Laboratory and radiologic evaluation of nutritional status in children

INTRODUCTION — The goal of nutritional assessment in childhood is to prevent nutritional disorders and the increased morbidity and mortality that accompany them. To meet this goal, pediatric clinicians must know the risk factors for obesity and malnutrition and must understand the normal and abnormal patterns of growth and the changes in body composition that occur during childhood and adolescence. In addition, they must be able to accurately perform and interpret the results of the nutritional evaluation.

Nutritional assessment is the quantitative evaluation of nutritional status. A comprehensive nutritional assessment has four components:

●Dietary, medical, and medication history

●Physical examination

●Growth, anthropometric, and body composition measurements

●Laboratory and radiologic tests

The laboratory and radiologic evaluation of nutritional disorders are reviewed here. The dietary history, clinical features of nutritional disorders, and measurements of growth and body composition are discussed separately. (See "Dietary history and recommended dietary intake in children" and "Indications for nutritional assessment in childhood" and "Measurement of growth in children" and "Measurement of body composition in children".)

UNDERNOURISHED CHILDREN

Laboratory tests — Laboratory tests are useful in the evaluation of children who are at risk for nutritional disorders for several reasons. They can:

●Identify nutritional deficiencies before clinical findings are evident (eg, iron deficiency)

●Confirm the presence of nutrient deficiencies that commonly are associated with specific disease entities (eg, fat-soluble vitamins in children with cystic fibrosis)

●Monitor recovery from malnutrition that occurs as a complication of illness

The laboratory evaluation of the child with or at risk for malnutrition is directed by the history and physical examination. The most valuable studies in the assessment of nutritional status in children are the hemoglobin concentration and red cell indices (mean corpuscular volume, mean corpuscular hemoglobin) and serum albumin or prealbumin (transthyretin) concentration. In addition, assessing the presence or absence of vitamin deficiency in patients at risk for malnutrition often is important. Potassium, phosphorus, and magnesium concentration and serum prealbumin and albumin concentration should be monitored during refeeding of malnourished children.

Hemoglobin and red blood cell indices — The hemoglobin concentration and red blood cell indices can be used to identify children with nutritional deficiencies of iron, folate, or vitamin B12 or with anemia of chronic disease. (See "Microcytosis/Microcytic anemia".)

Iron deficiency anemia, associated with hypochromic, microcytic red cell morphology, is the most common nutritional deficiency in children (picture 1). Plasma ferritin is the most sensitive measure of the adequacy of body iron status (figure 1 and table 1). However, ferritin is an acute-phase reactant and may be elevated during infectious or inflammatory illnesses. Additional tests that are useful in the evaluation of microcytic anemia include serum iron, total iron-binding capacity, and transferrin. (See "Iron deficiency in infants and children <12 years: Screening, prevention, clinical manifestations, and diagnosis" and "Iron requirements and iron deficiency in adolescents" and "Iron deficiency in infants and children <12 years: Screening, prevention, clinical manifestations, and diagnosis", section on 'Evaluation for suspected iron deficiency anemia'.)

A macrocytic anemia suggests the presence of folic acid and/or vitamin B12 deficiency (picture 2). (See "Clinical manifestations and diagnosis of vitamin B12 and folate deficiency".)

Children with chronic illness can have anemia on the basis of the above nutritional deficiencies or from their chronic disease. The anemia of chronic disease typically is normochromic, normocytic, and hypoproliferative. The laboratory hallmarks include a low serum iron, low iron-binding capacity, and a normal to increased serum ferritin concentration (table 2). (See "Anemia of chronic disease/anemia of inflammation".)

Transthyretin and albumin — Transthyretin (prealbumin) and albumin are surrogate markers of the adequacy of the diet over the short and long term, respectively [1-5]. In critical illness, these markers are negatively influenced by the acute-phase response (due to increases in vascular permeability and reprioritization of hepatic protein synthesis), so they do not accurately reflect nutrition status in children with inflammatory processes and disease. Transthyretin measurements are not useful in the routine evaluation of nutritional status, but they may be helpful in the evaluation of selected patients whose nutritional status is unclear after a global assessment to determine the adequacy of their recent dietary intake in the context of food availability, provision, and consumption [6].

