Short bowel syndrome (SBS) is the most common cause of pediatric intestinal failure. The goal of treatment for SBS is intestinal rehabilitation involving the transition from parenteral nutrition to enteral autonomy. In order to achieve this, intestinal adaptation must occur with resulting structural and functional changes. Enteral feeds are a necessary factor in the promotion of adaptation. Children with SBS have significant malabsorption necessitating close monitoring of growth and laboratory studies in order to prevent deficiencies and maintain adequate growth. With the many complexities of this vulnerable population, it is important to have a multidisciplinary approach to their care as demonstrated by the success of intestinal rehabilitation programs.
Intestinal failure occurs when the intestine is unable to absorb the necessary fluid and nutrition to support growth and development. The most common etiology of intestinal failure is short bowel syndrome (SBS), a term used to describe a critical loss of functional bowel length. Pediatric SBS often occurs as a result of surgical resection secondary to acquired gastrointestinal issues such as necrotizing enterocolitis or volvulus, or congenital anomalies such as gastroschisis and/ or intestinal atresias (see Table 1). The goal of intestinal rehabilitation is to promote adaptation, the process by which the remaining intestine undergoes functional and histological changes in order to increase absorption after resection.1 One of the most important stimulators of adaptation is intestinal exposure to nutrients. Over time, if carefully monitored and managed, most children with SBS will be able to transition from parenteral nutrition (PN) dependence to enteral autonomy.2
A thorough nutrition assessment is important for the management of pediatric patients with SBS. See Table 2 for baseline nutrition evaluation components. Nutrition reassessment should occur regularly with frequent reevaluation for the child on home PN. Evaluation can decrease in frequency according to the patient’s specific needs, but even older children who have become enterally autonomous require a full nutritional assessment at least annually. Management by a multidisciplinary team (including physician, pediatric surgeon, registered nurse, registered dietitian, and pharmacist) has been shown to improve morbidity and mortality for patients with SBS as well as decrease reliance on PN.3,4
Growth goals for patients with SBS are the same as other pediatric patients although growth failure is common.5-7 Weight gain at a lower percentile for age is acceptable while on PN if linear growth is tracking consistently along the child’s established growth curve. Children with SBS are at particularly high risk for growth failure in the first two years of life and during their adolescent years, both periods of high-expected growth.5,7 Some children who progress to enteral autonomy in their childhood years may require re-initiation of PN in their adolescent years if they demonstrate growth delays or other nutrient deficiencies.
Calculating Nutritional Needs
Provision of adequate calories and nutrients can promote age appropriate growth and development. Avoidance of overfeeding patients who are PNdependent is also critical in the prevention of intestinal failure associated liver disease (IFALD).8 Calories should be decreased for patients with excessive weight gain or those with weight-forlength or BMI >95th percentile for age. Generally, calories from PN are not reduced with introduction of enteral nutrition (EN) until tolerance and weight gain is established with feeds. As a result of malabsorption, enterally autonomous children with SBS may require enteral intake up to 200-250 kcal/kg/day in order to achieve adequate growth9,10 (Table 3).
Protein needs for these patients are also higher than expected for age due to increased gastrointestinal losses. Infants who are PN dependent may require up to 4 g/kg/day while older children may require 2-3 g/kg/day of protein from a combination of intake types even into adolescent years to maintain appropriate growth and development.9,10
Fluid needs to maintain hydration are typically higher than age matched controls due to high GI losses. Actual fluid needs may vary depending on the length of remaining bowel, portion of remaining bowel (those with preserved colon often have lower fluid requirements), and total daily stool or ostomy output. Some patients who are enterally autonomous may have even higher fluid requirements of up to 150-200 mL/kg due to higher GI losses. Furthermore, these increased losses often necessitate a higher sodium provision, both parenterally while receiving PN, and enterally, after enteral autonomy is attained.
