Ana Abad-Jorge, MS, RD, CNSCDirector, Dietetic Internship Program

PICU Nutrition SpecialistUniversity of Virginia Health System

Food Nutrition Conference & Expo 2009October 20th 2009

Learning Objectives Identify major diagnoses that predispose infants and

children to GI impairment and malabsorptionDiscuss the available research & controversy surrounding

formula selection based on level of protein hydrolysisDiscuss the advantages of breast milk for use in neonates

with GI impairmentReview available elemental and semi-elemental infant and

pediatric formulas for use with patients with persistent GI impairment despite trial of intact protein formula

Discuss current guidelines for enteral formula selection in pediatric patients with GI impairment based on age and degree of impairment.

Severe GI impairment & resulting malnutrition can occur as a result of the following:Malabsorption as a result of a deficit in nutrient

transport across the intestinal mucosa, i.e. Crohn’s Maldigestion due to intraluminal defects in the

digestion of nutrients, i.e., pancreatic or bile salt in-sufficiency or bacterial overgrowth, i.e. CF, SBS

Increased intestinal losses related to bowel resection with reduction in mucosal surface area, i.e. SBS and in severe Crohn’s.

Increased metabolic needs related to catabolic state of illness due to inflammation & infections: Crohn’s, CF

Challenges in Managing GI Impairment in Pediatric PatientsOften difficult to determine whether an intact versus a

hydrolyzed (semi-elemental) or elemental formula is needed.Challenging to determine the appropriate, well-tolerated

macronutrient distribution of carbohydrate, protein and fatOverall clinical course and nutritional outcomes are affected by

numerous factors and can vary significantly from patient to patient.

Severe GI impairment requiring specialized EN may occur in: Short bowel syndrome (SBS) Cystic Fibrosis Crohn’s Disease (severe cases) Others: pancreatitis, chronic diarrhea, severe allergies

Formula Comparison Studies in Severe GI Impairment: BASIC DEFINITIONS

Formula Type Macronutrient Content

Elemental (Monomeric)

Individual amino acids, glucose polymers, typically low in fat. Some with only 2-3% of fat as LCT.

Semi-elemental (oligomeric)

Peptides of varying chain length, simple sugars, glucose polymers or starch and fat, combination of LCT/MCT

Polymeric Intact proteins, complex carbohydrates, and mainly LCTs

Factors Impacting EN Management of SBS:

SBS characterized by: diarrhea, malabsorption, fluid and electrolyte disturbances & losses

Factors impacting clinical course: Remaining intestinal length and function of remaining

bowel Site and functional differences between the proximal

and distal small intestine.Presence of ileum, ileocecal valve, & colon

Thus …. EN management can vary significantly from patient to patient depending on above factors as well as: degree of intestinal adaptation & medical course

Guidelines for EN Initiation and Delivery After initial course of parenteral nutrition, EN is best

administered via continuous feeds.Gradual advancement of rate based on outcome

indicatorsdegree of abdominal distention frequency and consistency of stools ostomy output and…. growth (weight gain & linear growth)

Slow and gradual advancement of nutrient load promotes intestinal adaptation.

Eventual transition to …. nocturnal EN with small intermittent/bolus feeds via oral/EN delivery

Controversy Surrounding Enteral Formula Selection in SBS Historically, elemental, semi-elemental or peptide-

based formulas were recommended in SBS.However, research with adult patients has

demonstrated similar clinical outcomes and absorption when compared to polymeric formulas.

But what about formula selection in children?Advantages of complex nutrients in SBS:

Stimulate improved intestinal adaptation “Functional workload” hypothesis: the greater the

bowel must work to digest a nutrient, the greater the inducement to adapt.

What about formula selection in infants & children?Limited randomized clinical trials comparing

effectiveness of polymeric vs. elemental or peptide-based formulas in infants & children with SBS

Present standard of care in most U.S. healthcare institutions is to use protein hydrolysate (peptide based) or in some cases elemental formulas for children with SBS based on theoretical reasons.

Allergic response is more common in infants & children with a disruption in their mucosal barrier. Infants may develop allergy in management of SBS if exposed to macromolecules.

Limited Evidence Comparing Polymeric to Hydrolyzed Formula in Pediatric SBS Study: Ksiazyk, J. et al. (2002) J Pediatric

Gastroenterology & NutritionStudy Design: Prospective randomized cross-over

double-blind study lasting 60 days. N = 10 children, Formulas: Non-hydrolyzed whey vs. Hydrolyzed

Outcomes: Intestinal permeability, weight gain, and energy and nitrogen balance did not differ between infants fed polymeric versus hydrolyzed protein

Study Limitations: small sample size

Summary: EN Recommendations in Children with SBSDepending on extent of bowel resection and function of

the remaining gut, may begin with standard polymeric infant or pediatric formula.

