PEDIATRIC IBDGrowth and Nutrition

By

Karla Au Yeung, MD

MAJ, MC, USAR

3 November 2000

Objectives

• Epidemiology/Definition

• Complications/ Mechanisms– Malnutrition– Medication effects– Micronutrient deficiencies– Effects unique to pediatrics

• Specific Nutritional Therapy

Definition of Failed Growth

• Kleinman, et al

• Dec Ht > 0.3 SD per year

• growth velocity <5cm/yr

• Dec ht velocity > 2cm from preceding yr (during early to mid-puberty)

• Bone age and pubertal staging

Our Situation

• 25% of all IBD are pediatric --> infants– CD > UC 4:1

• Growth failure is unique to pediatric IBD– 30-50% of CD ped. Pts– 10% of UC ped. Pts

• Malnutrition/micronutrient deficiencies more likely due to increased metabolic needs for growth

Our Situation cont.

• Sole manifestation of IBD in 5% of pts

• Resemble anorexia nervosa – wt loss/anorexia sx more prevalent than GI sx

• IBD pts do not have disordered body image or fear becoming fat

• Problem: heights (weights) do not get recorded regularly for school-age kids

Problems We Face in This Situation

• 1. Growth/Nutrition is a problem before we meet the pt. – Possible direct effects of inflam. mediators– Anorexic effects of inflam. Mediators

• 2. Patients don’t feel well– Post-prandial pain --> dec. intake – anorexia (intake 55-80% of RDA of cal. Needs)

Complications cont.

• 3. Malabsorption– Protein Losing Enteropathy– Bacterial Overgrowth– Dec. surf. Area for absorption – Lactose intolerance– Micronutrient deficiencies– Rapid transit

Micronutrient Deficiencies

• Iron deficiency anemia is most common– Tx with iron dextran if resistant to oral Fe Tx

• Folate and B12

• Zinc deficiency (est. up to 40% pts)– lower in growth impaired teens with CD– Zinc repletion does not accelerate growth.

• Ca, Mg, Phos, Vit D - esp in adolescent pts.

Complications Cont.

• 3. Chronic Dec Energy and Protein intake– not able to keep up with needs– endocrine functions altered– 56% RDA was mean caloric intake in one study

Complications Cont.: Medications

• Steroids– alter linear growth

– proteolytic/ osteolytic

– inhibit bone growth

• Sulfasalazine– use folic acid

Complications Cont.

• 6. Time is our enemy– Eventual closure of the epiphyses – Stunted growth in 17% of pts with early delay

in growth– Especially important in the peripubertal age

• 7. Elemental Formulas – Can restore growth velocity– Bad taste, need for NGT/G-tube

Growth Failure at Presentation“Prepatterned”

• Motil, et al Gastroenterology 1993

• Regardless of pubertal development, at dx, 23-39% of pts had delayed growth

• Delay in linear growth persisted through puberty and was not reversed by surgery

• Sig. Neg. assoc. between linear growth and disease activity, but not medication Tx

Ht Velocity According to Severity of Symptoms

• Severity GI Sx- Griffiths, et al Gut 1993

012345678

Qui

esce

nt

Mil

d

Mod

erat

e

Seve

re

Ht Vel.

Cm/yr

Growth In Pediatric IBDGender Difference

• Sentongo, et al. JPGN 2000

• Prospective Study to measure anthropometry, DEXA, genetic potential, PCDAI, lifetime steroid use in relation to gender and disease activity

• Results:– Ht age Z inc. in male control compared to CD

pt. This difference not seen in females

Endocrinologic Issues

• Short stature evaluation:– secondary to IBD– constitutional delay– genetically short stature

• Other hormones– thyroid/growth hormone - non-contributory– gonadotropins/estrogen- affected by

malnutrition --> delayed pubertal maturation

Endocrine Cont.

• Insulin-like growth factor I– mediates growth

– nutritionally modulated

– low levels during fasting and quickly return to nl w/ feeding

– low in CD who are nutritionally impaired

Factors Affecting Bone Mass in IBD

• Hyams and others showed mouse calvarium and serum from active CD had impaired mineralization - not in UC or controls

• Osteoblast impaired by cytokine in CD serum: IL-1B, TNFa, IL-6

• STEROID– Dec. Formation (inhibit osteoblast)– Inc. Resorption (dec. gut absorption, Inc. PTH)

Risk Factors for Low Bone Mineral Density

• Semeao, et al J. Ped 1999• Life long risk of frax related to peak bone

mass• Peak bone mass is achieved during puberty-

early adulthood• Reports of up to 70% CD children with dec.

