Chapter 11: Normal Childhood Nutrition & Its Disorders

NUTRITION & GROWTH

The nutrient requirements of children are influenced by (1) growth rate, (2) body composition, and (3) composition of new growth. These factors vary with age and are especially important during early postnatal life. Growth rates are higher in early infancy than at any other period of life (Table 11–1). Growth rates normally decline rapidly starting in the second month of postnatal life (proportionately later in the preterm infant).

Nutrient requirements also depend on body composition. In the adult, the brain, which accounts for only 2% of body weight, contributes 19% to the total basal energy expenditure. In contrast, in a full-term neonate, the brain accounts for 10% of body weight and for 44% of total energy needs under basal conditions. Thus, in the young infant, total basal energy expenditure and the energy requirement of the brain are relatively high.

Composition of new tissue is a third factor influencing nutrient requirements. For example, fat should account for about 40% of weight gain between birth and 4 months but for only 3% between 24 and 36 months. The corresponding figures for protein are 11% and 21%; for water, 45% and 68%. The high rate of fat deposition in early infancy impacts not only for energy requirements but also for the optimal composition of infant feedings.

Because of the high nutrient requirements for growth and the body composition, the young infant is especially vulnerable to undernutrition. Slowed physical growth is an early and prominent sign of undernutrition in the young infant. The limited fat stores of the very young infant mean that energy reserves are modest. The relatively large size and continued growth of the brain render the central nervous system (CNS) especially vulnerable to the effects of malnutrition in early postnatal life.

ENERGY

The major determinants of energy expenditure are (1) basal metabolism, (2) physical activity, (3) growth, and (4) metabolic response to food. The efficiency of energy use may be a significant factor, and thermoregulation may contribute in extremes of ambient temperature if the body is inadequately clothed. Because adequate data on requirements for physical activity in infants and children are unavailable and because individual growth requirements vary, recommendations have been based on calculations of actual intakes by healthy subjects. Suggested guidelines for energy intake of infants and young children are given in Table 11–2. Also included in this table are calculated energy intakes of infants who are exclusively breast-fed. Weight gain velocity of breast-fed infants during the first 3 months equals and may exceed that of formula-fed infants, but from 6 to 12 months breast-fed infants typically weigh less and lose their body fat more than formula-fed babies and may show a decrease in weight gain velocity. In 2010, the United States adopted the use of the international growth charts developed by The World Health Organization (WHO) for children aged less than 24 months. The WHO charts are growth standards describing the growth of healthy breastfeeding infants under optimal conditions. The use of the WHO charts means that fewer US breastfed infants between the ages of 6 and 18 months will be classified as underweight. (See also section: Pediatric Undernutrition.)

After the first 4 years, energy requirements expressed on a body weight basis decline progressively. The estimated daily energy requirement is about 40 kcal/kg/day at the end of adolescence. Approximate daily energy requirements can be calculated by adding 100 kcal/y to the base of 1000 kcal/day at age 1 year. Appetite and growth are reliable indices of caloric needs in most healthy children, but intake also depends to some extent on the energy density of the food offered. Individual energy requirements of healthy infants and children vary considerably, and malnutrition and disease increase the variability. Preterm infant energy requirements can exceed 120 kcal/kg/day, especially during illness or when catch-up growth is desired.

One method of calculating requirements for malnourished patients is to base the calculations on the ideal body weight (ie, 50th percentile weight-for-length, or weight determined from current height and the 50th percentile body mass index [BMI] for age), rather than actual weight.

PROTEIN

Only amino acids and ammonium compounds are usable as sources of nitrogen in humans. Amino acids are provided through the digestion of dietary protein. Nitrogen is absorbed from the intestine as amino acids and short peptides. Absorption of nitrogen is more efficient from synthetic diets that contain peptides in addition to amino acids. Some intact proteins are absorbed in early postnatal life, a process that may be important in the development of protein tolerance or allergy.

Because there are no major stores of body protein, a regular dietary supply of protein is essential. In infants and children, optimal growth depends on an adequate dietary protein supply. Relatively subtle effects of protein deficiency are now recognized, especially those affecting tissues with rapid protein turnover rates, such as the immune system and the gastrointestinal (GI) mucosa.

Relative to body weight, rates of protein synthesis and turnover and accretion of body protein are exceptionally high in the infant, especially the preterm infant. Eighty percent of the dietary protein requirement of a preterm infant is used for growth, compared with only 20% in a 1-year-old child. Protein requirements per unit of body weight decline rapidly during infancy as growth velocity decreases. The protein content of human milk decreases from 1.4–1.6 g/100 mL in early lactation to 0.8–1.0 g/100 mL at 3–4 months, then to 0.7–0.8 g/100 mL after 6 months, consistent with the normal decline in growth velocity. Recent research suggests that the higher protein content of typical infant formulas (2–2.5g/100 mL) relative to breast milk is associated with excess weight gain. Regarding the sources of protein in complementary foods, more research is needed to compare the effect of various protein sources such as meat, dairy, and plants on the risk of overweight in infants and children.

The recommendations in Table 11–2 are derived chiefly from the Joint FAO/WHO/UNO Expert Committee and are similar to the Recommended Dietary Allowances (RDAs). They deliver a protein intake above the quantity provided in breast milk. The protein intake required to achieve protein deposition equivalent to the in utero rate in very low-birth-weight infants is 3.7–4.0 g/kg/day simultaneously with adequate energy intake. Protein requirements increase in the presence of skin or gut losses, burns, trauma, and infection. Requirements also increase during times of catch-up growth accompanying recovery from malnutrition (~0.2 g of protein per gram of new tissue deposited). Young infants experiencing rapid recovery may need as much as 1–2 g/kg/day of extra protein. By age 1 year, the extra protein requirement is unlikely to be more than 0.5 g/kg/day.

The quality of protein depends on its amino acid composition. Infants require 43% of protein as essential amino acids, and children require 36%. Adults cannot synthesize nine essential amino acids: histidine, isoleucine, leucine, lysine, methionine, phenylalanine, threonine, tryptophan, and valine. Cysteine and tyrosine are considered partially essential because their rates of synthesis from methionine and phenylalanine, respectively, are limited and may be inadequate in infants, the elderly, and those with malabsorption. In young infants, synthetic rates for cysteine, tyrosine, and, perhaps, taurine are insufficient for needs. Taurine, an amino acid used to conjugate bile acids, may also be conditionally essential in infancy. Lack of an essential amino acid leads to weight loss within 1–2 weeks. Wheat and rice are low in lysine, and legumes are low in methionine. Appropriate mixtures of vegetable protein are therefore necessary to achieve high protein quality.

Because the mechanisms for removal of excess nitrogen are efficient, moderate excesses of protein are not harmful and may help to ensure an adequate supply of certain micronutrients. Adverse effects of excessive protein intake may include increased calcium losses in urine and, over a life span, increased loss of renal mass. Excessive protein intake of more than 4 g/kg/day in older children and adolescents may also cause elevated blood urea nitrogen, acidosis, and hyperammonemia, and in the preterm infant more than 6 g/kg/day has caused failure to thrive, lethargy, and fever. Impaired capacity to deaminate proteins from liver insufficiency or to excrete excess nitrogen as urea from renal insufficiency can further limit tolerable protein intake.

LIPIDS

Fats are the main dietary energy source for infants and account for up to 50% of the energy in human milk. Over 98% of breast milk fat is triglyceride (TG), which has an energy density of 9 kcal/g. Fats can be stored efficiently in adipose tissue with a minimal energy cost of storage. This is especially important in the young infant. Fats are required for the absorption of fat-soluble vitamins and for myelination of the CNS. Fat also provides essential fatty acids (EFAs) necessary for brain development, for phospholipids in cell membranes, and for the synthesis of prostaglandins and leukotrienes. The EFAs are polyunsaturated fatty acids, linoleic acid (18:2ω6), and linolenic acid (18:3ω3). Arachidonic acid (20:4ω6) is derived from dietary linoleic acid and is present primarily in membrane phospholipids. Important derivatives of linolenic acid are eicosapentaenoic acid (20:6ω3) and docosahexaenoic acid (DHA, 22:6ω3) found in human milk and brain lipids. Visual acuity and possibly psychomotor development of formula-fed preterm infants is improved in formulas supplemented with DHA (22:6ω3) and ARA (20:4ω6). The benefits of long-chain polyunsaturated fatty acid supplementation in formulas for healthy term infants are unclear (though safety has been established).

