ICAN: Infant, Child, & Adolescent Nutrition

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1 Evidence-Based Practice Reports Nutritional Management of the Child With Crohn s Disease Daphna Rosen, RN, PNP, and Rita Marie John, DNP, EdD, CPNP Abstract: Nutritional management of Crohn s Disease (CD) is essential when working with the pediatric population. Treatment needs to target not only symptoms of the disease but also the associated growth failure and nutritional deficiencies. The principle nutritional therapy is the use of enteral nutrition, which has been shown to be safe and effective in both the induction of remission and maintenance in pediatric CD. Additional nutritional supplementation, including omega-3 fatty acids, probiotics, and glutamine, have been researched, but have not been proven effective. This article will address the role of nutritional therapy and management in pediatric CD, the different nutritional management options, the role of nutritional therapy in the induction and maintenance of remission, and recommendations for health care professionals who care for children with CD. Keywords: Crohn s disease; pediatric; nutrition; management; health care professional JR is a 14-year-old boy with newly diagnosed Crohn s Disease (CD). He presents with abdominal pain, weight loss, diarrhea, impaired linear growth, and pubertal impairment. What important nutritional deficits should the health care professional be aware of and evaluate? What are the different nutritional treatment and management options available for this patient? Nutritional deficits leading to growth and developmental impairments are hallmarks of pediatric CD. Nutritional management, therefore, needs to be at the forefront in the treatment of CD. This article will address common nutritional problems; the importance, benefits, and outcomes of nutritional therapy in both the induction and maintenance of disease remission; and recommendations for health care professionals in the nutritional management of CD. Overview CD is a cyclical disease, which involves chronic inflammation with periods of remission followed by relapse. 1 The disease, which can arise in any part of the intestine, is characterized by skip lesions, or granulomatous inflammations found commonly in the ileum, followed by the colon and small bowel, and gastroduodenal disease. 2,3 CD is commonly diagnosed in childhood and adolescence, with higher presentation occurring during the peripubertal years. 4 CD comprises 25% of the newly diagnosed cases of inflammatory The immediate goals of nutritional management are to induce and maintain remission to ultimately improve overall growth, development, and nutritional status. bowel disease. 1 Height and weight are significantly reduced in CD: 22% to 24% of children with CD reported a low BMI. 5 Clinical Presentation Clinical manifestations of CD can be abrupt, insidious, or poorly defined. 6 Although the most common abdominal symptoms include weight loss or poor weight gain, abdominal pain, and diarrhea, extraintestinal manifestations are common. 4 Table 1 summarizes the DOI: / From the Columbia University School of Nursing, New York, NY. Address correspondence to Daphna Rosen, Columbia University School of Nursing, 10 Overlook Terrace Apt 5E, New York, NY 10033; Dr2521@columbia.edu. For reprints and permissions queries, please visit SAGE s Web site at Copyright 2012 The Author(s) 111

2 April 2012 Table 1. Clinical Presentation Clinical Presentation Associated Manifestations Causes Poor weight gain/ Diarrhea 4 weight loss 4 Abdominal pain 4 Malnutrition 10 Growth failure 4 Impaired linear growth 10 Pubertal delay 11 Malnutrition 10 Nutritional Malnutrition 1 deficiencies 1 Decreased bone health 11 Low bone mineral density 11 Osteopenia 7 Osteoporosis 7 Reduced caloric intake or caloric malabsorption 12 Increased nutrient requirements 12 Increased nutrient losses 12 Drug nutrient interactions 12 Alteration of metabolism related to inflammation 51 Malnutrition 10 Corticosteroid therapy 10 Inflammatory mediators (IL-6, TNF-α) 51 Malnutrition 1,11 Poor oral intake 1 Corticosteroid therapy 11 Inflammation related to disease activity 11 Malabsorption 1 Abbreviations: IL, interleukin; TNF, tumor necrosis factor. clinical presentation of CD. Two thirds of children with CD will present with weight loss, one third will have permanent growth impairment, 7 and many will have a reduction in lean body mass. 8 Growth Failure Growth failure can be defined as delayed skeletal maturation and delayed pubertal onset. 10 Impaired linear growth will be present in up to 50% of pediatric CD patients, 4 with a greater percentage of adolescent males versus females presenting with growth failure. Adolescent males are at greater risk for growth impairments because their pubertal growth spurt occurs later and extends for a longer duration than females. 11 Growth failure results from inflammation of the intestine, treatment with steroids, changes in growth hormone secretion and insulin-like growth factor, and chronic undernutrition. 7,12 The insulin-like growth factor 1, total insulin growth factors, and IG-1 binding protein-3 (IGFBP- 3) are lower in children with active inflammatory bowel disease. 12 Chronic undernutrition is the main contributing factor in growth failure in CD. 7 Osteopenia and osteoporosis develop as a result of malabsorption of calcium and vitamin D, 13 decreased levels of vitamin K, 8 treatment with steroids, and chronic inflammation of the intestine. 2 In addition to impaired linear growth, pubertal delay is also seen in children who fail to achieve remission or those who have frequent relapses. 11 Close monitoring of pubertal advancement is extremely important in this patient population. Nutritional Deficiencies Both macronutrient and micronutrient deficiencies related to malnutrition are common in children with active CD. During remission, macronutrient deficiencies are rarely seen in patients. 