Malnutrition

The World Health Organization defines malnutrition as "the cellular imbalance between supply of nutrients and energy and the body's demand for them to ensure growth, maintenance, and specific functions."[3] More recently, the American Society for Parenteral and Enteral Nutrition (ASPEN) workgroup defined pediatric malnutrition [undernutrition] as "an imbalance between nutrient requirement and intake, resulting in cumulative deficits of energy, protein, or micronutrients that may negatively affect growth, development, and other relevant outcomes."[1]   Women and young children are the most adversely affected groups; one quarter to one half of women of child-bearing age in Africa and south Asia are underweight, which contributes to the number of low birth weight infants born annually.[4]

Malnutrition is globally the most important risk factor for illness and death, contributing to more than half of deaths in children worldwide; child malnutrition was associated with 54% of deaths in children in developing countries in 2001.[3, 4] Protein-energy malnutrition (PEM), first described in the 1920s, is observed most frequently in developing countries but has been described with increasing frequency in hospitalized and chronically ill children in the United States.[5] .  However, consensus guidelines now address malnutrition irrespective of etiology. ASPEN identified two alternative ways to diagnose malnutrition: BMI and unintentional weight loss. Among the various guidelines, the Subjective Global Assessment [SGA] is a highly validated tool which includes medical history and a physical assessment.[6] The main classification of malnutrition is either illness based [severe or moderate] or Non-illness based [severe to moderate] and were recently addressed.[7]

The effects of changing environmental conditions in increasing malnutrition is multifactorial. Poor environmental conditions may increase insect and protozoal infections and also contribute to environmental deficiencies in micronutrients. Overpopulation, more commonly seen in developing countries, can reduce food production, leading to inadequate food intake or intake of foods of poor nutritional quality. Conversely, the effects of malnutrition on individuals can create and maintain poverty, which can further hamper economic and social development.[4]

Kwashiorkor and marasmus are 2 forms of PEM that have been described but there has been a paradigm shift in diagnosing pediatric malnutrition. The new schema for defining malnutrition incorporates the concepts of chronicity, etiology, and pathogenesis of malnutrition; its relationship with inflammation; and its impact on functional outcomes.[1] The distinction between the 2 forms of PEM is based on the presence of edema (kwashiorkor) or absence of edema (marasmus). Marasmus involves inadequate intake of protein and calories, whereas a child with kwashiorkor has fair-to-normal calorie intake with inadequate protein intake. Although significant clinical differences between kwashiorkor and marasmus are noted, some studies suggest that marasmus represents an adaptation to starvation whereas kwashiorkor represents a dysadaptation to starvation. See the image below.

This infant presented with symptoms indicative of Kwashiorkor, a dietary protein deficiency. Note the angular stomatitis indicative of an accompanying Vitamin B deficiency as well. Image courtesy of the Centers for Disease Control and Prevention.

In addition to PEM, children may be affected by micronutrient deficiencies, which also have a detrimental effect on growth and development. The most common and clinically significant micronutrient deficiencies in children and childbearing women throughout the world include deficiencies of iron, iodine, zinc, and vitamin A and are estimated to affect as many as two billion people. Although fortification programs have helped diminish deficiencies of iodine and vitamin A in individuals in the United States, these deficiencies remain a significant cause of morbidity in developing countries, whereas deficiencies of vitamin C, B, and D have improved in recent years. Micronutrient deficiencies and protein and calorie deficiencies must be addressed for optimal growth and development to be attained in these individuals.

Malnutrition affects virtually every organ system. Dietary protein is needed to provide amino acids for synthesis of body proteins and other compounds that have various functional roles. Energy is essential for all biochemical and physiologic functions in the body. Furthermore, micronutrients are essential in many metabolic functions in the body as components and cofactors in enzymatic processes.

