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PEDIATRIC IBD Growth 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 Severe Moderate Mild Ht Vel. Quiescent Cm/yr 8 7 6 5 4 3 2 1 0 Growth In Pediatric IBD Gender 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 pubertyearly 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 metaanalysis (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 7 6 5 4 Cm/yr Obs yr Exp yr 3-D Column 3 3 2 1 0 Elemental Control 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.