With the significant risk of nutrient deficiencies, regular laboratory monitoring is required. This is especially important for patients who are on parenteral nutrition. There is significant variation in the frequency of lab monitoring recommended by different intestinal rehabilitation centers and authors.11-13 See Table 4 for a suggested lab monitoring protocol.
Careful management of PN by multidisciplinary intestinal rehabilitation teams has allowed for significant improvements in survival as a result of decreases in complications associated with PN and the required central venous access.14 Recent advances in PN include:
- New lipid formulations that have helped decrease IFALD and,
- Careful management of micronutrient delivery.
However, challenges remain with frequent product shortages of nearly all PN components.
Until recently, the only FDA-approved intravenous lipid emulsion (IVLE) in the U.S. was soybean oil-based Intralipid™ (Baxter/Fresenius Kabi). These products contain high levels of proinflammatory omega-6 fatty acids and hepatotoxic phytosterols shown to contribute to development and progression of IFALD.15 In order to minimize these negative effects, Intralipid™ doses are often restricted to 0.5-1.0g/kg/day with improvement in liver disease. This change typically necessitates an increase in glucose infusion rates to make up for lost lipid calories. High glucose infusion rates can further contribute to IFALD. To help address these issues, Omegaven™ (Fresenius Kabi), a fish oil-based lipid emulsion consisting of only omega-3 fatty acids, was introduced in the early 2000s. Because it was found to successfully reverse cholestasis in IFALD,16 Omegaven™ was FDA-approved in 2018 for use in children with PN-associated cholestasis. Concerns have been raised regarding development of fatty acid abnormalities related to the isolated provision of omega-3 fatty acids long-term. Recently the FDA approved SMOFlipid™ (Fresenius Kabi) for use in adults. It is currently being widely used off-label for children with SBS. SMOFlipid™ is a mixedlipid emulsion consisting of 30% soy, 30% MCT, 25% olive, and 15% fish oil. Studies of children with intestinal failure have shown prevention of IFALD with SMOFlipid™.17-19 Fish-oil lipid emulsion may still be necessary to treat cholestatic IFALD if it develops despite use of SMOFlipid™. While Omegaven™ is typically dosed at 1 gm/kg/ day, SMOFlipid™ has been shown to be safe at higher doses allowing for an improved balance of calories. There is evidence that at least 2 g/kg/day of SMOFlipid™ is necessary to prevent and treat essential fatty acid deficiency.20,21 With changes in the amount of fatty acids provided with various IVLE, it is suggested that the individual levels of fatty acids, specifically linoleic acid, alphalinolenic acid, Mead acid, and the triene-to-tetraene ratio all be taken into account when considering the fatty acid status of a patient.22 Table 5 compares the contents of the three IVLE commonly used in pediatric SBS.23
In order to promote adaptation and prevent intestinal atrophy, enteral feeds are started as soon as possible after intestinal resection.24,25 Some children can achieve nutritional goals by mouth while others may require a feeding tube. With the heterogenous nature of SBS, there is no optimal feeding regimen or advancement schedule that is appropriate for all patients, although in general, initial trophic feeds are started and advanced slowly. Advancement is continued if stool frequency and volume does not drastically increase. For patients with an ostomy, goal output is typically <30-40ml/kg/day, although patients may tolerate higher amounts without significant dehydration or electrolyte imbalances as long as the output and laboratory studies are carefully monitored.
Human breast milk is preferred as it contains growth factors, immunoglobulins, and other components that stimulate adaptation.26 If breast milk is not available, elemental formula has historically been used, although there is evidence in animal studies that more complex nutrients promote adaptation.27 Human studies have been small and do not clearly show benefit of one type of feeding over another.25 With a lower osmotic load, children with SBS often tolerate larger volumes of lower caloric density formula, so it is our practice to start with dilute standard infant formula. Typically, this involves starting with 15 kcal/oz formula for infants and 20 kcal/oz for older children and delaying increasing caloric density until tolerating goal volume feeds and PN is being weaned.