In addition to the impairment of physical growth and of cognitive and other physiologic functions, immune response changes occur early in the course of significant malnutrition in a child. These immune response changes correlate with poor outcomes and mimic the changes observed in children with acquired immune deficiency syndrome (AIDS). Loss of delayed hypersensitivity, fewer T lymphocytes, impaired lymphocyte response, impaired phagocytosis secondary to decreased complement and certain cytokines, and decreased secretory immunoglobulin A (IgA) are some changes that may occur. These immune changes predispose children to severe and chronic infections, most commonly, infectious diarrhea, which further compromises nutrition causing anorexia, decreased nutrient absorption, increased metabolic needs, and direct nutrient losses.

Early studies of malnourished children showed changes in the developing brain, including, a slowed rate of growth of the brain, lower brain weight, thinner cerebral cortex, decreased number of neurons, insufficient myelinization, and changes in the dendritic spines. More recently, neuroimaging studies have found severe alterations in the dendritic spine apparatus of cortical neurons in infants with severe protein-calorie malnutrition. These changes are similar to those described in patients with mental retardation of different causes. There have not been definite studies to show that these changes are causal rather than coincidental.[8]

Other pathologic changes include fatty degeneration of the liver and heart, atrophy of the small bowel, and decreased intravascular volume leading to secondary hyperaldosteronism.

Hormonal adaptation to the stress of malnutrition: The evolution of marasmus.

A classic example of a weight chart for a severely malnourished child.

Inadequate food intake is the most common cause of malnutrition worldwide. In developing countries, inadequate food intake is secondary to insufficient or inappropriate food supplies or early cessation of breastfeeding. In some areas, cultural and religious food customs may play a role. Inadequate sanitation further endangers children by increasing the risk of infectious diseases that increase nutritional losses and alters metabolic demands.

In developed countries, inadequate food intake is a less common cause of malnutrition. Instead, diseases and, in particular, chronic illnesses play an important role in the etiology of malnutrition. Children with chronic illness are at risk for nutritional problems for several reasons, including the following:

• Children with chronic illnesses frequently have anorexia, which leads to inadequate food intake.

• Increased inflammatory burden and increased metabolic demands can increase caloric need.

• Any chronic illness that involves the liver or small bowel affects nutrition adversely by impairing digestive and absorptive functions.

Chronic illnesses that commonly are associated with nutritional deficiencies include the following:

• Cystic fibrosis

• Chronic renal failure

• Childhood malignancies

• Congenital heart disease

• Neuromuscular diseases

• Chronic inflammatory bowel diseases

In addition, the following conditions place children at significant risk for the development of nutritional deficiencies:

• Prematurity

• Developmental delay

• In utero toxin exposure (ie, fetal alcohol exposure)

Children with multiple food allergies present a special nutritional challenge because of severe dietary restrictions. Patients with active allergic symptoms may have increased calorie and protein needs.

Guidelines on fruit juice intake for children by the American Academy of Pediatrics recommend that in the evaluation of children with malnutrition, the pediatrician should determine the amount of juice being consumed as excessive juice consumption may be associated with malnutrition (overnutrition and undernutrition).[9]

United States statistics

Fewer than 1% of all children in the United States have chronic malnutrition. Incidence of malnutrition is less than 10%, even in the highest risk group (children in shelters for the homeless). Some studies indicate that poor growth secondary to inadequate nutrition occurs in as many as 10% of children in rural areas. Studies of hospitalized children suggest that as many as one fourth of patients had some form of acute PEM and 27% had chronic PEM.

International statistics

The World Health Organization estimates that by the year 2015, the prevalence of malnutrition will have decreased to 17.6% globally, with 113.4 million children younger than 5 years affected as measured by low weight for age. The overwhelming majority of these children, 112.8 million, will live in developing countries with 70% of these children in Asia, particularly the southcentral region, and 26% in Africa. An additional 165 million (29.0%) children will have stunted length/height secondary to poor nutrition.