If significant gut resection and loss of ileum and/or ileocecal valve or polymeric formula not tolerated, use hydrolyzed protein (semi-elemental) formula.

If hydrolyzed, peptide-based formula is not well tolerated, as demonstrated by outcome indicators, switch to trial of elemental formula

In general, begin with continuous feeding schedule and slowly advance. Then, transition to nocturnal feeds with intermittent daytime feeds (oral and/or EN as indicated).

Enteral Nutrition in Children with Cystic FibrosisIndications: Patients who remain in nutritional failure

despite use of high calorie nutrition supplements and pancreatic enzymes

EN Delivery Options: Initial trial of nasogastric feedings OR Consultation and evaluation for G-tube or PEG placement

• Methods of Delivery:1. Nocturnal feedings over 10 – 12 hours2. Daytime oral feeds of high calorie foods and nutritional

supplements. Examples: milk with Instant Breakfast, 1.5 kcal/ml supplements or Scandishakes (Axcan Scandipharm)

3. Nocturnal feeds + intermittent PEG feeds

Enteral Formula Selection in Cystic Fibrosis

Standard polymeric formulas are usually tolerated as well as elemental or peptide based formulas providing that adequate enzymes are administered.

Study Study Design Results

Erskine et al. 1998J Pediatr 132: 265-269

Prospective study of 16 patients (8 boys+8 girls) Ages 4-20. Completed two 6-day nocturnal TF trials of: Nonelemental (Isocal) with enzyme replacement vs. Semi-elemental (Peptamen)

No differences bet-ween formulas in:• Fat absorption• Nitrogen absorption• Weight gain• Feeding tolerance (both well tolerated)

Enzyme Dosing in Nocturnal ENSource: Practical Gastroenterology, 2005

Method Dosing

Meal Dosing Method

•“Meal dose” of 150 – 250 Units/kg/meal at beginning of EN infusion•Half-meal dose of 75 -125 Units/kg/meal at end of EN infusion

Pancreatic Enzyme Powder

•Provide 2,000 Units lipase per gram of fat directly to the formula•Shake EN formula bag to distribute the enzyme and facilitate breakdown•Example: Viokase powder (limited supply). Alternative: Zenpep (Eurand)

Factors Contributing to Growth Failure in Crohn’s DiseaseMultifactorial etiologyConsequences of gut inflammationMost pronounced in severe Crohn’s disease, resistant

to conventional medical therapyDisturbances in growth hormone (GH)/insulin-like

growth factor (IGF) axisAdverse effects of corticosteroid therapy: impact on

linear growth

Effect of EN Protein on Crohn’s Disease Remission: Use of elemental formulas

Rationale: chemically synthesized amino acids, are thought to be antigen free and thus less likely to expose a patient’s intestinal mucosa to antigens, and inducing a Crohn’s “flare”.

Controversial study: Giaffer, North & Holdsworth, JPEN, 1990 Results: Significant reduction in Crohn’s Disease

Activity Index (CDAI) in patients on 10 days of elemental formula (Vivonex) compared to polymeric formula (Fortison) after 10 days of feeding

Results have not been duplicated since ….

Review of EN Formula Studies in Crohn’s DiseaseStudy Study Design Results

Rigaud et al. 1991(Adult Study)

Prospective study to induce remission. Formulas: elemental (Vivonex HN) vs. polymeric (Nutrison).CDAI scores measured last 7 days of 28 day feeding period.

No significant difference in clinical remission rates – (66% vs. 73%). Time to remission not signifi-cantly different.

Ludvigson, J.F. et al., 2004(Pediatric Study)

Randomized, non-blind, multicenter, controlled trial of N = 33 children: 16 received Elemental (E028), 17 received Nutrition Standard. PCDAI were compared at 6 weeks.

No significant dif-ference between the 2 groups in remission rate. No difference in decrease of PCDAI score. Pt. on Nutrison gained more weight

Enteral Nutrition Therapy for Inducing Remission in Crohn’s DiseaseCochrane Database Systematic Review 2007; (1):

CD000542, Zachos, M., Todeur, M. & Griffiths, A.M.Objective: to examine efficacy of formula protein

composition on remission rates in Crohn’s diseaseMeta-analysis of 9 studies including 170 patients treated

with elemental diet vs. 128 patients treated with non-elemental diet.