8 Table 2 lists common nutrient deficiencies. Pons et al 1 evaluated the dietary intake of children with active CD, those in remission, and healthy children (Table 3 ). Researchers found that children with active CD have lower nutrient intake compared with that of children who were healthy or in remission. 1 For example, lowered bone mineral density is common in children in CD 7,11 as a result of lactose intolerance, decreased calcium intake, 1 malnutrition, corticosteroid use, and inflammation related to disease activity. 11 As the intestine heals, the absorption of micronutrients and macronutrients improves. Micronutrient deficiencies in iron, folate, and vitamin B12 are commonly observed. However, levels of vitamin A, vitamin E, β-carotene, magnesium, selenium, and zinc can also be reduced. Daily supplementation with calcium and vitamin D have been associated with an increase in bone mineral density, 13,14 and iron supplementation can improve the quality of life. 15 Malnourished patients are at greater risk of infections, including sepsis and pneumonia. For patients who need surgery, the postoperative risks are higher with active CD. 8 Nutritional Management The majority of children with CD present with some form of impaired nutritional status; therefore, nutritional management must play an integral part in the treatment of CD. 7 Management of CD should be geared toward the 112

3 Table 2. Common Nutritional Deficiencies in Children With Active CD a Micronutrient Deficiencies Calcium Folate Vitamin B12 Zinc Selenium Iron Vitamin D Vitamin K Macronutrient Deficiencies Carbohydrates Fats a Adapted from Pons et al. 1 Protein induction of remission with the least number of side effects, thereby enabling improved growth and development. 16 The immediate goals of nutritional management are to induce and maintain remission to ultimately improve overall growth, development, and nutritional status. Exclusive enteral nutrition (EEN) is one option for the induction of remission in CD. Outside the United States, EEN therapy, lasting 6 to 12 weeks, is a popular method for inducing remission. However, in the United States, there are different recommendations regarding the nutritional management of pediatric CD. These are summarized in Table 4. Induction of Remission Unlike standard corticosteroid therapy, EEN therapy can benefit both growth and development and therefore should be considered as an alternative. 12 Not only has EEN therapy shown to be effective in the induction of remission, but it also has higher remission rates at follow-up than corticosteroid therapy despite use of the same maintenance regimen. 16 Table 3 summarizes the studies on the induction of remission. The major limitations in these studies are the small sample sizes and insufficient number of randomized control trials. Exclusive Enteral Nutrition Overview. Enteral diets are classified into amino acid based elemental feeds, oligo-based or polypeptide-based semielemental feeds, and polymeric or whole protein based diets. 32 Appendix A (online at can.sagepub.com) s the types of formulas, composition, and cost. The side effect profile of these diets are excellent, with the exception of the risk of refeeding syndrome. Although the exact mechanism involved in EEN is unknown, proposed mechanisms include bowel rest, which is thought to decrease intestinal metabolic activity; alteration of intestinal flora; immunological effects, including the alteration of direct anti-inflammatory effects; and nutritional enhancement, including the improvement of caloric intake and correction of nutrient deficiencies. 7,8,33 There are several goals of EEN as it relates to the induction of remission in CD, including the prevention or treatment of malnutrition, improvement in growth and development, and improvement in the quality of life. 11 According to the European Society for Clinical Nutrition and Metabolism s Guidelines on Enteral Nutrition (2006) and its guidelines on parenteral therapy (2009), EEN therapy should be considered first-line therapy in pediatric patients with CD. 8,30 Western Europeans hold a stronger belief in the efficacy of EEN than their US counterparts. Among Western Europeans, 79% reported believing in EEN to induce remission in comparison to 46% of US respondents. 34 The question then becomes whether EEN is necessary for the induction of remission or if partial enteral nutrition (PEN) as supplementation to a normal diet might have similar effects. Johnson et al 18 compared the effects of EEN with PEN in the induction of remission. Results showed that EEN yielded a greater remission rate than PEN, and PEN did not positively affect intestinal inflammation. The authors therefore recommend the use of EEN in the induction of disease remission. EEN has been shown to induce remission in 60% to 90% of children with CD, 40 with length of remission and relapse rate comparable to standard corticosteroid treatment. 30 Two metaanalyses reported no difference between steroid-induced remission and EENinduced remission. 35, 36 Day et al 37 found that EEN is most effective in the induction of disease remission when used in children with newly diagnosed CD; EEN induced remission in 80% of newly diagnosed patients versus 58% of children with long-standing disease. Beginning EEN therapy. The induction of remission via EEN involves a slow increase of enteral formula intake over a period of 2 to 3 days to ensure tolerance and reduce diarrhea. 34 Minor disturbances such as nausea and headache can occur, but the side effects decrease as adaptation to the diet occurs. EEN commences once tolerance is determined and continues for approximately 4 to 8 weeks. Elemental, semielemental, or polymeric formula may be used. 11 Growing infants, children, and adolescents have a high energy need especially in situations of prior weight loss or infection. The caloric needs for infants range from 80 to 120 kcal/kg/d with a protein requirement of 2.0 to 25 g/kg/d. 38 EEN can either be given orally or via a nasogastric (NG) tube, with oral administration being the preferred method. NG tube feedings may be used when a large volume of formula is required or when oral administration is not feasible. If a child is receiving enteral nutrition by NG tube, the infusion rates should start at 20 ml/h and increase up to 100 to 120 ml/h, depending on weight. The insertion of an NG tube can be a deterrent to the use of EEN, but studies have shown that children can be taught to swallow an NG tube at night and can receive up to 1000 kcal/night. 15 Rubio et al 19 conducted a study of 106 pediatric patients recently and compared fractionated oral therapy with continuous enteral feeding; they did not find any difference in induction 113