Transthyretin is a tetrameric unglycosylated plasma protein that is synthesized in the liver. Hepatic synthesis is exquisitely sensitive to the adequacy and levels of protein and energy intake. It is turned over rapidly, with a half-life of approximately two days [2,3]. A normal range for serum prealbumin in most laboratories is approximately 20 to 40 mg/dL, with borderline levels between 16 and 20 mg/dL and low levels <16 mg/dL. The threshold defining low levels is 13 mg/dL in children and 4 mg/dL in neonates [7].

Serum transthyretin concentrations fall rapidly during periods of poor dietary intake and rise to low-normal values within 10 days of initiation of nutritional therapy and adequate refeeding. Thus, prealbumin is a good predictor of the protein and energy adequacy of the diet in the days prior to testing and can serve as a marker of an acute reduction in food consumption. It is a more sensitive marker of mild malnutrition than are anthropometric measurements [1]. However, it is a negative acute-phase reactant and concentrations fall in the presence of infection due to increases in vascular permeability and reprioritization of hepatic protein synthesis. Therefore, prealbumin levels do not accurately reflect nutrition status in children with inflammatory processes [8].

Albumin also is synthesized in the liver but has a half-life of 14 to 20 days and is reflective of dietary intake during the preceding three weeks. Serum albumin concentrations gradually return to normal after initiation of nutritional therapy, but this may take up to three weeks [9]. Serum albumin is not a good nutritional marker in the setting of disorders causing large protein losses from the circulation, such as ascites, protein-losing enteropathy, renal losses, liver disease, or extensive burns and inflammation. Serum albumin, which reflects intravascular oncotic pressure, may predict enteral feeding tolerance. Higher protein and energy intake from enteral nutrition can be provided when serum albumin levels are greater than 30 g/L [10].

Serum albumin and transthyretin concentrations are inversely correlated with morbidity and mortality [11,12]. In one study of malnourished children, the mortality rate approximated 40 percent when serum albumin levels were below 15 g/L but averaged only 10 percent when serum albumin levels were 27 g/L [13].

Cellular immunity — The effects of nutritional disorders on cellular immunity can be estimated through the measurement of total lymphocyte count (TLC) and cutaneous delayed-type hypersensitivity testing [14]. Compromise of cell-mediated immunity is suggested by TLC less than 1000/mm³. (See "Laboratory evaluation of the immune system".)

Cutaneous delayed-type hypersensitivity testing is done with a series of common antigens (eg, Candida, tetanus toxoid, tuberculin [purified protein derivative], and trichophyton) and a glycerine control and is read 48 to 72 hours after placement. Compromise of cell-mediated immunity is suggested by induration that is less than 5 mm or less than the induration surrounding the control plus 5 mm. Delayed-type hypersensitivity testing is least useful during an acute illness because cell-mediated immunity may be depressed in this setting, even in the absence of malnutrition. (See "Laboratory evaluation of the immune system", section on 'Cutaneous delayed-type hypersensitivity'.)

Vitamins

●Children with malabsorptive or inflammatory conditions – The assessment for specific vitamin deficiencies may be necessary in children who have had intestinal resection or illnesses that are associated with gastrointestinal malabsorption or inflammation. The nutritional management of the following specific diseases is discussed in separate topic reviews:

•Inflammatory bowel disease (Crohn disease and ulcerative colitis) (see "Growth failure and pubertal delay in children with inflammatory bowel disease" and "Vitamin and mineral deficiencies in inflammatory bowel disease")

•Cystic fibrosis (see "Cystic fibrosis: Nutritional issues" and "Cystic fibrosis: Assessment and management of pancreatic insufficiency")

•Short bowel syndrome (see "Management of short bowel syndrome in children", section on 'Laboratory monitoring' and "Chronic complications of short bowel syndrome in children", section on 'Nutritional complications')

•Bariatric surgery (see "Surgical management of severe obesity in adolescents", section on 'Postoperative management')

The laboratory assessment of fat-soluble vitamins usually is more readily available than is that of water-soluble vitamins. Fat-soluble vitamin concentrations should be monitored in children with malabsorptive disorders, liver disease, inflammatory bowel disease, celiac disease, and failure to thrive. Fat-soluble vitamin concentrations generally should be monitored at six-month to yearly intervals in these children, depending on the history and severity of malabsorptive disease [15,16]. Serum concentrations of vitamin A, vitamin E, and 25-hydroxyvitamin D can be measured directly. Measurement of serum 1,25-dihydroxyvitamin D is rarely necessary or useful, except in the setting of certain inborn errors of vitamin D metabolism or chronic kidney disease. Prothrombin time is used as a proxy to measure vitamin K. Supplementation with individual fat-soluble vitamins is indicated if the serum concentrations are low or the prothrombin time is prolonged.

Deficiency of water-soluble vitamins is less common, and levels should be measured only when clinically indicated. As an example, measurement of serum folate and vitamin B12 levels is appropriate for patients with active Crohn disease [17]. Measurement of the other water-soluble vitamins is more problematic [18-22]. (See "Micronutrient deficiencies associated with protein-energy malnutrition in children" and "Overview of water-soluble vitamins".)

●Children in resource-limited settings – In resource-limited settings, malnutrition typically involves deficiencies of multiple micronutrients in addition to protein and energy. As a result, management of these children using empiric supplementation with a variety of vitamins and minerals, rather than targeted supplementation, usually is appropriate. (See "Malnutrition in children in resource-limited settings: Clinical assessment" and "Management of moderate acute malnutrition in children in resource-limited settings".)

Minerals — Assessment for specific mineral deficiencies also may be necessary in children with certain types of chronic illness. In particular, children with chronic inflammatory diseases (eg, Crohn disease and juvenile idiopathic arthritis) are at risk for metabolic bone disease and zinc deficiency. (See "Metabolic bone disease in inflammatory bowel disease" and "Growth failure and pubertal delay in children with inflammatory bowel disease", section on 'Clinical manifestations'.)

Inflammation can lower serum zinc, iron, and selenium concentrations by diverting them from the circulation; inflammation also elevates serum ferritin (a biomarker for iron stores) [23,24]. Moreover, hypoalbuminemia reduces the bioavailability of zinc because albumin serves as a carrier protein. Therefore, during an inflammatory state, these laboratory tests may not reflect nutrient stores. If an inflammatory state is suspected, C-reactive protein and albumin can be measured to help validate the accuracy of the mineral concentrations.

Zinc status usually is assessed by measuring plasma zinc concentrations, but they can fluctuate rapidly during infection [24]. (See "Zinc deficiency and supplementation in children".)

Plasma copper levels and ceruloplasmin levels are reduced in severe copper deficiency; levels of erythrocyte superoxide dismutase may be a better marker of mild or marginal deficiency if the laboratory assay is carefully standardized [25].

Others — Hypokalemia, hypophosphatemia, and hypomagnesemia caused by intracellular ion shifts may occur during the early refeeding period in malnourished children and can produce serious arrhythmias and muscle weakness. Serum potassium, phosphorus, and magnesium concentrations should be carefully monitored early in the course of aggressive rehabilitation of malnourished children and in those with anorexia nervosa [26,27]. (See "Hypophosphatemia: Clinical manifestations of phosphate depletion".)

