EN via nasogastric or orogastric tube is routinely used in premature infants younger than 32 weeks’ gestation because of uncoordinated suck, swallow, and breathing related to immaturity [26]. Human milk is the preferred feed because of its immunological benefits. Preterm infant formulas come fortified with protein, calcium/phosphorous, and a calorie density of 22–24 kcal/oz. to meet the high nutritional requirements of infants. A Cochrane systematic review of treatment trials did not provide evidence of any beneficial effect from transpyloric feeding over gastric feeding on feeding tolerance , growth, and development in preterm infants [27]. Therefore, gastric feedings administered by bolus or continuously is the preferred approach for EN in preterm infants, where its use appears to also have a role in preventing necrotizing enterocolitis [28] (see also Chap. 6 on “Enteral Nutrition in Preterm Neonates” and Chap. 7 on “Parenteral Nutrition in Premature Infants”).

Anorexia nervosa (AN) is a life-threatening psychiatric condition characterized by disordered eating behaviors, significantly lower than expected body weight, intense fear of becoming overweight, and a distorted body image. It is managed by a multidisciplinary team of health providers including psychiatrists, adolescent medicine pediatricians, nutritionists, and social workers. Indications for inpatient therapy include presence of suicidal or aggressive behaviors; severe bradycardia, hypotension, electrolyte imbalance, dehydration, and hypothermia; and medical complications, for example, seizures and pancreatitis [29]. Weight restoration is one of the major predicators for favorable short- and long-term outcomes in patients with AN [30]. Also, restoration of body weight is associated with improvements in malnutrition-induced cognitive impairments thus facilitating psychological and psychiatric therapy [31].

Nutritional support in AN remains very controversial. The oral feeding route is preferred; however, patients are given the option of voluntary or forced EN if resistant to therapy and/or severe malnutrition, that is, body mass index (BMI) < 13 kg/m² in adolescents [32] and weight-for-height z score < − 3 in younger children [33]. Other options like GT and PN are considered in young children or severe and chronic cases [29]. Follow-up of adults treated with EN during adolescence did not show any long-term benefits or adverse outcomes on growth, recovery, or persistence of AN or risk for development of psychiatric comorbidities [34]. The initial range of prescribed energy intake varies from 10–60 kcal/day to 1000 kcal/day and > 1900 kcal/day with progressive increase during the course of hospitalization [29, 30]. The main complication of nutritional management is risk for developing re-feeding syndrome: hypophosphatemia, hypokalemia, edema, and increased hepatic transaminases. The risk factors associated with re-feeding syndrome include greater severity of malnutrition, abnormal electrolytes prior to re-feeding, use of EN or PN, and weight loss > 15 % within the preceding 3 months [29, 30]. Patients may be preemptively treated with phosphate supplements during the early phases of nutritional management.

EN is part of the standard therapy used to prevent biochemical abnormalities, metabolic decompensation, and catabolism in patients with inherited disorders of metabolism, for example, hepatic glycogen storage disease (GSD) and enzyme deficiencies of the urea cycle. Patients with GSD type 1 (glucose-6-phosphatase deficiency) develop hypoglycemia and compensatory biochemical abnormalities of lactic acidosis, hyperuricemia, hyperlipidemia, and platelet dysfunction all stemming from the primary defect of inability to dephosphorylate glucose-6-phposphate to free glucose. Managing GSD type 1 involves overnight continuous high-carbohydrate feedings and frequent daytime feedings supplemented with uncooked cornstarch [35, 36]. EN consisting of a glucose/glucose polymer solution or a sucrose-free, lactose-free/low formula enriched with maltodextrin may be used. EN should be started within 1 h after the last meal. Likewise, an oral or EN should be given within 15 min after discontinuation of the continuous EN because of the risk for hypoglycemia. Gastrostomy is contraindicated in patients with GSD type 1b because of complications in case development of inflammatory bowel disease or local infections [36]. Continuous EN should provide a glucose infusion rate of 7–9 mg/kg/min in children younger than 6 years, 5–6 mg/kg/min in children aged 6–12 years, and 5 mg/kg/min in adolescents [36]. Intermittent feedings of uncooked cornstarch may be used if continuous nighttime EN is not an option. No significant differences in biochemical parameters or growth have been found between patients with GSD type 1 receiving overnight continuous EN compared to scheduled feeds of uncooked cornstarch [37, 38]. The starting dose for uncooked cornstarch is 0.25 g/kg and optimal dose is 1.75–2.5 g/kg of ideal body weight every 6 h [36, 37, 39]. Patients with GSD type 3 (debrancher enzyme deficiency) have impeded glycogenolysis; however, gluconeogenesis is endogenously enhanced to maintain adequate glucose production. Therefore, nutritional management of patients with GSD type 3 involves frequent high-protein feedings during the day and a high-protein snack at night. Patients with GSD IV (brancher enzyme deficiency), GSD VI (phosphorylase deficiency), and GSD IX (phosphorylase kinase deficiency) respond to the to the high-protein diets similar to what is recommended for patients with GSD type 3 [40].

