Enteral Nutrition in the Management of Pediatric Intestinal Failure

Abstract

Intestinal failure (IF) is an uncommon but devastating condition whose natural history has dramatically improved over the past 2 decades.1Duggan C.P. Gura K.M. Jaksic T. Clinical management of intestinal failure. Introduction: A multidisciplinary approach to intestinal failure. CRC Press, Boca Raton, FL2012Google Scholar Infants with IF because of severe short bowel syndrome (SBS) or other diagnoses previously considered incompatible with life are now routinely being saved and cared for in cutting edge, multidisciplinary programs. Enteral nutrition (EN) plays a central role in the management of children with IF. This review provides an overview of EN in pediatric IF, with specific emphasis on recent advances in clinical management, patient outcomes, and emerging therapies.DefinitionsIF occurs when there is a reduction of functional intestinal mass necessary for adequate digestion and absorption for nutrient, fluid, and growth requirements, resulting in the need for intensive nutritional support. The American Gastroenterological Association defines IF as the condition that results “from obstruction, dysmotility, surgical resection, congenital defect, or disease-associated loss of absorption and is characterized by the inability to maintain protein-energy, fluid, electrolyte, or micronutrient balance.”2O'Keefe S.J. Buchman A.L. Fishbein T.M. Jeejeebhoy K.N. Jeppesen P.B. Shaffer J. Short bowel syndrome and intestinal failure: consensus definitions and overview.Clin Gastroenterol Hepatol. 2006; 4: 6-10Abstract Full Text Full Text PDF PubMed Scopus (376) Google Scholar IF resulting from extensive intestinal resection is termed SBS (the common etiologies are listed in Table I), but other etiologies of IF are increasingly appreciated, including a wide range of gastrointestinal epithelial and motility disorders.Table IEtiologies of SBS in children in North AmericaCause of SBS in childrenSquires et al44Squires R.H. Duggan C. Teitelbaum D.H. Wales P.W. Balint J. Venick R. et al.Natural history of pediatric intestinal failure: initial report from the Pediatric Intestinal Failure Consortium.J Pediatr. 2012; 161: 723-728.e2Abstract Full Text Full Text PDF PubMed Scopus (312) Google Scholarn = 272Quiros-Tejeira63Quiros-Tejeira R.E. Ament M.E. Reyen L. Herzog F. Merjanian M. Olivares-Serrano N. et al.Long-term parenteral nutritional support and intestinal adaptation in children with short bowel syndrome: a 25-year experience.J Pediatr. 2004; 145: 157-163Abstract Full Text Full Text PDF PubMed Scopus (254) Google Scholarn = 78Wales et al64Wales P.W. de Silva N. Kim J. Lecce L. To T. Moore A. Neonatal short bowel syndrome: population-based estimates of incidence and mortality rates.J Pediatr Surg. 2004; 39: 690-695Abstract Full Text Full Text PDF PubMed Scopus (247) Google Scholarn = 40Necrotizing enterocolitis26%22%35%Congenital intestinal atrestia (jejunal, ileal, apple peel)10%24%10%Abdominal wall defects (gastroschisis, omphalocele)16%24%12.5%Volvulus9%20%10%Hirschsprung disease4%NR2.5%Meconium ileusNRNR20%Other∗The category “other” in the study by Squires et al includes multiple single diagnoses, whereas “other” in the Quiros-Tejeira study refers to postsurgical intestinal obstruction, congenital SBS, abdominal trauma, and small bowel lymphoma.28%10%10%∗ The category “other” in the study by Squires et al includes multiple single diagnoses, whereas “other” in the Quiros-Tejeira study refers to postsurgical intestinal obstruction, congenital SBS, abdominal trauma, and small bowel lymphoma. Open table in a new tab The goals of IF management are to support optimal nutritional status, promote quality of life, and limit morbidity and mortality by promoting enteral autonomy. Although life-saving, parenteral nutrition (PN) is associated with substantial morbidity, including IF-associated liver disease, catheter-related blood stream infections, and central line thrombus and malfunction. In addition, the social and financial burden for patients on prolonged PN is substantial, even with primarily outpatient management.3Winkler M.F. Smith C.E. Clinical, social, and economic impacts of home parenteral nutrition dependence in short bowel syndrome.JPEN