Clinical features of EFA omega-6 deficiency include growth failure, erythematous and scaly dermatitis, capillary fragility, increased fragility of erythrocytes, thrombocytopenia, poor wound healing, and susceptibility to infection. The clinical features of deficiency of omega-3 fatty acids are less well defined, but dermatitis and neurologic abnormalities including blurred vision, peripheral neuropathy, and weakness have been reported. Fatty fish are the best dietary source of omega-3 fatty acids. A high intake of fatty fish is associated with decreased platelet adhesiveness and decreased inflammatory response.

Up to 5%–10% of fatty acids in human milk are polyunsaturated, with the specific fatty acid profile reflective of maternal dietary intake. Most of these are omega-6 series with smaller amounts of long-chain omega-3 fatty acids. About 40% of breast milk fatty acids are monounsaturates, primarily oleic acid (18:1), and up to 10% of total fatty acids are medium-chain triglycerides (MCTs) (C₈ and C₁₀) with a calorie density of 7.6 kcal/g. In general, the percentage of calories derived from fat is a little lower in infant formulas than in human milk.

The American Academy of Pediatrics recommends that infants receive at least 30% of calories from fat, with at least 2.7% of total fat as linoleic acid and 1.75% of total fatty acids as linolenic. During at least the first year of life 40%–50% of energy requirements should be provided as fat. Children older than 2 years should be switched gradually to a diet containing approximately 30% of total calories from fat, with no more than 10% of calories from saturated fats.

β-Oxidation of fatty acids occurs in the mitochondria of muscle and liver. Carnitine is necessary for oxidation of the fatty acids, which must cross the mitochondrial membranes as acylcarnitine. Carnitine is synthesized in the human liver and kidneys from lysine and methionine. Carnitine needs of infants are met by breast milk or infant formulas. In the liver, substantial quantities of fatty acids are converted to ketone bodies, which are then released into the circulation as an important fuel for the brain of the young infant.

MCTs are sufficiently soluble that micelle formation is not required for transport across the intestinal mucosa. They are transported directly to the liver via the portal circulation. MCTs are rapidly metabolized in the liver, undergoing β-oxidation or ketogenesis. They do not require carnitine to enter the mitochondria. MCTs are useful for patients with luminal phase defects, absorptive defects, and chronic inflammatory bowel disease. The potential side effects of MCT administration include diarrhea when given in large quantities; high octanoic acid levels in patients with cirrhosis; and, if they are the only source of lipids, deficiency of EFA.

CARBOHYDRATES

The energy density of carbohydrate is 4 kcal/g. Approximately 40% of caloric intake in human milk is in the form of lactose, or milk sugar. Lactose supplies 20% of the total energy in cow’s milk. The percent of total energy in infant formulas from carbohydrate is similar to that of human milk.

The rate at which lactase hydrolyzes lactose to glucose and galactose in the intestinal brush border determines how quickly milk carbohydrates are absorbed. Lactase levels are highest in young infants, and decline with age depending on genetic factors. About 20% of nonwhite Hispanic and black children younger than 5 years have lactase deficiency. White children typically do not develop symptoms of lactose intolerance until they are at least 4 or 5 years of age, while nonwhite Hispanic, Asian American, and black children may develop these symptoms by 2 or 3 years of age. Lactose-intolerant children have varying symptoms depending on the specific activity of their intestinal lactase and the amount of lactose consumed. Galactose is preferentially converted to glycogen in the liver prior to conversion to glucose for subsequent oxidation. Infants with galactosemia, an inborn metabolic disease caused by deficient galactose-1-phosphate uridyltransferase, require a lactose-free diet starting in the neonatal period.

After the first 2 years of life, 50%–60% of energy requirements should be derived from carbohydrates, with no more than 10% from simple sugars as recommended by the WHO, or less than 25 g of sugar added to foods per day as recommended by the American Heart Association in 2016. These dietary guidelines are, unfortunately, not reflected in the diets of North American children, who typically derive 25% of their energy intake from sucrose and less than 20% from complex carbohydrates.

Children and adolescents in North America often consume large quantities of sucrose and high-fructose corn syrup in soft drinks and other sweetened beverages, candy, syrups, sweetened breakfast cereals, and a variety of processed foods. A high intake of these sugars, especially in the form of sweetened beverages, may predispose to obesity and insulin resistance, is a major risk factor for dental caries, and may be associated with an overall poorer quality diet, including high intake of saturated fat. Sucrase hydrolyzes sucrose to glucose and fructose in the brush border of the small intestine. Fructose absorption through facilitated diffusion occurs more slowly than glucose absorption through active transport. Fructose does not stimulate insulin secretion or enhance leptin production. Since both insulin and leptin play a role in regulation of food intake, consumption of fructose (eg, as high-fructose corn syrup) may contribute to increased energy intake and weight gain. Fructose is also easily converted to hepatic TGs, which may be undesirable in patients with insulin resistance/metabolic syndrome and cardiovascular disease risk.

Dietary fiber can be classified in two major types: nondigested carbohydrate (β1–4 linkages) and noncarbohydrate (lignin). Insoluble fibers (cellulose, hemicellulose, and lignin) increase stool bulk and water content and decrease gut transit time. Soluble fibers (pectins, mucilages, oat bran) bind bile acids and reduce lipid and cholesterol absorption. Pectins also slow gastric emptying and the rate of nutrient absorption. Few data regarding the fiber needs of children are available. The Dietary Reference Intakes recommend 14 g of fiber per 1000 kcal consumed. The American Academy of Pediatrics recommends that children older than 2 years consume in grams per day an amount of fiber equal to 5 plus the age in years. Fiber intakes are often low in North America. Children who have higher dietary fiber intakes have been found to consume more nutrient-dense diets than children with low-fiber intakes. In general, higher fiber diets are associated with lower risk of chronic diseases such as obesity, cardiovascular disease, and diabetes.

MAJOR MINERALS

Dietary sources, absorption, metabolism, and deficiency of the major minerals are summarized in Table 11–3. Recommended intakes are provided in Table 11–4.

TRACE ELEMENTS

Trace elements with a recognized role in human nutrition are iron, iodine, zinc, copper, selenium, manganese, molybdenum, chromium, cobalt (as a component of vitamin B₁₂), and fluoride. Information on food sources, functions, and deficiencies of the trace elements is summarized in Table 11–5. Supplemental fluoride recommendations are listed in Table 11–6. Dietary Reference Intakes of trace elements are summarized in Table 11–4. Iron deficiency is discussed in Chapter 30. Recent reviews emphasize the importance of recognizing the risk of iron deficiency without anemia during the first 2 years of life when brain development is rapidly progressing. Testing serum ferritin (and a concurrent marker of inflammation) in older breastfed infants and toddlers with limited dietary iron intake is recommended over checking for anemia (hemoglobin) alone, which identifies severe iron deficiency.

VITAMINS

In general, highly restrictive diets (eg, those in which entire food groups are absent) should prompt consideration of vitamin deficiencies. For example, numerous cases of scurvy have been reported in children with autism who have had markedly constrained diets. Untreated fat-malabsorption syndromes (eg, cystic fibrosis, celiac disease, short gut syndrome) are associated with deficiencies of fat-soluble vitamins. See Table 11–7 for other general circumstances that should prompt assessment for vitamin deficiencies.

Fat-Soluble Vitamins

Because they are insoluble in water, the fat-soluble vitamins require digestion and absorption of dietary fat and a carrier system for transport in the blood. Deficiencies of these vitamins develop more slowly than deficiencies of water-soluble vitamins because the body accumulates stores of the fat-soluble vitamins. Prematurity and some childhood conditions (especially those with fat malabsorption) place children at risk (see Table 11–7). Excessive intakes carry potential for toxicity (Table 11–8). A summary of reference intakes is found in Table 11–9. Dietary sources of fat-soluble vitamins, their absorption/metabolism, and causes and clinical features of deficiency are summarized in Table 11–10. Vitamin deficiency and related diagnostic laboratory findings and treatment are detailed in Table 11–11.

Recent recognition of low levels of 25-OH-vitamin D in a relatively large percentage of the population and the broad range of functions beyond calcium absorption have led many experts including the American Academy of Pediatrics to recommend a daily intake of at least 400 IU (10 mcg)/day for all infants, including those who are breast-fed, beginning shortly after birth.