The increased interest in whole food-based formulas has brought us commercially available, nutritionally complete products that resemble a blenderized feed. While some patients require blenderized feeds to be diluted, as they often have a high caloric density, others, especially those with a colon segment, tolerate them well. There is a likely benefit from the significant fiber content in many blenderized formulas which not only acts as a prebiotic, but slows down intestinal transit allowing more time for absorption, and provides the fuel for colonocytes to make short chain fatty acids providing additional calories to the patient.28,29
Children with SBS are at high risk for developing oral aversion due to their complicated medical history and the limitations on enteral feeds early on. It can also be a limiting factor in the ability to wean a patient off of PN as patients tend to tolerate larger amounts of food orally even if they do not tolerate larger volumes or more calorically dense formula. In order to avoid oral aversion, it is important to start oral feeds as early as possible even if the feed volume is minimal. With improvements in long-term PN management, there is less pressure to quickly advance enteral feeds allowing infants to develop the necessary oral skills. Although many programs use gastrostomy tubes for slow continuous feeding, delay of gastrostomy placement may help achieve these early oral feeding goals and prevent development of oral aversion by focusing all feeding efforts on the oral route. If patients are being tube fed, feeds can be held to allow for bottle feeds several times per day. A nocturnal regimen can give the child time off the pump during the day and help to stimulate hunger to aid in oral intake.
As the child approaches 6 months corrected age, age-appropriate foods should be introduced with a focus on vegetables, proteins, and complex carbohydrates. Children with SBS need to follow a diet low in sugar (natural, added, sugar alcohols [sorbitol, mannitol, xylitol, erythritol], or artificial sweeteners) as sugars and sweeteners can create an osmotic load contributing to increased stool output. Sugars can also worsen small intestinal bacterial overgrowth which can cause diarrhea, abdominal distention, emesis, poor growth, intestinal bleeding, and may contribute to IFALD.30 While some sugar and artificial sweeteners may be tolerated, following the recommendation to avoid sweet tasting food in young children may prevent them from developing a preference for sweet foods.
Children with SBS are at high risk for multiple micronutrient deficiencies while receiving full PN, during the transition to enteral nutrition, and once enterally autonomous.31 In recent years, PN component shortages have become more common resulting in deficiencies.32 In order to address individual trace element deficiencies in PN-dependent patients, it is important to be able to adjust them individually. Use of commercially available standard pediatric PN trace element solutions can also result in manganese and chromium toxicity as these micronutrients are both found as contaminants in PN. For these reasons, separate dosing of trace elements is recommended for pediatric SBS patients.
The degree of micronutrient risk and deficiencies vary depending on the length of bowel and which portions of the intestine remain. Those with loss of the terminal ileum are at higher risk for fat soluble vitamin deficiencies, vitamin B12 deficiency, as well as essential fatty acid deficiency. With increased overall gastrointestinal losses, patients are also at risk of sodium, magnesium, and zinc deficiencies. While there are numerous deficiencies seen in SBS, some of the most common include iron, fat-soluble vitamins, vitamin B12, and iodine.
Iron deficiency is the most common deficiency seen in SBS. Iron infusions are often needed for those receiving significant amounts of PN and enteral supplementation in those off PN. Iron is not typically included in PN, although iron dextran has been added to lipid-free PN by some groups.33 While children who have reached enteral autonomy will likely tolerate enteral iron supplementation, children receiving full PN support will likely require IV iron infusions to treat and prevent iron deficiency. Iron sucrose has traditionally been used anywhere from weekly to monthly in order to replete and maintain iron stores. More recently ferric carboxymaltose has been used in patients with inflammatory bowel disease with iron deficiency. It is given at a higher dose than iron sucrose and has structural alterations that lead to longer duration of drug activity.34 Hypophosphatemia, which can be severe and symptomatic, has been associated with ferric carboxymaltose making it essential to follow patient labs and clinical status in the weeks following infusion.35,36 With careful monitoring, ferric carboxymaltose may help SBS patients require less frequent infusions (and line access) with improved iron status.
