Marialena Mouzaki Anne Marie Griffiths
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Treatment of Active Crohn Disease
Evidence of Efficacy
Most data concerning the efficacy of EEN in treat- ing active Crohn disease relate to clinical end- points. Response to EEN has been associated with endoscopic healing in uncontrolled studies. In a recent controlled trial among 35 children treated for active Crohn disease, clinical response was as- sociated with endoscopic improvement in 77%
with EEN, but in only 33% with steroids [7] . Patient Selection
Roughly 50–60% of Crohn disease patients treated with EEN achieve clinical remission [3] . The re- sponse depends on the patient population. Recent- onset disease may be more responsive [3] , perhaps contributing to the superior response rates report- ed in small trials conducted exclusively among children and summarized in a meta-analysis of outcomes in paediatric trials [8] . Although contro- versial, predominantly small intestinal inflamma- tion is considered more likely to respond to EEN, compared with isolated Crohn colitis [6, 9] . This may be a reflection of the fact that Crohn colitis is particularly difficult to control. European and American guidelines advocate in favour of EEN use, irrespective of disease location [5, 10] . EEN is not used to treat ulcerative colitis.
Therapeutic Regimens
Exclusive versus Supplementary Enteral Nutrition
To be successful, EEN should be the sole source of nutrition. Allowance of regular food during treatment of active disease compromises its effi- cacy [11] and may induce satiety and intolerance of the amounts of prescribed formula.
Screening for micronutrient deficiencies (e.g.
vitamin D) should guide the need for supplemen- tation. The micronutrient content of the formula, as well as its mucosal healing effects, is also ex- pected to assist in the correction of nutritional imbalances [12] .
Mode of Administration
Liquid diets may be sipped orally or administered via a silastic nasogastric feeding tube (NG tube;
size: 6 or 8 Fr). Most children learn to insert the NG tube and administer the formula overnight.
The tube is removed each morning to facilitate daytime activities. When use over a period of months is contemplated, an indwelling gastros- tomy tube may be inserted.
Target Volume and Calories
EEN should provide 100% of the patient’s esti- mated caloric and protein requirements. These are calculated using normal predictive equations (e.g. Schofield, WHO equation, etc.; summarized in the clinical guidelines by the NASPGHAN Committee on Inflammatory Bowel Disease) [5] . In the setting of malnutrition, ideal body weight (the weight for the patient’s age that corresponds to the same percentile on the growth chart as their height percentile) should be used instead of ac- tual weight to prevent underfeeding. An activity factor should be added for the estimation of total energy requirements. Maintenance fluid volumes do not have to be provided exclusively via EEN as consumption of clear fluids is also allowed.
When using NG feeding, infusion rates should be increased in a stepwise manner considering tol- erance. The duration of infusion is gradually de- creased. A sample protocol for the gradual increase to full feeds is given in table 1 . Most young patients aim to complete the infusion over 10–14 h.
Choice of Formula
Polymeric, peptide-based and amino acid-based formulae have all been used to treat active Crohn disease [3] . There is general agreement that the protein content of liquid diets does not influence their efficacy [3] . Dietary lipids, however, can modulate inflammation by a variety of mecha- nisms which influence cellular production of cytokines and eicosanoids [3, 13] . While the amount and type of fat may modulate inflamma- tory pathways, the therapeutic success achieved
Koletzko B, et al. (eds): Pediatric Nutrition in Practice. World Rev Nutr Diet. Basel, Karger, 2015, vol 113, pp 239–243 DOI: 10.1159/000360345
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with a variety of both polymeric (usually high- fat) and elemental (usually low-fat) formulae suggests that efficacy does not depend solely on fat content.
For those determined to drink the liquid diet, a polymeric formula must be used because of its greater palatability. If the formula is to be admin- istered by NG tube, its palatability becomes un- important. Given the influence of fat content on efficacy, a conventional elemental liquid diet (low fat content) may offer some therapeutic advan-
tage. The treatment benefit of a low-fat compared with a conventional polymeric diet is admittedly small [3] .