Results: No significant differences in diet formulations; Significant heterogeneity was not present. No significant difference in efficacy of elemental vs. non-elemental diets for induction of remission of Crohn’s disease.

Effect of Enteral Nutrition Fat on Crohn’s Disease RemissionOmega-6 PUFAs: precursor of arachidonic acid

Leads to increased production of inflammatory eicosanoids, i.e. series-2 prostaglandins and series-4 leukotriences

Accentuate the inflammatory response in Crohn’sOmega-3 PUFAs: such as linolenic acid, precursors of

eicosapentanoic acid (EPA) and docosahexanoic acid (DHA)Leads to production of series-3 prostaglandins and series

5 leukotriencesLess inflammatory & may be protective in Crohn’s

Study: Dietary Fat Attenuates Role of EN in Crohn’s Remission: Bamba et al. 2003Sample: 28 patients randomized to low fat (3.06 gm),

medium fat (16.56 gm) & high fat (30 gm) per day elemental diets for 4 weeks.

The 3 formulas had identical total calories, nitrogen source, vitamins, minerals; differed in fat & carbohydrate content

Results: Remission rates were 80%, 40%, and 25% respectively

for high, medium and low fat diets.Extra fat in medium and high fat groups were made up

of LCT: linoleic (52%), oleic (24%) & linolenic (8%).

Summary of Formula Selection Guidelines:

Short Bowel Syndrome: Depending on degree of bowel resection, function of remaining bowel and presence of IC valve, ileum or colon, begin with polymeric formula, and if not tolerated, advance to semi-elemental, and last option would be elemental.

Cystic Fibrosis: When using EN for CF patients with growth failure, begin with a standard polymeric formula with appropriate enzyme supplementation; overall more cost effective.

Crohn’s Disease: In severe Crohn’s with associated growth failure, begin EN with standard polymeric. Only if not well tolerated, consider semi-elemental.

“Our” Approach to EN Management of Severe GI Impairment

“Based on lack of clear data showing a definitive advantage to starting children with GI impairment on a hydrolyzed protein or elemental formula, our approach is to use a standard polymeric infant or pediatric formula initially, as the first choice for therapy for most children, even those who have the potential for severe GI impairment. In the face of persistent intolerance and malabsorption, when other causes have been ruled out, trials of semi-elemental and elemental amino-acid based formulas may be required.”

Abad-Jorge, A. and Roman, B. Support Line, 2007; 29(2): 3 – 11.

•Breast milk•Semi-elemental •Elemental formulas

Use of Breast Milk in Severe GI Impairment

Study: Andorsky et al, 2001, J PediatrDesign: Retrospective chart review among SBS

infants (n = 30)Results: Percentage of days fed with BM was

negatively correlated with duration of PN. The mean number of days on PN was significantly lower in breast-fed infants compared with formula fed infants.

Possible cause: unique nutrient blend in breast milk with sIgA, nucleotides, trophic peptides, leukocytes, growth hormone and long-chain fatty acids (DHA).

Hydrolyzed Formulas for Use in Infants with SBS or Severe GI Impairment (0.67 kcal/ml)

Nutrient Pregestimil Lipil Alimentum Advance

Protein 1.9 gm per 100 ml (11%)Hydrolyzed casein

1.9 gm per 100 ml (11%)Hydrolyzed casein

Carbohydrate 6.8 gm per 100 ml (41%)Corn syrup & Tapioca

6.8 gm per 100 ml (41%)Tapioca & sucrose

Fat(Both have DHA & ARA)

3.8 gm per 100 ml (48%)MCT oil & corn oilLCT - 45%MCT - 55%

3.8 gm per 100 ml (48%)MCT oil, soy, safflowerLCT - 67%MCT - 33%

OsmolalitymOsm/kg

340 370

Elemental Formulas for Use in Infants with SBS, Severe GI Impairment or Allergy (Powdered, not available commercially, order from manufact.)

Nutrient Neocate Infant(0.67 kcal/ml)

EleCare(1.0 kcal/ml)

Protein 2.08 gm per 100 ml (12%)Free amino acids

3.01 gm per 100 ml (15%)Free amino acids

Carbohydrate 7.8 gm per 100 ml (47%)Corn syrup solids

10.7 gm per 100 ml (43%)Corn syrup solids

Fat 3.0 gm per 100 ml (41%)Safflower, soy, coconutLCT - 95%MCT - 5%

4.8 gm per 100 ml (42%)Safflower, coconut, soyLCT - 67%MCT - 33%

OsmolalitymOsm/kg

375 396

Infant Formulas: Cost Comparison(Costs may vary based on location)