Fat malabsorption is a common complication of SBS and a factor in the development of fatsoluble vitamin deficiencies. The doses of fatsoluble vitamins required for enterally autonomous patients can be quite high secondary to significant malabsorption. Vitamin A deficiency tends to respond well to enteral supplementation while vitamin E often requires a water-soluble formulation to optimize absorption. The dose of vitamin D included in the parenteral multivitamin is rarely enough to prevent vitamin D deficiency requiring additional supplementation.37 With no separate parenteral form of vitamin D available in the United States, vitamin D deficiency that is refractory to enteral supplementation may require transition to calcitriol. There is a significant amount of vitamin E in both SMOFlipid™ and Omegaven™, typically preventing vitamin E deficiency until patients are off intravenous lipids (Table 5).
Vitamin B12 requires the terminal ileum for foodbound B12 absorption. Deficiency can lead to megaloblastic anemia and irreversible neurologic changes. As it is supplemented in PN, deficiency is often not an issue until patients are enterally autonomous. For monitoring, it is important to check both a B12 and methylmalonic acid level, as serum B12 levels can be unreliable.38 Elevated methylmalonic acid levels are found in B12 deficiency, but can also be seen in small intestinal bacterial overgrowth so it is important to evaluate the patient’s entire clinical picture when interpreting these labs.39,40 Supplementation for children with SBS is most reliable in the injectable and nasal forms although sublingual preparations may be used as well. Oral B12 supplements are typically not useful in SBS due to significant malabsorption, the loss of the distal ileum in many patients, and the small amount of B12 that is passively absorbed when given in high doses via the oral route.38
Iodine is another micronutrient of concern for children who are fully dependent on PN (>70% of calories provided by PN) as it is not routinely included in PN solutions in the United States and is important for growth and development. Monitoring of thyroid hormones, thyroglobulin, as well as urine iodine levels can help identify patients with iodine deficiency.11,41 Iodine deficiency should be considered for urinary iodine levels <100 mcg/L; <50 mcg/L indicates moderate, and <20 mcg/L, severe deficiency.42 Repletion of iodine can be difficult to achieve in children who are fully PN dependent, as they will not likely absorb an enteral supplement such as iodized salt. The use of ultradilute potassium iodide or topical iodine may be useful.43
Nutritional management is a major focus of intestinal rehabilitation in children with pediatric SBS. Multidisciplinary intestinal rehabilitation programs have been shown to improve the care and outcomes for this medically and surgically complex population. With careful monitoring of growth and nutritional lab values, prevention of complications associated with PN, and transition to enteral feeds with slow advancement, intestinal adaptation and enteral autonomy is achievable in most children with SBS.
- Tappenden KA: Intestinal adaptation following resection. J Parenter Enteral Nutr. 2014;38(1 Suppl):23S-31S.
- Fallon EM, Mitchell PD, Nehra D, et al: Neonates with short bowel syndrome: an optimistic future for parenteral nutrition independence. JAMA Surg. 2014;149(7):663-70.
- Stanger JD, Oliveira C, Blackmore C, et al: The impact of multidisciplinary intestinal rehabilitation programs on the outcome of pediatric patients with intestinal failure: a systematic review and meta-analysis. J Pediatr Surg. 2013;48(5):983-92.
- Vlug LE, Nagelkerke SCJ, Jonkers-Schuitema CF, et al: The role of a nutrition support team in the management of intestinal failure patients. Nutrients. 2020;12(1):172.
- McLaughlin CM, Channabasappa N, Pace J, et al: Growth trajectory in children with short bowel syndrome during the first 2 years of life. J Pediatr Gastroenterol Nutr. 2018;66(3):484-8.
- Pichler J, Chomtho S, Fewtrell M, et al: Growth and bone health in pediatric intestinal failure patients receiving long-term parenteral nutrition. Am J Clin Nutr. 2013;97(6):1260-9.
