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Dr. Valeria Cohran: Short Bowel Syndrome/Intestinal Failure in Pediatrics 2026

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Recently, Dr. Valeria Cohran gave our group a terrific update on Short Bowel Syndrome (SBS)/Intestinal Failure (IF). My notes below may contain errors in transcription and in omission. Along with my notes, I have included many of her slides. Dr. Cohran has been a leader in intestinal rehabilitation. Among many accomplishments, she was the 2025 recipient of the 2025 Margaret Stallings NASPGHAN Distinguished Service Award.

Key points:

  • Most children with SBS/IF are able to taper off parenteral nutrition (PN). Even ~30% of those with extreme SBS (<10% of expected bowel length) are able to achieve enteral autonomy.
  • SBS/IF due to NEC has a generally more favorable outcome than other etiologies
  • Stoma takedown is associated with better outcomes (eg. more likely to taper off PN). (Raghu et al. JPEN. 2023;47:1047-55). Taking down stoma may be beneficial if unable to taper PN and in those developing liver disease
  • SBS/IF caretakers spend a median of 29 hrs/week managing PN, enteral nutrition, medications, and other tasks
  • In the nursery, one study reported that NICU patients with IF spent a median of 150 days and cost more than $500K
  • Overall, advances in SBS/IF management have been associated with lower death rates and lower intestinal transplant rates (~30 ITx last year), yet similar rates of achieving enteral autonomy
Overall, Group 1 SBS is least likely to achieve enteral autonomy
Intestinal length with maximal increase in first year of life
•N=362 children in over 26 centers world-wide, started 2018 (enrolled if PN >2 months)
Multi-organ effects of SBS
  • Fish oil based lipid emulsions do not always work; cirrhosis can still develop even with minimal biochemical marker alterations
  • IFALD mortality is associated with degree of conjugated hyperbilirubinemia, though we are not seeing this complication much with current management
  • GLP-2 can reduce PN requirements by more than 20% in the majority of those with SBS/IF and may help achieve enteral autonomy in about 20%. However, their use requires close monitoring for fluid overload and electrolyte disturbances
  • Lots of disparities noted along socioeconomic variables. For outpatient management, home nursing care is not available in some neighborhoods

Related blog posts:

Dr. Danielle Wendel: Management of Short Bowel Syndrome

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Two years ago, Dr. Wendel gave our group a great lecture on short bowel syndrome (SVS). One of the neonatologists in attendance invited her back to provide a state of the art update. While this 2026 lecture covered some of the same issues, there were important updates and insights.

My notes below may contain errors in transcription and in omission. In addition, the information provided is based on what is done in Seattle. However, there is not a lot of evidence for much of what is done in intestinal rehabilitation. Thus, there is variation in practice at different centers and what works for one patient might not work for another. Following my notes, I have included many of her slides.

Diet:

  • Enteral feedings promote intestinal adaptation. Pediatric patients with SBS require much higher calories with enteral nutrition and may have hyperphagia as a compensatory mechanism
  • Breastmilk and/or Standard formula likely help promote intestinal adaptation better than hydrolysates and elemental formulas. In addition, it may help reduce the development of food allergies which are increased in children with SBS
  • Oral feedings have many advantages over NG or GT feedings when feasible. The ability to consume solid foods is quite helpful in reducing diarrhea. Also, encouraging oral feedings may help reduce feeding aversions. As such, GT placement is avoided if possible in Seattle
  • Key diet advice: avoid sweet tasting food/drink, especially in the first few years of life while they are developing their palate/food preferences
  • Feed osmolarity/caloric density: Most children with SBS tolerate lower caloric density (15-20 cal/oz) and more volume orally rather than higher caloric density/lower volume feeds

Parenteral Nutrition:

  • Lipid emulsions: SMOFlipid at 2 gm/day can help prevent essential fatty acid deficiency (EFA). Omegaven may need to be dosed at 1.5 gm/day to prevent EFA. If used for short-term and low dose, standard intralipid can be useful
  • HAL (aka TPN): Typically weaning calories is done before weaning volume. Cycling HAL (delivering over fewer hours) can be started prior to discharge. Watch for tolerance of the glucose infusion rate (JH: I prefer the terms HAL = hyperalimentation or PN=parenteral nutrition. TPN =total parenteral nutrition. Most patients are receiving parenteral nutrition but not total parenteral nutrition.)

