THE EFFECT OF HIGH CALORIC DIET ON NUTRITIONAL PARAMETERS OF CHILDREN WITH THALASSAEMIA MAJOR. Ashraf T Soliman MD, PhD Professor of Pediatrics and Endocrinology
Thalassemia Ht 102 cm HtSDS = -5.98
Transfusion related iron overload. T2-weighted spin-echo section demonstrates clearly the abnormally low signal in both the liver and spleen (white arrowhead) when compared with adjacent muscle (black arrowhead). The liver parenchyma signal is normally equal to or slightly greater than that of muscle.
Haemochromatosis. Despite the motion artefact, the abnormally low signal in the atrophic right lobe of the liver is evident on (B) the T2-weighted section (white arrowhead). The accumulation of iron in the pancreas is so marked as to reduce signal abnormally on both the T2-weighted and T1-weighted sections (A, black arrowheads).
Cholelithiasis. Plain film showing faceted opaque gallstones.
Thalassemia & Growth Impaired growth involving both height and weight accompanying thalassaemia major poses diagnostic and therapeutic problems.
POSTNATAL HUMAN GROWTH INFANTILE PHASE CHILDHOOD PHASE PUBERTAL GROWTH SPURT (Rapid) Nutrition Insulin, IGF-I T4 (Slow) GH IGF-I Nutrition Nutrition (Spurt) Sex-steroids GH IGF-I
IGF-I/BP system GH is the major regulator of IGF-I and BP3 IGF-I is regulated by stimulatory and inhibitory components of the IGFBPs system IGF-I and BP3 are positively related to nutritional status and insulin. 10
Etiology? of growth/ nutrition impairment (multifactorial) Chronic hypoxaemia Hepatic impairment (siderosis and hepatitis) Nutritional deficiencies (protein/calorie, folic acid, zinc, vitamins? malabsorption Endocrinopathy Desferrioxamine toxicity Disturbed Ca + homeostasis Hypermetabolism (Increased energy expenditure in BM, heart) 11
Possible etiology of undernutrion 1. Nutritional deprivation with or without feeding difficulties arising from fatigue and breathlessness and psychiologic problems 2. Increased energy expenditure secondary to hypermetabolism with or without heart failure,
3. Gastrointestinal hypoxia which consequently produces anorexia and malabsorption, 4. Reduction of biosynthetic activity of liver, secondary to hemosiderosis and hepatitis. 5. Disturbance of the endocrine functions
Thalassemia & IGF-I IGF-I has a 3-fold function as a mediator of the growth promoting action of GH, as a potent mitogenic factor, and as a metabolic regulator with insulin-like activity. Although GH is the main regulator of IGF-I synthesis, however, nutrition, sex steroids, thyrxoxine, insulin and glucocorticoid can modify IGF-I synthesis.
Alteration of IGF-I regulation may provide an attractive explanation for growth impairment associated with thalassemia major.
Two Questions Do Children with Beta Thalassemia have a form of undernutrition? ( Nutritional Parameters) Can this be corrected By nutritional supplementation? (effect on growth and IGF-I)
Subjects: Thalassaemia (n= 100) (all patients) Normal age-matched children (n=200) CSS (n=30) GHD (n=25) 17
Transfusion Status Thalassaemia : On regular transfusion to keep Hb > 9g Desferroxamine therapy (IM or SC) 3 times weekly. On folic acid supplement Vaccinated (pneumococci). 18
I. Growth and Pubertal Survey Anthropomet ry: Wt, Ht, HtSDS, BMI, MAC, SFT, GV (1yr) Dietary evaluation (quality, quantity) Investigation: OGTT T4, TSH IGF-I Stool fat 19
HtSDS in patients and controls HtSDS 0.5 0-0.5-1 -1.5-2 -2.5-3 -3.5 0.4-1.4-2 -3.5 Normal SCD Thalass GHD 20
GVSDS in patients and controls GVSDS 0.5 0-0.5-1 -1.5-2 -2.5-3 0.21-1.02-1.2-2.9 Normal SCD Thalass GHD 21
Mid-arm Circumference MAC (cm) 20 18 16 14 12 10 8 6 4 2 0 19.8 16.5 14.3 Normal CSS Thalass 22
Triceps skin-fold thickness 12 11 SFT (mm) 10 9 8 9.2 8 7 6.7 6 5 Normal CSS Thalass 23
Thalassaemia (HtSDS) HtSDS HtSDS 49% 17% 49% < -2 34% >-1 <-1 >-2 <-2 83% < -1 17 % > -1 24
Normal Children (HtSDS) 18 % 3% HtSDS 79 % > -1 <-1 >-2 < -2 3% < -2 21 % <-1 79 % > -1 25
GVSDS < -1 in patients and controls SCD 51% Thalass 56% Normal 9% 0% 20% 40% 60% 80% 26
Nutrituional Parameters Thalassaemia 49% had HtSDS <-2 and 83% <-1 Small Subcutaneous fat Small mid-arm circumference 27
