Malnutrition in children in resource-limited settings: Clinical assessment

INTRODUCTION — Undernutrition is a critical determinant of mortality and morbidity in young children worldwide: It is associated with approximately one-half of all deaths in children under five years of age [1].

In this topic review, we use the term "malnutrition" in its traditional sense, referring to undernutrition (wasting, stunting, or micronutrient deficiencies), although some authors use the term more broadly to encompass overnutrition/obesity. Indeed, many low- and middle-income countries have substantial problems with both undernutrition and overweight/obesity, sometimes termed the "double burden of malnutrition" [2].

The major forms of malnutrition are marasmus (wasting) and kwashiorkor (edematous malnutrition), with or without associated stunting. The clinical assessment of the child with malnutrition includes distinguishing between these types, assessing their severity, and identifying acute life-threatening complications, including sepsis and acute dehydration. These children are at risk for micronutrient deficiencies, as detailed in a separate topic review. (See "Micronutrient deficiencies associated with protein-energy malnutrition in children".)

Traditionally, malnutrition in resource-limited settings is primary malnutrition that results from inadequate food supply caused by socioeconomic, political, and environmental factors. However, secondary malnutrition due to chronic diseases can also exist concurrently in these settings.

Treatment of malnutrition in resource-limited settings is discussed in the following topic reviews:

●(See "Management of moderate acute malnutrition in children in resource-limited settings".)

●(See "Management of uncomplicated severe acute malnutrition in children in resource-limited settings".)

●(See "Management of complicated severe acute malnutrition in children in resource-limited settings".)

●(See "Micronutrient deficiencies associated with protein-energy malnutrition in children".)

EPIDEMIOLOGY

●Acute malnutrition – Approximately 31.8 million children (4.5 percent of all children under five years of age worldwide) have moderate wasting (indicating moderate acute malnutrition [MAM]) [3]. An additional 13.6 million children in this age group have severe wasting (indicating severe acute malnutrition [SAM]) [4]. MAM and SAM are primarily a problem in resource-limited settings and especially South Asia (including Afghanistan, India, Pakistan, Bangladesh, and Nepal) and sub-Saharan Africa. They are uncommon in North America, Australia, and other resource-abundant settings.

●Chronic malnutrition – Many more children (149.2 million; approximately 22 percent) have stunting (faltering linear growth), reflecting chronic undernutrition [3]. The prevalence of stunting has gradually declined in most regions during the past three decades (from 39.3 percent in 1990 to 22 percent in 2020), associated with improvements in education, socioeconomic status, sanitation, access to maternal health services, and family planning [5]. Nonetheless, the prevalence of stunting remains unacceptably high in many regions, particularly South Asia and sub-Saharan Africa, where it affects more than 30 percent of children [3,5]. Stunting rates in sub-Saharan Africa have finally begun to decline [4].

CHRONIC MALNUTRITION — Stunting is a marker for chronic malnutrition and is often present in children with acute malnutrition. Stunting is often accompanied by features of acute malnutrition, such as poor weight gain and deficits in lean body mass and adipose tissue. Other features include reduced physical activity, mental apathy, and retarded psychomotor and mental development [6-8].

ACUTE MALNUTRITION — Severe acute malnutrition (SAM), also known as "severe wasting and/or nutritional edema" [9], is associated with one of two classical syndromes: marasmus (wasting syndrome) and kwashiorkor (edematous malnutrition), or a combination of the two (marasmic kwashiorkor). Children with acute malnutrition appear wasted (or show a decrease in mid-upper arm circumference [MUAC], weight-for-length, and/or body mass index), whereas children with chronic malnutrition have stunted linear growth and/or are underweight. Malnourished children may also suffer from numerous associated complications, including dehydration, infection, and vitamin deficiencies. (See 'Evaluation for comorbid conditions' below and 'Specific nutrient deficiencies' below.)

The division into acute (wasting) and chronic malnutrition (stunting) is an oversimplification. In one study, many children who were either wasted or stunted at two years of age had suffered from the other form of malnutrition earlier in life [10]. Hence, wasting and stunting should be taken to represent different ways to adapt to suboptimal nutrition, either by restraining weight (wasting) or height (stunting) [11].

Clinical subtypes — SAM can be divided into clinical subtypes based on the presence or absence of edema. Malnutrition without edema is known as marasmus or wasting, and malnutrition with edema is known as kwashiorkor (or edematous malnutrition). Distinguishing physical features are listed in the table (table 1). In the past, children with kwashiorkor were previously thought to have worse outcomes compared with those with marasmus, but more recent large studies demonstrate that children with kwashiorkor tend to have better outcomes, perhaps due to the additional burden of higher rates of human immunodeficiency virus (HIV) and diarrheal dehydration among those with marasmus [12-14].