Formula Name Cost per 100 kcal

Enfamil Lipil $0.72

Similac Advance $0.76

Pregestimil Lipil $1.29

Alimentum Advance $1.27

Neocate Infant $2.08

EleCare $1.68

Hydrolyzed Formulas in Children > 1 year: How to Select

Indicated for children > 1 year of age, who have severe malabsorption or allergic complications and who demonstrate intolerance to intact protein formulas

Semi-elemental: Peptamen Junior (Nestle Nutrition): Ready to feed, also

available in 1.5 kcal/ml, and with PreBioPepdite Junior (Nutricia, North America): PowderedVital Junior (Ross Products Division)

• Selection Decision: Which formula to use? Decision individualized based on patient tolerance. A higher fat/lower carb blend may be better tolerated in some children due to reduced lactate & gas production.

Hydrolyzed Formulas for Use in Children with SBS or Severe GI Impairment (1.0 kcal/ml)Nutrient Peptamen Junior Pepdite Junior

Protein 3.0 gm per 100 ml (12%)Whey hydrolysate

3.1 gm per 100 ml (12%)Soy & meat hydrolysates + free amino acids

Carbohydrate(sucrose-free)

13.8 gm per 100 ml (55%)Maltodextrin, corn starch

10.6 gm per 100 ml (42%)Maltodextrin, corn syrup

Fat 3.85 gm per 100 ml (33%)Coconut, soy, canola, soy oil, lecithinLCT - 40%MCT - 60%

5.0 gm per 100 ml (46%)Coconut, safflower, and soy oilLCT - 65%MCT - 35%

mOsm/kg 260 430

Elemental Formulas in Children > 1 year: How to Select

Indicated for the young child whose severe GI impairment is related to protein allergies & unable to tolerate hydrolysate formulas.

Elemental: EleCare (Ross Products): powdered Neocate One + (Nutricia, North America): powderedEO28 Splash (Nutricia): flavored, available in tetrapaksNeocate Junior (Nutricia): powdered, higher in fat

Selection Decision: Which formula to use? Decision individualized based on: patient tolerance, cost & availability.

Elemental Formulas for Use in Children with SBS, Severe GI Impairment or Allergy (Powder Base)

Nutrient Neocate One +(1.0 kcal/ml)

Neocate Junior(1.0 kcal/ml)

Protein 2.5 gm per 100 ml (10%)Free amino acids

3.3 gm per 100 ml (12%)Free amino acids

Carbohydrate 14.6 gm per 100 ml (58%)Corn syrup solids

10.4 gm per 100 ml (42%)Corn syrup solids

Fat 3.5 gm per 100 ml (32%)Coconut, canola, safflowerLCT - 65%MCT - 35%

5.0 gm per 100 ml (46%)Coconut, canola,safflowerLCT - 65%MCT - 35%

mOsm/kgIndication

610Multiple food allergies

590Mult. allergy, Malabsorp.

Infant

Yes

No

Normal GI Function?

Normal GI Function?

Yes YesStandard Pediatric Formula

(PediaSure)

Standard Infant

Formula (Enfamil or

Similac)No

No

Malabsorption, GI disease & Dysfunction

Malabsorption, GI disease & Dysfunction

Semi-elemental Pediatric Formula

(Pepdite Jr.) Elemental Pediatric (EleCare)

Semi-elemental

Infant Formula

(Pregestimil or Alimentum)

Elemental Infant

(Neocate Infant)Not tolerated Not tolerated

Summary & ConclusionsThe literature does not clearly support the

advantages of semi-elemental or elemental formulas over polymeric, intact protein formulas in the management of severe GI impairment such as SBS, cystic fibrosis or Crohn’s disease.

Use a standard polymeric infant or pediatric formula initially, as the first choice for therapy for most children, even those who have the potential for severe GI impairment.

If standard formula not tolerated, take a systematic approach to formula selection.

Summary & ConclusionsFirst, start with a semi-elemental or hydrolyzed

formula (less expensive than elemental)If malabsorption, diarrhea & growth failure

persist, then consider elemental formula.Select formula which will be covered by 3rd party

payers, Medicaid or covered by the WIC program.Allow a reasonable trial period of 3 -5 days before

evaluating the need to change formulas.Consider other factors: a) Medications should be

reviewed. b) Consider addition of water soluble fiber to the formula. i.e. pectin

ReferencesReferences available as a handout.All proprietary product information was

obtained from the manufacturer’s website.

Ana Abad-Jorge, MS, RD, CNSCPediatric Nutrition Support Specialist

UVA Health SystemCharlottesville, VAara6t@virginia.edu