J Parenter Enteral Nutr. 2014; 38: 32S-37SCrossref PubMed Scopus (70) Google Scholar Limiting the duration of PN by promoting enteral autonomy has been shown to decrease complications4Javid P.J. Collier S. Richardson D. Iglesias J. Gura K. Lo C. et al.The role of enteral nutrition in the reversal of parenteral nutrition-associated liver dysfunction in infants.J Pediatr Surg. 2005; 40: 1015-1018Abstract Full Text Full Text PDF PubMed Scopus (95) Google Scholar and improve survival for pediatric patients with IF.5Hess R.A. Welch K.B. Brown P.I. Teitelbaum D.H. Survival outcomes of pediatric intestinal failure patients: analysis of factors contributing to improved survival over the past two decades.J Surg Res. 2011; 170: 27-31Abstract Full Text Full Text PDF PubMed Scopus (88) Google ScholarIn order to successfully transition from PN to EN, the intestinal epithelium must adapt to optimize nutrient absorption. Depending on the severity of IF, full enteral autonomy may not always be possible. Fortunately, outcomes for pediatric patients with IF have been steadily improving, and prognostic biomarkers exist to aid in predicting clinical outcomes such as achievement of full EN. In addition, the introduction of novel therapies offer hope for enhancing the adaptive mechanisms of the small bowel and optimizing intestinal function.6Jeppesen P.B. New approaches to the treatments of short bowel syndrome-associated intestinal failure.Curr Opin Gastroenterol. 2014; 30: 182-188Crossref PubMed Scopus (27) Google ScholarEnteral Feeding in IFDeprivation of enteral calories, often termed “gut rest” in the setting of surgical or other interventions, causes atrophy of the intestinal mucosa, even in the presence of adequate PN support.7Feldman E.J. Dowling R.H. McNaughton J. Peters T.J. Effects of oral versus intravenous nutrition on intestinal adaptation after small bowel resection in the dog.Gastroenterology. 1976; 70: 712-719Abstract Full Text PDF PubMed Scopus (295) Google Scholar, 8McManus J.P. Isselbacher K.J. Effect of fasting versus feeding on the rat small intestine. Morphological, biochemical, and functional differences.Gastroenterology. 1970; 59: 214-221Abstract Full Text PDF PubMed Google Scholar, 9Castillo R.O. Feng J.J. Stevenson D.K. Kwong L.K. Altered maturation of small intestinal function in the absence of intraluminal nutrients: rapid normalization with refeeding.Am J Clin Nutr. 1991; 53: 558-561PubMed Google Scholar Upon reintroduction of EN, the surgically or functionally shortened intestine must undergo structural and functional adaptations to best absorb luminal nutrients. The histologic hallmark of this compensatory response is intestinal epithelial cell hyperplasia, including increased villus height and crypt depth. Gross anatomic adaptations include bowel lengthening and dilatation. These processes, classically termed “intestinal adaptation”5Hess R.A. Welch K.B. Brown P.I. Teitelbaum D.H. Survival outcomes of pediatric intestinal failure patients: analysis of factors contributing to improved survival over the past two decades.J Surg Res. 2011; 170: 27-31Abstract Full Text Full Text PDF PubMed Scopus (88) Google Scholar, 6Jeppesen P.B. New approaches to the treatments of short bowel syndrome-associated intestinal failure.Curr Opin Gastroenterol. 2014; 30: 182-188Crossref PubMed Scopus (27) Google Scholar are promoted by a combination of mechanical, humoral, and luminal factors,10Williamson R.C. Intestinal adaptation (first of two parts). Structural, functional and cytokinetic changes.N Engl J Med. 1978; 298: 1393-1402Crossref PubMed Scopus (476) Google Scholar, 11Williamson R.C. Intestinal adaptation (second of two parts). Mechanisms of control.N Engl J Med. 1978; 298: 1444-1450Crossref PubMed Scopus (264) Google Scholar and are likely driven by molecular signaling pathways. For example, increased expression of the Jagged-1 protein via the Notch-1 signaling pathway results in proliferation of small intestinal crypt epithelial cells.12Chen G. Sun L. Yu M. Meng D. Wang W. Yang Y. et al.The Jagged-1/Notch-1/Hes-1 pathway is involved in intestinal adaptation in a massive small bowel resection rat model.Dig Dis Sci. 2013; 58: 2478-2486Crossref PubMed Scopus (18) Google Scholar In a study of greyhound dogs fed either intravenous or EN after jejunal resection, enteral feeding resulted in increased villus height and improved glucose absorption, demonstrating that the provision of luminal contents is essential to optimal postresection intestinal function.7Feldman E.J. Dowling R.H. McNaughton J. Peters T.J. Effects of oral versus intravenous nutrition on intestinal adaptation after small bowel resection in the dog.Gastroenterology. 