Inherited defects in urea synthesis are inborn errors of nitrogen detoxification and arginine synthesis due to defects in the urea cycle enzymes namely carbamylphosphate synthetase 1, ornithine transcarbamylase, arginosuccinate synthetase, arginosuccinate lyase, and arginase [41]. They may present at any age with symptoms ranging from poor feeding to coma shock and death. Other clinical symptoms may include lethargy, vomiting, ataxia, confusion, behavior changes, hypotonia or spasticity, hyperventilation (leading to respiratory alkalosis), and seizures. The main biochemical abnormalities are hyperammonemia and increased plasma concentrations of glutamine [42]. The symptoms of metabolic crisis are usually precipitated by protein intake in excess of what the patient can metabolize, catabolism of lean body mass resulting from intercurrent infection, trauma, inadequate energy intake, or inadequate intake of protein or essential amino acids . Management of patients with urea cycle defects involves a combination of carefully restricting protein intake and therapy with nitrogen-scavenging drugs, for example, sodium benzoate, sodium phenyl acetate, or sodium phenyl butyrate [41]. The nutritional management includes: (1) administration of sufficient energy to support anabolism, (2) restriction of protein intake to that tolerated by the patient without producing excess NH3, (3) provision of essential amino acids in adequate amounts to support growth, (4) supplementation of “conditionally” essential arginine or citrulline in all except arginase deficiency, and (5) provision of all required minerals and vitamins in adequate amounts for age [43]. During hyperammonemic metabolic crisis, the nutritional management consists of providing high-energy low-protein intakes [44]. Successful long-term management requires a dedicated metabolics dietician and physician to make dietary adjustments and closely monitor progress. Patients with neurological handicaps or developmental delays, feeding difficulties, poor appetite/refusal of food, compliance problems with the diet, and/or medications will require use of nasogastric or gastrostomy feeding tubes to ensure adequate intake [41, 45]. Patients in metabolic crisis with symptomatic hyperammonemia (> 500 μM/L) and/or lack of response despite 4 h of medical treatment should have management escalated to dialysis [41].

Traditionally, PN is given as the first option for nutrition support in children undergoing chemotherapy and/or bone marrow/stem cell transplant. The reasons cited range from intestinal injury and poor GI tolerance secondary to conditioning and myeloablative therapy; intestinal graft versus host disease (GVHD), oral mucositis, epistaxis, and parental refusal of EN. However, whenever GI function permits, EN is equally as effective as PN, associated with lower risk for infection, and more cost-effective [49–52]. A prospective study comparing EN and PN in children with bone marrow transplants had poor enrolment into the EN group. Initiation of EN prior to transplant was associated with better overall tolerance. The EN group was also less likely to develop cholestasis [51]. A more recent Cochrane database review of nutrition support in patients of all ages with bone marrow or stem cell transplants failed to find evaluable data that properly compared efficacy and superiority of EN versus PN. However, the overall findings suggested that in patients without GI symptoms, intravenous fluids and oral diet should be considered as preference to PN [53].

