "SLAMENGHI" factors for carotenoid bioavailability and bioconversion. Int J Vitam Nutr Res. 1998;68(6):37 1-377.
27. Dary O, Mora JO; International Vitamin A Consultative Group. Food fortification to reduce vitamin A deficiency: International Vitamin A Consultative Group recommendations. J Nutr. 2002;132(9 Suppl):2927S2933S.
28. Sommer A, Tarwotjo I, Katz J. Increased risk of xerophthalmia following diarrhea and respiratory disease. Am J Clin Nutr. 1987;45(5): 977-980.
29. World Health Organization. Micronutrient Deficiencies: Eliminating Iodine Deficiency Disorders. Available at: http://www.who.int/ nut/idd.htm. Accessed July 8, 2004.
30. World Health Organization. Proportion of General Population with Insufficient Iodine Intake. Available at: http://www3.who.int/ whosis/mn/mn_iodine. Accessed July 8, 2004.
31. Cao XY, Jiang XM, Kareem A, et al. Iodination of irrigation water as a method of supplying iodine to a severely iodine-deficient population in Xinjiang, China. Lancet. 1994; 344(8915):107-110.
32. Delange F, Burgi H, Chen ZP, Dunn JT World status of monitoring of iodine deficiency disorders control programs. Thyroid. 2002; 12(10):915-924.
33. Hambidge M. Human zinc deficiency. J Nutr. 2000,130(5 Suppl): 1 344S- 1349S.
34. Wada L, King JC. Effect of low zinc intakes on basal metabolic rate, thyroid hormones and protein utilization in adult men. / Nutr. 1986; 116(6):1045-1053.
35. Rahman MM, Waned MA, Fuchs GJ, Baqui AH, Alvarez JO. Synergistic effect of zinc and vitamin A on the biochemical indexes of vitamin A nutrition in children. Am J Clin Nutr. 2002;75(l):92-98.
36. Shrimpton R. Zinc Deficiency. In: Semba RD, Bloem MW, eds. Nutrition and Health in Developing Countries. Totowa, NJ: Humana Press: 2001:307-326.
37. Louis D. Common Vitamin D deficiency rickets. In: Glorieux FH, ed. Rickets. New York. NY: Raven Press; 1991.
38. Okonofua F, Gill DS, Alabi ZO, et al. Rickets in Nigerian children: a consequence of calcium malnutrition. Metabolism. 1991;40(2): 209-213.
39. Bwibo NO, Neumann CG. Rickets in preschool children in Child Survival Project. Presented at: Kenya Pediatric Association BiAnnual Conference; August 27-31, 2003; Mombasa, Kenya.
40. Allen LH, Rosado JL, Casterline JE, et al. Vitamin B 12 deficiency and malabsorption are highly prevalent in rural Mexican communities. Am J Clin Nutr. 1995;62(5):1013-1019.
41. Neumann CG, Murphy SP, Bwibo NO, CuIloway DC. Low B- 12 content in breast milk of rural Kenyan women on predominantly maize diets. AB #3367. FAESB Journal. 1993;7:A581.
42. Siekmann JH, Allen LH, Bwibo NO, et al. Kenyan school children have multiple micronutrient deficiencies, but increased plasma vitamin B- 12 is the only detectable micronutrient response to meat or milk supplementation. J Nutr. 2003; 1 33(11 Suppl 2): 3972S-3980S.
43. Neumann CG, Stephenson LS. Other nutritionally related problems-interaction of nutrition and infection. In: Strickland GT, ed. Hunter's Tropical Medicine. 7th ed. Philadelphia, PA: WB Saunders; 1991:947-950.
44. Keusch GT, Farthing MJG. Nutrition and infection. Annual Rev Nutr. 1986;6:131-154.
45. King FS, Burgess A. Nutrition for Developing Countries. 2nd ed. New York, NY: Oxford University Press; 1995.
46. World Nutrition Overview. SUSTAIN Web site. Available at: http://www.sustaintech.org/ world/index. htm. Accessed September 7, 2004.
47. Stollhoff K, Schulte FJ. Vitamin B 12 and brain development. Eur J Pediatr. 1987;146(2):201-205.
48. Graham SM, Arvela OM, Wise GA. Longterm neurologic consequences of nutritional vitamin B12 deficiency in infants. J Pediatr. 1992;121(5Ptl):710-714.
49. Louwman WJ, van Dusseldorp M, van de Vijver FJR, et al. Signs of impaired cognitive function in adolescents with marginal cobalamin status. Am J Clin Nutr. 2000; 72(3):762-769.
50. Allen LH, Penland JG, Boy E, DeBaessa Y, Rogers LM. Cognitive and neuromotor performance of Guatemalan schoolers with deficient, marginal and normal plasma B- 12. FASEBJ. 1999:1 3: A544.
51. Haddad EH, Berk LS. Kettering JD, Hubbard RW, Peters WR. Dietary intake and biochemical, hematologic, and immune status of vegans compared with nonvegetarians. Am J Clin Nutr. 1999:70(3 Suppl):586S-593S.
Anthropometric Cutoffs for Stunting, Underweight, and Wasting*
Effects of Micronutrient Deficiencies