Water-Soluble Vitamins

Deficiencies of water-soluble vitamins are generally uncommon in the United States because of the abundant food supply and fortification of prepared foods. Cases of deficiencies (eg scurvy) in children with special needs (eg autism) have been reported in the context of sharply restricted diets. Most bread and wheat products are fortified with B vitamins, including the mandatory addition of folic acid to enriched grain products since 1998. Folic acid supplements (400 mcg/day) during the periconceptional period protect against neural tube defects. Dietary intakes of folic acid from natural foods and enriched products are also protective. Biological roles of water-soluble vitamins are listed in Table 11–12. The risk of toxicity from water-soluble vitamins is not as great as that associated with fat-soluble vitamins because excesses are excreted in the urine. However, deficiencies of these vitamins develop more quickly than fat-soluble vitamins because of limited stores, with the exception of vitamin B₁₂. Major dietary sources of the water-soluble vitamins are listed in Table 11–13. Additional salient details are summarized in Tables 11–7, 11–14, and 11–15.

Carnitine is synthesized in the liver and kidneys from lysine and methionine. In certain circumstances (Table 11–14), synthesis is inadequate, and carnitine can then be considered a vitamin. A dietary supply of other organic compounds, such as inositol, may also be required in certain circumstances.

BREAST-FEEDING

Breast-feeding provides optimal nutrition for the normal infant during the early months of life. The WHO recommends exclusive breast-feeding for approximately the first 6 months of life, with continued breast-feeding along with appropriate complementary foods through the first 2 years of life. Numerous immunologic factors in breast milk (including secretory immunoglobulin A [IgA], lysozyme, lactoferrin, bifidus factor, oligosaccharides, and macrophages) provide protection against GI and upper respiratory infections.

In developing countries, lack of refrigeration and contaminated water supplies make formula feeding especially hazardous. Although formulas are made to resemble breast milk, they cannot replicate the nutritional or immune composition of human milk. Additional differences of physiologic importance continue to be identified. Furthermore, breastfeeding can foster the maternal-child bond.

Breast-feeding is the predominant initial mode of feeding young infants in the United States. Unfortunately, breast-feeding rates remain low among several subpopulations, including low-income, minority, and young mothers. Many mothers face obstacles in maintaining lactation once they return to work, and rates of breast-feeding at 6 months are considerably less than the goal of 50%. Use of an electric breast pump can help to maintain lactation when mothers and infants are separated for extended periods.

Absolute contraindications to breast-feeding are rare. They include active tuberculosis (in the mother) and galactosemia (in the infant). Breast-feeding is associated with maternal-to-child transmission of human immunodeficiency virus (HIV), but the risk is influenced by duration and pattern of breast-feeding and maternal factors, including immunologic status and presence of mastitis. Complete avoidance of breast-feeding by HIV-infected women is presently the only mechanism to prevent maternal-infant transmission. HIV-infected mothers in developed countries are recommended to refrain from breast-feeding if safe alternatives are available. In developing countries, the use of antiretroviral therapy (ART) and exclusive breast-feeding is encouraged; if ART is not available, avoidance of breast-feeding may be considered. The protection of the child against diarrheal illness and malnutrition may outweigh the risk of HIV transmission via breast milk. In such circumstances, HIV-infected women should be encouraged to exclusively breast-feed for 6 months. Mixed feeding should be avoided because of the increased risk of HIV transmission.

In newborns less than 1750 g, human milk should be fortified to increase protein, calcium, phosphorus, micronutrient content, and caloric density. Breast-fed infants with cystic fibrosis can be breast-fed successfully if exogenous pancreatic enzymes are provided. All infants with cystic fibrosis should receive supplemental vitamins A, D, E, K, and sodium chloride. Those with growth faltering should receive caloric supplementation.

Support of Breast-Feeding

In developed countries, health professionals play a significant role in supporting and promoting breast-feeding. Perinatal hospital routines and early pediatric care have a great influence on the successful initiation of breast-feeding by promoting prenatal and postpartum education, frequent mother-baby contact, advice about breast-feeding technique, demand feeding, rooming-in, avoidance of bottle supplements, and early follow-up after delivery. Increasing maternal confidence, family support, adequate maternity leave, and advice about common problems such as sore nipples can foster success. Medical providers can follow best practices and advocate for hospital policies that support breast-feeding.

Very few women are physically unable to nurse their babies, but both maternal and/or infant factors can impact successful initiation of nursing and lactogenesis. Mothers with obesity and/or insulin resistance often have delayed lactogenesis, and thus a potential need for additional breastfeeding support to establish successful lactation should be anticipated. The newborn is generally fed ad libitum every 2–3 hours, with longer intervals (4–5 hours) at night. Thus, a newborn infant nurses at least 8–10 times a day, stimulating a generous milk supply. In neonates, a loose stool is often passed with each feeding; later (at age 3–4 months), there may be an interval of several days between stools. Failure to pass several stools a day in the early weeks of breast-feeding suggests inadequate milk intake. Expressing milk using an electric breast pump may be indicated if the mother returns to work or if the infant is preterm, cannot suck adequately, or is hospitalized.

Technique of Breast-Feeding

Breast-feeding can be started as soon as both mother and baby are stable after delivery, ideally within the first 30–60 minutes. Correct positioning and breast-feeding technique are necessary to ensure effective nipple stimulation and breast emptying with minimal nipple discomfort.

To nurse while the mother is sitting, the infant should be held at the height of the breast and turned to face the mother so that their abdomens touch. The mother’s arms supporting the infant should be held tightly at her side, bringing the baby’s head in line with her breast. The breast should be supported by the lower fingers of her free hand, with the nipple compressed between the thumb and index fingers to make it more protractile. When the infant opens its mouth, the mother should quickly insert as much nipple and areola as possible.

The most common cause of early poor weight gain in breast-fed infants is poorly managed mammary engorgement, which rapidly decreases milk supply. Unrelieved engorgement can result from long intervals between feeding, improper infant suckling, a nondemanding infant, sore nipples, maternal or infant illness, nursing from only one breast, and latching difficulties. Poor technique, maternal dehydration, or excessive fatigue can contribute. Some infants may need waking to feed at night. Primary lactation failure occurs in less than 5% of women.

A sensible guideline for duration of feeding is 5 minutes per breast at each feeding the first day, 10 minutes on each side at each feeding the second day, and 10–15 minutes per side thereafter. A vigorous infant can obtain most of the available milk in 5–7 minutes, but additional sucking time ensures breast emptying, promotes milk production, and satisfies the infant’s sucking urge. The side on which feeding is commenced should be alternated. The mother may break suction gently after nursing by inserting her finger between the baby’s gums.

Follow-up

Assessment before discharge should identify dyads needing additional support. All mother-infant pairs require early follow-up. The second through fourth days postpartum when milk secretion becomes copious is a critical time. Failure to empty the breasts during this time can cause engorgement, which quickly leads to diminished milk production.

Common Problems

Nipple tenderness requires attention to proper positioning of the infant and correct latch-on. Nursing for shorter periods, beginning feedings on the less sore side, air drying the nipples well after nursing, and use of lanolin cream may provide relief. Severe nipple pain and cracking usually indicate improper latch. Temporary pumping may be needed.

Breast-feeding jaundice is exaggerated physiologic jaundice associated with low intake of breast milk, infrequent stooling, and poor weight gain (see Chapter 2). If possible, the jaundice should be managed by increasing the frequency of nursing and, if necessary, augmenting the infant’s sucking with regular breast pumping. Supplemental feedings may be necessary, but care should be taken not to decrease breast milk production further.

In a small percentage of breast-fed infants, hyperbilirubinemia with jaundice is caused by an unidentified property of the milk that inhibits conjugation of bilirubin. In severe cases, interruption of breast-feeding for 24–36 hours may be necessary. The mother’s breast should be emptied with an electric breast pump during this period.

The symptoms of mastitis include flu-like symptoms with breast tenderness, firmness, and erythema. Antibiotic therapy covering β-lactamase–producing organisms should be given for 10 days. Analgesics may be necessary, but breast-feeding should be continued. Breast pumping may be helpful adjunctive therapy.

Maternal Drug Use

Factors playing a role in the transmission of drugs in breast milk include the route of administration, dosage, molecular weight, pH, and protein binding. Generally, any drug prescribed to a newborn can be consumed by the breast-feeding mother without ill effect. Very few drugs are absolutely contraindicated in breast-feeding mothers; these include radioactive compounds, antimetabolites, lithium, diazepam, chloramphenicol, antithyroid drugs, and tetracycline. For up-to-date information, a regional drug center should be consulted.