Supplemental nutrition should be given to children with renal failure to promote positive nitrogen balance and meet energy needs [4]. Children with chronic renal failure are at risk for malnutrition and growth retardation from persistent anorexia, inadequate protein calorie intake, chronic metabolic acidosis, azotemia, hormonal and metabolic disturbances, and catabolic diseases associated with uremia, for example, infections. Long-term EN is effective in preventing growth retardation in children with chronic renal disease and persistent anorexia, especially if started before the age of 2 years [54, 55] but singly may not lead to catch-up growth [56]. There is a positive correlation between efficacy of dialysis and linear of children with chronic renal failure [57]. Therefore, the combination of aggressive nutrition support with whey protein-based formulas in children age < 2 years, whole protein enteral formula (1–1.5 kcal/mL) in older children [58], and enhanced dialysis is necessary for inducing growth in children with chronic renal failure [59]. Growth hormone therapy is recommended if there is persistent growth retardation despite adequate nutrition support [58, 60]. Ultimately, catch-up growth in height is mainly seen in children who undergo renal transplant before the age of 6 years [61].

Inadequate calorie intake is the predominant cause of growth failure in infants and children with congenital heart disease. Different approaches for nutrition intervention are utilized during the preoperative, postoperative, and post-discharge periods, respectively [62]. Infants with cyanotic congenital heart disease and complex ventricular lesions are particularly susceptible to malnutrition and growth failure [63]. Approximately, 50 % of infants with surgically treated uni-ventricular lesions get discharged home on EN via nasogastric or GT [64]. The causes of malnutrition include an imbalance between energy intake and increased expenditure particularly in children with congestive heart failure. Infants with severe congenital heart disease have normal resting energy expenditure [65, 66] but increased total energy expenditure [67], thus indicating that they expend large amounts of energy above basal requirements, which places them at risk for inadequate calorie intake when feeding at normal rates. Perioperative injury to the recurrent laryngeal nerve may lead to feeding difficulties from swallowing dysfunction and vocal cord paralysis [68]. Other contributing factors include pulmonary hypertension, tachypnea and fatigue interfering with oral feeding, medications associated with anorexia, for example, diuretics, prescription of fat-restricted diets in patients who develop chylous effusions, and GI nutrient loss in patients who develop post-Fontan protein-losing enteropathy. Post-Fontan protein-losing enteropathy is managed with therapies directed at improving cardiac hemodynamics and controlling inflammation [69].

A syndrome of intractable diarrhea of infancy was first described by Avery et al in 1968. Its definition, presentation, and outcome have considerably changed during the past two decades [70]. This syndrome could now be defined as persistent diarrhea despite prolonged bowel rest requiring long term-total parenteral nutrition (TPN) in children when no effective treatment is available [71, 72]. According to that definition, EN in this circumstance is indicated and often effective [73]. In fact, the reduction of digestive secretions, villous atrophy, and acquired brush border disaccharidase deficiency lead to malabsorption and malnutrition . Most of the time, a short course of PN followed by protracted CEN provides control of the disease within 6–8 weeks [74, 75]. In a prospective study of CEN versus PN, Orenstein showed that the resolution of diarrhea was faster in the enterally fed group [75]. The use of CEN in children and mainly infants with protracted diarrhea presenting also severe malnutrition may prove difficult. If the response to CEN is not good enough to provide rapidly adequate caloric supplies with resolution of diarrhea, PN should be started. Such decisions must be taken by experienced teams in specialized and well-staffed units. Severely malnourished infants with some types of particularly severe celiac disease , intolerance to cow milk proteins, protein hydrolysates, or with specific malabsorption syndromes, such as Anderson’s disease may also benefit from CEN [76].

SBS is the leading cause of intestinal failure in newborns as well as infants and young children, and it is most commonly the result of an extensive intestinal resection during the neonatal period. EN is often used in these circumstances, although several controversies over the ideal nutritional treatment of children with SBS remain [77]. Of note, intestinal failure may also lead to liver disease [78] (see also Chap. 43 on “Short Bowel Syndrome”).