- Miyasaka EA, Brown PI, Kadoura S, et al: The adolescent child with short bowel syndrome: new onset of failure to thrive and need for increased nutritional supplementation. J Pediatr Surg. 2010;45(6):1280-6.
- Ching YA, Gura K, Modi B, et al: Pediatric intestinal failure: nutrition, pharmacologic, and surgical approaches. Nutr Clin Pract. 2007;22(6):653-63.
- Rossi L, Kadamba P, Hugosson C, et al: Pediatric short bowel syndrome: adaptation after massive small bowel resection. J Pediatr Gastroenterol Nutr. 2007;45(2):213-21.
- Mirtallo J, Canada T, Johnson D, et al: Safe practices for parenteral nutrition. J Parenter Enteral Nutr. 2004;28(6):S39-70.
- Zemrani B, Bines JE: Monitoring of long-term parenteral nutrition in children with intestinal failure. JGH Open. 2019;3(2):163-72.
- Cole CR, Kocoshis SA: Nutrition management of infants with surgical short bowel syndrome and intestinal failure. Nutr Clin Prac. 2013;28(4):421-8.
- Nucci AM, Ellsworth K, Michalski A, et al: Survey of nutrition management practices in centers for pediatric intestinal rehabilitation. Nutr Clin Pract. 2018;33(4):528-38.
- Merritt RJ, Cohran V, Raphael BP, et al: Intestinal rehabilitation programs in the management of pediatric intestinal failure and short bowel syndrome. J Pediatr Gastroenterol Nutr. 2017;65(5):588-96.
- Khalaf RT, Sokol RJ: New insights into intestinal failure-associated liver disease in children. Hepatology. 2020;71(4):1486-98.
- Nandivada P, Fell GL, Gura KM, et al: Lipid emulsions in the treatment and prevention of parenteral nutrition-associated liver disease in infants and children. Am J Clin Nutr. 2016;103(2):629S-34S.
- Diamond IR, Grant RC, Pencharz PB, et al: Preventing the progression of intestinal failure-associated liver disease in infants using a composite lipid emulsion: A pilot randomized controlled trial of SMOFlipid. J Parenter Enteral Nutr. 2017;41(5):866-877.
- Goulet O, Antébi H, Wolf C, et al: A new intravenous fat emulsion containing soybean oil, medium-chain triglycerides, olive oil, and fish oil: a single-center, double-blind randomized study on efficacy and safety in pediatric patients receiving home parenteral nutrition. J Parenter Enteral Nutr. 2010;34(5):485-95.
- Ho BE, Chan SC, Faino AV, et al: Evaluation of SMOFlipid in Pediatric Intestinal-Failure Patients and Its Effects on Essential Fatty Acid Levels. J Parenter Enteral Nutr. 2020 May 15.
- Carey AN, Rudie C, Mitchell PD, et al: Essential fatty acid status in surgical infants receiving parenteral nutrition with a composite lipid emulsion: a case series. J Parenter Enteral Nutr. 2019;43(2):305- 310.
- Memon N, Hussein K, Hegyi T, et al: Essential fatty acid deficiency with SMOFlipid reduction in an infant with intestinal failure-associated liver disease. J Parenter Enteral Nutr. 2019;43(3):438-441.
- Gramlich L, Ireton-Jones C, Miles JM, et al: Essential fatty acid requirements and intravenous lipid emulsions. J Parenter Enteral Nutr. 2019;43(6):697-707.
- Vanek VW, Seidner DL, Allen P, et al: A.S.P.E.N. position paper: Clinical role for alternative intravenous fat emulsions. Nutr Clin Pract. 2012;27(2):150-92.
- Castillo RO, Feng JJ, Stevenson DK, et al: Altered maturation of small intestinal function in the absence of intraluminal nutrients: rapid normalization with refeeding. Am J Clin Nutr. 1991;53(2):558-61.