Maternal use of illicit or recreational drugs may be a contraindication to breast-feeding, but the risks to the infant should be balanced by the benefits of milk and breast-feeding. Expression of milk for a feeding or two after use of a drug is not an acceptable compromise. The breast-fed infants of mothers taking methadone alone as part of a treatment program have generally not experienced ill effects when the dose is less than 40 mg/day.

Nutrient Composition

The nutrient composition of human milk is compared to that of cow’s milk and formulas in Table 11–16. Outstanding characteristics include (1) lower but highly bioavailable protein content, which is adequate for the normal infant; (2) generous quantity of EFAs; (3) long-chain polyunsaturated fatty acids, of which DHA is thought to be especially important; (4) relatively low sodium and solute load; and (5) lower concentration of highly bioavailable minerals, which are adequate for the needs of normal breast-fed infants for approximately 6 months.

Complementary Feeding

The AAP and the WHO recommend the introduction of solid foods in normal infants at about 6 months of age. Fortified cereals, fruits, vegetables, and meats should complement the breast milk diet. Meats are an important source of iron and zinc, both of which are low in human milk by 6 months. Pureed meats may be introduced as an early complementary food. Single-ingredient complementary foods are introduced one at a time at 3- to 4-day intervals before a new food is given. Fruit juice is not necessary, and if given should be in a cup, not a bottle, and less than 4 oz/day. Whole cow’s milk can be introduced after the first year of life. Breast-feeding should ideally continue for at least 12 months.

While breast milk, dairy, soy, legume, and other vegetable sources of protein can provide adequate protein for growth, vegetarian foods are impractical as sources of iron or zinc. A vegetarian diet places older breastfed infants and toddlers at risk for iron and zinc deficiency because of their high requirements during rapid growth and because animal-based foods are best sources of these nutrients. To meet requirements, infants and toddlers consuming vegetarian diets should be offered fortified foods, including cereals and formula or daily supplementation of iron and zinc. A vegan diet that omits all animal protein sources will require supplementation of vitamin B₁₂ as well. Guidance from a pediatric registered dietitian is suggested for families seeking for their infant or toddler to follow a vegetarian or vegan diet to ensure adequate protein, calorie, vitamin, and micronutrient intakes.

Results of recent large-scale randomized controlled trials have shifted recommended practice around peanut consumption in infancy by the AAP and National Institute of Allergy and Infectious Diseases (NIAID). For infants with severe eczema or egg allergy but without evidence of active peanut sensitization by skin prick test or specific peanut IgE, introduction of 6–7 g/wk of peanut protein served as a puree is recommended beginning at 4–6 months to reduce the risk of peanut allergy. Infants with less severe eczema are recommended to start consuming peanut purees around 6 months. Furthermore, it was the expert opinion of the NIAID panel that infants without risk factors for food allergy should have age appropriate peanut-containing products introduced into the diet with other purees and solid foods in a manner consistent with familial and cultural norms.

SPECIAL DIETARY PRODUCTS FOR INFANTS

Soy Protein Formulas

The medical indications for soy formulas are rare: galactosemia and hereditary lactase deficiency. Soy formulas provide an option when a vegetarian diet is preferred. Soy protein formulas are often used in cases of suspected intolerance to cow’s milk protein, though cow’s milk hydrolysate formulas are preferred because 30%–40% of infants intolerant to cow’s milk protein will also react to soy protein. In contrast to this T-cell–mediated protein intolerance, those infants with less commonly documented IgE-mediated allergy to cow’s milk protein do not typically cross-react to soy formula. The estrogenic properties of isoflavones from soy had raised concern about potential reproductive system effects, but an Expert Committee of the National Toxicology program found minimal concern for potential harm in their 2011 report.

Semi-elemental & Elemental Formulas

Semi-elemental formulas include protein hydrolysate formulas. The major nitrogen source of most of these products is casein hydrolysate, supplemented with selected amino acids, but partial hydrolysates of whey are also available. These formulas contain an abundance of EFA from vegetable oil; certain brands also provide substantial amounts of MCTs. Elemental formulas are available with free amino acids and varying levels and types of fat components.

Semi-elemental and elemental formulas are invaluable for infants with malabsorption syndromes. They are also effective in infants who cannot tolerate cow’s milk and soy protein. Controlled trials suggest that for infants with a family history of atopic disease, partial hydrolysate formulas may delay or prevent atopic disease compared to standard cow milk protein-based formula.

Formula Additives

Occasionally, it may be necessary to increase the caloric density of an infant feeding to provide more calories or to restrict fluid intake. Concentrating formula to 24–26 kcal/oz is usually well tolerated, delivers an acceptable renal solute load, and increases the density of all the nutrients. Beyond this, individual macronutrient additives (Table 11–17) are usually employed to achieve the desired caloric density (up to 30 kcal/oz) based on the infant’s needs and underlying condition(s). A pediatric dietitian can provide guidance in formulating calorically dense infant formula feedings. The caloric density of breast milk can be increased by adding infant formula powder or any of the additives used with infant formula. Because of their specialized nutrient composition, human milk fortifiers are generally used only for preterm infants.

Special Formulas

Special formulas are those in which one component, often an amino acid, is reduced in concentration or removed for the dietary management of a specific inborn metabolic disease. Also included under this heading are formulas designed for specific disease states, such as hepatic failure, pulmonary failure with chronic carbon dioxide retention, and renal failure. These condition-specific formulas were formulated primarily for critically ill adults and are used sparingly in those populations; thus, they should be used in pediatrics only with clear indication and caution.

Complete information regarding the composition of formulas can be found in reference texts and in the manufacturers’ literature.

Because diet impacts the development of chronic diseases such as diabetes, obesity, and cardiovascular disease, learning healthy eating behaviors at a young age is an important preventative measure.

Salient features of the diet for children older than 2 years include the following:

1. Three regular meals per day, and one or two healthful snacks.

2. A variety of foods: diet should be nutritionally complete and promote optimal growth and activity.

3. Fat less than 35% of total calories (severe fat restriction < 10% may result in an energy deficit and growth failure). Saturated fats should provide less than 10% of total calories. Monounsaturated fats should provide 10% or more of caloric intake. Trans-fatty acids should provide less than 1% of total calories.

4. Cholesterol intake less than 100 mg/1000 kcal/day, to a maximum of 300 mg/day.

5. Carbohydrates should provide 45%–65% of daily caloric intake, less than 10% in the form of simple sugars. A high-fiber, whole-grain–based diet is recommended.

6. Limitation of grazing behavior, eating while watching television, and the consumption of soft drinks and other sweetened beverages.

7. Limitation of sodium intake by limiting processed foods and added salt.

8. Consumption of lean cuts of meats, poultry, and fish should be encouraged. Skim or low-fat milk, and vegetable oils (especially canola or olive oil) should be used. Plentiful amounts of fruits and vegetables are recommended. The consumption of processed foods, sugar-sweetened drinks, desserts, and candy should be limited. The American Academy of Pediatrics has endorsed use of low-fat milk in children after 12 months of age.

Lifestyle counseling for children should also include maintenance of a BMI in the healthy range; regular physical activity, limiting sedentary behaviors; avoidance of smoking; and screening for hypertension starting at age 3 years. Current recommendations from the National Heart Lung and Blood Institute are to routinely screen all children for familial hyperlipidemia using a fasting or non-fasting lipid panel once at age 9–11, and to consider screening children at younger ages who have additional risk factors (obesity, diabetes, family history of preterm cardiovascular disease). The preferred time for screening occurs before puberty, a period in which hormonal changes render lipids unreliable in predicting levels in adulthood.

PEDIATRIC UNDERNUTRITION

General Considerations

Pediatric undernutrition is usually multifactorial in origin, and successful treatment depends on accurate identification and management of those factors. The terms “organic” and “nonorganic” failure to thrive, though still used by many medical professionals, are not helpful because any systemic illness or chronic condition can cause growth impairment and yet may also be compounded by psychosocial problems.

Clinical Findings

A. Definitions

Failure to thrive is an imprecise term used to describe growth faltering in infants and young children whose weight curve has fallen by two major percentile channels from a previously established rate of growth, or whose weight for length falls below the 5th percentile (see Chapter 9). The WHO growth charts (http://www.who.int/childgrowth/en/) should be used for all infants less than 24 months as these charts reflect the slower velocity of weight gain for healthy breast-fed infants without formula supplementation. Differences in weight gain are particularly notable after 6 months of age. The acute loss of weight, or failure to gain weight at the expected rate, produces a condition of reduced weight for height known as wasting. The reduction in height for age, as is seen with more chronic malnutrition, is termed stunting.