Duration of EEN
The required duration of EEN has not been well defined. Improvements in clinical and laboratory parameters occur quickly, often by 2 weeks, but the optimal time for achievement of mucosal healing has not been established. Most gastroen- terologists suggest continuing the therapy for a
Table 1. Proposed protocol for the initiation of EEN
Initial rate of feeds Start with half of the target hourly volume and give continuously over 24 h
Increasing feeds Increase by 10 ml/h every 3–6 h, depending on symptoms Cycling feeds Decrease the overall feed duration by 2–3 h every day; the rate is
determined by the total volume to be given over the desired number of hours
Final goal of feeds The maximum rate is usually 6–8 ml/kg/h; the final duration of feeding is 10–14 h
Table 2. Sample protocol for reintroduction of solid foods Day of
introduction
Type of food Examples
1–4 Grains; low fibre White flour bread, crackers, pasta, rice Hot cereal: cream of wheat
Cold cereal (low fat, low fibre) 5–9 Meat, fish and
alternatives;
low fibre, low fat
Plain (not fried, not processed) lamb, veal, beef, pork, chicken, turkey
Fish (low fat) Tofu Eggs 10–14 Fruits and vegetables;
low fibre, low fat
Raw fruits without skin/seeds Canned fruits without skin/seeds Cooked vegetables without skin/seeds 15–17 Dairy; low fat Milk, yogurt, cheese
18 Regular diet Slowly increasing fat and fibre content based on tolerance
242 Mouzaki Griffiths
minimum of 6 weeks, longer if ideal weight has not been reached yet.
Reintroduction of Solid Food
Foods are usually reintroduced gradually. It may be prudent, particularly if there are intestinal strictures, to offer a low-fibre diet initially follow- ing completion of the enteral nutrition regimen.
A sample order of food reintroduction is given in table 2 .
Facilitation of Linear Growth
Impairment of linear growth commonly compli- cates Crohn disease. The major contributing fac- tors are the direct growth-inhibiting effects of proinflammatory cytokines produced by the in- flamed intestine and chronic undernutrition [14] . Inappropriate use of chronic corticosteroid ther- apy will also impede linear growth. Other treat- ment strategies, which induce mucosal healing, will be associated with reduced cytokine produc- tion and will facilitate growth as long as the con- trol of inflammation can be sustained. Resump- tion of normal linear growth is a marker of thera- peutic success. Conversely, if a child merely gains weight but does not grow normally in height, it can be assumed that the inflamed intestine is not healing, and that other anti-inflammatory inter- ventions must be adopted.
Maintenance of Clinical Remission
Symptoms tend to recur following the cessation of enteral nutrition. In most studies, 60–70% of pa- tients experience a symptomatic relapse within 12 months of enteral nutrition [3] . Two nutritional strategies can be considered to maintain remis- sion: firstly, ‘cyclical EEN’, meaning administra- tion of a liquid diet and avoidance of regular food 1 month out of 4, or, secondly, ‘supplementary en- teral nutrition’. The latter, which has been em- ployed primarily if nocturnal NG feeding is used, involves continuation of such feeding 4–5 times weekly as supplement to an unrestricted ad libitum daytime diet [15] . In Europe, the most common strategy to maintain clinical remission following EEN is institution of immunomodulatory drugs.
Conclusions
• Exacerbations of Crohn disease, particularly involving the small intestine, may be treated with 4–6 weeks of EEN
• Use of palatable polymeric formulae may avoid the need for nocturnal NG infusion • Because relapse is common following cessa-
tion of enteral nutrition, strategies to maintain remission must be planned
• Sustained, normal linear growth is a marker of success of therapy
5 Critch J, Day AS, Otley A, et al: Use of enteral nutrition for the control of intes- tinal inflammation in pediatric Crohn disease. J Pediatr Gastroenterol Nutr 2012; 54: 298–305.
6 Buchanan E, Gaunt WW, Cardigan T, et al: The use of exclusive enteral nutrition for induction of remission in children with Crohn’s disease demonstrates that disease phenotype does not influence clinical remission. Aliment Pharmacol Ther 2009; 30: 501–507.
References
1 Voitk AJ, Echave V, Feller JH, et al: Ex- perience with elemental diet in the treat- ment of inflammatory bowel disease: is this primary therapy? Arch Surg 1973;
107: 329–333.
2 Levine A, Milo T, Buller H, Markowitz J:
Consensus and controversy in the man- agement of pediatric Crohn disease: an international survey. J Pediatr Gastroen- terol Nutr 2003; 36: 464–469.
3 Zachos M, Tondeur M, Griffiths AM: En- teral nutritional therapy for induction of remission in Crohn’s disease. Cochrane Database Syst Rev 2007; 1:CD000542.
4 Leach ST, Mitchell HM, Eng WR, Zhang L, Day AS: Sustained modulation of in- testinal bacteria by exclusive enteral nutrition used to treat children with Crohn’s disease. Aliment Pharmacol Ther 2008; 28: 724–733.
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7 Borrelli O, Cordischi L, Cirulli M, et al:
Polymeric diet alone versus corticoste- roids in the treatment of active pediatric Crohn’s disease: a randomized con- trolled open-label trial. Clin Gastroen- terol Hepatol 2006; 4: 744–753.