Ostomy/Stool Output:

  • Output goals: Most pediatric patients can tolerate output of 50 mL/kg/day of ostomy output  (if being supported by PN), though less than 30 mL/kg/day is more physiologic
  • Iron: Parenteral iron is typically needed. Seattle team prefers ferric carboxymaltose as it may deliver enough iron for 6-12 months in one infusion
  • Acid suppression: While acid suppression can sometimes be beneficial by lowering gastric output, if possible avoid long-term use as it may increase risk of bacterial overgrowth along with other infections
  • Excessive stool output (via stoma or per rectum) is when it is more than the patient’s baseline. This should prompt investigation for potential causes including diet/osmotic agent, bacterial overgrowth and infections
  • Pancreatic enzymes: It is unclear if pancreatic enzymes (PERT, Relizorb) will improve stool output due to lack of data
  • Teduglutide can reduce the need for HAL. It is a hormone (like insulin) and sustained effects are generally not seen when it is stopped. However, especially in patients close to coming off HAL, it may be beneficial

Monitoring:

  • Nutrient deficiencies: Close monitoring for nutrient deficiencies is needed and often even more important when no longer receiving HAL
  • Urine sodium more than 30 is a goal. Sodium depletion interferes with growth and can contribute to other electrolye disturbances (eg. hypokalemia)

CLABSI:

  • Antibiotics: Treatment starts with a broad-spectrum antibiotic and wait to add specific gram-positive coverage unless ill-appearing or gram-positive organism starts growing. Vancomycin is not used frequently in Seattle due to concerns of renal toxicity. In patients with gram-positive infection, linezolid is often used
  • Minimum of 48 Hours For All Fevers: Everyone with SBS and with fever (greater than or equal to 100.4) stays for at least 48 hrs on broad spectrum IV antibiotics
  • Locks: Sodium bicarb locks help prevent CLABSI and appear to have similar infection prevention as ethanol locks. Ethanol locks have been difficult to get coverage.

SIBO:

  • Medications: Metronidazole is generally 1st line agent and gentamicin (IV formulation given enterally) is a 2nd line agent in Seattle. Rifaximin would be potentially their 1st line agent if it were easier to get covered

Related blog posts:

Disclaimer: This blog, gutsandgrowth, assumes no responsibility for any use or operation of any method, product, instruction, concept or idea contained in the material herein or for any injury or damage to persons or property (whether products liability, negligence or otherwise) resulting from such use or operation. These blog posts are for educational purposes only. Specific dosing of medications (along with potential adverse effects) should be confirmed by prescribing physician.  Because of rapid advances in the medical sciences, the gutsandgrowth blog cautions that independent verification should be made of diagnosis and drug dosages. The reader is solely responsible for the conduct of any suggested test or procedure.  This content is not a substitute for medical advice, diagnosis or treatment provided by a qualified healthcare provider. Always seek the advice of your physician or other qualified health provider with any questions you may have regarding a condition.

Long-Acting GLP-2 Analogue Glepaglutide Reduces Parenteral Support

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PB Jeppesen et al. Gastroenterol 2025; 168: 701-713. Open Access! Glepaglutide, a Long-Acting Glucagon-like Peptide-2 Analogue, Reduces Parenteral Support in Patients With Short Bowel Syndrome: A Phase 3 Randomized Controlled Trial

Background: “GLP-2 is a specific, endogenous, intestinal, pro-adaptive factor that plays a key role in enhancing intestinal mucosal morphology, function, and integrity under normal and pathophysiological conditions. The introduction of GLP-2 analogue treatment has been a paradigm shift in the treatment of SBS, targeting the pathophysiology of SBS by aiming to reinforce the structural and functional integrity of the remaining intestine. Exogenous GLP-2 induces significant hyperplasia of the small intestinal mucosal epithelium via stimulation of stem cell proliferation in the crypts and via inhibition of apoptosis in the villi…