The typical pattern for mild pediatric undernutrition is decreased weight, with normal height and head circumference. In more chronic malnutrition, linear growth will slow relative to the standard for age, although this should also prompt consideration of nonnutritional etiologies. The term severe acute malnutrition (SAM) has generally replaced the term protein energy malnutrition. SAM is used to describe children with severe wasting called marasmus (< 3 SD weight for height) and Kwashiorkor, also known as edematous malnutrition. Significant protein deprivation, possibly with additional insults such as infection, may produce kwashiorkor.

B. Risk Factors

Multiple medical conditions can cause pediatric undernutrition, and a thorough discussion is beyond the scope of this chapter. However, the most common cause is inadequate dietary intake. In young infants, a weak or uncoordinated suck may be the causative factor. Congenital heart disease, breathing problems (eg, laryngomalacia), and other physical problems that may interfere with normal feeding. Inappropriate formula mixing or a family’s dietary beliefs may lead to hypocaloric or unbalanced dietary intakes. Diets restricted because of suspected food allergies or intolerances may result in inadequate intake of calories, protein, or specific micronutrients. Deficiencies of iron or zinc occur in older breast-fed infants whose diets are low in meats or fortified foods, and in toddlers not taking fortified formula or not consuming good dietary sources. Cases of severe malnutrition and kwashiorkor have occurred in infants of parents who substitute milk alternatives (eg, rice, hemp, or almond milk or unfortified soy milk) for infant formula. Such plant source “milks” are hypocaloric, provide an incomplete protein source (ie, low in quality and quantity of protein), and are not adequately fortified with all essential micronutrients to meet infant requirements.

C. Assessment

1. Measurement of weight for age; length/height for age; occipital frontal circumference (OFC) for age (for < 2 years age), weight for length; and calculation of percent ideal body weight (current weight/median weight [50th percentile] for current length). Assess for downward crossing of growth percentiles (acute malnutrition) and for linear growth stunting (chronic malnutrition).

2. History should include details of diet intake and feeding patterns (including restrictive intake, grazing feeding pattern, inappropriate foods for age and development, excessive juice, sugar-sweetened beverages, or water intake); past medical history, including birth and developmental history; family history; social history; and review of systems.

3. Physical examination should include careful examination of skin (for rashes), mouth, eyes, nails, and hair for signs of micronutrient and protein deficiencies, as well as for abnormal neurologic function (eg, loss of deep tendon reflexes, abnormal strength and tone).

4. Laboratory studies are generally of low yield for diagnosis of growth faltering in the absence of other findings, and should be reserved for moderately severe cases of malnutrition. In such cases, risk of and suspicion for nutrient deficiencies and systemic pathology should guide studies ordered. Typical screening laboratories include chemistry panel; complete blood count; and iron panel, including ferritin (and marker of inflammation, eg, CRP or ESR). Thyroid function testing is indicated with linear growth faltering. Serology for celiac disease may also be warranted for toddlers, especially with short stature or linear growth faltering. Guidelines for screening for inborn errors of metabolism are available.

5. Some infants are naturally small and have weight for age percentile values below the 5th percentile and may have length and head circumferences at higher percentiles. Such infants are often called “constitutionally small,” as their thinness was present from birth, there was no evidence of intrauterine growth restriction, their mothers had small stature and usually thinness, and the family growth pattern is similar. Mothers of such normally small children should not be discouraged from breast-feeding and should not be counseled to prematurely add food supplements. Workup for failure to thrive is not indicated in these infants and evaluations or referrals for growth failure or child neglect from underfeeding are not warranted.

Refeeding syndrome may occur with nutritional rehabilitation of infants or children with SAM. It is important to monitor for hypophosphatemia, hypokalemia, hypomagnesemia, and hyperglycemia for the first roughly 3–4 days in which caloric intake is advanced to the goal desired for weight gain during nutritional rehabilitation (until stable). Calorie intake should be increased slowly to avoid metabolic instability. More frequent monitoring of electrolytes may be needed if significant amounts of IV dextrose or TPN are used during the initial rehabilitation of a severely malnourished child, and enteral feeding is preferred when possible.

Treatment

Poor eating is often a learned behavior. Families should be counseled regarding choices of foods that are appropriate for the age and developmental level of the child. Increasing the caloric density of foods is associated with increased daily caloric intake and improved weight gain. Food sources should contain both fat and protein to achieve repletion of both lean body mass and fat stores. Micronutrient deficiencies should be corrected. For repletion of iron, 3–6 mg/kg/day, divided BID, can be initiated if acute inflammation has been excluded. Acute inflammation should be allowed to resolve prior to initiating iron supplementation. For zinc, 1 mg/kg/day for 1–2 months, ideally administered several hours apart from iron supplement, is typically adequate. Children should have structured meal times (eg, three meals and two to three snacks during the day), ideally at the same time other family members eat. Consultation with a pediatric dietitian can be helpful for educating the family. Poor feeding may be related to family dysfunction. Children whose households are chaotic and children who are abused, neglected, or exposed to poorly controlled mental illness may be described as poor eaters, and may fail to gain. Careful assessment of the social environment of such children is critical, and disposition options may include support services, close medical follow-up visits, family counseling, and even foster placement while a parent receives therapy.

PEDIATRIC OVERWEIGHT & OBESITY

General Considerations

The prevalence of childhood and adolescent obesity has increased rapidly in the United States and many other parts of the world. Currently in the United States, 18.5% of 2–19-year-olds have obesity, with even higher rates among subpopulations of minority and economically disadvantaged children. The increasing prevalence of childhood obesity is related to a complex combination of socioeconomic, epigenetic, and biologic factors.

Childhood obesity, especially when severe, is associated with significant comorbidities. The probability of obesity persisting into adulthood has been estimated to increase from 20% at 4 years to 80% by adolescence. Rates of persistence from early childhood are much higher when one or both parents have obesity. Obesity is associated with cardiovascular and endocrine abnormalities (eg, dyslipidemia, insulin resistance, and type 2 diabetes), orthopedic problems, pulmonary complications (eg, obstructive sleep apnea), and mental health problems (Table 11–18).

Clinical Findings

A. Definitions

BMI is the standard measure of obesity in adults and children. BMI is correlated with more accurate measures of body fatness and is calculated with readily available information: weight and height (kg/m²). Routine plotting of the BMI on age- and gender-appropriate charts (http://www.cdc.gov/growthcharts) can identify those with excess weight. BMI between the 85th and 95th percentiles for age and sex identifies those who are overweight. Obesity is defined as BMI at or above the 95th percentile and is associated with increased risk of secondary complications. Severe obesity is characterized by BMI for age and sex at or above the 99th percentile and is associated with greatly increased risk of comorbidity. An alternate definition of severe obesity recommended by the American Heart Association numerically approximates the 99th percentile, but provides a framework for clinicians to better gauge progress for children with severe obesity. This standard defines severe obesity class 2 as above 120% of the 95th percentile for a given age and gender, and severe obesity class 3 as above 140% of the 95th percentile. The degree of obesity as a percent of the 95th percentile can be tracked on special growth charts created for this purpose. An upward change in BMI percentiles in any range should prompt evaluation and possible treatment. For children younger than 2 years, weight for length greater than 95th percentile indicates overweight and warrants further assessment, especially of energy intake and feeding behaviors.

B. Risk Factors

There are multiple risk factors for developing obesity, reflecting the complex relationships between genetic and environmental factors. Family history is a strong risk factor. Parental obesity, especially in both parents, strongly increases the odds of a child becoming an obese adult.

Risk factors in the home environment offer targets for intervention. Consumption of sugar-sweetened beverages, lack of family meals, large portion sizes, foods prepared outside the home, television viewing, video gaming, poor sleep, and lack of activity are all associated with risk of excessive weight gain.

C. Assessment

Early recognition of rapid weight gain or high-risk behaviors is important. Anticipatory guidance or intervention earlier in childhood and before weight gain becomes severe is more likely to be successful than delayed intervention. Routine evaluation at well-child visits should include the following:

1. Measurement of weight and height, calculation of BMI, and plotting on age- and sex-appropriate growth charts (http://www.cdc.gov/growthcharts). Evaluate for upward crossing of BMI percentile channels.