Currently, more than half of young children in South Asia have PEM, which is 6.5 times the prevalence in the western hemisphere. In sub-Saharan Africa, 30% of children have PEM. Despite marked improvements globally in the prevalence of malnutrition, rates of undernutrition and stunting have continued to rise in Africa, where rates of undernutrition and stunting have risen from 24% to 26.8% and 47.3% to 48%, respectively, since 1990, with the worst increases occurring in the eastern region of Africa.[3]

Children are most vulnerable to the effects of malnutrition in infancy and early childhood. Premature infants have special nutritional needs that are not met with traditional feeding recommendations; they require fortified human milk or specially designed preterm formula until later in infancy. Children are susceptible to malnutrition for differing reasons. During adolescence, self-imposed dietary restrictions contribute to the incidence of nutritional deficiencies.

Paradoxically, a massive global epidemic of obesity, especially in countries in rapid economic transition, is simultaneously emerging in children and adolescents. The concurrent manifestation of both undernutrition and overweight/obesity has been termed the double burden of malnutrition (DBM). The greatest concentration of the DBM is found in sub-Saharan Africa, South Asia, and East Asia and the Pacific region.[10]

Children who have chronic malnutrition, especially those with intrauterine growth retardation and with onset at an early age, do not achieve their full growth potential or regain cognitive deficits. Although malnutrition is rare in the United States and other industrialized countries, over half of childhood mortality in developing countries is either directly or indirectly secondary to malnutrition.

Morbidity/mortality

Malnutrition is directly responsible for 300,000 deaths per year in children younger than 5 years in developing countries and contributes indirectly to more than half the deaths in childhood worldwide.

The adverse effects of malnutrition include physical and developmental manifestations. Poor weight gain and slowing of linear growth occur. Impairment of immunologic functions in these children mimics those observed in children with AIDS, predisposing them to opportunistic and other typical childhood infections.

In developing countries, poor perinatal conditions account for 23% of deaths in children younger than five. Malnourished women are at high risk of giving birth to low birth weight infants. Many low birth weight infants (15-20% of all births worldwide)[11]  face severe short-term and long-term health consequences, such as growth failure in infancy and childhood, which increases risk of morbidity and early death.[4]

Children who are chronically malnourished exhibit behavioral changes, including irritability, apathy and decreased social responsiveness, anxiety, and attention deficits. In addition, infants and young children who have malnutrition frequently demonstrate developmental delay in delayed achievement of motor skills, delayed mental development, and may have permanent cognitive deficits. The degree of delay and deficit depends on the severity and duration of nutritional compromise and the age at which malnutrition occurs. In general, nutritional insults at younger ages have worse outcomes. Dose-dependent relationships between impaired growth and poor school performance and decreased intellectual achievement have been shown.[4, 12, 13, 14]

Although death from malnutrition in the United States is rare, in developing countries, more than 50% of the 10 million deaths each year are either directly or indirectly secondary to malnutrition in children younger than 5 years.[3]  A meta-analysis by Karunaratne et al identified six independent factors associated with mortality in children hospitalized for complicated severe acute malnutrition: HIV infection, diarrhea, pneumonia, shock, lack of appetite, and lower weight-for-height z score.[15]

Clinical signs and symptoms of protein-energy malnutrition (PEM) include the following:

• Poor weight gain

• Slowing of linear growth

• Behavioral changes - Irritability, apathy, decreased social responsiveness, anxiety, and attention deficits

Some of the clinical signs and symptoms of specific micronutrient deficiencies may closely resemble those observed in PEM. Deficiencies of micronutrients, including vitamins, minerals, and trace elements have been well described. The most common and clinically significant deficiencies include the following:

• Iron - Fatigue, anemia, decreased cognitive function, headache, glossitis, and nail changes

• Iodine - Goiter, developmental delay, and mental retardation

• Vitamin D - Poor growth, rickets, and hypocalcemia

• Vitamin A - Night blindness, xerophthalmia, poor growth, and hair changes

• Folate - Glossitis, anemia (megaloblastic), and neural tube defects (in fetuses of women without folate supplementation)

• Zinc - Anemia, dwarfism, hepatosplenomegaly, hyperpigmentation and hypogonadism, acrodermatitis enteropathica, diminished immune response, poor wound healing

Physical findings that are associated with PEM include the following:[2] ​

• Decreased subcutaneous tissue: Areas that are most affected are the legs, arms, buttocks, and face.