GH ug Thal : GH after stimulation 20 18 16 14 12 10 8 6 4 2 0 GH-b After clonidine GH-p 18.6 6.2 4.2 18 16 14 12 10 8 6 4 2 0 GH-b After glucagon 16.7 6.8 3.9 GH-p Thal CSS GHD 28
IGF-I in patients and CSS IGF-I ng/dl 168 200 150 82 49 100 50 Thalass GHD CSS 0 29
IGF - IGF - Thal: IGF-I generation IGF-I generation IGF-I increments after GH 250 200 150 153 227 158 100 90 80 70 60 50 73 95 100 50 48 0 IGF-I-b 87 IGF-I-a Thal CSS GHD 40 30 20 10 0 38 Thal CSS GHD 30
IGFBP3 IGF-BP3 in Thalassemia IGFBP3 (mg/l) 2.5 2 2.1 1.5 1 1.2 1.1 0.5 0 Thal CSS GHD
IGFBP3 after GH injection 3.5 3 2.5 2 1.5 Thalassemia CSS GHD 1 0.5 0 Before GH After GH
IGFBP3 Thal: GH/IGF-I/BP3 axis Children with thal: High incidence of GHD and GH-NSD Lower IGF-I vs CSS Decreased IGF-I synthesis after GH vs CSS and GHD Lower IGFBP3 vs CSS 2.5 2 1.5 1 0.5 0 IGFBP3 (mg/l) 2.1 1.2 1.1 Thal CSS GHD 33
Thalassemic Children Have: (answer to 1 st question) 1. Impaired linear growth 2. Subnormal nutritional parameters 3. Decreased IGF-I and BP3 4. Decreased ability to generate IGF-I even after GH injection.
Is that correctable by nutritional supplementation? 2 nd question
Nutrition & IGF-I in Thalassemia we measured circulating concentration of insulin-like growth factor-i (IGF-I) and albumin, and evaluated the nutritional parameters, before and after nutritional supplementation for 12 weeks, in 15 prepubertal randomly-selected children with thalassaemia major compared to 15 age-matched thalassaemic children without nutritional supplementation.
Nutritional Supllementation 30 prepubertal children with thalassaemia major All children underwent regular transfusions to keep the hemoglobin (Hb) concentration > 10 g/dl. All were taking folic acid supplements and iron chelation with daily I M/ SC desferoxamine.
Patients Criteria Children with heart involvement, DM or IGT, impaired hepatic function, hypothyroidism or GHD deficiency were excluded from the study. Normal Stool Fat concentration /day Normal Dietary intake (Quantitative and Qualitative) Normal serum albumin concentration
Their caloric intake increased by 30-50% of the total energy requirements by increasing mainly : the neutral fats ( corn oil, butter, margarine, fatty cheese and egg yolk) & complex carbohydrates distributed on 3 meals and 2 snacks daily, keeping the protein intake at approximately 1.5-2 g/kg/day vitamins and minerals = 100-150% of (RDA)
During each clinic visit: (q 2 w) Anthropometric measurements Dietary evaluation / supplementation
None of the children reported significant gastrointestinal symptoms including abdominal pain, distention or vomiting Mild diarrhea occurred in three thalassaemic patients but did not necessitate stopping the nutritional supplementation.
Weight, BMI and IGF-I before vs after nutritional supplementation 199 200 150 100 69 89 50 26.7 27.6 32 0 Thal. Before Thal. After Controls Weight BMI IGF-I
Results Children with thalassaemia major, without endocrinopathy or cardiomyopathy : were significantly shorter and had smaller MAC and triceps SFT compared to normal agematched children denoting a degree of undernutrition, despite apparently normal food intake.
Why The hypermetabolic status with increased resting metabolic rate and oxygen consumption secondary to anemia, increased cardiac work and bone marrow hyperactivity. The combination of normal intake and elevated metabolic rate per kilogram of body weight reduces the energy available for growth and can produce a considerable degree of undernutrition.
Thalassaemic patients : Had significantly lower serum IGF-I concentrations vs normal children. Increased their IGF-I and SCFT, weight and BMI after nutritional supplementation
Conclusion This improvement of the nutritional status (weight, MAC, SFT) and increased IGF-I production after introducing highcaloric diet proved that part of the growth impairment of these patients is correctable by proper nutritional intervention to compensate for their hypermetabolic status of these patients.
Recommendation It is recommended that this nutritional support should be considered in every treatment protocol for these patients