2. History regarding diet and activity patterns (Table 11–19); family history, and review of systems. Physical examination should include blood pressure measurement, distribution of adiposity (central vs generalized); markers of comorbidities, such as acanthosis nigricans, hirsutism, hepatomegaly, orthopedic abnormalities; and physical stigmata of genetic syndromes (eg, Prader-Willi syndrome).

3. Laboratory studies are recommended as follows for children beginning by age 10 years or at onset of puberty. Consider testing at younger ages with severe obesity but not younger than 2 years:

   • Overweight with personal or family history of heart disease risk factors—fasting lipid profile, fasting glucose and/or hemoglobin A_1c, alanine aminotransferase (ALT).

   • Obese—fasting lipid profile, fasting glucose and/or hemoglobin A_1c, ALT.

   • Other studies should be guided by findings in the history and physical.

Treatment

Treatment should be based on risk factors, including age, severity of obesity, and comorbidities, as well as family history. For children with uncomplicated obesity, the primary goal is to achieve healthy eating and activity patterns, not necessarily to achieve ideal body weight. For children with a secondary complication, improvement of the complication is an important goal. In general, weight goals for children with obesity range from weight maintenance to up to 1 lb/mo weight loss for those younger than 12 years, and up to 2 lb/wk for those older than 12 years. More rapid weight loss should be monitored for pathologic causes that may be associated with nutrient deficiencies and linear growth stunting (Table 11–20).

Treatment focused on behavior changes in the context of family involvement has been associated with sustained weight loss and decreases in BMI. Clinicians should assess the family’s readiness to take action. Motivational interviewing is effective in the treatment of excess weight gain in children. This form of counseling uses open-ended questioning and reflective statements to explore and resolve ambivalence toward change, and accepts resistance nonjudgmentally. Providers should engage the family in collaborative decision-making about which behavior change goals will be targeted. Improving dietary habits and activity levels concurrently is desirable for successful weight management. The entire family should adopt healthy eating patterns, with parents modeling healthy food choices, controlling foods brought into the home, and guiding appropriate portion sizes. The American Academy of Pediatrics recommends very limited screen time for children younger than 2 years, a maximum of 2 h/day of television and video games for older children, with lower levels recommended for children during attempts at BMI reduction.

A “staged approach” for treatment has been proposed, with the initial level depending on the severity of overweight, the age of the child, the readiness of the family to implement changes, the preferences of the parents and child, and the skills of the health care provider. The U.S. Preventive Services Task Force has identified that interventions most likely to be successful for childhood obesity treatment are intensive, with 25 or more contact hours.

1. Prevention plus: Counseling regarding problem areas identified by screening questions (see Table 11–19); emphasis on lifestyle changes, including healthy eating and physical activity patterns.

2. Structured weight management: Provides more specific and structured dietary pattern, such as meal planning, exercise prescription, and behavior change goals. This may be done in the primary care setting. Generally, referral to at least one ancillary health professional will be required: dietitian, behavior specialist, and/or physical therapist. Monitoring is monthly or tailored to patient and family’s needs.

3. Comprehensive multidisciplinary: This level further increases the structure of therapeutic interventions and support, employs a multidisciplinary team, and may involve weekly group meetings.

4. Tertiary care intervention: This level is for patients who have not been successful at the other intervention levels or who have severe obesity. Interventions are prescribed by a multidisciplinary team, and may include intensive behavior therapy, specialized diets, medications, and surgery.

Pharmacotherapy can be an adjunct to dietary, activity, and behavioral treatment. Orlistat, a lipase inhibitor, is approved for patients older than 12 years, but other medications approved for use in adults are used off-label by providers who have expertise in obesity medicine. Bariatric surgery is performed in some centers for adolescents with severe obesity. In carefully selected and closely monitored patients, surgery can result in significant weight loss with a reduction or resolution of comorbidities, including type 2 diabetes, more frequently than in adults undergoing the same surgery.

ENTERAL

Indications

Enteral nutrition support is indicated when a patient cannot adequately meet nutritional needs by oral intake alone and has a functioning GI tract. This method of support can be used for short- and long-term delivery of nutrition. Even when the gut cannot absorb 100% of nutritional needs, some enteral feedings should be attempted. Enteral nutrition, full or partial, has many benefits:

1. Maintaining gut mucosal integrity

2. Preserving gut-associated lymphoid tissue

3. Stimulating gut hormones and bile flow

Access Devices

Nasogastric feeding tubes can be used for supplemental enteral feedings, but generally are not used for more than 3 months because of the complications of otitis media and sinusitis. Initiation of nasogastric feeding usually requires a brief hospital stay to ensure tolerance to feedings and to allow for parental instruction in tube placement and feeding administration.

If long-term feeding support is anticipated, a more permanent feeding device, such as a gastrostomy tube, may be considered. Referral to a home care company is necessary for equipment and other services such as nursing visits and dietitian follow-up.

Table 11–21 suggests appropriate timing for initiation and advancement of drip and bolus feedings, according to a child’s age. Clinical status and tolerance to feedings should ultimately guide their advancement.

Monitoring

Monitoring the adequacy of enteral feeding depends on nutritional goals. For critically ill patients in the intensive care unit, provision of enteral nutrition in the first 48 hours is associated with lower mortality. Even when calorie and protein goals cannot be met, provision of more than 60% protein goals enterally is associated with lower odds of mortality in mechanically ventilated children. Evaluating normal growth parameters in critically ill infants and children can be skewed by fluid status changes and loss of muscle mass. While weight and linear growth must still be followed, other measures such as mid-arm muscle circumference may provide another measure to assess nutritional adequacy. Frequent assessment of anthropometrics, medical status changes, biochemical indices, and tolerance to enteral feeds with documentation of delivered nutrition intake versus goal intake is essential in managing this nutritionally challenging population.

For more stable hospitalized young infants and malnourished children, growth data should be regularly obtained and evaluated based on age appropriate growth charts. Hydration status should be assessed carefully at the initiation of enteral feeding and regularly thereafter. Either constipation or diarrhea can be problems, and attention to stool frequency, volume, and consistency can help guide management. When diarrhea occurs, factors such as infection, hypertonic enteral medications, antibiotic use, and alteration in normal gut flora should be addressed.

In medically stable patients, the enteral feeding schedule should be developmentally appropriate (eg, 5–6 small feedings/day for a toddler). When night drip feedings are used in conjunction with daytime feeds, it is suggested that less than 50% of goal calories be delivered at night so as to maintain a daytime sense of hunger and satiety. This will be especially important once a transition to oral intake begins.

PARENTERAL NUTRITION

Indications

A. Peripheral Parenteral Nutrition

Peripheral parenteral nutrition is indicated when complete enteral feeding is temporarily impossible or undesirable. Short-term partial intravenous (IV) nutrition via a peripheral vein is a preferred alternative to administration of dextrose and electrolyte solutions alone. Because of the osmolality of the solutions required, it is usually impossible to achieve total calorie and protein needs with parenteral nutrition via a peripheral vein.

B. Total Parenteral Nutrition

Total parenteral nutrition (TPN) should be provided only when clearly indicated. Apart from the expense, numerous risks are associated with this method of feeding (see the section Complications). Even when TPN is indicated, every effort should be made to provide at least a minimum of nutrients enterally to help preserve the integrity of the GI mucosa and of GI function.

The primary indication for TPN is the loss of function of the GI tract that prohibits the provision of required nutrients by the enteral route. Important examples include short bowel syndrome, some congenital defects of the GI tract, and prematurity.

In recent years, a number of injectable essential nutrients have been in short supply in the US pharmaceutical market. Shortages have included IV lipids, multivitamins mixtures, and trace minerals. Deficiencies of these micronutrients have led to significant medical morbidity. Nutrition support teams should develop clinical guidelines to ensure injectable micronutrients are available for those patients who have the greatest need, for example, preterm infants and children with long-term dependence upon TPN. Policies to promote use of enteral micronutrient preparations can also help to reduce the reliance on parenteral supplies. National recommendations for the management of IV essential nutrient shortages are available from the American Society for Parenteral and Enteral Nutrition (ASPEN): http://www.nutritioncare.org/News/Product_Shortages/Parenteral_Nutrition_Multivitamin_Product_Shortage_Considerations/.