8 Heuschkel RB, Menache CC, Megerian JT, Baird AE: Enteral nutrition and cor- ticosteroids in the treatment of acute Crohn’s disease in children. J Pediatr Gastroenterol Nutr 2000; 31: 8–15.
9 Afzal NA, Davies S, Paintin M, Arnaud- Battandier F, Walker-Smith JA, Murch S, Heuschkel R, Fell J: Colonic Crohn’s disease in children does not respond well to treatment with enteral nutrition if the ileum is not involved. Dig Dis Sci 2005; 50: 1471–1475.
10 Sandhu BK, Fell JM, Beattie RM, Mitton SG, Wilson DC, Jenkins H; IBD Working Group of the British Society of Paediat- ric Gastroenterology, Hepatology, and Nutrition: Guidelines for the manage- ment of inflammatory bowel disease in children in the United Kingdom. J Pedi- atr Gastroenterol Nutr 2010; 50(suppl 1):
S1–S13.
11 Johnson T, Macdonald S, Hill SM, Thomas A, Murphy MS: Treatment of active Crohn’s disease in children using partial enteral nutrition with liquid for- mula: a randomized controlled trial. Gut 2006; 55: 356–361.
12 Gerasimidis K, Talwar D, Duncan A, Moyes P, Buchanan E, Hassan K, O’Reilly D, McGrogan P, Edwards CA:
Impact of exclusive enteral nutrition on body composition and circulating mi- cronutrients in plasma and erythrocytes of children with active Crohn’s disease.
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13 Gassull MA, Fernỏndez-Baủares F, Ca- bré E, Papo M, Giaffer MH, Sánchez- Lombraủa JL, Richart C, Malchow H, González-Huix F, Esteve M: Fat compo- sition may be a clue to explain the pri- mary therapeutic effect of enteral nutri- tion in Crohn’s disease: results of a double blind randomized multicentre European trial. Gut 2002; 51: 164–168.
14 Walters T, Griffiths A: Mechanisms of growth impairment in pediatric Crohn’s disease. Nat Rev Gastroenterol Hepatol 2009; 6: 513–523.
15 Wilschanski M, Sherman P, Pencharz P, Davis L, Corey M, Griffiths A: Supple- mentary enteral nutrition maintains remission in paediatric Crohn’s disease.
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3 Nutritional Challenges in Special Conditions and Diseases
Key Words
Cystic fibrosis ã Nutritional status ã Pancreatic enzymes ã Gastrostomy
Key Messages
• Survival from cystic fibrosis (CF) has substantially improved over the past four decades. The advance in nutritional management is one factor which has contributed to this change
• This chapter reviews the basic defect of CF and how it influences nutritional status
• Normal growth and development can be achieved in CF, and to this end, nutritional counseling is para- mount at all ages. The prevention and early detec- tion of growth failure is the key to successful nutri- tional counseling
• An approach to the CF patient who is not thriving and an outline of nutritional management is pro- posed © 2015 S. Karger AG, Basel
Introduction
Cystic fibrosis (CF) is the most common life- threatening autosomal recessive disease in Cau- casians with an incidence of 1 in 2,500 live births.
The disease is caused by mutations in the cftr gene on chromosome 7, which codes for a cAMP-reg- ulated chloride channel [1] . Nonfunctioning CFTR protein affects epithelial ion and water
transport in a variety of organs including the re- spiratory, gastrointestinal, hepatobiliary, repro- ductive and sweat glands. The lack of CFTR func- tion in the pancreatic duct is responsible for ob- struction and autodigestion of the pancreas in utero, leading to exocrine pancreatic insufficien- cy (PI) in 85% of CF infants.
The early growth of infants with PI due to CF is dependent on the age at diagnosis. Clinical di- agnosis may be difficult unless meconium ileus occurs, typically in only 15% of cases. The re- maining patients are diagnosed later, mainly pre- senting with failure to thrive with steatorrhea, ac- companied in some cases with respiratory symp- toms. An increasing number of countries have initiated newborn screening for CF using a se- rum marker of PI, and this has been shown to facilitate an earlier diagnosis with better growth and nutritional status [2] . Longer-term studies after neonatal screening are now revealing re- duced pulmonary disease progression [3] .
Numerous studies have shown that under- weight and poor linear growth in children and malnutrition in adults are independent factors predicting mortality [4, 5] . Together with this, undernutrition has been shown to have an ad- verse effect on the outcome of lung transplanta- tion [6] . These data reinforce the importance of the prevention and early detection of growth fail- ure, leading to the aggressive management of nu-
Koletzko B, et al. (eds): Pediatric Nutrition in Practice. World Rev Nutr Diet. Basel, Karger, 2015, vol 113, pp 244–249 DOI: 10.1159/000367876