4 April 2012 Table 3. Characteristics of Included Studies Author (Year Published) Aim of Study Participants Methods Findings Nutritional deficiencies Pons et al 1 (2009) To compare dietary intake and growth in children with CD and healthy children 63 Children (age range years); 18 with active CD, 23 with CD in remission, 22 healthy controls Nonrandomized controlled trial; food frequency questionnaire was used to assess dietary intake Dietary intake is lower in children with active CD when compared with both healthy children and children in remission; carbohydrate intake was lower in those with active CD than in controls (P =.03); fat intake was lower in those with active CD than in controls (P =.06); protein intake was similar between all groups (P =.09) Induction of remission Berni Canani et al 16 (2006) To evaluate the efficacy of different enteral formulas (elemental, semielemental, and polymeric) and corticosteroids in their achievement of maintenance of disease remission 47 Patients (age range 7-17 years); 37 received 8 weeks of nutritional therapy, and 10 received corticosteroids Retrospective study with medical record Similar remission rates; 86.5% using nutritional therapy achieved remission versus 90% using corticosteroids (no statistical values reported). Nutritional therapy yielded greater mucosal healing and durations of remission (P <.001) Day et al 37 (2006) To show the success of enteral nutrition in induction of remission and maintenance in pediatric CD 27 Children (age range years); 15 with newly diagnosed CD solely with exclusive enteral nutrition and 12 with long-standing disease managed with EEN and medications Retrospective study with case record In all, 80% of newly diagnosed patients (P <.0001) and 58% of patients with long-standing disease (P <.0001) achieved remission. EEN is a safe and effective therapy Johnson et al 17 (2006) To compare partial enteral therapy and total enteral therapy in the treatment of active CD 50 Children (age range years); 24 received total enteral nutrition, 26 received partial enteral nutrition RCT Total enteral nutrition had greater remission rates than partial enteral nutrition (P =.035); partial enteral nutrition did not have an impact on mucosal inflammation Ludvigsson et al 18 (2004) To compare the efficacy and safety of elemental and polymeric diets as the primary therapy in active pediatric CD 33 Children (age range years); 16 received Elemental 028 Extra formula, 17 received Nutrison Standard formula Multicenter RCT No significant difference between the remission rates of elemental and polymeric diets in 6 weeks (P =.438); greater weight gain with polymeric versus elemental formula (P =.001) (continued) 114

5 Table 3. (continued) Author (Year Published) Aim of Study Participants Methods Findings Rodrigues et al 9 (2007) To assess if polymeric formula was associated with an increased rate of adherence when compared with elemental formula 98 Children; 53 receiving elemental formula and 45 receiving polymeric formula Retrospective study with medical record Adherence levels were relatively equal (P =.84); lower rates of NG tube administration with polymeric formula versus elemental formula (P =.02) Rubio et al 19 (2011) To compare the efficacy of fractionated oral versus continuous enteral feeding on induction of remission in pediatric CD 106 Children (age range ); 45 received EEN via the oral route; 61 received EEN via continuous enteral feeding for a period of 8 weeks Retrospective study with medical record No significant differences in rates of remission between the 2 groups (P =.157); similar compliance rates observed (90% vs 87%) Maintenance of remission Takagi et al 20 (2006) To evaluate the efficacy of supplemental enteral nutrition as half the daily caloric intake during remission as compared with a normal diet 51 Patients (mean age of 30.8); 26 with half their caloric intake coming from enteral formula and 25 with a normal diet RCT Relapse rate was lower in those who continued using the enteral formula for half of daily caloric intake than those on a normal diet (no statistical values were reported) Wilschanski et al 21 (1996) To evaluate if continuation of nocturnal enteral nutrition as supplementation to a normal diet increased the length of remission in pediatric CD 65 Children (age range 7-17 years) with active CD, treated with EEN for 4 weeks; 28 of those who achieved remission continued nocturnal supplementation in addition to normal diet Medical record Relapse rates at 6 and 12 months were lower in those receiving nocturnal supplementation (P <.02); improvement in linear growth was seen in those receiving nocturnal supplementation when used prior to puberty versus those who did not (P =.057) Long-term outcomes of enteral nutrition Knight et al 22 (2005) To show the shortand long-term effects of enteral nutrition as primary therapy in pediatric CD 79 Patients (age range years); 44 chose enteral nutrition, and 35 chose steroid therapy Nonrandomized trial; patients were given the choice of enteral nutrition or steroid therapy. Long-term follow-up ranged from 1 to 7 years In all, 47% of patients avoided steroid use for 1 to 7 years; steroid use was postponed for a median of 68 weeks for those who required steroids; 38% remained in remission for 1 to 7 years (no statistical values reported) (continued) 115

