Malnutrition and Diarrhea: Working Group Report of the First World Congress of Pediatric Gastroenterology, Hepatology, and Nutrition

I. SUMMARY OF THE PROBLEM Definition Malnutrition is the lay term for protein-energy malnutrition (PEM), which results when the body's needs for protein, energy fuels, or both cannot be satisfied by the diet. The entity includes a spectrum of clinical manifestations, depending on the relative intensity of protein or energy deficiency, the severity, and the duration of the deficiencies, the age of the individual, the cause of the deficiency, and the association with other nutritional or infectious diseases. Dietary protein and energy deficiencies usually occur together, but sometimes one predominates and if severe enough may lead to the clinical syndrome of kwashiorkor (predominantly protein deficiency) or marasmus (mainly energy deficiency). Marasmic-kwashiorkor is a combination of energy and protein deficiency. It may be difficult to recognize which of the deficiencies predominates in milder forms of the disease. The origin of PEM can be primary, when it is the result of inadequate food intake, or secondary, when it is the result of diseases that lead to low food ingestion, inadequate nutrient absorption, increased nutritional requirements, or increased nutrient losses (1). Protein-energy malnutrition is commonly assessed by weight for age, height for age, or weight for height. Waterlow (2) has suggested the terms "wasting" for a deficit in weight for height, and "stunting" for a deficit in height for age. Infants and children may then fall into one of four categories: a) normal; b) wasted but not stunted (suffering from acute PEM); c) wasted and stunted (suffering from acute and chronic PEM); and d) stunted but not wasted (past PEM with present adequate nutrition, or "nutritional dwarfs"). The intensity of the wasting and stunting can be graded by calculating weight as a percentage of the reference median weight for height, and height as a percentage of the reference median height for age. Other anthropometric measurements such as body mass index, arm circumference, and arm circumference to head circumference ratio have been used in children and adults to assess PEM. Many changes in biochemical or physiologic parameters have been noted in malnutrition, and some blood and serum tests have been used to evaluate PEM. However, these tests are not always available, not always easy to use, and are more expensive than anthropometric measurements. Diarrhea resulting from the malabsorption of water and nutrients is manifest by an increase in stool frequency, a decrease in stool consistency, or both. It is commonly associated with PEM. Persistent diarrhea is diarrhea that occurs every day for at least 14 days. It encompasses episodes of presumed infectious diarrhea that have an acute onset and persist for 2 weeks or longer but does not include known causes of chronic or recurrent diarrhea. Dysentery is diarrhea with visible blood present in the stool. In PEM, there is decreased gastric and pancreatic function. Bile production is normal to low, with a tendency for low conjugated bile acid concentrations. These changes in intestinal function coupled with a tendency for irregularities in intestinal motility and bacterial overgrowth increase the likelihood of diarrhea occurring in the malnourished infant or child. Infections of the gastrointestinal tract caused by viruses, bacteria, or parasites also may contribute to diarrhea. A cluster of risk factors has been identified by the World Health Organization that predispose infants and children to the development of persistent diarrhea. Included are: (a) host factors, such as young age, malnutrition, and impaired immune function; (b) environmental factors, among them overcrowding, inadequate hygiene, living in close contact with animals, and fecal–oral transmission of enteric pathogens; (c) previous infections, such as acute diarrhea, previous persistent diarrhea or respiratory tract infection; (d) pre-illness feeding practices, such as the recent introduction of milk, especially animal milk; (e) microbial isolates during the acute phase of the illness, such as enteroadherent Escherichia coli, shigella, and multiple pathogens; and (f) drug usage during acute diarrhea, for example, antimicrobial therapy or antiparasitic drugs. History It has long been recognized that inadequate food intake produces weight loss and growth retardation and when prolonged leads to emaciation or marasmus. It took much longer to understand the nature of the edematous forms of PEM or kwashiorkor. Edematous PEM and its treatment was first carefully studied by Cicely Williams in the 1930s in what is now Ghana. She used the term "kwashiorkor," which is a word from the Ga tribe for "the sickness the older child gets when the next baby is born." Later, in the 1950s, the nature and importance of this disease gained worldwide attention. By the 1950s, more than 40 names had been given to the clinical syndrome. Today, the term protein-energy (or protein-calorie) malnutrition is universally accepted In more developed countries, the severe forms of PEM have been eliminated for the most part. However, malnutrition has been associated in these countries with mild growth retardation and nutrition-related disorders, including iron deficiency. Subclinical deficiencies of other micronutrients such as vitamin A, zinc, copper, and perhaps other elements may contribute to suboptimal growth or health. Marginal nutrient intake during pregnancy coupled with maternal alcohol or cigarette use or drug abuse and dysfunctional families also may contribute to malnutrition in developed countries. There have been better outcomes from episodes of acute childhood diarrhea in malnourished children over the past 20 years, largely because of the more effective and widespread use of oral rehydration therapy (ORT). Recently, more attention is being given to those acute episodes that become persistent because of the serious adverse effects on growth and nutritional status and the demanding and frustrating management problem persistent diarrhea poses. Frequency There are 149.6 million children today younger than 5 years of age (26.7% of the world's children) who are malnourished. Nevertheless, there has clearly been significant progress when compared with the 175.7 million children (37.4% of the world's children) who were malnourished in 1980. Although the continuing global burden of malnutrition is rooted in poverty, underdevelopment, and inequality, some of the additional reasons behind PEM's persistence can be found by looking at the regional trends and numbers of children affected. As an illustration, in some areas the drop in percentage of prevalence has not been as rapid as the rise in population. As a result, in Africa, for example, the actual number of malnourished children has, in fact, risen. In addition, natural disasters, wars, civil disturbances, and population displacement have all contributed to continuing high rates of malnutrition. Geographically, more than two thirds (72%) of the world's malnourished children live in Asia (especially south Asia), whereas 25.6% are found in Africa, and only 2.3% in Latin America (Table 1).TABLE 1: Global and regional trends in the estimated prevalence of protein-energy malnutrition in underweight children under five, since 1980 (in millions) *Intrauterine growth retardation (IUGR) may contribute to malnutrition early in life. It has been estimated that at least 13.7 million infants are born every year at term with low birth weight (LBW), representing 11% of all newborns in developing countries. This rate is approximately 6 times higher in developing countries than in developed countries. Low birth weight, defined as <2,500 g, affects 16.4% of all newborns (preterm and term). Overall, nearly 75% of all affected newborns are born in Asia, especially south Asia, where the prevalence of LBW may range from 25% to 45%, 20% in Africa, and about 5% in Latin America. Many developing countries currently exceed the internationally recommended IUGR (>20%) and LBW (>15%) cut-off levels for triggering public health actions aimed at preventing fetal growth retardation. Investigation using 1980 population estimates put the annual rate of diarrheal episodes worldwide at 744 million, resulting in 4.6 million deaths. A more recent update showed that the incidence of diarrhea (2.6 episodes per child per year) was unchanged, but the global mortality of diarrheal disease was lower (3.3 million deaths/year). Experience from studies in Asia and Latin America shows that 3% to 23% of all episodes of acute diarrhea last longer than 2 weeks. In developed countries such as the United States, there is lower morbidity and mortality from diarrheal disease: approximately 500 annual reported diarrheal disease deaths in the United States in infants and children between 1 month and 4 years of age. Advances in the Field In Utero PEM Most human embryos have the potential for a long and healthy life. From the moment of conception, however, adverse environmental forces limit this potential (3). Intrauterine growth retardation due to maternal malnutrition is an important factor; but so is the diet at all ages, cigarette smoking, a sedentary lifestyle, the use of drugs, and other factors. Scrimshaw notes that no matter what combination of poor nutrition and other environmental factors is responsible for fetal growth retardation, the concept of the fetal origins of adult disease are valid (4). There is evidence from British populations that low birth weight at term and, in some cases, low weight at 1 year of age are associated with an increased adult risk of hypertension, coronary heart disease, non–insulin-dependent diabetes, and autoimmune thyroid disease (4). These data have also been corroborated by data from other parts of the world such as India or aboriginal populations in Australia. Other studies have shown that iodine deficiency during pregnancy affects fetal brain development at a critical stage and can permanently affect cognitive