- Olieman JF, Penning C, Ijsselstijn H, et al: Enteral nutrition in children with short-bowel syndrome: current evidence and recommendations for the clinician. J Am Diet Assoc. 2010;110(3):420-6.
- Pereira-Fantini PM, Thomas SL, Taylor RG, et al: Colostrum supplementation restores insulin-like growth factor -1 levels and alters muscle morphology following massive small bowel resection. J Parenter Enteral Nutr. 2008;32(3):266-75.
- Bines JE, Taylor RG, Justice F, et al: Influence of diet complexity on intestinal adaptation following massive small bowel resection in a preclinical model. J Gastroenterol Hepatol. 2002;17(11):1170-9.
- Kles KA, Chang EB: Short-chain fatty acids impact on intestinal adaptation, inflammation, carcinoma, and failure. Gastroenterology. 2006;130(2 Suppl 1):S100-5.
- Samela K, Mokha J, Emerick K, et al: Transition to a tube feeding formula eith real food ingredients in pediatric patients with intestinal failure. Nutr Clin Pract. 2017;32(2):277-81.
- Rodriguez D, Ryan P, Toro Monjaraz EM, et al: Small intestinal bacterial overgrowth in children: A state-of-the-art review. Front Pediatr. 2019;7(1):1-19.
- Ubesie AC, Kocoshis SA, Mezoff AG, et al: Multiple micronutrient deficiencies among patients with intestinal failure during and after transition to enteral nutrition. J Pediatr. 2013;163(6):1692-6.
- Smith A, Feuling MB, Larson-Nath C, et al: Laboratory monitoring of children on home parenteral nutrition: a prospective study. J Parenter Enteral Nutr. 2018;42(1):148-55.
- Lee D, Barsky D, Hughes R, et al: Evaluation of the safety of iron dextran with parenteral nutrition in the paediatric inpatient setting. Nutr diet. 2017;74(5):471-5.
- Laass MW, Straub S, Chainey S, et al: Effectiveness and safety of ferric carboxymaltose treatment in children and adolescents with inflammatory bowel disease and other gastrointestinal diseases. BMC gastroenterology. 2014;14:184.
- Wolf M, Chertow GM, Macdougall IC, et al: Randomized trial of intravenous iron-induced hypophosphatemia. JCI Insight. 2018;3(23):e124486.
- Anand G, Schmid C: Severe hypophosphataemia after intravenous iron administration. BMJ Case Rep. 2017 Mar 13;2017:bcr2016219160.
- Ubesie AC, Heubi JE, Kocoshis SA, et al: Vitamin D deficiency and low bone mineral density in pediatric and young adult intestinal failure. J Pediatr Gastroenterol Nutr. 2013;57(3):372-6.
- Stabler SP: Vitamin B12 deficiency. N Engl J Med. 2013;368(21):2041-2.
- Jimenez L, Stamm DA, Depaula B, et al: Is serum methylmalonic acid a reliable biomarker of vitamin B12 status in children with short bowel syndrome: a case series. J Pediatr. 2018;192:259-261.
- Davis ET, Strogach I, Carobene M, et al. Paradoxical Elevation of Both Serum B12 and Methylmalonic Acid Levels in Assessing B12 Status in Children with Short-Bowel Syndrome. JPEN J Parenter Enteral Nutr. 2020 Jan 27.
- Cicalese MP, Bruzzese E, Guarino A, et al: Requesting iodine supplementation in children on parenteral nutrition. Clin Nutr. 2009;28(3):256-9.
- Johnsen JC, Reese SA, Mackay M, et al: Assessing selenium, manganese, and iodine status in pediatric patients receiving parenteral nutrition. Nutr Clin Pract. 2017;32(4):552-6.
- Ikomi C, Cole CR, Vale E, et al: Hypothyroidism and iodine deficiency in children on chronic parenteral nutrition. Pediatrics. 2018;141(4):e20173046.