Marasmus — Marasmus is characterized by low weight-for-height and reduced MUAC, reflecting wasting of muscle mass and depletion of body fat stores. It is the most common form of protein-energy malnutrition and is thought to be caused by inadequate intake of all nutrients but especially dietary energy sources (total calories).

Other physical examination findings may include:

●Head that appears large relative to the body, with staring eyes

●Emaciated and weak appearance

●Irritable and fretful affect

●Bradycardia, hypotension, and hypothermia

●Thin, dry skin

●Shrunken arms, thighs, and buttocks, with redundant skin folds caused by loss of subcutaneous fat (picture 1)

●Thin, sparse hair that is easily plucked

Kwashiorkor (edematous malnutrition) — Kwashiorkor is characterized by symmetric peripheral pitting edema that begins in the most dependent regions and proceeds cranially as time progresses, often involving the presacral area, genitalia, and periorbital area, with or without anasarca (severe generalized edema). There is marked muscle atrophy with normal or even increased body fat. Malnutrition is considered severe if any edema is present, regardless of other anthropometric values.

Other physical examination findings include:

●Apathetic, listless affect

●Rounded prominence of the cheeks ("moon face")

●Pursed appearance of the mouth

●Thin, dry, peeling skin with confluent areas of hyperkeratosis and hyperpigmentation (picture 2)

●Dry, dull, hypopigmented hair that falls out or is easily plucked

●Hepatomegaly (from fatty liver infiltrates)

●Distended abdomen with dilated intestinal loops

●Bradycardia, hypotension, and hypothermia

●Despite generalized edema, most children have loose inner inguinal skin folds

Edema is assessed by pressing down firmly on the third to fourth tarsal bones on the dorsum of the foot for three to five seconds and then assessing for pitting edema for two to three seconds [15].

Edema in malnutrition is graded in the following manner [16]:

●Mild (1+) – Edema involves only the feet

●Moderate (2+) – Edema involves the feet and legs and/or the upper limbs

●Severe (3+) – Generalized edema or moderate plus facial edema

Intermittent periods of adequate dietary intake restores hair color, occasionally resulting in alternating loss of hair color interspersed between bands of normal pigmentation ("flag sign") (picture 3). Stunting (reduced height for age) is often superimposed on both marasmus and kwashiorkor, reflecting not only inadequate caloric intake but also the cumulative effects of chronic poverty, food insecurity, and infectious risks that these children face.

Some children have features of both marasmus and kwashiorkor, sometimes known as marasmic kwashiorkor.

Pathophysiology — SAM affects many organ systems (figure 1):

●Cardiovascular system – Children with either marasmus or kwashiorkor have precarious fluid balance; the infusion of saline may cause an increase in venous pressure and acute heart failure, whereas a decrease in blood volume can compromise tissue perfusion. In children with marasmus, cardiac output and stroke volume are reduced in proportion to the loss of lean body mass; hence, cardiac index (which relates cardiac output to body surface area) is normal. However, there is a threshold beyond which cardiac dysfunction occurs [17]. Another study documented that cardiac function measurements, including myocardial mass, return to normal by day 7 of hospitalization [18]. All children with SAM tolerated boluses of intravenous fluids, and some may have actually had hypovolemia. The exact approach to fluid management and cardiac dysfunction in children with SAM needs to be further elucidated.

●Lungs – Surprisingly, children treated for SAM do not experience negative effects with regard to later lung function [19].

●Liver – Hepatomegaly from fatty liver is common, especially in kwashiorkor [20]. Hepatic gluconeogenesis is reduced in patients with hypoalbuminemia, which increases the risk of hypoglycemia, and energy production from substrates such as galactose and fructose is also impaired. There is severely reduced hepatic metabolism and excretion of toxins, as well as reduced hepatic synthesis of proteins including albumin and production of abnormal metabolites of amino acids.

●Genitourinary system – Glomerular filtration rate is reduced, and the capacity of the kidney to excrete sodium, excess acid, or a water load is greatly reduced. Urinary tract infections are common [21].