Catheter Selection & Position

An indwelling central venous catheter is preferred for long-term IV nutrition. For periods of up to 3–4 weeks, a percutaneous central venous catheter threaded into the superior vena cava from a peripheral vein can be used. For the infusion of dextrose concentrations higher than 12.5%, the tip of the catheter should be located in the superior vena cava. Catheter positioning in the right atrium has been associated with complications, including arrhythmias and thrombus. After placement, a chest radiograph must be obtained to check catheter position. If the catheter is to be used for nutrition and medications, a double-lumen catheter is preferred.

Complications

A. Mechanical Complications

1. Related to catheter insertion or to erosion of catheter through a major blood vessel: Complications include trauma to adjacent tissues and organs, damage to the brachial plexus, hydrothorax, pericardial effusion with potential cardiac tamponade, pneumothorax, hemothorax, and cerebrospinal fluid penetration. The catheter may slip during dressing or tubing changes, or the patient may manipulate the line.

2. Clotting of the catheter: Addition of heparin (1000 U/L) to the solution is an effective means of preventing this complication. If an occluded catheter does not respond to heparin flushing, recombinant tissue plasminogen activator may be effective.

3. Related to composition of infusate: Calcium phosphate precipitation may occur if excess amounts of calcium or phosphorus are administered. Factors that increase the risk of calcium phosphate precipitation include increased pH and decreased concentrations of amino acids. Precipitation of medications incompatible with TPN or lipids can also cause clotting.

B. Septic Complications

Septic complications are the most common cause of nonelective catheter removal, but strict use of aseptic technique and limiting entry into the catheter can reduce the rates of line sepsis. Fever over 38–38.5°C in a patient with a central catheter should be considered a line infection until proved otherwise. Cultures should be obtained and IV antibiotics empirically initiated. Removing the catheter may be necessary with certain infections (eg, fungal), and catheter replacement may be deferred until infection is treated.

C. Metabolic Complications

Many of the metabolic complications of IV nutrition are related to deficiencies or excesses of nutrients in administered fluids, whereas uncommon, specific deficiencies still occur, especially in the preterm infant. Safe and effective IV nourishment requires attention to the nutrient balance, electrolyte composition, and delivery rate of the infusate and careful monitoring, especially when the composition or delivery rate is changed. The most challenging metabolic complication is cholestasis, particularly common in preterm infants of very low birth weight with prolonged feeding intolerance, infants with congenital gut disorders requiring surgery, such as those with gastroschisis, and infants with short gut syndrome following surgical resections for disorders such as necrotizing enterocolitis. See discussion on parenteral nutrition-associated cholestasis (PNAC) in Chapter 22 for details.

NUTRIENT REQUIREMENTS & DELIVERY

Energy

When patients are fed intravenously, no fat and carbohydrate intakes are unabsorbed, and no energy is used in nutrient absorption. These factors account for at least 7% of energy in the diet of the enterally fed patient. The intravenously fed patient usually expends less energy in physical activity. Average energy requirements may therefore be lower in children fed intravenously, by a total of 10%–15%. Caloric guidelines for the IV feeding of infants and young children are outlined below.

The guidelines are averages, and individuals vary considerably. Factors significantly increasing the energy requirement estimates include exposure to cold environment, fever, sepsis, burns, trauma, cardiac or pulmonary disease, and catch-up growth after malnutrition.

With few exceptions, such as some cases of respiratory insufficiency, at least 50%–60% of energy requirements are provided as glucose. Up to 40% of calories may be provided by IV fat emulsions.

Dextrose

The energy density of IV dextrose (monohydrate) is 3.4 kcal/g. Dextrose is the main energy source provided by total IV feeding. IV dextrose suppresses gluconeogenesis and can be oxidized directly, especially by the brain, red and white blood cells, and wounds. Because of the high osmolality, concentrations of dextrose greater than 10%–12.5% cannot be delivered via a peripheral vein or improperly positioned central line.

Dosing guidelines: The standard initial quantity of dextrose administered will vary by age (Table 11–22). Tolerance to IV dextrose normally increases rapidly due to suppression of hepatic glucose production. Dextrose can be increased by 2.5 g/kg/day, by 2.5%–5%/day, or by 2–3 mg/kg/min/day if there is no glucosuria or hyperglycemia. Standard final infusates for infants via a properly positioned central venous line usually range from 15% to 25% dextrose, though concentrations of up to 30% dextrose may be used at low flow rates. Tolerance to IV dextrose loads is markedly diminished in the preterm neonate and in hypermetabolic states.

Problems associated with IV dextrose administration include hyperglycemia, hyperosmolality, and glucosuria (often with osmotic diuresis and dehydration). Possible causes of hyperglycemia include the following: (1) inadvertent infusion of higher dextrose rates than ordered and achieving higher glucose concentrations than desired, (2) uneven flow rate, (3) sepsis, (4) a stress situation (including administration of catecholamines or corticosteroids), and (5) pancreatitis. If these causes have been addressed and severe hyperglycemia persists, use of insulin may be considered. IV insulin reduces hyperglycemia by suppressing hepatic glucose production and increasing glucose uptake by muscle and fat tissues. It usually increases plasma lactate concentrations, but does not necessarily increase glucose oxidation rates; it may also decrease the oxidation of fatty acids, resulting in less energy for metabolism. Use of IV insulin also increases the risk of hypoglycemia. Furthermore, excessive dextrose infusion paired with insulin infusion can exceed mitochondrial oxidation capacity, produce excess reactive oxidation species leading to cell death and inflammation. Intensive care management strategies that promote enteral feeding and reduce IV dextrose exposure have improved outcomes for critically ill patients. Hence, insulin should be used very cautiously and enteral feeding is strongly preferred. A standard IV dose is 1 U/4 g of carbohydrate, but much smaller quantities may be adequate and, usually, one starts with 0.2–0.3 U/4 g of carbohydrate.

Hypoglycemia may occur after an abrupt decrease in or cessation of IV glucose. When cyclic IV nutrition is provided, the IV glucose load should be decreased steadily for 1–2 hours prior to discontinuing the infusion. If the central line must be removed, the IV dextrose should be tapered gradually over several hours.

Oxidation rates for infused dextrose decrease with age. It is important to note that the ranges for dextrose administration provided in Table 11–22 are guidelines and that individual patients may require either less or more dextrose. Quantities of dextrose in excess of maximal glucose oxidation rates are used initially to replace depleted glycogen stores; hepatic lipogenesis occurs thereafter. Excess hepatic lipogenesis may lead to a fatty liver (steatosis). Lipogenesis produces carbon dioxide, as does glucose oxidation. Thus, excess dextrose may elevate the PaCO₂ and aggravate respiratory insufficiency or impede weaning from a respirator.

Lipids

The energy density of 20% lipid emulsions is 10 kcal/g of lipid or 2 kcal/mL. Intravenous lipid emulsions can be plant based or fish oil based. Plant-based lipids are derived from either soybean or safflower oil and consist of more than 50% linoleic acid and 4%–9% linolenic acid. This high level of linoleic acid is not ideal due to the proinflammatory potential of omega-6 fatty acids, except when small quantities of lipid are being given to prevent an EFA deficiency. Further disadvantages of soy-based lipid emulsions include phytosterols that contribute to hepatic inflammation and less biologically active Vitamin E. An alternative lipid emulsion recently approved for use in the United States is SMOFlipid, which is composed of 30% Soybean oil, 30% Medium-chain triglycerides, 25% Olive oil, and 15% Fish oil. The addition of fish oil increases the amount of omega-3 fatty acids and decreases inflammatory potential, as does the addition of Vitamin E. The only available lipid emulsion composed of 100% fish oil is Omegaven. It is not recommended for use as a monotherapy. Recent research indicates favorable outcomes associated with the use of SMOFlipid including a decreased incidence of TPN-induced liver injury. Because 10% and 20% lipid emulsions contain the same concentrations of phospholipids, a 10% solution delivers more phospholipid per gram of lipid than a 20% solution. Twenty percent lipid emulsions are preferred. IV lipid is often used to provide 30%–40% of calorie needs for infants and up to 30% of calorie needs in older children and teens.

Lipoprotein lipase (LPL) activity is the rate-limiting factor in the metabolism and clearance of fat emulsions from the circulation. LPL activity is inhibited or decreased by malnutrition, leukotrienes, immaturity, growth hormone, hypercholesterolemia, hyperphospholipidemia, and theophylline. LPL activity is enhanced by glucose, insulin, lipid, catecholamines, and exercise. Heparin releases LPL from the endothelium into the circulation and enhances the rate of hydrolysis and clearance of TGs. In small preterm infants, low-dose heparin infusions may increase tolerance to IV lipid emulsion.