6 April 2012 Table 3. (continued) Author (Year Published) Aim of Study Participants Methods Findings Berni Canani et al 16 (2006) To evaluate the efficacy of different enteral formulas (elemental, semielemental, and polymeric) and corticosteroids in their achievement of maintenance of disease remission 47 Patients (age range 7-17 years); 37 received 8 weeks of nutritional therapy, and 10 received corticosteroids Retrospective study with medical record Similar remission rates; 86.5% using nutritional therapy achieved remission versus 90% using corticosteroids (no statistical values reported); those on nutritional therapy showed greater mucosal healing and durations of remission (P <.001); duration of remission was longer in those who achieved remission via nutritional therapy (no statistical values reported) Yamamoto et al 23 (2007) To evaluate the impact of enteral nutrition of clinical and endoscopic disease recurrence following resection 40 Patients (mean age 32 years) who required resection for ileal or ileocolonic CD; 20 received nocturnal enteral nutrition; 20 had a normal diet and no food restrictions Prospective, nonrandomized, parallel, controlled study Enteral nutrition reduced clinical and endoscopic disease recurrence at 1 year follow-up (clinical recurrence rate of enteral nutrition versus nonenteral nutrition P =.027) Alternative nutritional supplements Akobeng et al 24 (2000) To evaluate the efficacy of glutamine-enriched formula in the treatment of active CD 18 Children (age range years); 9 received glutamineenriched polymeric formula, and 9 received standard lowglutamine polymeric formula RCT Glutamine-enriched polymeric formula has no advantages over standard formula and was less effective in decreasing disease activity; there was no significant difference between remission rates in experimental and control groups (P =.5) Bousvaros et al 25 (2005) To evaluate the role of LGG in the maintenance of pediatric CD 75 Patients (age range 5-21 years); 39 received LGG, and 36 received placebo Double-blinded RCT LGG s role in the maintenance of remission is not supported; relapse rates were similar between both the control and experimental groups (P =.18) Feagan et al 26 (2008) To evaluate the effect of high-dose omega-3 free fatty acids on the maintenance of CD remission EPIC 1: 383 adult patients; 183 receiving omega-3 and 180 receiving placebo EPIC 2: 375 adult patients; 187 receiving omega-3 and 188 receiving placebo 2 Double-blind, placebo-controlled RCTs No significant differences were shown in time to relapse or disease activity during 1 year of follow-up in either trial (EPIC 1, P =.30; EPIC 2, P =.48) Abbreviations: CD, Crohn s disease; EEN, exclusive enteral nutrition; RCT, randomized controlled trial; NG, nasogastric; LGG, Lactobacillus GG. 116

7 Table 4. Formal and Informal Nutritional Recommendations Regarding Enteral Nutrition in Management of CD American Dietetic Association 27 World Gastroenterology Organization Practice Guidelines 28 The American Society for Parenteral & Enteral Nutrition 29 The European Society for Clinical Nutrition and Metabolism Clinical Practice Guidelines 30 The Japanese Society for Pediatric Gastroenterology, Hepatology, and Nutrition 31 Crohn s and Colitis Foundation of America 24 Abbreviations: CD, Crohn s disease; IBD, irritable bowel disease. of remission, with similar compliance rates between oral and NG feeding (90% and 87%). According to the European Guidelines, induction of a normal diet is not permitted during EEN therapy 30 and is associated with a lower remission rate in a recent pediatric study. 17 Eat small meals every 3-4 hours When symptomatic, use low-fiber food Drink adequate fluids Eat foods with probiotic and prebiotic added Take a daily multivitamin When asymptomatic, introduce 1 new food Diet is a consideration and a liquid diet, predigested formula can reduce inflammation in children with CD Vitamin and mineral supplementation should be used during malnutrition or decreased oral intake Probiotics have not been shown to decrease symptoms of CD There are limited data to show that oligosaccharides, disaccharides, monosaccharides, and polyols can reduce symptoms of IBD Enteral nutrition should be used with pediatric CD patients with growth reduction Enteral therapy should be used to maintain nutrition status in times of decreased oral intake To treat undernutrition, poor growth, and maintenance of remission, enteral nutrition is recommended Whole protein formulas are preferred Insufficient data to recommend glutamine, n-3fatty acids or other pharmaconutrients B12 and folate should be measured annually Elemental formula and oral mesalazine should be used at the onset and during remission of the disease Special liquid diet may be helpful Restrict high-fiber food Eat smaller meals at frequent intervals Limit milk if lactose intolerant Polymeric formula. Polymeric formulas are more palatable than elemental formulas and thus can be taken orally 33 without significant difference in the induction of remission. 39 Rodrigues et al 9 found that although there was no increase in adherence to therapy, there was a decrease in the number of patients requiring NG administration of the formula. The authors also noted that both polymeric and elemental formulas are comparable in efficacy. Similarly, Day et al 37 found that polymeric formula has greater oral tolerability when compared with elemental formula and can therefore be given without an NG tube. Ludvigsson et al 18 found that a polymeric diet has better treatment outcomes than an elemental diet. Pros and cons. There are many benefits to the use of EEN for the induction of remission in the pediatric population. It is important to note that there are very few negative side effects related to this therapeutic option, and the child is able to avoid all corticosteroid-associated side effects, including impaired linear growth, decreased bone density, and cosmetic side effects. 37 EEN yields a greater improvement in nutritional status, linear growth, and mucosal healing than corticosteroid therapy. Linear growth improvement is partly achieved through control of mucosal inflammation. 16 Finally, EEN use decreases the need for corticosteroids. 40 Although there are many benefits to EEN use, there are some drawbacks to consider. Although compliance with therapy can be upward of 90% in pediatric patients, 12,19 it is still one of the greatest potential problems associated with this therapeutic modality. Lack of formula palatability can decrease compliance. However, polymeric formula is more palatable than elemental formula, and commercially available flavorings can be added. 7 Similarly, a large volume of formula is required for efficacy an amount not all patients are capable of consuming. NG tube feeds are always an option because some formulas can be concentrated. 7 The cost of the formula and lifestyle modifications may be a deterrent in the use of this therapy. 4 Finally, food exclusion with a liquid diet is difficult to maintain and can affect compliance. 39 Maintenance of Remission Nutrition remains a top priority once remission is achieved. Enteral nutrition, when taken as an oral supplement 117