●Gastrointestinal tract – Production of gastric acid is reduced. Exocrine pancreatic insufficiency is almost universal in severe malnutrition; children with kwashiorkor have more severe pancreatic insufficiency than those with severe wasting [22]. However, pancreatic enzyme replacement therapy does not improve weight gain [22]. The mucosa of the small intestine is atrophied, and production of digestive enzymes and membrane nutrient transporters is reduced. Lactase deficiency is common, leading to lactose malabsorption [23], and absorption of all nutrients is reduced. Intestinal motility is reduced, and this can be worsened by potassium and magnesium deficiencies, potentially leading to ileus. Environmental enteric dysfunction, also known as malnutrition enteropathy, is associated with villous atrophy, mucosal thinning, increased intestinal permeability, loss of tight junction proteins (leading to loss of gut barrier function), lymphocytic infiltration, and gut dysbiosis [24-26]. Luminal bacterial overgrowth is common, and the diminished gut barrier function, which normally limits translocation of bacteria and their toxins, can lead to bacteremia and sepsis.

●Immune system – Immune dysfunction and infections are closely associated with malnutrition and are probably both a cause and consequence of malnutrition [27,28]. Severely malnourished children are at extremely high risk for superimposed infections [29]. Multiple immune functions are diminished in marasmus; the mechanisms include alterations in gut barrier function, intestinal dysbiosis and mucosal immunity, reduced production of proinflammatory cytokines by adipose tissue ("adipokines"), and micronutrient deficiencies [30]. Lymph glands, tonsils, and the thymus are atrophied. Thymus size is inversely proportional to the duration of malnutrition [31] and improves with treatment of malnutrition [32]. Cell-mediated (T cell) immunity, immunoglobulin A (IgA) levels in secretions, complement levels, and phagocytosis are all diminished. Although the acute phase immune response is intact, the typical signs of infection, such as leukocytosis and fever, are frequently absent [33]. Septic shock is often associated with hypoglycemia and hypothermia (see 'Sepsis' below). Other inflammatory mediators (including interleukin-6 and C-reactive protein) are increased, particularly in kwashiorkor (edematous malnutrition) [33,34].

●Endocrine system – Insulin levels are reduced, and the child may be glucose intolerant. Growth hormone levels are increased, but levels of its downstream effector, insulin-like growth factor 1 (IGF-1), are reduced. Cortisol levels are usually increased.

●Central nervous system – Approximately 20 percent of children have abnormal findings on brain magnetic resonance imaging (MRI), such as cerebral atrophy, dilated ventricles, and periventricular white matter changes [35]. In the majority of patients, these gross changes resolve with treatment.

●Metabolism and circulation – The basal metabolic rate is reduced by approximately 30 percent but rises markedly during the recovery period [36,37]. Both heat generation and heat loss are impaired, so that the child becomes hypothermic in a cold environment and hyperthermic in a hot environment [38]. Intestinal absorption of nutrients and blood glucose clearance are reduced in edematous malnutrition and marasmus, but endogenous glucose production is significantly reduced in children with hypoalbuminemia, with or without edematous malnutrition [39-41].

●Cellular function – Sodium pump activity is reduced, and cell membranes are more permeable than normal, resulting in an increase in intracellular sodium and a decrease in intracellular potassium and magnesium. Protein synthesis is reduced.

●Skin and glands – The skin and subcutaneous fat are atrophied, which causes loose skin folds. Many signs of dehydration are unreliable. As examples, the eyes may appear sunken because of loss of subcutaneous fat in the orbit and the child may have dryness of mouth and eyes as well as reduced sweat production because of atrophied sweat, tear, and salivary glands. (See 'Distinguishing sepsis from dehydration' below.)

Pathogenesis — Multiple theories have been advanced to explain the edema in edematous malnutrition:

●Protein deficiency/hypoalbuminemia – In the past, dietary protein deficiency was thought to be the key factor underlying edematous malnutrition. This assumption was based on observations that many patients with kwashiorkor have hypoalbuminemia, which was thought to be a consequence of inadequate nutrients for protein synthesis. In addition, albumin concentrations generally increase within the first two weeks of refeeding (albeit subtly), and edematous malnutrition has features similar to congenital nephrotic syndrome, in which the primary pathology is renal loss of albumin [42]. However, multiple lines of evidence have shown that inadequate intake of dietary protein is not the primary trigger for edematous malnutrition. As examples, some patients have edematous malnutrition without hypoalbuminemia, others develop edematous malnutrition despite adequate proportion of protein in the diet (eg, in exclusively breastfed infants), and others recover from edematous malnutrition with supportive care even without enhancing the protein content of the diet [43-45].

Thus, neither protein deficiency nor hypoalbuminemia appear to be the primary cause of the edema in kwashiorkor. Instead, hypoalbuminemia appears to be a common complication and may contribute to the edema in many patients by permitting movement of fluid from the vascular space into the interstitium; this is compounded by retention of sodium and water by the kidneys. The carbohydrate component of the diet increases insulin levels, which further enhances renal reabsorption of sodium and water. (See "Pathophysiology and etiology of edema in children".)