performance. Iron deficiency during infancy has the same kind of lasting effect on cognitive performance. Low weight for age of preschool children has been reflected in poorer neurointegration in lower socioeconomic groups but not in middle and upper socioeconomic groups. Nutritional supplementation during pregnancy and early childhood has been reflected 15 years later in better scholastic achievement and cognitive performance than in control groups (4). However, some studies of intrauterine malnutrition have not shown it to be closely associated with disease in older children and adults. Although it is clear that catastrophic events in utero can adversely affect the fetus and child, additional studies are needed for us to better understand the relationship of nutrition in utero and optimal growth and development. Helicobacter pylori and PEM Helicobacter pylori (Hp) infection is probably the most common bacterial infection in the world. The pathogenicity of this bacteria has been recognized since 1983 in the developed world, where the prevalence is 20% to 40%. Its role in gastric and duodenal disease is certain, and its low recurrence rate justifies eradication. In the developing world, the prevalence of Hp infection is over 80%, with contamination being maximal in children. Transmission is oro-oral and feco-oral. Crowded living conditions are an important factor. In newborns, Hp infection may be the primary event for chronic malnutrition and diarrhea syndrome with failure to thrive. In one study, Hp infection was examined in Gambian infants and children, who were at risk of chronic diarrhea and undernutrition (5). In this prospective study, investigators noted that those infants with sustained Hp infection grew less well than those who were infection free. The authors speculated that Hp, acquired in infancy, could be the "key that opens the door" to enteric infection in childhood, leading to recurrent diarrhea, malnutrition, and growth failure. Other investigators, however, have found that Hp infection does not appear to be a risk factor for malnutrition and persistent diarrhea in children. Treatment Modalities Oral Rehydration Therapy/Enteral Feedings. Oral rehydration therapy has been a major advance and has saved the lives of many children with acute diarrhea. However, persistent diarrhea is now a major problem because of its strong negative impact on nutritional status and because persistent diarrhea and dysentery are now major causes of death in infants and young children. The use of ORT and early refeeding during acute diarrhea is an important principle to help to reduce duration, severity, and the negative nutritional impact of diarrhea. Because severely malnourished children with diarrhea are deficient in potassium and have abnormally high levels of sodium, ORT needs to be tailored to their needs (6). The rehydration solution should contain less sodium and more potassium than the standard WHO-recommended solution, and magnesium, zinc, and copper are needed to correct deficiencies of these minerals. The rehydration solution for severely malnourished (ReSoMal) infants and children is available commercially in some countries. Alternatively, it may be prepared by modifying the standard WHO-recommended oral rehydration solution by the addition of water, sucrose and a mineral mix (Table 2). The exact amount given to the severely malnourished child with diarrhea should be determined by how much the child will drink, the amount of ongoing losses in the stool, and whether the child is vomiting or has signs of overhydration. Recommendations for the mixing and administration of this solution are given elsewhere (6).TABLE 2: Composition of an oral rehydration solution for severely malnourished children (ReSoMal) *Although the benefit of early reinstitution of enteral feeding in children with acute diarrhea has been well documented, the optimal route of therapy in malnourished children with persistent diarrhea is the subject of controversy (7). It has been suggested that enteral nutrition may not be possible if stool losses exceed 30 g/kg/d. However, in the context of the developing world, parenteral nutrition is clearly impractical. Despite limitations, the option of intravenous feeding does save lives in circumstances in which there is an unsatisfactory response to enteral therapy with clinical deterioration, and this therapy should be available in specialized hospitals in the developing world. The various therapeutic options for enteral nutrition in malnourished children with diarrhea, once they have been adequately hydrated, include 1) elemental diets; 2) milk-based diets including human, animal, or soy milk; 3) chicken-based feedings; and 4) traditional local diets. Given the limitations of nutritional rehabilitation in hospitals and the magnitude of the problem of malnutrition and diarrhea in the developing world, it is natural that considerable interest and effort has been expended in developing traditional diets suitable for the nutritional rehabilitation in the community (7). However, malnourished children with diarrhea selected for traditional food-based therapies must be screened for therapy failure and appropriate therapeutic adjustments made if necessary. Micronutrients. Before 1980, most attention given to nutrition in developing countries focused on PEM. New understanding concerning the effects of micronutrient deficiencies, particularly iron, vitamin A and zinc, and improved technologies and logistics for the delivery of micronutrients have made possible important and attractive achievements more recently. In considering iron, the nutritional requirements for hematopoiesis are known to be similar to those of other tissues. However, turnover of blood cells is normally greater than that of other tissues of the body, and the availability of iron may become rate limiting. Frequently depressed iron absorption from inadequate intake or decreased iron availability from diets with high phytate or gastrointestinal blood loss, contribute to iron deficiency. The close correlation between iron and zinc deficiency in at-risk populations suggests that poor dietary intake and decreased bioavailability both may play an important role. Conservative estimates indicate that at least 700 million individuals worldwide have overt iron-deficiency anemia. Iron deficiency in children can result in impaired mental development and may have long-term deleterious effects on cognitive and behavioral performance, and iron supplementation should be considered in many parts of the world during periods of risk, such as during pregnancy and early childhood. Similarly, there is emerging evidence of widespread subclinical zinc deficiency in populations with high prevalence of stunting and malnutrition. Recent studies of vitamin A have stressed the importance of this micronutrient in bolstering host defense. Weekly low-dose vitamin A supplementation to children in a region of subclinical deficiency protected underweight children from acute lower respiratory infection (ALRI) and severe diarrhea (8). In another study, the beneficial effect of periodic vitamin A supplementation on diarrhea and ALRI in children was evaluated in a randomized, double-blind, placebo-controlled community trial in Brazil (9). With the standard definition of diarrhea (>3 liquid or semi-liquid stools in 24 hours), the effect of vitamin A on mean daily prevalence did not reach significance, but because the definition of diarrhea was made more stringent by defining diarrhea as greater than 6 stools/day, a significant benefit became apparent, and the vitamin A–treated group had a 23% lower diarrhea prevalence. Vitamin A supplementation had no effect on the incidence of ALRI. The authors concluded that vitamin A supplementation may be important in lowering mortality from diarrhea (9). A meta-analysis of vitamin A supplementation trials has conclusively shown a 30% reduction in childhood mortality (10). A study of zinc supplementation and its effect on diarrhea and respiratory infections was conducted in Guatemala, where investigators found high rates of diarrhea and respiratory infection (11). Zinc supplementation produced a 67% reduction in the percentage of children who had one or more episodes of persistent diarrhea. Additional studies support the role of zinc supplementation in the prevention and treatment of diarrhea. Two recent pooled analyses of zinc supplementation in the prevention and treatment of diarrhea have indicated a 41% reduction in the incidence of ARI and 11% to 18% reduction in diarrhea episodes (12) as well as a reduction in the severity and duration of diarrhea (13). Rotavirus Vaccine. In July 1999, the CDC in the United States recommended that health care providers postpone the use of the rhesus rotavirus vaccine-tetravalent (RRV-TV) for infants (14). This action was based on reports of intussusception among infants who received the vaccine. The manufacturer, in consultation with the Food and Drug Administration, then voluntarily ceased further distribution of RRV-TV. The relationship between intussusception and RRV-TV merits further research because the findings could impact directly on the use of other rotavirus vaccines. The worldwide burden of rotavirus disease remains substantial. Thus, the decision to withdraw the vaccine may not be applicable to other settings, in which the burden of disease is substantially higher and the risks and benefits of rotavirus vaccination could be It has been suggested that in developing countries the high mortality rate and the morbidity burden of rotavirus infection early introduction of a once it has been to be effective in such The effect of intussusception needs further but it must be that this vaccine a severe gastrointestinal disease that affects children have been studied to whether they could decrease diarrheal disease. In the prevention and management of acute diarrhea, the treatment of recurrent diarrhea, as well as the control of diarrhea, to be areas of significant potential A including and to be for the of the of acute diarrhea in children