The short half-life of 5–7 minutes for circulating native GLP-232 is a significant practical limitation for its use in a therapeutic setting. This is improved for the currently marketed GLP-2 analogue teduglutide, which has a half-life in circulation of approximately 2 hours.33 However, treatment is time-consuming due to the requirement for daily drug product reconstitution and dosing…

Glepaglutide is a novel, long-acting GLP-2 analogue in a stable, aqueous formulation for subcutaneous administration to treat patients with SBS. The stability in aqueous solution allows for dosing of glepaglutide as a ready-to-use liquid formulation. The mean effective half-life is 88 hours,34 which enables extension of the dosing interval beyond daily dosing.”

Methods: In this placebo-controlled, randomized, parallel-group, double-blind, phase 3 trial, adult patients (n=106) with SBS with intestinal failure requiring PS ≥3 d/wk were randomized 1:1:1 to 24 weeks of glepaglutide 10 mg twice weekly or once weekly or placebo

Key findings:

  • Glepaglutide twice weekly significantly reduced weekly PS volumes from baseline to week 24 vs placebo (mean change, −5.13 vs −2.85 L/wk; P = .0039; primary end point).
  • The improvement with glepaglutide was more prominent in those without a colon in continuity.
  • Mean concentrations of citrulline (a biomarker for enterocyte mass) increase 47% and 19% from baseline in the TW and OW treatment groups vs 5% in the placebo group
  • Serious adverse events were more common in both glepaglutide groups (28.6% and 11.4% for TW and OW respectively) compared to 5.6% for placebo. Specific risks of the active treatment included injection site reactions (common). Stoma complications (swelling of stoma nipple) along with GI events (nausea, vomiting and pain) were reported in more than 10% of patients. One patient developed cholecystitis and one developed a generalized rash in the active treatment group.
  • 61 of 70 patients (87%) treated with glepaglutide developed anti-drug antibodies. However, the authors found no apparent association with glepaglutide pharmacokinetics.
The improvement in parenteral support was more notable in those without the colon in continuity
Difference compared to placebo: 14.1% more of patients receiving twice weekly dosing and 11.2% more of patients receiving once weekly dosing of glepaglutide achieved enteral autonomy.

My take: This study shows that glepaglutide, like its GLP-2 analogue predecessor teduglutide, reduces the volume of parenteral support for patients with SBS. Due to its longer half-life, less frequent dosing is an added benefit compared to teduglutide.

Drawbacks for this group of medications include the potential for long-term adverse effects, endoscopic monitoring (possibly both upper endoscopy and colonoscopy), substantial costs, and reversion of intestinal failure severity when the medications are stopped.

Related blog posts:

Practical Intestinal Rehabilitation (Part 2)

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We had an brilliant lecture given to our group by Danielle Wendel who leads Seattle Children’s Intestinal Rehabilitation team. My notes below may contain errors in transcription and in omission. In addition, the information provided is based on what is done in Seattle. However, there is not a lot of evidence for much of what is done in intestinal rehabilitation. Thus, there is variation in practice at different centers and what works for one patient might not work for another. Following my notes, I have included many of her slides (same slides as yesterday’s post).

CLABSI Pointers:

  • -At Seattle, with suspected CLABSI, usually central blood culture obtained without peripheral blood culture. (Peripheral blood cultures have not helped their team improve management)
  • -Everyone with SBS and with fever (greater than or equal to 100.4) stays for at least 48 hrs on broad spectrum IV antibiotics (choice based on local sensitivities) through the central line until it is conclusively determined if they have a CLABSI (which still carry a significant mortality risk)
  • -Sodium bicarbonate lock experience has been good (8.4% solution, 1.5 mL lock for the entire time off PN in all tunneled CVL flushed in at the end of the dwell). It has become a good substitute for ethanol locks.  Their experience will be published soon.  Since sodium bicarbonate lock does not need to be withdrawn, it has been associated with less line breakage.  Several lock solutions (KiteLock and Taurolidine) are not currently available in the U.S.  KiteLock is about to be studied in Seattle.
  • -At Seattle, all CLABSI are treated  through the line and every effort is made to salvage and/or repair lines.  Line replacement increases risk of losing central IV access.
  • -Line is removed for fungal infections
  • -The Seattle team prefers tunneled CVC