Other laboratory abnormalities that can be seen in patients with malnutrition include [28-30]:

●Low concentrations of serum sodium (caused by increased total body water associated with starvation)

●Low concentrations of blood urea nitrogen reflecting poor protein intake

●Low concentrations of zinc or magnesium in children with chronic diarrhea

●Low concentrations of trace minerals in children receiving parenteral nutrition without trace minerals or inadequate amounts of trace elements relative to requirements

Radiologic evaluation — Studies of bone age and bone density are useful in the evaluation of children with malnutrition. Bone age may be indicated in children with short stature or delayed or advanced sexual maturation. Radiographs of the child's wrist and hand are obtained to determine differences in bone formation for the child's chronologic age compared with reference standards for children of comparable age and sex [31]. (See "Causes of short stature", section on 'Undernutrition' and "Diagnostic approach to children and adolescents with short stature", section on 'Is there evidence of delayed or accelerated growth?'.)

Bone density studies may be indicated in children who are at risk for osteopenia (eg, adolescents with anorexia nervosa or inflammatory bowel disease). Bone density is assessed radiographically with scans of the whole body, spine, or hip to determine total body bone mineral content or areal density of the selected sites. These values are compared with reference standards for children of comparable ages and sex and expressed as Z-scores. (See "Overview of dual-energy x-ray absorptiometry".)

CHILDREN WITH OBESITY — Laboratory studies in children with obesity can help to identify complications of the obesity (eg, insulin resistance, hypercholesterolemia, polycystic ovary syndrome, or fatty liver disease).

Suggested clinical and laboratory evaluations for children with obesity are summarized in the table (table 3) and discussed in more detail separately. (See "Clinical evaluation of the child or adolescent with obesity".)

The evaluation includes radiographs of the hip and knees for children with suspected slipped capital femoral epiphysis and Blount disease, respectively. (See "Overview of the health consequences of obesity in children and adolescents", section on 'Orthopedic'.)

SUMMARY AND RECOMMENDATIONS

●Overview – The laboratory evaluation of the child with or at risk for malnutrition is directed by the history and physical examination. The extent of the evaluation and selection of specific tests depends on the degree of the nutritional problem and on the underlying disease, if any. (See "Dietary history and recommended dietary intake in children" and "Indications for nutritional assessment in childhood".)

●Undernourished children

•Complete blood count – The hemoglobin concentration and red cell indices (mean corpuscular volume, mean corpuscular hemoglobin) are used to identify children with nutritional deficiencies of iron, folate, or vitamin B12 or with anemia of chronic disease. (See 'Hemoglobin and red blood cell indices' above.)

•Transthyretin and albumin – Serum concentrations of transthyretin and albumin are good indicators of the adequacy of short- and long-term dietary intake, respectively. These hepatic markers, however, are negative acute-phase reactants and will not adequately reflect nutritional status in children with inflammation or infection. (See 'Transthyretin and albumin' above.)

•Potassium, phosphorus, and magnesium – During the refeeding of malnourished children, potassium, phosphorus, and magnesium concentration and serum prealbumin and albumin concentrations should be monitored. (See 'Minerals' above.)

•Vitamin deficiencies – Children with illnesses associated with gastrointestinal malabsorption or inflammation are at risk for a variety of vitamin deficiencies. The assessment for specific vitamin deficiencies may be necessary in children who have illnesses that are associated with gastrointestinal malabsorption or inflammation. In most of these patients, fat-soluble vitamin concentrations should be monitored at six-month to yearly intervals. (See 'Vitamins' above.)

An inflammatory state may lower the serum concentrations of certain micronutrients, including zinc, selenium, and iron, and elevate serum ferritin (a biomarker for iron stores). (See 'Minerals' above.)

•Radiographs – Radiographic measurement of bone age is helpful in assessing a child with short stature and delayed or advanced sexual maturation. (See 'Radiologic evaluation' above and "Causes of short stature".)

●Children with obesity – In children with obesity, laboratory studies are sometimes indicated to identify possible endocrine causes of the weight gain, such as hypothyroidism or Cushing's syndrome, or complications of the obesity, such as insulin resistance, hypercholesterolemia, polycystic ovary syndrome, or fatty liver disease (table 3). (See 'Children with obesity' above and "Clinical evaluation of the child or adolescent with obesity".)