1976; 70: 712-719Abstract Full Text PDF PubMed Scopus (295) Google Scholar In addition, numerous hormones including secretin, neurotensin, peptide YY, and glucagon-like peptide 2 (GLP-2) have been shown to be important mediators of intestinal adaptation.13Guan X. Karpen H.E. Stephens J. Bukowski J.T. Niu S. Zhang G. et al.GLP-2 receptor localizes to enteric neurons and endocrine cells expressing vasoactive peptides and mediates increased blood flow.Gastroenterology. 2006; 130: 150-164Abstract Full Text Full Text PDF PubMed Scopus (203) Google Scholar, 14Bahrami J. Yusta B. Drucker D.J. ErbB activity links the glucagon-like peptide-2 receptor to refeeding-induced adaptation in the murine small bowel.Gastroenterology. 2010; 138: 2447-2456Abstract Full Text Full Text PDF PubMed Scopus (51) Google Scholar, 15Dube P.E. Rowland K.J. Brubaker P.L. Glucagon-like peptide-2 activates beta-catenin signaling in the mouse intestinal crypt: role of insulin-like growth factor-I.Endocrinology. 2008; 149: 291-301Crossref PubMed Scopus (65) Google ScholarThe degree of intestinal adaptation differs by anatomic location along the gastrointestinal tract, with the ileum having a greater ability to adapt compared with the more proximal small bowel.16Tappenden K.A. Pathophysiology of short bowel syndrome: considerations of resected and residual anatomy.JPEN J Parenter Enteral Nutr. 2014; 38: 14S-22SCrossref PubMed Scopus (105) Google Scholar Other factors that predispose to successful intestinal adaptation, as defined by successful weaning from PN support, include younger patient age,17Caniano D.A. Starr J. Ginn-Pease M.E. Extensive short-bowel syndrome in neonates: outcome in the 1980s.Surgery. 1989; 105: 119-124PubMed Google Scholar longer residual bowel length,18Spencer A.U. Neaga A. West B. Safran J. Brown P. Btaiche I. et al.Pediatric short bowel syndrome: redefining predictors of success.Ann Surg. 2005; 242 (discussion 9-12): 403-409PubMed Google Scholar intact ileocecal valve,18Spencer A.U. Neaga A. West B. Safran J. Brown P. Btaiche I. et al.Pediatric short bowel syndrome: redefining predictors of success.Ann Surg. 2005; 242 (discussion 9-12): 403-409PubMed Google Scholar absence of gastrointestinal mucosal inflammation,19Kaufman S.S. Loseke C.A. Lupo J.V. Young R.J. Murray N.D. Pinch L.W. et al.Influence of bacterial overgrowth and intestinal inflammation on duration of parenteral nutrition in children with short bowel syndrome.J Pediatr. 1997; 131: 356-361Abstract Full Text PDF PubMed Scopus (220) Google Scholar absence of cholestasis,20Andorsky D.J. Lund D.P. Lillehei C.W. Jaksic T. Dicanzio J. Richardson D.S. et al.Nutritional and other postoperative management of neonates with short bowel syndrome correlates with clinical outcomes.J Pediatr. 2001; 139: 27-33Abstract Full Text Full Text PDF PubMed Scopus (365) Google Scholar and normal gastrointestinal motility.21Guarino A. De Marco G. Italian National Network for Pediatric Intestinal F. Natural history of intestinal failure, investigated through a national network-based approach.J Pediatr Gastroenterol Nutr. 2003; 37: 136-141Crossref PubMed Scopus (66) Google ScholarThe timing of advancement and composition of enteral feeds likely play an important roles in achieving enteral autonomy. The prompt initiation of enteral feeding after bowel resection has been shown to decrease the duration of hospitalization,22Vanderhoof J.A. Young R.J. Enteral and parenteral nutrition in the care of patients with short-bowel syndrome.Best Pract Res Clin Gastroenterol. 2003; 17: 997-1015Abstract Full Text Full Text PDF PubMed Scopus (56) Google Scholar and increase the rate of achieving enteral autonomy23Sondheimer J.M. Cadnapaphornchai M. Sontag M. Zerbe G.O. Predicting the duration of dependence on parenteral nutrition after neonatal intestinal resection.J Pediatr. 