when used The use of other particularly to the of infants may have a effect acute diarrheal diseases. In the effect of to be most significant diarrhea In developing countries, studies have indicated a significant benefit of in the treatment of acute and persistent diarrhea, which may be to its However, the and populations used in studies conducted concerning the use of Nevertheless, it is clear that these are an important of the diarrhea in infants and children. all severely malnourished children with diarrhea have bacterial infections when first to the (6). Many have infections caused by treatment of bacteria infections with effective the nutritional response to and malnourished children with diarrhea should have a concerning which are to be The should be into used for which are given to all severely malnourished children, and used for which are given when a child is not or a infection is (6). The importance of various such as a water and is well A recent of has clearly improved child and diarrheal morbidity and mortality of and hygiene, and food is of such as micronutrient supplementation and disease prevention have been However, technologies to be further such as the prevention of low birth A control that of has been because there is evidence that are of diarrheal disease. group of investigators this problem a of the effect of on diarrhea incidence in the of was by the use of in the to eliminated the population in the and the incidence of diarrhea was lower in the compared to the times other than the there was no in diarrhea morbidity between and The authors concluded that control may have an impact on diarrhea incidence similar or greater that of the currently recommended by for diarrheal disease control in developing countries In considering other investigators have noted that the of nutrients in the of a major cause of malnutrition. by the potential of to the nutritional of at the of in a of that the of vitamin A and iron in the diet because of increased levels of these nutrients in the Although not for the for these nutritional Treatment can be into a) b) nutritional status and c) nutritional rehabilitation (1). The most conditions are the and that diarrhea, infections, severe and severe vitamin A deficiency in PEM. these conditions are the next of therapy is to nutrient as and as on the that the is to the malnourished nutritional treatment must to deleterious It is to with a liquid or by depending on the age and The last stage of treatment usually 2 to weeks when the child is and The infant or child must to adequate of protein, and other especially when traditional are into the diet. and must be and persistent diarrhea, intestinal and other must be should be during this as of on Global Health Malnutrition remains one of the most common causes of morbidity and mortality among children the world. of the children younger 5 years of age from wasting and are at risk of death or severe of growth and development (6). The of malnutrition infants and children at risk for diarrhea. persistent diarrhea in children may lead to nutritional Thus, persistent diarrhea has been a nutritional and optimal nutritional therapy is the of treatment (7). The of poverty, poor inadequate and infections and malnutrition is in the syndrome. OF infections, and natural and are among the causes of PEM associated with diarrhea. control and prevention that include food production and and In addition, studies are to how to and micronutrients to the world's Treatment of Diarrhea by Malnutrition that the of poverty, infections, and natural and should be to nutrients and food to populations to be to and support local and when nutrients and an to the treatment of malnutrition associated with diarrhea should be to during treatment a) rehydration with on oral b) feeding of a defined diet of and c) micronutrient supplementation and perhaps a to the malnourished child with diarrhea. in malnourished children with diarrhea commonly occurs during the first and has been to A has been for the treatment of children with severe malnutrition and diarrhea, with the of mortality The authors of this study compared severely malnourished children with diarrhea to 5 years by and those by a that rehydration with an on oral In the study, there were children on the who were with oral rehydration solution, compared with in the group of expensive was less in children on the than in the other group and children on the had episodes of There were children on treatment who compared with 30 of the children on the The authors of the study that a should be considered in all children with diarrhea and severe malnutrition In during the phase of there should be of intravenous therapy where possible and the use of a rehydration solution should be used to the the should not more than to of energy and about 1 The for this is to the body's The phase when has been and with of protein can be given of Diarrhea and Malnutrition of diarrhea and PEM should 1) nutrition and of an adequate diet with perhaps supplementation of selected 2) and 3) and 4) and