In neonatal abdominal surgery for congenital or acquired disease, CEN, usually combined with PN, offers prolonged nutritional support which has transformed the prognosis in many conditions and is particularly important in the following situations: (1) reduction of the absorptive surface with enterocutaneous fistulae or extensive intestinal resection; (2) functional disorders of gut motility, such as malfunctions of duodenojejunal anastomosis, “plastic” peritonitis after repeated interventions, gastroschisis, and omphalocele.

Chronic intestinal pseudo-obstruction syndrome is a disabling disorder of enteral feeding characterized by repetitive episodes or continuous symptoms and signs of bowel obstruction, including radiographic documentation of dilated bowel with air–fluid levels, in the absence of fixed-lumen-occluding condition [79]. Pseudo-obstruction is classified as “congenital” if newborn infants present with symptoms persisting for the first 2 months of life. “Acquired” pseudo-obstruction applies when previously well patients present with feeding intolerance from pseudo-obstruction symptoms persisting longer than 6 months [79]. Most patients with intestinal pseudo-obstruction require decompression stomas, ileostomies, and colostomies to relieve the recurring obstruction symptoms. Long-term PN is required in a significant proportion of children with pseudo-obstruction [80–82], and even then, administration of at least small volumes of CEN is essential and encouraged for prevention of PN-associated liver disease [83] and maintenance of bowel mucosal integrity [84].

Enteral feeding has been used for many years, particularly in Europe, not only to improve nutritional status and growth but also to influence disease activity in patients with Crohn’s disease [85–94] . It was shown that CEN diet is as effective as high-dose corticosteroids in inducing remission in pediatric patients with Crohn’s disease and has the added benefit of improved growth and development without the steroid side effects [95, 96]. However, serial meta-analysis conducted by Griffiths et al. in 1995, 2001, and 2007 suggested that therapy with EN was inferior to corticosteroids for inducing clinical response in patients with active Crohn’s disease [97–99]. All three analyses largely included adult studies, and several pediatric studies showing striking efficacy were excluded owing to methodological weakness. A more recent meta-analysis that focused on 11 randomized controlled pediatric studies still reported similar efficacy for EN and corticosteroids for inducing remission in Crohn’s disease but also cited limited data [100]. The benefits of EN appear to be more favorable in children than adults including correction of impaired growth. Thus, EN is an underused therapy with the advantage of preserving growth while remission is achieved and therefore must be promoted [101]. There is no relevant data showing any significant difference in clinical outcome based on composition of the EN, that is, elemental, protein hydrolysates, or polymeric formula. Indeed, the beneficial effect in achieving remission appears not to be related to the mode of delivery or to the type of diet (no beneficial effect of elemental versus polymeric or semi-elemental) but rather to the reduced antigen load and mostly to changes in the intestinal microbiota [95]. Removal of antigenic material, alteration in intestinal micro flora, changes in gut hormone levels, and the presence of bioactive transforming growth factor-β (TGFβ-1) in casein-based formulas may all play a role in the clinical success of EN [102, 103]. Glutamine-enriched polymeric diet offered no advantage over a standard low-glutamine polymeric diet in the treatment of active Crohn’s disease [104]. EN may be also helpful in correction or maintenance of the nutritional state, especially during a relapse of Crohn’s disease [96] . EN is part of the preparation for surgical procedure and may be useful during recovery, especially after intestinal resections or enterostomies. In case of severe digestive involvement during Schönlein–Henoch purpura, CEN can be used as nutritional support in the absence of occlusion [105] More on the treatment of Crohn’s disease can be found in Chap. 28 .