BMD• Evaluated several parameters for risks

Risk Factors for Low Bone Mineral Density

• Inc. # hosp. Days• Inc. PCDAI• Hypoalbuminemia• NGT/TPN• Flagyl/Asacol

– unreliable because such routine use

• 6MP (32% pts)• >7.5 mg/day of

steroid exposure • >5000mg accum

steroid use• Duration of steroid

>12 mos

Low BMD Risks cont.

• NOT Correlated• Site of Dz• Age Dx• Duration DZ• H/o surgery

• Conclusion:– Use this as criteria to

decide who needs DEXA and when

– Risk of dec. bone mass is not just due to steroid use.

Labs to Evaluate Osteopenia

• Serum Ca, Phos, Alk Phos• Vit D, Vit D metabolites, Alk phos

isoenzymes, GGT, PTH• BONE AGE

– Impt for interpreting BMD– Impt for estimating growth delay

• Dual Xray Densitometry/absorptiometry– 1SD below mean = osteopenia

Treatment of Osteopenia

• Tx underlying disorder

• Nutritional rehabilitation

• Consider malabsorption and tx

• Bone is mineralized at max dose of steroid of 0.3mg/kg qod

• Substitute steroid for immunomod. Asap

• Ca supplement when well

Treatment of Osteopenia

• Vit D supplement: no evidence that excess beyond RDA is needed– except liver dz, deficiency, dietary restriction

• Weight Bearing exercise helps mineralize bone

• Bisphosphonates– dec. turnover of bone– side effects/ longterm effects on growing bones

RDA for Calcium

• 0-6 months• 6-12 months• 1-3 years• 4-8 years• 9-13 years

• 210mg• 270 mg• 500 mg• 800 mg• 1300 mg

Dietary Calcium Sources

• Dairy products• Meat, fish with bone• Broccoli• Bok choy• Kale

Enteral Nutrition: Intro

• Possible Mechanisms:

• 1. Dec. Antigen load to the GI tract

• 2. Alter intestinal microbial flora

• 3. Dec. intestinal synthesis of inflammatory mediators via reduction of dietary fat

• 4. Provision of micronutrients to diseased bowel

Enteral Nutrition cont.

• Formula composition for protein and/or fat source have not proven to make a difference in studies– Common practice for remission is elemental or

semi-elemental formula

• Dec. ratio of n-6 to n-3 polyunsat fatty acids– dec. precursors for arachidonate-derived

eicosanoid synthesis (n-6) (fish-oil tx)

Enteral Nutrition Intro cont.

• Factors for Relative Benefit of Enteral Nutrition as Primary Therapy– Mostly small bowel dz– Prepubertal– Acute Malnutrition/Growth Failure– Motivated patient/family

• Not as good as steroid compared in meta-analysis (relapse 70% in one year)- but growth improved on nutrition tx.

Enteral Nutrition Support

• Three possible strategies

• 1. Begin with nutritional therapy alone– elemental formula only for 4-6 wks

• 2. Nutritional supplement to increase caloric intake and reverse growth delay

• 3. Prevent relapses– intermittent administration

Supplementary Enteral Nutrition Maintains Remission

• Wilschanski, et al Gut 1996

• Tx 65 pts active CD with elemental formula overnight 4-6 weeks: 72% remission– 43% relapse by 6 mos– 60% relapse by 12 mos

• If continued NGT fdg with daytime reg. diet, even less relapse rate

• Suggest macro/micronutrient effect vs. Ag

Chronic Intermittent Elemental Diet

• Belli, et al Gastroenterology 1988

• 7 boys/ 1 girl CD/growth delayed

• 1st year observe

• 2nd year, elemental diet group/control grp– E. diet q 4months for 1 month

• Treat prn with medication (sulfa/pred)

RESULTS

• No pt dropped out

• Ave caloric intake of 133% during ED Tx compared to 106% between tx.

• ED grp grew 7cm the 2nd year

• ED grp gained more weight

• ED grp dec. prednisone intake (22vs89 mg/kg/year)

• ED grp CDAI dec. significantly

Absolute Height Changes

0

1

2

3

4

5

6

7

Elemental Control

Obs yrExp yr3-D Column 3

Cm/yr

Conclusion to This Study

• This is tolerable and effective method for maintaining remission with nutrition tx

• Not only did pts have increased height and weight, but they also had dec. steroid use.

• In past studies, even though pts achieve longer remission with steroids, linear growth was not improved much

• problem: small study

Conclusions

• Growth delay is something intrinsic to Crohn’s disease in addition to malnutrition from a multitude of reasons.

• Induce remission and minimize daily steroids ASAP - consider nutritional tx

• Improve energy/nutrient deficiencies• Account for catch up growth• Limited time available in puberty pt.