• Edema: Areas that are most affected are the distal extremities and anasarca (generalized edema). See the image below.

This infant presented with symptoms indicative of a dietary protein deficiency, including edema and ridging of the toenails. Image courtesy of the Centers for Disease Control and Prevention.

Other physical findings associated with PEM are as follows:

• Oral changes

  • Cheilosis

  • Angular stomatitis

  • Papillar atrophy

• Abdominal findings

  • Abdominal distension secondary to poor abdominal musculature

  • Hepatomegaly secondary to fatty infiltration

• Skin changes

  • Dry peeling skin with raw exposed areas

  • Hyperpigmented plaques over areas of trauma

• Nail changes: Nails become fissured or ridged.

• Hair changes: Hair is thin, sparse, brittle, easily pulled out, and turns a dull brown or reddish color.

The most helpful laboratory studies in assessing malnutrition in a child are hematological studies and laboratory studies evaluating protein status:

• Hematological studies should include a CBC count with RBC indices and a peripheral smear. This could also help exclude anemias from nutritional deficiencies such as iron, folate, and vitamin B-12 deficiencies.

• Measures of protein nutritional status include serum albumin, retinol-binding protein, prealbumin, transferrin, creatinine, and BUN levels. Retinol-binding protein, prealbumin, and transferrin determinations are much better short-term indicators of protein status than albumin. However, in the field, a better measure of long-term malnutrition is serum albumin because of its longer half-life.

Additional diagnostic evaluation includes the following:

• In children who have a history of adequate food intake and signs/symptoms of malnutrition, focus on identifying the cause of malnutrition. Perform laboratory studies based on information from a complete history and physical examination.

• Initial diagnostic laboratory studies include a CBC count, sedimentation rate, serum electrolytes, and urinalysis and culture. Stool specimens should be obtained if the child has a history of abnormal stools or stooling patterns or if the family uses an unreliable or questionable source of water.

• Additional studies may focus on thyroid functions or sweat chloride tests, particularly if height velocity is abnormal. Further diagnostic studies should be determined as dictated by the history and physical examination. For example, laboratory tests evaluating renal function, such as phosphorus and calcium, should be obtained in the presence of renal symptoms. Children with suspected liver disease should have triglyceride and vitamin levels obtained, while zinc levels should be obtained in patients with chronic diarrhea.

Celiac serology is a useful screening test and should be considered, especially if there is a family history of celiac disease or if other autoimmune diseases, such as type I diabetes mellitus, are present.

Other tests include the following:

• Practical nutritional assessment

  • Complete history, including a detailed dietary history

  • Growth measurements, including weight and length/height; head circumference in children younger than 3 years

  • Complete physical examination

• Sensitive measures of nutritional status and failure to thrive

  • Percentiles:
    • Weight or weight for height less than 3^rd or 5^th percentile on standard growth curves
    • Standard Deviation Score
    • Weight ,2 standard deviations below mean for gender and age
    • Weight for height < 2 standard deviations below mean for gender and age
  • Z scores*
    • -2.0 less of weight for age or height for age or weight for height
    • - *Z scores are calculated by (Observed weight-mean weight)/standard deviation of reference population

Height-for-age or weight-for-height measurements greater than 2 standard deviations below the mean for age

Following evaluation of the child's nutritional status and identification of the underlying etiology of the malnutrition, dietary intervention in collaboration with a dietitian or other nutritional professionals should be initiated. Children with edema must be assessed carefully for actual nutritional status because edema may mask the severity of malnutrition. Children with chronic malnutrition may require caloric intakes more than 120-150 kcal/kg/d to achieve appropriate weight gain. The formula for determining adequate caloric intake is:

kcal/kg = (RDA for age X ideal weight)/actual weight

Additionally, any micronutrient deficiencies must be corrected for the child to attain appropriate growth and development. Most children with mild malnutrition respond to increased oral caloric intake and supplementation with vitamin, iron, and folate supplements. The requirement for increased protein is met typically by increasing the food intake, which, in turn, increases both protein and caloric intake. Adequacy of intake is determined by monitoring weight gain.