Malnutrition and impaired growth affects approximately 23 % of children with cystic fibrosis (CF) [106], and growth within the normal range of weight-for-length and BMI is associated with better pulmonary function and long-term survival. In 2008, the CF Foundation recommended that growth assessment using percent ideal body weight (% IBW) be discontinued, and instead rely on age-appropriate weight-for-length percentiles in children aged < 2 years, and BMI percentiles in children aged 2–20 years. The nutritional goals in children with CF are to maintain and support growth at weight-for-length or BMI at or above the 50th percentile [106]. Growth abnormalities in patients with CF have a multifactorial etiology including active CF-pulmonary or sinus disease, inadequate or ineffective pancreatic enzyme therapy, inadequate calorie intake, anorexia, presence of CF-related hepatobiliary disease, CF-related diabetes, infectious enteritis , small bowel bacterial overgrowth, and other comorbid intestinal conditions including, for example, celiac disease , inflammatory bowel disease and SBS [107]. Whereas these disorders require specific therapy, nutrition monitoring and intervention in patients with CF should always be implemented regardless of comorbid disease. Improved weight status in patients with CF often requires energy and protein intakes ranging from 110 to 200 % of normal needs in healthy people [108, 109]. However, even with an optimal approach to oral feeding, some patients respond poorly to nutritional counseling alone. Therefore, use of EN to supplement dietary intake is recommended to help restore and maintain nutritional status, especially in children aged 13 years and older who present with persistent growth deficits despite nutrition counseling [106]. The utilization of supplemental EN by patients with CF increased from 8.5 % in 2001 to 11.1 % in 2011 [110] thus indicating greater engagement of nutritional therapy. EN is generally performed during the night over 8–10 h with the initial goal of providing 30–50 % of the estimated requirements [107]. Patients with CF are then asked to eat and drink as much as possible during the daytime. Standard formulas containing intact protein, long-chain fat and calorie densities of 1.5–2.0 kcal/mL are generally well tolerated with appropriate dosing and administration of pancreatic enzymes [107, 111] Semi-elemental formulas may be tolerated better in patients with excessive anorexia, bloating, or nausea. The data are unclear whether formulas with medium-chain triglycerides are advantageous over regular formula in patients with CF [107].

Nasogastric tube (NGT) feeding is generally used as a first step. The tube is passed every night, 1–2 h after dinner, and removed in the early morning before physical therapy so that patients are not disturbed during the daytime for school attendance. In some children, NGT becomes increasingly uncomfortable because of nausea, vomiting, nasal discomfort as a result of nasal polyposis , or dislodgement during coughing in cases of pulmonary exacerbation. PEG is the preferred modality for administering home nocturnal EN when long-term EN is anticipated. Generally, PEGs are perceived well by patients with CF who rely on EN therapy for poor weight gain or weight loss. On the contrary, patients and families without PEGs were found to be apathetic towards their value, citing fear of interference with activities, embarrassment, pain, and discomfort [112]. Therefore, there is need for more accurate information about benefits and lifestyle in patients with PEGs. Good early childhood nutritional status is associated with better pulmonary function and long-term survival in patients with CF [113]. However, poor growth and advanced lung disease have been associated with poor outcomes regardless of adherence to EN [114]. There is also currently insufficient evidence to determine whether nutritional rehabilitation after onset of malnutrition improves pulmonary function in patients with advanced CF-related lung disease. Therefore, the importance of a proactive approach of growth monitoring and early nutritional intervention to optimize growth in children and adolescents with CF. It is important to assess for gastroesophageal reflux before starting EN. Patients should also be monitored for glucose intolerance during administration of EN, especially during illness, therapy with steroids, and if not gaining weight. Insulin therapy should be administered as needed in patients with glucose intolerance [107].