In general, adverse effects of IV lipid can be avoided by starting with modest quantities and advancing cautiously in light of results of TG monitoring and clinical circumstances. Monitoring TGs is particularly important in cases of severe sepsis. It should continue periodically with long-term use.

IV lipid dosing guidelines: Check serum TGs before starting and after increasing the dose. Commence with 1 g/kg/day, given over 12–20 hours or 24 hours in small preterm infants. Advance by 0.5–1.0 g/kg/day, every 1–2 days, up to goal (see Table 11–22). As a general rule, do not increase the dose if the serum TG level is above 400 mg/dL during infusion or if the level is greater than 250 mg/dL 6–12 hours after cessation of the lipid infusion.

Serum TG levels above 400–600 mg/dL may precipitate pancreatitis. In patients for whom normal amounts of IV lipid are contraindicated, 4%–8% of calories as IV lipid should be provided to prevent EFA deficiency. Neonates and malnourished pediatric patients receiving lipid-free parenteral nutrition are at high risk for EFA deficiency.

Nitrogen

One gram of nitrogen is produced by 6.25 g of protein (1 g of protein contains 16% nitrogen). Caloric density of protein is equal to 4 kcal/g.

A. Protein Requirements

Protein requirements for IV feeding are the same as those for normal oral feeding (see Table 11–2).

B. Intravenous Amino Acid Solutions

Nitrogen requirements can be met by commercially available amino acid solutions. For infants, including preterm infants, accumulating evidence suggests that the use of TrophAmine (McGaw) is associated with a more normal plasma amino acid profile, superior nitrogen retention, and a lower incidence of cholestasis. TrophAmine contains 60% essential amino acids, is relatively high in branched-chain amino acids, contains taurine, and is compatible with the addition of cysteine within 24–48 hours after administration. The dose of added cysteine is 40 mg/g of TrophAmine. The relatively low pH of TrophAmine enhances solubility of calcium and phosphorus.

C. Dosing Guidelines

Amino acids can be started at 1–2 g/kg/day in most patients (see Table 11–22). In severely malnourished infants, the initial amount should be 1 g/kg/day. In infants of very low birth weight, there is evidence that higher initial amounts of amino acids are tolerated with little indication of protein “toxicity.” Larger quantities of amino acids in relation to calories can minimize a negative nitrogen balance even when the infusate is hypocaloric. Amino acid intake can be advanced by 0.5–1.0 g/kg/day toward the goal. Normally the final infusate will contain 2%–3% amino acids, depending on the rate of infusion. Concentration should not be advanced beyond 2% in peripheral vein infusates due to osmolality.

D. Monitoring

Monitoring for tolerance of the IV amino acid solutions should include blood urea nitrogen. Serum alkaline phosphatase, γ-glutamyltransferase, and bilirubin should be monitored to detect the onset of cholestatic liver disease.

Minerals & Electrolytes

A. Calcium, Phosphorus, and Magnesium

Intravenously fed preterm and full-term infants should be given relatively high amounts of calcium and phosphorus. Current recommendations are as follows: calcium, 500–600 mg/L; phosphorus, 400–450 mg/L; and magnesium, 50–70 mg/L. After 1 year of age, the recommendations are as follows: calcium, 200–400 mg/L; phosphorus, 150–300 mg/L; and magnesium, 20–40 mg/L. The ratio of calcium to phosphorous should be 1.3:1.0 by weight or 1:1 by molar ratio. These recommendations are deliberately presented as milligrams per liter of infusate to avoid inadvertent administration of concentrations of calcium and phosphorus that are high enough to precipitate in the tubing. During periods of fluid restriction, care must be taken not to inadvertently increase the concentration of calcium and phosphorus in the infusate. These recommendations assume an average fluid intake of 120–150 mL/kg/day and an infusate of 25 g of amino acid per liter. With lower amino acid concentrations, the concentrations of calcium and phosphorus should be decreased.

B. Electrolytes

Standard recommendations are given in Table 11–23. After chloride requirements are met, the remainder of the anion required to balance the cation should be given as acetate to avoid the possibility of acidosis resulting from excessive chloride. Electrolyte concentrations should be modified based on the flow rate and if indications dictate for the individual patient. IV sodium should be administered sparingly in the severely malnourished patient because of impaired membrane function and high intracellular sodium levels. Conversely, generous quantities of potassium and phosphorus may be needed.

C. Trace Elements

Recommended IV intakes of trace elements are as follows: zinc 100 mcg/kg, copper 20 mcg/kg, manganese 1 mcg/kg, chromium 0.2 mcg/kg, selenium 2 mcg/kg, and iodide 1 mcg/kg. Of note, IV zinc requirements may be as high as 400 mcg/kg for preterm infants and can be up to 250 mcg/kg for infants with short bowel syndrome and significant GI losses of zinc. When IV nutrition is supplemental or limited to fewer than 2 weeks, and preexisting nutritional deficiencies are absent, only zinc need routinely be added.

IV copper requirements are relatively low in the young infant because of the presence of hepatic copper stores. These are significant even in the 28-week fetus. Circulating levels of copper and manganese should be monitored in the presence of cholestatic liver disease. If monitoring is not feasible, temporary withdrawal of added copper and manganese is advisable in cholestasis.

Copper and manganese are excreted primarily in the bile, but selenium, chromium, and molybdenum are excreted primarily in the urine. These trace elements, therefore, should be administered with caution in the presence of renal failure.

Vitamins

Three vitamin formulations are available for use in pediatric parenteral nutrition: MVI Pediatric (Hospira), Infuvite Pediatric (Baxter), and the adult formulation MVI-12 (Astra-Zeneca). Detailed content information is available from manufacturers as well as from the Federal Drug Administration (FDA). Recommended MVI dosing is as follows: 5 mL for children weighing more than 3 kg, 3.25 mL for infants 1–3 kg, and 1.5 mL for infants weighing less than 1 kg. Children older than 11 years can receive 10 mL of the adult formulation, MVI-12. It is important to note that MVI-12 contains no vitamin K. For dosing considerations during national shortages, recommendations are available from the American Society for Parenteral and Enteral Nutrition (ASPEN). It is essential to follow national guidelines in order to prevent deficiencies and use available products appropriately.

IV lipid preparations contain enough tocopherol to affect total blood tocopherol levels. The majority of tocopherol in soybean oil emulsion is γ-tocopherol, which has substantially less biologic activity than the α-tocopherol present in safflower oil emulsions.

A dose of 40 IU/kg/day of vitamin D (maximum 400 IU/day) is adequate for both full-term and preterm infants.

Fluid Requirements

The initial fluid volume and subsequent increments in flow rate are determined by basic fluid requirements, the patient’s clinical status, and the extent to which additional fluid administration can be tolerated and may be required to achieve adequate nutrient intake. Calculation of initial fluid volumes to be administered should be based on standard pediatric practice. If replacement fluids are required for ongoing abnormal losses, these should be administered via a separate line.

Monitoring

Vital signs should be checked on each shift. With a central catheter in situ, a fever of more than 38.5°C requires peripheral and central-line blood cultures, urine culture, complete physical examination, and examination of the IV entry point. Instability of vital signs, elevated white blood cell count with left shift, and glycosuria suggest sepsis. Removal of the central venous catheter should be considered if the patient is toxic or unresponsive to antibiotics.

A. Physical Examination

Monitor especially for hepatomegaly (differential diagnoses include fluid overload, congestive heart failure, steatosis, and hepatitis) and edema (differential diagnoses include fluid overload, congestive heart failure, hypoalbuminemia, and thrombosis of superior vena cava).

B. Intake and Output Record

Calories and volume delivered should be calculated from the previous day’s intake and output records (that which was delivered rather than that which was ordered). The following entries should be noted on flow sheets: IV, enteral, and total fluid (mL/kg/day); dextrose (g/kg/day or mg/kg/min); protein (g/kg/day); lipids (g/kg/day); energy (kcal/kg/day); and percent of energy from enteral nutrition.

C. Growth, Urine, and Blood

Routine monitoring guidelines are given in Table 11–24. These are minimum requirements, except in the very long-term stable patient. Individual variables should be monitored more frequently as indicated, as should additional variables or clinical indications. For example, a blood ammonia analysis should be ordered for an infant with lethargy, pallor, poor growth, acidosis, azotemia, or abnormal liver test results.