SIBO Pointers:

  • -Testing is problematic.  Breath tests are not reliable in kids with SBS.  Duodenal aspirates are often not helpful and have a number of technical difficulties; also, it is unclear whether a duodenal aspirate is representative of the bacteria in the more distal bowel.
  • -Metronidazole is their first line choice.  Gentamicin (IV formulation given enterally) is their 2nd choice.  Rifaximin is their 3rd line.  Rifaximin would possibly be used earlier in treatment except for difficulty getting covered.  When used, they crush up pills rather than have it compounded to avoid sweeteners.

Teduglutide

  • -Best to start if a patient is is > 1yo and on stable TPN (not able to wean)
  • -Make sure patient is using a tiny needle (not adult needle in package)
  • -Anticipate long-term treatment (?indefinite)

GI Bleeding Pointers:

  • This is being seen frequently. 
  • Etiologies include anastomotic ulcers and IBD-like lesions.   If a patient is not improving with standard approaches and possibly resection, could need an anti-TNF type agent.
  •  At Seattle, they are very selective about patients appropriate for a STEP procedure as this may be associated with more frequent bleeding over time due to the many staples used. Hand-sewn tapering may be a better option for many patients.
  • With the challenging decisions required for these bleeding patients, discussion with an experienced intestinal rehab center may be helpful.

Disclaimer: This blog, gutsandgrowth, assumes no responsibility for any use or operation of any method, product, instruction, concept or idea contained in the material herein or for any injury or damage to persons or property (whether products liability, negligence or otherwise) resulting from such use or operation. These blog posts are for educational purposes only. Specific dosing of medications (along with potential adverse effects) should be confirmed by prescribing physician.  Because of rapid advances in the medical sciences, the gutsandgrowth blog cautions that independent verification should be made of diagnosis and drug dosages. The reader is solely responsible for the conduct of any suggested test or procedure.  This content is not a substitute for medical advice, diagnosis or treatment provided by a qualified healthcare provider. Always seek the advice of your physician or other qualified health provider with any questions you may have regarding a condition.

Teduglutide-Induced Polyps

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J Salazar et al. JPGN Reports 4(4):p e389. Open Access! Gastric Foveolar Hyperplastic Polyps in 2 Children With Short Bowel Syndrome on Long-Term Teduglutide

I have not been an enthusiastic early adopter of teduglutide. Though it has been shown to reduce HAL volumes in those with short bowel syndrome (SBS), this tends to revert with cessation of treatment. In addition, it has a very high cost and long-term adverse effects are unclear. Currently the manufacturer recommends a colonoscopy after 1 year of treatment.

This case report by Salazar et al identified two children who developed foveolar hyperplastic gastric polyps after receiving teduglutide.

Discussion points:

  • “There have been increasing reports of both benign and malignant small bowel polyp development. In trials of pediatric patients, limited to 12 and 24 weeks, initial upper endoscopy and colonoscopies were not required. In addition, postexposure upper endoscopy and colonoscopy was not the standard of care (9,13,16). Thus, the incidence of intestinal polyp formation on teduglutide treatment in pediatric patients remains unknown.”
  • “A recent retrospective review of adult patients with SBS showed increased small bowel polyp formation in 8 out of 35 patients (22.9%) on long-term teduglutide use… 3 were identified as adenomas with low-grade dysplasia… (14)”
  • “In general, isolated foveolar hyperplasia has not been identified as a premalignant lesion…The connection between foveolar hyperplasia and development of dysplasia, though, remains poorly understood, and further work delineating the natural history of foveolar polyps in the context of teduglutide is important.”