A Cochrane Database of Systematic Reviews study noted that micronutrient powders (MNPs), which are single-dose packets containing multiple vitamins and minerals in powder form for sprinkling onto any semisolid food, can effectively reduce anemia and iron deficiency in children aged 6-23 months. While the benefits of this intervention as a survival strategy or on developmental outcomes are unclear, the use of MNP is possibly comparable to daily iron supplementation and better than placebo or no intervention.[16]

In mild-to-moderate cases of malnutrition, initial assessment and nutritional intervention may be done in the outpatient setting. A patient with malnutrition may require hospitalization based on the severity and instability of the clinical situation. Hospitalization of patients with suspected malnutrition secondary to neglect allows observation of the interactions between parent/caregiver and child and documentation of actual intake and feeding difficulties. It may also be warranted in cases where dehydration and acidosis complicate the clinical picture. In moderate-to-severe cases of malnutrition, enteral supplementation via tube feedings may be necessary.

A study by Stobaugh et al found that the proportion of children that recovered from moderate acute malnutrition was significantly higher in the group that received ready-to-use supplementary food containing dairy ingredients in the form of whey permeate and whey protein concentrate than in the group that received soy ready-to-use supplementary food. The authors added that this study highlighted the importance of milk protein in the treatment of moderate acute malnutrition.[17]

Any child at risk for nutritional deficiency should be referred to a registered dietitian or other nutritional professional for a complete nutritional assessment and dietary counseling.

In the United States, children with poor nutrition secondary to inadequate intake should be referred to the appropriate social agencies to assist the family in obtaining resources and providing ongoing care for the child.

Other subspecialty referrals are based on findings in the initial evaluation that may indicate a specific cause of inadequate nutrition other than inadequate food intake.

Dietary guidelines were released by the US Department of Health and Human Services and the US Department of Agriculture in 2020.[18]

Protein, energy, and other nutrient requirements vary with age, sex, and activity levels.

Following careful assessment of the child's nutritional status, initiate nutritional intervention in collaboration with nutrition support personnel.

Children with chronic malnutrition may require caloric intakes in excess of 120-150 kcal/kg/d to achieve appropriate weight gain. The diet must include adequate amounts of protein and other macronutrients.

Any micronutrient deficiencies must be diagnosed and corrected to achieve adequate somatic growth and psychomotor development.

Monitor patients closely for growth and resolution of clinical signs and symptoms of malnutrition. Follow-up should be based on the severity of the illness, age of the patient, and the patient's initial response to intervention.

Minimal intervals between visits should give the patient sufficient time to show a change in the measured parameter. For example, in infants beyond the newborn stage, the time needed to show an appreciable change in weight is 7 days. A 4-week interval is needed to document changes in length, and an 8-week interval is needed to document a change in height.

Prevention of malnutrition in children starts with an emphasis on prenatal nutrition and good prenatal care. Health care providers should emphasize the importance of breastfeeding in the first year of life. Promotion of breastfeeding is particularly crucial in developing countries where safe alternatives to human milk are unavailable. In addition to the promotion of breastfeeding, health care providers should counsel parents on the appropriate introduction of nutritious supplemental foods. Health care providers should continue to provide age-appropriate nutritional counseling at every opportunity.

Programs addressing micronutrient supplementation and fortification have been successful at decreasing the incidence of specific micronutrient deficiencies (eg, iodine, vitamin D) in many countries, and supplementation in pregnant women has also been beneficial.[19, 20] These programs should be promoted more in developing countries. In addition, research demonstrates that zinc supplementation can help reduce the duration and severity of acute and persistent diarrheal illnesses in children in areas where diarrhea is a significant cause of mortality and is recommended by the World Health Organization and UNICEF.[21, 22] Additional fortification programs should be developed to address other common nutritional deficiencies such as iron deficiency, which continues to be significant problem throughout the world.

Improvement in hygiene practices and sanitation reduces the incidence of infectious diseases, which decreases the incidence of malnutrition in developing countries.