●Oxidant stress – Excessive oxidant stress has been proposed as a cause of edematous malnutrition. However, a trial to prevent this form of malnutrition with antioxidant supplementation was not successful [46], leading to the conclusion that antioxidant depletion may be a consequence rather than a cause of kwashiorkor.

●Microbiome – Strong evidence suggests that edematous malnutrition is caused by changes in the intestinal microbiome, in conjunction with a specific diet. In one study, malnutrition was induced in mice by transfer of the fecal microbiota from malnourished children if they were also fed the local nutrient-poor diet eaten by the children [47]. Neither the fecal microbiota transfer nor the local diet alone was sufficient to cause the malnutrition. This and other studies support the concept that changes in fecal microbiota and/or virome observed in malnutrition are causes rather than effects of malnutrition and that the dysbiosis might be reversible with specially designed therapeutic foods [47-51]. Severe malnutrition may interfere with the normal development of the intestinal microbiome, leading to an immature bacterial population that could potentially lead to other health consequences [47,52]. More recently, studies have shown that specific "families" of microbiota are associated with normal maturation of the infant microbiome and may serve as the "scaffolding" upon which the rest of the normal microbiome thrives [53]. These microbiota are disrupted by malnutrition, but the return of these bacteria may serve as a strong signal of future health. Finally, changes in the duodenal microbiome mediate the environmental enteric dysfunction seen in malnutrition [26].

CLINICAL ASSESSMENT

Anthropometrics — The degree of acute and chronic malnutrition, manifested as wasting or edema, and linear stunting, respectively, is assessed clinically using various anthropometric measurements (table 2) [54]. The assessment methods are based upon the assumption that during periods of nutritional deprivation, weight deficits occur initially, followed by faltering length or height and, finally, by lagging head circumference growth. Estimates of the severity and duration of nutritional deprivation provide guidelines for the nutritional rehabilitation of the malnourished child [55].

Z-scores — The severity of wasting or stunting is defined by comparing a child's weight and height measurements with those of a population reference standard. Population growth standards were developed by the World Health Organization (WHO) in 2006; these describe normal child growth from birth to five years from a variety of populations, under optimal environmental conditions. The individual's weight-for-height and height-for-age relative to the population mean are expressed as Z-scores. These charts are available online at the WHO website. (See "Measurement of growth in children".)

Z-scores also may be determined using the following calculators, which are based on the WHO child growth standards:

●For ages 0 to 23 months – Boys (calculator 1); girls (calculator 2). These calculators return Z-scores and percentiles for weight-for-length and length-for-age, which can also be obtained from these WHO charts (figure 2A-D).

●For ages 24 to 59 months – Boys (calculator 3); girls (calculator 4). These calculators return Z-scores and percentiles for weight-for-height and height-for-age, which can also be obtained from these WHO charts (figure 3A-D)

Mid-upper arm circumference — The mid-upper arm circumference (MUAC) is an accurate and efficient way to screen for wasting [56]. It is especially valuable as a field measure in settings during which time, equipment, or trained personnel are limited, such as famines and refugee crises.

A MUAC of <115 mm is used to define severe wasting in children 6 to 59 months of age. A single cutoff can be used because it is reasonably independent of age and sex in young children. This cutoff is fairly sensitive for detecting severe wasting [9,57]. One study suggested somewhat higher cutoffs based on age group identify children with wasting, but the higher thresholds would also reduce the specificity of the measure [58].

Advantages of the MUAC compared with weight-for-length Z-scores (WLZ) are that it is a better predictor of mortality, is easier to perform, and is not as affected by dehydration [56]. On the other hand, WLZ may detect another 40 percent of children with severe acute malnutrition (SAM) who have normal MUAC values and WLZ scores are better correlated with a number of biochemical indices of malnutrition associated with clinical morbidity [59]. Thus, the combination of both MUAC and WLZ is optimal for sensitivity and identifying children at greatest risk [59,60].

Diagnostic criteria — WHO has developed criteria for the classification of moderate or severe malnutrition in children [54]. These criteria are based upon the degree of wasting and stunting and the presence of edema, which are not mutually exclusive (table 2).