Mechanisms leading to protein-energy malnutrition and requirement for EN in infants and children with chronic liver disease are multifactorial and dependent on the type of liver injury [115]. Malnutrition in cholestatic liver disorders is from reduced biliary secretion and intraluminal bile concentrations resulting in malabsorption of lipids and fat-soluble vitamins [116]. Protein and energy requirements are increased by different mechanisms including hypermetabolism [117], portosystemic shunting and ascites , futile metabolic pathways [118], and the energy demands from complications such as sepsis or variceal bleeding [119]. Liver disease from inborn errors of metabolism, for example, galactosemia, tyrosinemia, GSD, and Wilson’s disease requires specific dietary restrictions and EN feeding protocols to prevent hypoglycemia and other forms of metabolic decompensation. Patients with fulminant hepatic failure may be well nourished and nutritionally independent at clinical presentation but later require EN because of impaired mental status. Anorexia is common in children with chronic liver disease resulting from organomegaly, abdominal pressure effects of ascites, congested gastric mucosa, reduced motility from portal hypertension , central effects of unidentified toxins, dietary manipulations such as fluid restriction, or use of unpalatable feeds. Several factors contribute to long-chain polyunsaturated fatty acids (PUFAs) deficiency including low PUFAs intake, malabsorption, and disturbed metabolism of long-chain PUFAs. Finally, the interaction of growth hormone with insulin-like growth factor 1(IGF-1) and its binding proteins constitute an important mechanism linking nutrition and growth .

The most common cause of cirrhosis in children is biliary atresia , and the only definitive therapy is liver transplantation [120]. A total of 60–80 % of affected children are moderately to severely malnourished prior to transplantation [116], and poor nutritional status prior to transplantation is associated with prolonged hospital stay, increased risk for death at high cost of medical care [119, 121, 122]. Supplemental EN or PN to improve nutritional status is the one intervention known to improve pre- and posttransplant growth and clinical outcomes in children with end-stage liver disease [123–127]

Anorexia, inadequate calorie intake, and failure to thrive are prevalent in children with chronic liver disease [116]; therefore, EN is recommended to supplement per oral food intake [119]. NGT feeding may be safely used without increased risk for bleeding in patients with portal hypertension varices [128, 129]. PEGs should be avoided in children with chronic liver disease and portal hypertension because of likely portal-hypertensive gastropathy with increased bleeding risk from gastric varices [119]. MCTs are nutritionally advantageous in patients with cholestasis because of no bile requirement for digestion and rapidly absorbed into the portal circulation. MCTs may be administered separately as supplements; however, the selected EN should not contain more than 80 % of fat as MCT because of risk for inducing essential fatty acid deficiency [130] . Children with weight-for-length z scores < − 3 fall into the category of severe malnutrition and > 9-fold risk for mortality [131] therefore should be prioritized for nutritional intervention. Patients with chronic cholestatic liver disease have increased metabolism [117], futile metabolic pathways [118], and malabsorption; therefore, the goal for supplemental EN to enable a daily calorie intake of 140–200 % of estimated requirements [116]. Children with chronic cholestatic liver disease should continue receiving fat-soluble vitamins (A, D, E and K) regardless of amounts listed in EN [132]. Protein intake of infants and children should not be restricted except in cases of intractable encephalopathy [132], and, even in these cases, protein intake should remain within the adequate intake range of 1–2 g/kg/day [133] and accompanied by sufficient intake of nonprotein calories to prevent inappropriate utilization of protein for energy synthesis [134]. Children with cholestatic liver disease have increased requirements for branched-chain amino acids (BCAA) compared to healthy controls [135]. However, nutritional outcome studies using either BCAA-enriched or standard formulas reported growth benefits in all recipients of EN [123, 124]. Furthermore, a Cochrane review did not find BCAA-enriched formula protective against encephalopathy when compared to iso-nitrogenous non-BCAA enriched formulas [136] Therefore, there is currently insufficient evidence to recommend the use of BCAA-enriched formulas over standard non-BCAA enriched formula .

Nutritional management of chylothorax involves adherence to EN or an oral diet enriched with medium-chain triglycerides and restricted in long-chain triglycerides and supplementation with essential fatty acids and fat-soluble vitamins [137]. Nutrition support during the preoperative period utilizes EN in infants who are hemodynamically stable and early use of PN if otherwise. The immediate postoperative period is characterized by fluid restrictions and hemodynamic instability and therefore requires active involvement of a dietician and reliance on PN to meet goal calories. Once hemodynamic stability is established, enteral feeding is introduced while following standardized protocols that include screening for swallowing dysfunction and management of GI symptoms, for example, reflux. Nutrition surveillance should be performed continually pre- and post discharge to guide further interventions including use of calorie-dense formula and home tube feeds [62].