1998; 132: 80-84Abstract Full Text Full Text PDF PubMed Scopus (162) Google Scholar in neonates with SBS. Thus, feeds should be started as soon as postoperative ileus resolves. A guideline for enteral feeding advancement is provided in Figure. As with many aspects of medical care for infants with IF, this algorithm has not been rigorously tested, but provides a helpful approach.Although data are few, the optimal choice for EN in infants with IF seems to be human milk, which contains growth factors and immunoglobulins that may promote intestinal adaptation.24Pereira-Fantini P.M. Thomas S.L. Taylor R.G. Nagy E. Sourial M. Fuller P.J. et al.Colostrum supplementation restores insulin-like growth factor -1 levels and alters muscle morphology following massive small bowel resection.JPEN J Parenter Enteral Nutr. 2008; 32: 266-275Crossref PubMed Scopus (38) Google Scholar, 25Bines J. Francis D. Hill D. Reducing parenteral requirement in children with short bowel syndrome: impact of an amino acid-based complete infant formula.J Pediatr Gastroenterol Nutr. 1998; 26: 123-128Crossref PubMed Scopus (115) Google Scholar Emerging evidence also suggests that human milk may help prevent IF-associated liver disease, although the exact mechanism is unknown.26Kulkarni S. Mercado V. Rios M. Arboleda R. Gomara R. Muinos W. et al.Breast milk is better than formula milk in preventing parenteral nutrition-associated liver disease in infants receiving prolonged parenteral nutrition.J Pediatr Gastroenterol Nutr. 2013; 57: 383-388Crossref PubMed Scopus (18) Google Scholar If human milk is unavailable, amino acid-based formulas have been associated with improved outcomes.20Andorsky D.J. Lund D.P. Lillehei C.W. Jaksic T. Dicanzio J. Richardson D.S. et al.Nutritional and other postoperative management of neonates with short bowel syndrome correlates with clinical outcomes.J Pediatr. 2001; 139: 27-33Abstract Full Text Full Text PDF PubMed Scopus (365) Google Scholar Scarce human data exist with respect to whether various macronutrients (long vs medium vs short chain fats; intact vs hydrolyzed vs amino acid proteins) are associated with better short- or long-term outcomes. Animal data support the concept that intact macronutrients (eg, long chain fatty acids) stimulate better adaptation, but human data are limited.Dietary fiber is metabolized by colonic bacteria into short-chain fatty acids, which provide an additional energy source and enhance the ability of the colon to absorb water. In select patients with IF with an intact colon and ileocecal valve, supplementation with dietary fiber may be helpful in reducing diarrhea. This was demonstrated in a case series of infants with SBS who experienced an improvement in diarrhea with the addition of 2 g/kg/d of dietary fiber.27Drenckpohl D. Hocker J. Shareef M. Vegunta R. Colgan C. Adding dietary green beans resolves the diarrhea associated with bowel surgery in neonates: a case study.Nutr Clin Pract. 2005; 20: 674-677Crossref PubMed Scopus (17) Google Scholar Further study of dietary fiber supplementation in children with IF is needed.Bolus enteral feeding produces cyclical changes in gastrointestinal hormones and is generally regarded as most closely mimicking true gastrointestinal physiology.28Braegger C. Decsi T. Dias J.A. Hartman C. Kolacek S. Koletzko B. et al.Practical approach to paediatric enteral nutrition: a comment by the ESPGHAN committee on nutrition.J Pediatr Gastroenterol Nutr. 2010; 51: 110-122Crossref PubMed Scopus (186) Google Scholar In patients with intestinal diseases including SBS, however, continuous EN has been shown to improve intestinal nutrient absorption and weight gain,29Parker P. Stroop S. Greene H. A controlled comparison of continuous versus intermittent feeding in the treatment of infants with intestinal disease.J Pediatr. 1981; 99: 360-364Abstract Full Text PDF PubMed Scopus (127) Google Scholar, 30Joly F. Dray X. Corcos O. Barbot L. Kapel N. Messing B. Tube feeding improves intestinal absorption in short bowel syndrome patients.Gastroenterology. 2009; 136: 824-831Abstract Full Text Full Text PDF PubMed Scopus (101) Google Scholar and may be better tolerated than bolus feeding.31Olieman J.F. Penning C. Ijsselstijn H. Escher J.C. Joosten K.F. Hulst J.M. et al.Enteral nutrition in children with short-bowel syndrome: current evidence and recommendations for the clinician.J Am Diet Assoc. 