Children 6 through 59 months — For this age group, diagnostic criteria are:

●Severe acute malnutrition (SAM), also termed "severe wasting and/or nutritional edema" [9]:

•MUAC <115 mm, or

•Weight-for-length Z-score <-3, or

•Bilateral pitting edema

●Moderate acute malnutrition (MAM), also termed "moderate wasting":

•MUAC 115 to 124 mm, or

•Weight-for-length Z-score -2 to -3

●Stunting (indicates chronic malnutrition):

•Moderate stunting – Height or length Z-score -2 to -3

•Severe stunting – Height or length Z-score <-3

These definitions of SAM are recommended by the WHO as criteria for identifying patients who require urgent treatment [61]. The type of treatment program (outpatient or inpatient) depends on the patient's overall clinical status, appetite, and comorbid disease. (See "Management of complicated severe acute malnutrition in children in resource-limited settings", section on 'Classification by age and severity'.)

When possible, both parameters should be considered in the assessment of malnutrition [62].

Infants <6 months — For infants under 6 months of age, any of the following criteria may be used to define SAM [63-66]:

●Weight-for-age Z-score (WAZ) <-3 SD

●Weight-for-length Z-score (WLZ) <-3 SD

●MUAC <11 cm (for ages 6 weeks to 6 months)

●Presence of edema

Each of these measures has advantages and disadvantages in this population [56,67]. Several studies demonstrate that MUAC <11 cm is highly associated with mortality in this age group [68-70]. One of these studies showed that MUAC and WAZ are better predictors of mortality than WLZ [70].

Children 5 years and older — For children over five years of age and adolescents, the WHO recommends the use of body mass index-for-age Z-scores to screen for malnutrition. Alternatively, MUAC-for-age Z-score charts for children between 5 and 19 years have been developed. In these charts, when cutoffs of -2 for moderate malnutrition and -3 for severe malnutrition are used, they have been shown to correlate with mortality in Africa [71]. Hence, MUAC-for-age Z-scores may be an alternative method to screen for malnutrition in children 5 to 19 years of age.

ADMISSION AND DISCHARGE CRITERIA — The World Health Organization (WHO) has suggested criteria for management of severe malnutrition in various settings [61]. These guidelines enumerate criteria for admission and discharge from an inpatient nutrition rehabilitation program for children 6 through 59 months (algorithm 1B) or infants younger than six months (algorithm 1A). They also enumerate criteria for discharge from outpatient monitoring of a child who has recovered from severe malnutrition. Hospital admission is indicated for children who have acute complications, fail an appetite test, or have untreated HIV or tuberculosis or when other considerations preclude safe and effective outpatient management. Note that the appetite test is not a good predictor of treatment outcomes and thus should not be used as the sole determinant of suitability for outpatient management [72]. (See "Management of uncomplicated severe acute malnutrition in children in resource-limited settings", section on 'Indications for inpatient care'.)

The parameter(s) used to monitor for recovery from malnutrition should be based on those used to make the diagnosis of severe malnutrition. Thus, children with a low mid-upper arm circumference (MUAC) should be monitored for gains in MUAC and children with low weight-for-length Z-score should be monitored for gains in weight [73].

EVALUATION FOR COMORBID CONDITIONS — A summary of the history and physical examination that should be used in the assessment of a malnourished child is presented in the tables (table 3A-B). Details of the assessment are discussed in the sections below.

Distinguishing sepsis from dehydration — For children with malnutrition, an important initial step is to determine whether dehydration and/or septic shock is present. Distinguishing between these conditions can be difficult but is important, particularly in the fragile child with edematous malnutrition. This is because both conditions manifest signs of hypovolemia and because many of the classical signs of dehydration are unreliable [74,75]. However, there are also some key distinguishing characteristics, as outlined in the table (table 4).

When clear distinguishing features are not present, it is often necessary to treat the child for both dehydration and septic shock. The World Health Organization (WHO) recommends antibiotic treatment for children with severe malnutrition, but the choice and course depends on whether there is clinical evidence of infection. (See "Management of complicated severe acute malnutrition in children in resource-limited settings", section on 'Infection'.)

●Common features of dehydration and septic shock – In patients with severe malnutrition, the following findings can be caused by either dehydration or septic shock [74,75]:

•Weak or absent radial pulse – This is a sign of shock from either severe dehydration or sepsis. As hypovolemia develops, the pulse rate increases and the pulse becomes weaker. If the pulse in the carotid, femoral, or brachial artery is weak, the child is at risk of dying and must be treated urgently.

•Cold hands and feet – This is a sign of both severe dehydration and septic shock. It should be assessed with the back of the hand.

•Urine flow – Urine flow diminishes as dehydration or septic shock worsens. In severe dehydration or full-blown septic shock, no urine is formed.

●Features suggesting dehydration

•History of diarrhea – A child with dehydration usually has a history of watery diarrhea. Small mucoid stools are commonly seen in severe malnutrition but do not cause dehydration. A child with signs of dehydration but without watery diarrhea should be treated as having septic shock [74,75].

•Thirst – Drinking eagerly is a reliable sign of mild dehydration. In infants, this may be expressed as restlessness. Thirst is not a symptom of septic shock [74].

•Sunken eyes – This is a helpful sign of dehydration but only if the onset is recent, according to the parent or caregiver [74].

Many other traditional signs of dehydration are unreliable in a malnourished child [74], as discussed below. (See 'Evaluation for dehydration' below.)

●Features suggesting septic shock

•Hypothermia – When present, hypothermia can be a sign of serious infection, including septic shock. It is not a sign of dehydration [74,75]. However, children with severe malnutrition also may be hypothermic in the absence of infection.

•Features of incipient septic shock – The child is usually limp, apathetic, and profoundly anorexic but is neither thirsty nor restless [74,75].

•Features of established septic shock – The superficial veins, such as the external jugular and scalp veins, are dilated rather than constricted. The veins in the lungs also may become engorged, making the lungs stiffer than normal. For this reason, the child may groan, grunt, have a shallow cough, and appear to have difficulty breathing. As shock worsens, kidney, liver, intestinal, or cardiac failure may occur. There may be vomiting of blood mixed with stomach contents ("coffee-ground" vomit), blood in the stool, and abdominal distension with "abdominal splash"; intestinal fluid may be visible on radiograph. When a child reaches this stage, survival is unlikely [74,75].

Sepsis — The severely malnourished child is typically exposed to infection because of inadequate sanitation and food preservation and is at increased risk for sepsis because of impaired immune defenses. The acute phase immune response is reduced in the setting of malnutrition, so typical signs of infection, such as leukocytosis and fever, are frequently absent [33]. Septic shock is often associated with hypoglycemia and hypothermia. (See 'Pathophysiology' above.)

Diarrhea and dehydration — Diarrhea is a serious and often fatal event in children with severe malnutrition. Its presence is also a strong predictor of mortality among children with complicated severe acute malnutrition (SAM) [76]. Although treatment and prevention of dehydration are essential, care of these children must also focus on careful management of their malnutrition and treatment of other infections [74,75].

Definitions and types of diarrhea — Diarrhea is the passage of loose or watery stools three or more times daily, as defined by the WHO.

The consistency and volume of the stools are the most important characteristics for distinguishing diarrhea from normal stool patterns. Diarrheal stools are watery or loose. Frequent passing of formed stools is not diarrhea. Babies fed only breast milk often pass loose, "pasty" stools; this also is not diarrhea [77,78]. Starved infants pass frequent, small-volume (less than 10 grams), green liquid stools. These "starvation stools" can be differentiated from diarrhea by inspection [75].

When a child presents with malnutrition and diarrhea, the type of diarrhea helps to predict potential complications [75,79]:

●Acute watery diarrhea, which lasts several hours or days. The main danger is dehydration; acute malnutrition occurs if feeding is not continued.

●Acute bloody diarrhea, which is also called dysentery. The main dangers are intestinal damage, sepsis, and acute malnutrition; dehydration may also occur.

●Persistent diarrhea that lasts 14 days or longer. The main danger is chronic malnutrition and serious nonintestinal infection; dehydration and vitamin deficiencies may also occur.

An approach to assessing the cause of diarrhea in a child in resource-limited settings is discussed in a separate topic review. (See "Persistent diarrhea in children in resource-limited settings", section on 'Diagnostic approach'.)

Evaluation for dehydration — Assessment of hydration status in malnourished children is difficult because many of the above signs are unreliable [74]. Skin turgor appears poor in children with marasmus, owing to the absence of subcutaneous fat; their eyes may also appear sunken. Conversely, children with edematous malnutrition may have normal skin turgor despite dehydration. In both types of malnutrition, the child's irritability or apathy makes assessment difficult [75].

It is often impossible to distinguish reliably between mild dehydration and severe dehydration in children with severe malnutrition [74]. Signs that remain useful for assessing hydration status include eagerness to drink (a sign of mild dehydration), lethargy, cool and moist extremities, weak or absent radial pulse, and reduced or absent urine flow (signs of severe dehydration) [74,75]. It can also be difficult to distinguish severe dehydration from septic shock because both conditions reflect hypovolemia and reduced blood flow to vital organs [74,75]. (See 'Distinguishing sepsis from dehydration' above.)

Management of dehydration in a child with more than mild malnutrition should take place in a hospital. Rehydration and refeeding are discussed in a separate topic review. (See "Management of complicated severe acute malnutrition in children in resource-limited settings", section on 'Dehydration'.)

Children with diarrhea who do not meet criteria for malnutrition should be evaluated for dehydration using standard clinical signs and symptoms. Signs of early (mild) dehydration include thirst, decreased skin turgor, dry mucus membranes, sunken eyes, and absence of tears when crying. Signs of severe dehydration include altered consciousness, lack of urine output, weak pulse, and poor perfusion (table 5) [74,75]. (See "Clinical assessment of hypovolemia (dehydration) in children".)

Other infections — In addition to assessing hydration, the child should be evaluated for evidence of infection by assessing for fever, bloody stools, and respiratory distress. Fever may be caused by severe dehydration or by a nonintestinal infection, such as malaria or pneumonia [75]. However, the absence of fever does not exclude the possibility of infection, because the acute phase response is attenuated in malnutrition. (See 'Pathophysiology' above.)

Shigella and Campylobacter infections often present with bloody diarrhea, and both should be treated in malnourished children [75]. Empiric therapy generally should be directed against Shigella, based on the known sensitivities of local strains. (See "Persistent diarrhea in children in resource-limited settings", section on 'Antimicrobials'.)

Children with respiratory distress should be evaluated with a chest radiograph if available, but the radiographic signs of pneumonia may be less prominent in malnourished children than in well-nourished children [74]. Children with presumed or established pneumonia should be treated with antibiotics. (See "Management of complicated severe acute malnutrition in children in resource-limited settings" and "Management of complicated severe acute malnutrition in children in resource-limited settings", section on 'Infection'.)

Dermatosis of kwashiorkor — Kwashiorkor (edematous malnutrition) may be accompanied by a nonspecific scaly dermatitis, which is often reddish-brown and resembles flaking paint (picture 2 and table 3B) [80,81]. It often involves the perineum, groin, limbs, ears, and armpits. The presence of widespread lesions with depigmentation, flaking, and cracked skin indicates worse disease. The lesions may weep and easily become infected.

These lesions should be washed with an antibacterial solution (eg, potassium permanganate) and covered with sterile dressings. Affected infants and children should be treated with systemic antibiotics to prevent infection, but the antibiotic coverage is similar to that for children with acute malnutrition without dermatosis. (See "Management of complicated severe acute malnutrition in children in resource-limited settings", section on 'Infection'.)

SPECIFIC NUTRIENT DEFICIENCIES — The initial evaluation of a malnourished child should assess for the following stigmata of specific micronutrient deficiencies (table 6 and table 7). When present, these require specific treatment in addition to usual nutritional rehabilitation:

●Vitamin A deficiency – Characterized by ocular findings with corneal cloudiness, ulceration and xerosis (picture 4), and Bitot spots (picture 5).

●Vitamin D deficiency – Characterized by skeletal changes with beading of the ribs (rachitic rosary), widening of the wrists, or bowed legs (picture 6). (See "Overview of rickets in children".)

●Thiamine deficiency – Characterized by neurologic changes with aphonia, peripheral neuropathy, nystagmus, ophthalmoplegia, cerebellar ataxia, confusion, or coma (dry beriberi) or by cardiovascular dysfunction, with cardiomegaly and congestive heart failure (wet beriberi). (See "Overview of water-soluble vitamins", section on 'Vitamin B1 (thiamine)'.)

●Zinc deficiency – Characterized by bullous dermatitis, affecting the perioral and perianal areas of the body, with pustular, moist, flaming red, easily denuded skin (picture 7).

Assessment for these nutrients in malnourished children is discussed in a separate topic review. (See "Micronutrient deficiencies associated with protein-energy malnutrition in children".)

Essential nutrient deficiencies are sometimes grouped by those that interfere with growth (type 2) or those that do not (type 1). Isolated deficiencies of vitamins A and D, thiamine, folate, and iron are characterized by biochemical abnormalities or specific clinical symptoms without anthropometric changes, a pattern that has been termed a "type 1" nutrient deficiency (table 7) [78]. Deficiencies of other nutrients, including protein, potassium, sodium, phosphorus, sulfur, zinc, and magnesium tend to cause reduced growth rate without specific signs or diagnostic biochemical changes; this pattern is sometimes termed a "type 2" nutrient deficiency. Affected children frequently have persistent diarrhea and anorexia and usually are deficient in multiple nutrients. The diagnosis of this type of deficiency is made by a growth response to a complete diet that includes sufficient quantities of these nutrients [78]. Zinc deficiency can be considered both type 1 and type 2 deficiency because it is also associated with some specific signs and symptoms (eg, acral dermatitis, hypogeusia) and appears to increase risk for diarrhea through unclear mechanisms.

Most cases of malnutrition in resource-limited settings involve deficiencies of multiple micronutrients in addition to protein and energy; treatment requires restoration of all nutrients rather than targeted supplementation. Treatment protocols designed by the World Health Organization (WHO) for children with severe malnutrition include multiple vitamin supplementation as part of the therapeutic nutritional approach. A variety of other vitamins and minerals, including zinc, are also included in the standard vitamin and mineral supplements used for nutritional rehabilitation. The dose of zinc used is usually sufficient to cover the needs of malnourished children with or without diarrhea [75]. (See "Management of complicated severe acute malnutrition in children in resource-limited settings" and "Zinc deficiency and supplementation in children".)

SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Pediatric malnutrition".)

SUMMARY AND RECOMMENDATIONS

●Clinical types of malnutrition – Acute malnutrition (undernutrition) can be divided into clinical subtypes of marasmus (malnutrition without edema) or kwashiorkor (malnutrition with edema) (table 1). Many children have features of both of these subtypes. (See 'Clinical subtypes' above.)

•Marasmus - Characterized by the wasting of muscle mass and depletion of body fat stores. It is the most common form of protein-energy malnutrition and is caused by inadequate intake of all nutrients but especially dietary energy sources (total calories). Affected children usually have some degree of stunting (suggesting chronic malnutrition), as well as wasting. (See 'Marasmus' above.)

•Kwashiorkor (edematous malnutrition) – Characterized by peripheral or generalized edema, with marked muscle atrophy with normal or increased body fat. Because any degree of edema in a malnourished child significantly worsens the child's prognosis, kwashiorkor is by definition severe malnutrition. Affected children usually have hepatomegaly and may have anorexia, dermatoses, and hair changes. (See 'Kwashiorkor (edematous malnutrition)' above.)

Children with either type of malnutrition are at risk for secondary infections and for fluid overload. (See 'Pathophysiology' above.)

●Clinical assessment – A summary of the history and physical examination that should be used in the assessment of a malnourished child is presented in the tables (table 3A-B).

•Severity and classification – Acute malnutrition typically causes wasting (with reduced weight-for-length), while chronic malnutrition causes both wasting and stunting (with reduced height-for-age). The severity of the malnutrition can be categorized based on mid-upper arm circumference (MUAC) and/or standard deviations below the population mean (Z-scores) (table 2). (See 'Anthropometrics' above and 'Diagnostic criteria' above.)

•Evaluation for sepsis and dehydration – Children with malnutrition should be evaluated for sepsis and severe dehydration. The features of dehydration and shock often overlap, particularly in advanced stages, so empiric treatment for both disorders is often appropriate. Both sepsis and severe dehydration cause poor tissue perfusion with weak pulses, cold hands and feet, and reduced urine flow (table 4). Children with dehydration tend to be thirsty, have a history of diarrhea, and may have sunken eyes (table 5). Specific signs of septic shock include hypothermia and lack of thirst. (See 'Distinguishing sepsis from dehydration' above.)

In malnourished children, skin turgor is not always a reliable measure of hydration status. Skin turgor may give the false appearance of dehydration in children with marasmus (because of absent subcutaneous fat) or the false appearance of normal hydration in children with kwashiorkor (because of edema). (See 'Evaluation for dehydration' above.)

•Other infections – The child should be evaluated for evidence of infection by assessing for fever, bloody stools, and respiratory distress. (See 'Other infections' above.)

●Disposition – Criteria for admission and discharge from nutrition rehabilitation programs depend upon anthropometry and the child's appetite and clinical condition, or anthropometry alone for infants younger than six months (algorithm 1A-B). (See 'Admission and discharge criteria' above and 'Evaluation for comorbid conditions' above.)

●Specific nutrient deficiencies – Malnourished children usually have deficiencies of specific nutrients, particularly vitamins A and D, folate, and iron, which are sometimes associated with specific clinical symptoms (table 7). In addition, they are deficient in one or more nutrients required for growth, including protein, electrolytes, and zinc. (See 'Specific nutrient deficiencies' above and "Micronutrient deficiencies associated with protein-energy malnutrition in children".)

Vitamin and mineral supplements are routinely included in nutritional rehabilitation protocols. (See "Management of complicated severe acute malnutrition in children in resource-limited settings".)

ACKNOWLEDGMENT — The UpToDate editorial staff acknowledges Buford L Nichols, MD, who contributed to earlier versions of this topic review.