Related article: A Fifi et al. JPGN 2023; 77: 666-671. This is a post-hoc analysis showing improving stool consistency in 101 patients treated in open-label studies. Patients had mean drop of 20 mL/kg/day in parental fluid volume (compared to 7 mL/kg/day in the standard care treatment group).

My take: This case report indicates that endoscopic monitoring (possibly both upper endoscopy and colonoscopy) is needed in teduglutide-exposed patients. In addition, careful consent of the patients is prudent indicating the uncertain long-term effects. Finally, it would be a good idea to enroll all patients in a registry as well.

Related blog posts:

Tile mosaic in Lagos, Portugal

Is GLP2 Worth $300K per Year?

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E Ramos Boluda et al. JPGN 2020; 71: 734-739. Experience With Teduglutide in Pediatric Short Bowel Syndrome: First Real-life Data

S Hill. JPGN 2020; 71: 697-698 (editorial) Use of GLP-2 May Herald a New Era of Improved Outcome of Short Bowel Syndrome-associated Intestinal Failure

The study and associated editorial highlight the effectiveness of GLP-2 in a prospective cohort of 17 patients with short bowel syndrome. It is noted that Dr. Hill has received funding from the pharmaceutical manufacturer of the product.

Key findings:

  •  A total of 12 of 17 patients achieved parenteral independence: 3 patients after 3 months of treatment, 4 patients at 6 months, and 5 after 12 months.
  • The percentage able to wean off parenteral nutrition was 17%, 44%, and 60% at 3, 6, and 12 months respectively. Only 1 patient did not exhibit improvement
  • Plasma citrulline levels, a marker for enteral autonomy, increased from a baseline average of 20 micromol/l to 37.5, 46.75, and37.9at 3, 6, and 12 months respectively.
  • Adverse reactions included abdominal pain 30%, nauseas 18%, injection-site reactions 22%, and headache 16%.

Both the editorial and the study comment briefly on the cost of the therapy. The editorial also notes the current recommendation for surveillance endoscopy in view of a hypothetical risk of malignancy.

My take: Is GLP2 Worth the Cost? It probably depends on who is paying and long-term safety data. Perhaps, we will develop tools to improve prediction of which patients will achieve enteral autonomy with GLP2 who would otherwise require ongoing parenteral nutrition.

Related blog posts:

FDA News: FDA Warning for FMT, IB-Stim Device Approval, Teduglutide Approval

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1.From John Pohl Twitter Feed:  FDA Warns of One Death Linked to Fecal Transplants (6/13/19)

An excerpt:

The consent should include, at a minimum, a statement that the use of FMT to treat C. difficile is investigational and a discussion of its potential risks.

“Two immunocompromised adults who received investigational FMT developed invasive infections caused by extended-spectrum beta-lactamase (ESBL)-producing Escherichia coli (E.coli). One of the individuals died,” the agency said Thursday…

Openbiome, a nonprofit stool bank based in Cambridge, MA, told Focus: “We are saddened to hear of the recent patient death due to an infection from a multi-drug resistant organism (MDRO) transmitted through a fecal transplant. OpenBiome material was not involved. OpenBiome screens its donors and fecal transplant material for MDROs and related risk factors, and this serious event further highlights the importance of rigorous screening and clinical oversight for all fecal transplant procedures.”

 2. FDA approval for IB-stim (a.k.a. Neuro-stim) device.

Link:: FDA permits marketing of first medical device for relief of pain associated with irritable bowel syndrome in patients 11-18 years of age

An excerpt:

IB-Stim treatment resulted in at least a 30% decrease in usual pain at the end of three weeks in 52% of treated patients compared to 30% of patients who received the placebo, and at least a 30% decrease in worst pain in 59% of treated patients compared with 26% of patients who received the placebo.

:Kovacic K1, Hainsworth K2, Sood M1, Chelimsky G1, Unteutsch R1, Nugent M3, Simpson P3, Miranda A4. 2017 Oct;2(10):727-737. doi: 10.1016/S2468-1253(17)30253-4. Epub 2017 Aug 18.