8 April 2012 with a normal diet, can play a role in the maintenance of disease remission. 4 Supplemental enteral nutrition can help reduce the risk of relapse; provide continued improvement of nutritional status, growth, and development 41 ; facilitate catch-up growth; and help support weight gain. There is no significant difference in the maintenance of remission between elemental and polymeric formulas. 12 There are various delivery methods of enteral nutrition, including overnight NG tube feeds, oral supplementation to a regular diet, or intermittent cycles alternating EEN with a normal diet. 42 Nocturnal supplementation, specifically, allows for the child to maintain a normal diet throughout the day while continuing the benefits of additional calories and nutrients at night. This should be considered for those children who lack improvement in nutritional status despite concurrent treatment of the disease. With this method, the child is able to remove the NG tube prior to school. 43 A recent systematic of enteral nutrition for the maintenance of remission concluded that the level of evidence was not high because of a small sample size and lack of consistency between the studies. However, authors also concluded that supplemental enteral therapy can be helpful in maintaining remission. 44 In a study of adult patients with CD, Takagi et al 20 found that when patients continue to consume elemental formula for half of their daily calories, the relapse rate was lower than for those who did not. Wilschanski et al 21 conducted a study in which 28 children with remission induced by EEN were maintained by a regular diet with overnight supplementation. Two recent s pointed to the use of EEN for induction of remission of CD with supplemental enteral therapy as part 4, 45 of maintenance therapy. The use of enteral nutrition during maintenance can delay and decrease the need for corticosteroids. 4 Drawbacks of enteral nutrition during maintenance of remission are also similar to those during induction of remission. These include palatability of the formula, ease of use of supplemental formula, and lifestyle changes involved when using nutritional therapy. Knight et al 22 found that when given the option of using either corticosteroids or supplemental enteral feeds, only 55% of their patients elected to use the supplemental enteral feeds. Although they did not explore the reasons, it seems likely that the lifestyle changes are too great. There are several different approaches to the reintroduction of a normal diet during remission, which ranges between 1 and 12 weeks. 4 The most common approach is a gradual reintroduction of a normal diet. One meal is added every 2 to 3 days with a simultaneous reduction in enteral formula volume. Similarly, other approaches involve the graduation from liquids to soft foods and then a normal diet or gradual reintroduction of low-fat, low-fiber foods initially before the introduction of a normal diet. 11 Food intolerances are not uncommon, and it is suggested that after remission with EEN, a new food item should be introduced every few days. 15 Common food intolerances include wheat, milk, vegetables, citrus fruit, tomatoes, and yeast. 15 Other approaches include the immediate reintroduction of a normal diet with an immediate decrease in overnight formula feeds. 4 Once food is reintroduced, the question then becomes what a child should eat when in remission. In general, diet during remission should be varied and include fruits, vegetables, meat, oil, fish, fiber, and dairy products. Milk should not be restricted unless the child is lactose intolerant. If this is the case, it is important to add other calcium-enriched products. 46 The North American Society for Pediatric Gastroenterology, Hepatology and Nutrition recommends a balanced diet that includes all nutrients, based on the Food Guide Pyramid for children with CD. 47 Dietary supplementation should also be considered during remission, including calcium, vitamin D, and iron supplements. 46 Iron supplementation can improve the quality of life. 7 In addition, if the patient is receiving sulfasalazine as part of his or her medical therapy, vitamin B12 supplementation will be needed. 15 Long-term Outcomes of Enteral Nutrition After achieving an initial remission of CD, the question then becomes what impact enteral nutrition has on the length of remission. Berni Canani et al 16 found that nutritional therapy has a greater healing effect on the intestinal mucosa when compared with corticosteroid therapy. This effect on the mucosa was associated with a decrease in relapse rate within 1 year, indicating that the degree of mucosa healing is important in longterm remission rates. Similarly, Knight et al 22 conducted a study evaluating the long-term effects of enteral nutrition use. The authors found that the vast majority of those who received enteral nutrition achieved remission, with 38% remaining in remission from 1 to 7 years. Those who chose to continue with steroid therapy following relapse avoided steroids for a median of 68 weeks, which was related to enteral formula use. The use of enteral nutrition can also have an impact on disease recurrence. Typically, disease recurrence is high following bowel resection. 23 Yamamoto et al 23 conducted a study evaluating the effects of long-term enteral nutrition on the rates of clinical and endoscopic recurrence of the disease after resection in adult patients. Results indicated that long-term enteral nutrition decreased the rate of disease recurrence both clinically and endoscopically, with only 1 patient experiencing disease recurrence. Alternative Nutritional Supplements Omega-3 free fatty acids. Omega-3 free fatty acids are substances that can be found in marine life and can provide various health benefits. One possible important benefit is a decrease in the arachidonic acid found in inflammatory cells. 48 Feagan et al 26 conducted 2 trials evaluating the effects of omega-3 free fatty acids on the maintenance of CD in the adult population. The results indicated that there was no difference between placebo and omega-3 free fatty acid on the length of remission. Turner et al 48 also came to a similar conclusion, 118

9 stating that data do not support the use of omega-3 free fatty acids in the maintenance of CD. Probiotics. Probiotics are oral nutritional supplements containing microorganisms that can offer health benefits by altering host microflora. 49 Mechanisms of action include anti-inflammatory properties related to the production of anti-inflammatory cytokines and the suppression of proinflammatory cytokines, enhancement of the gut barrier, and, importantly, the regulation of mucosal immune response. 50 Guandalini 50 does not recommend the use of probiotics because of the lack of positive evidence. Similarly, Bousvaros et al 25 evaluated the effects of Lactobacillus GG on the maintenance of pediatric CD. Results indicated that both Lactobacillus GG and placebo had the same effect on disease relapse rate. Therefore, the authors concluded that there is no role for probiotics as supplemental therapy in the maintenance of pediatric CD. Finally, the American Academy of Pediatrics also does not recommend the use of probiotics in children because of the lack of efficacy in the maintenance of CD. 49 Glutamine. Glutamine, a nonessential amino acid, may be protective against intestinal mucosal atrophy and therefore play a role in the maintenance of CD. 12 Animal studies on the effects of glutamine in inflammatory bowel disease have shown positive results, including decreased weight loss, less severe mucosal damage, and reduced disease activity. Akobeng et al 24 conducted a study evaluating the efficacy of using glutamineenriched formula as a treatment for active CD. Results indicated that a glutamineenriched polymeric formula held no advantages over a standard low-glutamine formula. The authors, therefore, do not recommend the use of glutamine-enriched formula in the treatment of CD. Table 3 summarizes studies evaluating different alternative nutritional supplements. Summary Like JR, children with CD experience growth and development delays, along with many other nutritional deficits. Treatment and management of the disease not only has to target the associated symptoms but also the nutritional deficits and growth impairment. Nutritional therapy is optimal for a patient like JR. The goal of nutritional therapy is to help improve nutritional status, promote growth and development, and induce and maintain disease remission. EEN has been shown to be as effective as corticosteroids in the induction of remission of pediatric CD, without the side effect profile of standard steroid therapy. Enteral nutrition has also been shown to be useful in supplementation with an oral diet. No specific dietary restrictions are recommended during the maintenance of remission. Supplementation with omega-3 free fatty acids, probiotics, or glutamine has not been proven to be useful in the maintenance of remission of pediatric CD. Role of the Health Care Professional Clinical Practice The gastroenterologist, primary care provider, dietitian, registered nurse, nurse practitioner, and social worker are part of the multidisciplinary team in the management of the child with CD. 10 Nutritional monitoring is fundamental in the management of this population. Periodic assessment of growth and nutritional status is imperative and should begin at diagnosis and continue every 6 months. 7 Box 1 s the components of nutritional assessment. If dietary intake of micronutrients is inadequate, it is appropriate to suggest nutritional supplementation with multivitamins, calcium supplements, and vitamin D supplements. 40 Measuring B12 levels and folate levels should be done annually in patients with ileal CD. 8 Because food intolerances are individual to each patient, patients should be encouraged to keep a food diary and have it ed at each visit to assess any possible intolerance to foods. If caloric intake is deficient, consideration of supplemental enteral nutrition is appropriate. Physical activity should be recommended and encouraged, with no limitation as to activity type. Bed rest should also be discouraged. 40 Patient and family education, collaboration with all team members, and motivation are essential in the nutritional therapy of pediatric CD. Both the patient and family have to be prepared and willing to implement the lifestyle changes necessary for such management. Working as part of a multidisciplinary team can improve education and understanding of this treatment option. The team members help facilitate the motivation necessary to comply with and complete prescribed therapies. 16 It is important to monitor the patient and family s ability and willingness to comply with a plan of care and alter the plan if noncompliance becomes problem. 40 The best way to ensure compliance is to discuss treatment options and use shared decision making to develop an individualized plan. It is vital to discuss with both the child and family the nutritional effects of CD on the child s body, especially focusing on growth and pubertal development in adolescence. Impairments in these parameters can have a significant psychosocial impact on the child. Concerns about body image are ranked high among the adolescent population with CD, especially when differences between peers become increasingly obvious. 51 Support Groups The lives of both the child and family are altered when the child is diagnosed with CD, and as a result, support groups can be beneficial to this population. Both the patient and family should be put in contact with others who have completed the same therapy because it can benefit children to hear positive outcomes. 37 Patients and families can be directed to the Crohn s & Colitis Foundation of America, which has chapters available by state, some of which have special programs for children and adolescents. These chapters provide support resources, including community outreach, support groups, and various educational 119

10 April 2012 Box 1. Assessment of Nutritional Status in Patient With Crohn s Disease. 1. Assessment of growth: height for age, weight for age, BMI Assessment of Tanner stages Assessment of caloric intake Assessment of nutrient intake 40 Protein Fat Carbohydrates Vitamin D Calcium Iron Vitamin B12 Folate Zinc materials for patients, families, and health care providers. 52 Education Nutrition and nutritional management of this patient population is crucial. Members of the health care team need to be educated regarding general nutrition, the common nutritional deficiencies seen in CD, the importance of micronutrient dietary supplementation, nutritional therapy during both active and remissive states of CD, and the importance of compliance with treatment. It is essential for the team members to work with the dietitian and gastroenterologist to encourage the patient to maintain a balanced diet with adequate caloric and nutritional intake when not receiving EEN. It is also important to keep up to date on current research regarding the management of this population. Working with a trained, registered dietitian can help team members understand the disease process, treatment, and side effects of the alternative treatment options. Future Research Nutritional management of the child with CD has come very far since its beginnings; however, there are still many aspects that need further research. There are few large, randomized controlled trials evaluating different nutritional therapies in the pediatric population. Rather, most studies include small patient populations and are not randomized. In addition, there needs to be additional studies on the mechanism of action in nutrition therapy. Additional research is required to determine whether the partial use of enteral feeds can be effective in inducing remission. Further research is also necessary in the area of diet and dietary management of CD, specifically in the area of triggers or irritants. There appears to be no official consensus on the protocol of reintroducing a regular diet following EEN. It would be beneficial to develop a guideline for food reintroduction that is best for the patient. As mentioned, compliance with nutritional therapy, especially regarding the use of enteral formula, is problematic. Research should explore new ways to flavor the formula for palatability or concentrate it to decrease the volume of intake. It would also be beneficial to increase the amount of research evaluating the long-term benefits and outcomes of enteral nutrition and nutritional management in the pediatric population. Finally, additional research is needed in the area of alternative nutritional therapies and supplementation, including prebiotics and other complementary and alternative medicine modalities. Author s Notes The authors declared no potential conflicts of interest with respect to the research, authorship, and/ or publication of this article. References 1. Pons R, Whitten KE, Woodhead H, Leach ST, Lemberg DA, Day AS. Dietary intakes of children with Crohn s disease. Br J Nutr. 2009;102: Walsh A, Mabee J, Trivedi K. Inflammatory bowel disease. Prim Care. 2011;38: Szigethy E, Mclafferty L, Goyal A. Inflammatory bowel disease. Child Adolesc Psychiatr Clin N Am. 2010;19: Otley AR, Russell RK, Day AS. Nutritional therapy for the treatment of pediatric Crohn s disease. Expert Rev Clin Immunol. 2010;6: Kugathasan S, Nebel J, Skelton JA, et al. Body mass index in children with newly diagnosed inflammatory bowel disease: observations from two multicenter North American inception cohorts. J Pediatr. 2007;151: Akobeng AK. Crohn s disease: current treatment options. Arch Dis Child. 2008;93: Wiskin AE, Wootton SA, Beattie RM. Nutritional issues in pediatric Crohn s disease. Nutr Clin Pract. 2007;22: Van Gossum A, Cabre E, Hebuterne X, et al. ESPEN guidelines on parenteral nutrition: gastroenterology. Eur Soc Clin Nutr Metab. 2009;28: Rodrigues AF, Johnson T, Davies P, Murphy MS. Does polymeric formula improve adherence to liquid diet therapy in children with active Crohn s disease? Arch Dis Child. 2007;92: Heuschkel R, Salvestrini C, Beattie RM, Hildebrand H, Walters T, Griffiths A. Guidelines for the management of growth failure in childhood inflammatory bowel disease. Inflamm Bowel Dis. 2008;14: Day AS, Whitten KE, de Jong NSH. Nutrition and nutritional management of Crohn s disease in children and adolescents. Curr Nutr Food Sci. 2006;2: El-Matary W. Enteral nutrition as a primary therapy of Crohn s disease: the pediatric perspective. Nutr Clin Pract. 2009;24: Levin AD, Wadhera V, Leach ST, et al. Vitamin D deficiency in children with inflammatory bowel disease. Dig Dis Sci. 2011;56: Siffledeen JS, Fedorak RN, Siminoski K, et al. Randomized trial of etidronate plus calcium and vitamin D for treatment of low bone mineral density in Crohn s disease. Clin Gastroenterol Hepatol. 2005;3: Lochs H. Basics in clinical nutrition: nutritional support in inflammatory bowel disease. e-spen. 2010;5:e100-e Berni Canani R, Terrin G, Borrelli O, et al. Short- and long-term therapeutic efficacy of nutritional therapy and corticosteroids in paediatric Crohn s disease. Dig Liver Dis. 2006;38: Johnson T, Macdonald S, Hill SM, Thomas A, Murphy MS. Treatment of active Crohn s disease in children using partial enteral nutrition with liquid formula: a randomised controlled trial. Gut. 2006;55:

11 18. Ludvigsson JF, Krantz M, Bodin L, Stenhammar L, Lindquist B. Elemental versus polymeric enteral nutrition in paediatric Crohn s disease: a multicentre randomized controlled trail. Acta Paediatr. 2004;93: Rubio A, Pigmeir J, Garnier-Lengline S, et al. The efficacy of exclusive nutrition therapy in paediatric Crohn s disease, comparing fractionated oral vs. continuous enteral feeding. Aliment Pharmacol Ther. 2011;33: Takagi S, Utsunomiya K, Kuriyama S, et al. Effectiveness of an half elemental diet as maintenance therapy for Crohn s disease: a randomized-controlled trial. Aliment Pharmacol Ther. 2006;24: Wilschanski M, Sharman P, Pencharz P, Davis L, Corey M, Griffith A. Supplementary enteral nutrition maintains remission in paediatric Crohn s disease. Gut. 1996;38: Knight C, El-Matary W, Spray C, Sandhu BK. Long-term outcome of nutritional therapy in paediatric Crohn s disease. Clin Nutr. 2005;24: Yamamoto T, Nakahigashi M, Umegae S, Kitagawa T, Matsumoto K. Impact of long-term enteral nutrition on clinical and endoscopic recurrence after resection for Crohn s disease: a prospective, nonrandomized, parallel, controlled study. Aliment Pharmacol Ther. 2007;25: Akobeng AK, Miller V, Stanton J, Elbadri AM, Thomas AG. Double-blind randomized controlled trial of glutamine-enriched polymeric diet in the treatment of active Crohn s disease. J Pediatr Gastroenterol Nutr. 2000;30: Blind_Randomized_Controlled_Trial_of.22.aspx. Accessed February 3, Bousvaros A, Guandalini S, Baldassano RN, et al. A randomized, double-blind trial of Lactobacillus GG versus placebo in addition to standard maintenance therapy for children with Crohn s disease. Inflamm Bowel Dis. 2005;11: Feagan BG, Sandborn WJ, Mittmann U, et al. Omega-3 free fatty acids for the maintenance of remission in Crohn s disease: the EPIC Randomized Controlled Trials. JAMA. 2008;299: Academy of Nutrition and Dietetics. Accessed December 20, Bernstein CN, Fried M, Krabshuis JH, et al. World Gastroenterology Organization Practice guidelines for diagnosis and management of IBD in Inflamm Bowel Dis. 2010;16: ASPEN Board of Directors and the Clinical Guidelines Task Force. Guidelines for the use of parenteral and enteral nutrition in adult and pediatric patients, JPEN J Parenter Enteral Nutr. 2009;33: Lochs H, Dejong C, Hammarqvist F, et al. ESPEN guidelines on enteral nutrition: gastroenterology. Clin Nutr. 2006;25: Working Group of Japanese Society for Pediatric Gastroenterology, Hepatology and Nutrition; Konno M, Kobabayashi A, Tomamasa T, et al. Guidelines for the treatment of Crohn s disease patient in remission. Pediatr Int. 2006;22: Tighe MP, Cummings F, Afzal NA. Nutrition and inflammatory bowel disease: primary or adjuvant therapy. Curr Opin Clin Nutr Metab Care. 2011;14: Makola D. Elemental and semi-elemental formulas: are they superior to polymeric formulas? Pract Gastroenterol. 2005;34: Scholz D. The role of nutrition in etiology of inflammatory bowel disease. Curr Probl Pediatr Adolesc Health Care. 2011;41: Heuschkel RB, Menache CC, Megerian JT, Baird AE. Enteral nutrition and corticosteroids in the treatment of acute Crohn s disease in children. J Pediatr Gastroenterol Nutr. 2000;31: Dziechciarz P, Horvath, Chamir R, Szajewska H. Meta-analysis: enteral nutrition in active Crohn s disease in children. Aliment Pharmacol Ther. 2007;26: Day AS, Whitten KE, Lemberg DA, et al. Exclusive enteral feeding as primary therapy for Crohn s disease in Australian children and adolescents: a feasible and effective approach. J Gastroenterol Hepatol. 2006; 21(10): Nelms M, Sucher K, Long S. Nutrition Therapy and Pathophysiology. Belmont, CA: Thomson Wadsworth; Rajendran N, Kumar D. Role of diet in the management of inflammatory bowel disease. World J Gastroenterol. 2010;16: Rufo PA, Bousvaros A. Current therapy of inflammatory bowel disease in children. Paediatr Drugs. 2006;8: Sandhu BK, Fell JM, Beattie RM, et al. Guidelines for the management of inflammatory bowel disease in children in the United Kingdom [published online ahead of print January 13, 2010]. J Pediatr Gastroenterol Nutr. doi: / MPG.0b013e3181c92c El-Matary W, Zachos M. Nutritional therapy. In: Mamula P, Markowitz JE, Baldassano R, eds. Pediatric Inflammatory Bowel Disease. New York, NY: Springer; 2008: Kappelman MD, Bousvaros A. Nutritional concerns in pediatric inflammatory bowel disease patients. Mol Nutr Food Res. 2008;52: Yamamoto T, Nakahigashi M, Umegae S, Matsumoto K. Enteral nutrition for the maintenance of remission in Crohn s disease: a systematic. Eur J Gastroenterol Hepatol. 2010;22: Wilson DC, Thomas AG, Croft NM, Newby E, Akobeng AK, Sawczendo A. Systemic of the evidence base for the medical treatment of paediatric inflammatory bowel disease. J Pediatr Gastroenterol Nutr. 2010;50:S14-S Lucendo AJ, De Rezende LC. Importance of nutrition in inflammatory bowel disease. World J Gastroenterol. 2009;15: Kleinman RE, Baldassano RN, Caplan A, et al. Nutrition support for pediatric patients with inflammatory bowel disease: a clinical report of the North American Society for Pediatric Gastroenterology, Hepatology and Nutrition. J Pediatr Gastroenterol Nutr. 2004;39: Fulltext/2004/07000/Nutrition_Support_for_ Pediatric_Patients_With.5.aspx. Accessed February 3, Turner D, Zlotkin SH, Shah PS, Griffiths AM. Omega 3 fatty acids (fish oil) for maintenance of remission in Crohn s disease. Cochrane Database Syst Rev. 2009;1:CD Thomas DW, Greer FR; American Academy of Pediatrics Committee on Nutrition, American Academy of Pediatrics Section on Gastroenterology, Hepatology, and Nutrition. Probiotics and prebiotics in pediatrics. Pediatrics. 2010;126: Guandalini S. Update on the role of probiotics in the therapy of pediatric inflammatory bowel disease. Expert Rev Clin Immunol. 2010;6: Walters TD, Griffiths AM. Growth impairment in pediatric inflammatory bowel disease. In: Mamula P, Markowitz JE, Baldassano R, eds. Pediatric Inflammatory Bowel Disease. New York, NY: Springer; 2008: Crohn s & Colitis Foundation of America. Accessed May 31,