2010; 110: 420-426Abstract Full Text Full Text PDF PubMed Scopus (86) Google Scholar We commonly employ an approach that uses both modalities (eg, continuous feeding at night and bolus feeding during the day). In addition, the introduction of complementary, age-appropriate foods between 4-6 months of age, as well as oral boluses of human milk/formula as soon as tolerated, is helpful to stimulate oral-motor development and prevent feeding aversion.32Goulet O. Ruemmele F. Lacaille F. Colomb V. Irreversible intestinal failure.J Pediatr Gastroenterol Nutr. 2004; 38: 250-269Crossref PubMed Scopus (307) Google Scholar More studies are needed to identify prognostic factors in achieving enteral autonomy.Micronutrient and Vitamin DeficienciesNutrients are differentially absorbed in various locations throughout the small intestine, and therefore, the type of bowel resected will predispose to specific micronutrient and vitamin deficiencies (Table II). For example, a patient with duodenal resection is at risk for iron and folate deficiency, whereas a patient with ileal resection is at risk for a deficiency of vitamin B12 and bile acid malabsorption. Bile acid deficiency may in turn predispose to deficiencies of the fat-soluble vitamins A, D, E, and K. Extensive small bowel resection predisposes to generalized carbohydrate fat, and protein malabsorption.33Duro D. Jaksic T. Duggan C. Multiple micronutrient deficiencies in a child with short bowel syndrome and normal somatic growth.J Pediatr Gastroenterol Nutr. 2008; 46: 461-464Crossref PubMed Scopus (17) Google ScholarTable IIAnatomic resection and risk of deficiencies in SBSSite of resectionRisk of nutrient deficiencyDuodenumIron, folateJejunumCalcium, zincIleumVitamin B12, bile acids, fat-soluble vitamins (A, D, E, K)Ileocecal valveMacronutrient malabsorption (because of faster intestinal transit) Open table in a new tab Micronutrients play important roles in the maintenance of gastrointestinal structure and function, including mucosal immunity, and deficiencies of minerals or vitamins may inhibit intestinal adaptation. In a study of vitamin A deficient and sufficient rats with small bowel resection, vitamin A deficiency was associated with compromised intestinal adaptation including impaired crypt proliferation, decreased enterocyte migration, and increased crypt cell apoptosis.34Swartz-Basile D.A. Wang L. Tang Y. Pitt H.A. Rubin D.C. Levin M.S. Vitamin A deficiency inhibits intestinal adaptation by modulating apoptosis, proliferation, and enterocyte migration.Am J Physiol Gastrointest Liver Physiol. 2003; 285: G424-G432Crossref PubMed Scopus (40) Google Scholar Zinc deficiency has been shown to impede adaptive mucosal growth in response to extensive bowel resection in rats.35Vanderhoof J.A. Park J.H. Grandjean C.J. Effect of zinc deficiency on mucosal hyperplasia following 70% bowel resection.Am J Clin Nutr. 1986; 44: 670-677PubMed Google ScholarDespite the use of PN and concomitant parenteral multivitamins, patients with IF remain at risk of micronutrient deficiencies, even or perhaps especially after achieving enteral autonomy. A longitudinal study of 30 children with IF by Yang et al found a high prevalence of micronutrient deficiencies in patients receiving partial PN support, including copper (56%), iron (46%), selenium (35%), and zinc (31%).36Yang C.F. Duro D. Zurakowski D. Lee M. Jaksic T. Duggan C. High prevalence of multiple micronutrient deficiencies in children with intestinal failure: a longitudinal study.J Pediatr. 2011; 159: 39-44.e1Abstract Full Text Full Text PDF PubMed Scopus (87) Google Scholar A similar study by Ubesie et al showed a significant reduction in the proportion of patients with iron deficiency after transition to EN, although the burden of iron deficiency remained high (61%).37Ubesie A.C. Kocoshis S.A. Mezoff A.G. Henderson C.J. Helmrath M.A. Cole C.R. Multiple micronutrient deficiencies among patients with intestinal failure during and after transition to enteral nutrition.J Pediatr. 2013; 163: 1692-1696Abstract Full Text Full Text PDF PubMed Scopus (45) Google Scholar Vitamin E status also improved.The full discontinuation of PN also appears to worsen some micronutrient and vitamin deficiencies. For example, Yang et al found that the prevalence of vitamin D deficiency increased from 20% to 68% after transition to full EN, and the prevalence of zinc deficiency increased from 31% to 67%.36Yang C.F. Duro D. Zurakowski D. Lee M. Jaksic T. Duggan C. High prevalence of multiple micronutrient deficiencies in children with intestinal failure: a longitudinal study.J Pediatr. 2011; 159: 39-44.e1Abstract Full Text Full Text PDF PubMed Scopus (87) Google Scholar Several factors were associated with the development of vitamin and micronutrient deficiencies, including lower height-for-age z-score, lack of multivitamin supplementation, and absence of the ileocecal valve. These results support the conclusion that patients with IF remain at risk for nutrient deficiency even with full enteral feeding and emphasize the importance of supplementation with a multivitamin preparation containing water soluble forms of fat soluble vitamins, as well as zinc. Furthermore, adequate somatic growth does not preclude the presence of micronutrient deficiencies, emphasizing the importance of routine biochemical monitoring and comprehensive follow-up in these patients during transitions in feeding.33Duro D. Jaksic T. Duggan C. Multiple micronutrient deficiencies in a child with short bowel syndrome and normal somatic growth.J Pediatr Gastroenterol Nutr. 2008; 46: 461-464Crossref PubMed Scopus (17) Google Scholar After achieving enteral autonomy, careful monitoring of growth variables should continue. Appropriate interval growth signals adequate intestinal adaptation and sufficient absorptive capacity, and impaired growth may signal the need to resume specialized nutrition.38Goulet O. Olieman J. Ksiazyk J. Spolidoro J. Tibboe D. Kohler H. et al.Neonatal short bowel syndrome as a model of intestinal failure: physiological background for enteral feeding.Clin Nutr. 2013; 32: 162-171Abstract Full Text Full Text PDF PubMed Scopus (101) Google ScholarAn emerging challenge in caring for patients with IF is frequent shortages of intravenous micronutrient and electrolyte preparations. During critical micronutrient shortages, patients who are unable to tolerate enteral supplementation may experience adverse outcomes. In 2012, the US Centers for Disease Control and Prevention issued a report of 7 infants receiving PN lacking zinc, 6 of whom developed symptoms consistent with zinc deficiency dermatitis, which resolved with zinc administration.39Ruktanonchai D. Lowe M. Norton S.A. Garret T. Soghier L. Weiss E. et al.Zinc deficiency-associated dermatitis in infants during a nationwide shortage of injectable zinc - Washington, DC, and Houston, Texas, 2012-2013.MMWR Morb Mortal Wkly Rep. 2014; 63: 35-37PubMed Google Scholar In 2013, a shortage of parenteral selenium led to biochemical selenium deficiency in 5 infants with IF receiving PN as the sole source of nutrition.40Davis C. Javid P.J. Horslen S. Selenium deficiency in pediatric patients with intestinal failure as a consequence of drug shortage.JPEN J Parenter Enteral Nutr. 2014; 38: 115-118Crossref PubMed Scopus (23) Google Scholar During a national shortage of parenteral copper in 2012, several cases of acquired copper deficiency, manifesting as bone disease, were reported.41Oestreich A.E. Cole C.R. Vigorous periosteal reaction secondary to copper deficiency in an infant on total parenteral nutrition.Pediatr Radiol. 2013; 43: 1411-1413Crossref PubMed Scopus (3) Google Scholar, 42Marquardt M.L. Done S.L. Sandrock M. Berdon W.E. Feldman K.W. Copper deficiency presenting as metabolic bone disease in extremely low birth weight, short-gut infants.Pediatrics. 2012; 130: e695-e698Crossref PubMed Scopus (39) Google Scholar During a recent shortage of parenteral phosphorus, providers utilized the absorptive capacity of the rectum and repleted phosphorus via administration of hypertonic sodium-phosphate enema.43Kemmerly T. Vuong C. Kaunitz J.D. A Novel phosphorus repletion strategy in a patient with duodenal perforation.Nutr Clin Pract. 2014; 29: 402-405Crossref PubMed Scopus (3) Google Scholar Advocacy and regulatory steps are needed to prevent substantial morbidity from nutrient shortages in this susceptible population.Outcomes of IFAn important challenge in the care of patients with IF is the limited longitudinal data available to guide clinical decisions. The Pediatric Intestinal Failure Consortium is a group of 14 pediatric centers with multidisciplinary intestinal rehabilitation programs. A study of 272 infants with IF reported that the cumulative incidence of sustained enteral autonomy at 3 years was 44%; 26% died and 23% underwent intestinal transplantation.44Squires R.H. Duggan C. Teitelbaum D.H. Wales P.W. Balint J. Venick R. et al.Natural history of pediatric intestinal failure: initial report from the Pediatric Intestinal Failure Consortium.J Pediatr. 2012; 161: 723-728.e2Abstract Full Text Full Text PDF PubMed Scopus (312) Google Scholar Notably, 30% of patients who achieved enteral autonomy took longer than 12 months to do so, often requiring 36-48 months of PN and transitional periods before tolerating a full enteral diet. In a study of 80 pediatric patients with SBS, Spencer et al showed that 64% (51 patients) had successfully weaned off PN during a mean follow-up period of 5.1 years.18Spencer A.U. Neaga A. West B. Safran J. Brown P. Btaiche I. et al.Pediatric short bowel syndrome: redefining predictors of success.Ann Surg. 2005; 242 (discussion 9-12): 403-409PubMed Google Scholar The strongest reported clinical predictors of enteral autonomy included a residual bowel length greater than 10% of expected and the presence of the ileocecal valve. Underlying diagnosis and receiving care at a specialized rehabilitation center have also been identified as predictors of enteral autonomy.45Fallon E.M. Mitchell P.D. Nehra D. Potemkin A.K. O'Loughlin A.A. Gura K.M. et al.Neonates with short bowel syndrome: an optimistic future for parenteral nutrition independence.JAMA Surg. 2014; 149: 663-670Crossref PubMed Scopus (79) Google ScholarIn addition to clinical factors which may predict the ability to wean from PN, plasma citrulline has emerged as a promising biomarker. Citrulline is a nonessential amino acid produced by the enterocytes of the small bowel, and plasma citrulline concentration has been shown to reflect intestinal mass in various gastrointestinal diseases including enteropathies such as celiac disease, HIV-enteropathy, and IF.46Crenn P. Coudray-Lucas C. Thuillier F. Cynober L. Messing B. Postabsorptive plasma citrulline concentration is a marker of absorptive enterocyte mass and intestinal failure in humans.Gastroenterology. 2000; 119: 1496-1505Abstract Full Text Full Text PDF PubMed Scopus (387) Google Scholar In a study of 24 children with SBS, a citrulline concentration of ≥19 micromol/L had a 94% sensitivity and 64% specificity for the prediction of enteral autonomy.47Rhoads J.M. Plunkett E. Galanko J. Lichtman S. Taylor L. Maynor A. et al.Serum citrulline levels correlate with enteral tolerance and bowel length in infants with short bowel syndrome.J Pediatr. 2005; 146: 542-547Abstract Full Text Full Text PDF PubMed Scopus (128) Google Scholar In a study of 27 pediatric patients with SBS, citrulline concentrations >15 micromol/L predicted the attainment of enteral autonomy.48Fitzgibbons S. Ching Y.A. Valim C. Zhou J. Iglesias J. Duggan C. et al.Relationship between serum citrulline levels and progression to parenteral nutrition independence in children with short bowel syndrome.J Pediatr Surg. 2009; 44: 928-932Abstract Full Text Full Text PDF PubMed Scopus (74) Google Scholar Larger, prospective studies of this potential biomarker are needed.Emerging TherapiesTwo recent medical therapies have recently emerged for the treatment of IF: GLP-2 and somatropin (human growth hormone). The endogenous peptide GLP-2 is secreted by intestinal L cells and enhances nutrient absorption and increases mucosal surface area, but has a short half-life due to degradation by the enzyme dipeptidyl peptidase IV.49Drucker D.J. Gut adaptation and the glucagon-like peptides.Gut. 2002; 50: 428-435Crossref PubMed Scopus (102) Google Scholar Teduglutide is a human recombinant GLP-2 analogue engineered with a single amino acid substitution, resulting in a longer half-life, allowing daily subcutaneous dosing.50Jeppesen P.B. Sanguinetti E.L. Buchman A. Howard L. Scolapio J.S. Ziegler T.R. e