Link to abstract of relevant study:  Neurostimulation for abdominal pain-related functional gastrointestinal disorders in adolescents: a randomised, double-blind, sham-controlled trial.

3. FDA Approves Gattex (Teduglutide) for Pediatric SBS

From CenterWatch: Gattex New FDA Drug Approval

Pediatric SBS: “In a 24-week pediatric study 59 pediatric patients with SBS aged 1 year through 17 years chose whether to receive Gattex or standard of care (SOC)…Based on patient-diary data, patients who received Gattex 0.05 mg/kg/day experienced a 42% mean reduction in PS volume (mL/kg/day) from baseline (-23 mL/kg/day from baseline). At week 24, 38% of patients (10/26) were able to reduce PS infusion by at least 1 day per week. Patients reduced their PS infusion time by 3 hours per day on average compared to baseline.”

Related blog post: Teduglutide for SBS

Jeppesen PB, Pertkiewicz M, Messing B, Iyer K, Seidner DL, O’keefe SJ, Forbes A, Heinze H, Joelsson B Teduglutide reduces need for parenteral support among patients with short bowel syndrome with intestinal failure. Gastroenterology 2012 Dec;143(6):1473-1481

Jeppesen PB, Gilroy R, Pertkiewicz M, Allard JP, Messing B, O’Keefe SJ Randomised placebo-controlled trial of teduglutide in reducing parenteral nutrition and/or intravenous fluid requirements in patients with short bowel syndrome. Gut 2011 Jul;60(7):902-14.

#NASPGHAN17 Annual Meeting Notes (Part 2): Year in Review

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This blog entry has abbreviated/summarized this presentation. Though not intentional, some important material is likely to have been omitted; in addition, transcription errors are possible as well.

This first slide shows the growth in NASPGHAN membership:

Year in Review

Melvin Heyman  Editor, JPGN

This lecture reviewed a number of influential studies that have been published in the past year.  After brief review of the study, Dr. Heyman summarized the key take-home point.

 

Nutrition Week (Day 4) Trophic Hormone for Pediatric Short Bowel Syndrome

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A recent study (BA Carter et al. J Pediatr 2017; 181: 102-11) provides some preliminary data on the use of glucagon-like peptide-2 (GLP-2) (Teduglutide) for pediatric short bowel syndrome (SBS).

This was a 12-week, open-label study in patients aged 1-17 years with intestinal failure (IF) associated with SBS. Prior to the study, patients had shown little to minimal advance in enteral nutrition for at least 3 months. Three doses of GLP-2 (0.0125 mg/kg/d, 0.025 mg/kg/day, and 0.05 mg/kg/day).

Key findings:

  • All treated patients (37) experienced mild or moderate adverse effects, including vomiting, pyrexia, catheter-related complications, and upper respiratory tract infections. No serious adverse events were identified. In the 5 patients who received standard care, adverse effects were recorded as well, including upper respiratory tract infections in 2 (40%) which was similar to the other groups.
  • By week 12, parenteral nutrition (PN) volume and calories were reduced in the higher dosed groups.  In the 0.025 mg/kg/day group, PN volume dropped by 41% and calories by 45%.  In the 0.05 mg/kg/day group, PN volume dropped by 25% and calories by 52%. Virtually no change in these parameters occurred in the lowest dose (0.0125 mg/kg/day) with no change in volume and 6% drop in calories.
  • Enteral feeding volume occurred in all groups: 22%, 32%, and 40% in the groups and was directly related to the GLP-2 dosing.
  • Citrulline levels (a biomarker of enteral autonomy) were monitored “but the results were clouded by wide variability of baseline values.”  In adult studies, citrulline levels increased significantly.

My take: This open-label study has many limitations; further studies are planned (ClinicalTrials.gov, NCT02682381). Nevertheless, this study indicates that GLP-2 holds promise as a therapy for SBS/IF.

Another slide in a recent lecture on PNALD (slide derived from Conrad Cole lecture in Octobler 2015 -available at Pediatric Nutritionist Blog, slide 49):

screenshot-109

Related blog posts: