NUTRITIONAL SUPPORT OF PAEDIATRIC PATIENTS

Abstract: An enteral composition for paediatric patients. The composition is made up of a protein source, a carbohydrate source and a lipid source. The protein source provides 10 % to 14 % of the total calories and is in the form of casein and whey. The lipid source is a mixture of medium and long chain triglycerides of which at least 20 % are medium chain triglycerides. The composition may be used for providing nutrition to a paediatric patient; especially patients suffering from cerebral palsy or recovering from trauma, burns or surgery and having moderate needs for tissue repair.

Description: Nutritional Support of Paediatric Patients This invention relates to an enteral composition for use in the treatment and nutritional support of paediatric patients and the methods for the treatment and nutritional support of paediatric patients. The measurement of diet adequacy in patients, especially paediatric patients, is difficult. Increases in a child's weight and length only grossly reflect nutritional progress. The daily requirements for adequate nutrition are especially significant for the growing child compared with the adult. The relative need for protein, vitamins and minerals remains constant and is greater than that of adults. Moreover, requirements for various vitamins depend on the intake of calories, protein, fat, carbohydrate and specific amino acids. While the nutritional needs ofthe paediatric patient differ from adult patients, in health care settings, adult nutritional formulas are the primary form of elemental nutrition currently being used for children. Naturally, adult formulas do no take into effect the known nutritional needs ofthe paediatric patient. Adult nutritional products must be diluted to decrease concentrations of, for example, protein, sodium, chloride and the renal solute load to levels recommended for children. This dilution reduces the concentrations of other needed nutrients that are often already in concentrations too low for children (i.e. calcium and phosphorous). Thus, providing a nutritional formula designed specifically for children would be advantageous. A whole protein enteral formula sold under the trademark PEDIASURE® is currently available from Ross Laboratories for nutritional therapy of paediatric patients. PEDIASURE® contains 12% protein, 44% carbohydrates, and 44% fat. The whole protein formula has a protein composition of 82% casein and 18% whey. Although PEDIASURE® is formulated for children, it is designed to provide nutrition for a limited population, namely children of 1 to 6 years old. As a result thereof, while PEDIASURE® may meet the Recommended Daily Allowances (RDAs), set by the National Academy of Sciences-National Research Council (NAS-NRC), for children 1 to 6 years old in 1000 calories, it requires 1300 calories to meet the RDA of children ages 7 to 10 years. Therefore, a need exists for a nutritional formula designed to meet the nutritional needs of a larger base of paediatric patients as well as paediatric patients recovering from trauma, post-surgical and moderate traumatic injuries and burns. Accordingly, in one aspect, this invention provides an enteral composition suitable for paediatric patients. The enteral composition comprises: a protein source providing 10% to 14% ofthe total calories, the protein source comprising casein and whey and providing relatively rapid gastric emptying and reduced gastric reflux; a carbohydrate source; and a lipid source comprising a mixture of medium and long chain triglycerides, at least 20% ofthe lipid source being medium chain triglycerides. Preferably, the protein source comprises casein and whey, most preferably about 50% casein and 50% whey, to improve the rate of gastric emptying and reduce the incidence of gastric reflux as compared to diets containing only casein or predominantly casein. The protein preferably also provides a rich source of cysteine; for example the composition may contain about 0.15% of calories as cysteine (about 350 mg/l 000 calories). The carbohydrate source preferably provides about 40% to about 60% ofthe total calories ofthe composition. The carbohydrate source is maltodextrin, corn starch or sucrose, and mixtures thereof. The lipid source preferably provides about 30% to about 40% ofthe total calories ofthe composition. The long chain triglycerides are preferably selected from soy oil, canola oil, residual milk fat, and soy lecithin. Preferably the lipid source has an omega-3 to omega-6 fatty acid ratio of approximately 4: 1 to 6: 1. The composition may further includes at least 100% ofthe NAS-NRC RDA for children of all vitamins and minerals per 100 kcals. In another aspect, this invention provides a method for providing nutrition to a paediatric patient. The method comprises the step of administering to the patient a therapeutically effective amount of an enteral composition comprising: a protein source comprising about 10% to about 14% ofthe total calories; a carbohydrate source; and a lipid source comprising a mixture of medium and long chain trigly¬ cerides; the lipid source having an omega-3 to omega-6 fatty acid ratio of about 4:1 to about 6: 1 and the medium chain triglycerides comprising at least 25% ofthe lipid source. In another aspect, this invention provides a method for providing nutrition to a paediatric patient with moderate needs for tissue repair recovering from trauma, burns or surgery or suffering from cerebral palsy. The method comprises the step of administering to the patient a therapeutically effective amount of an enteral composition comprising: a cysteine-rich protein source which provides about 10% to about 14% ofthe total calories ofthe composition; a carbohydrate source; and a lipid source comprising a mixture of medium and long chain triglycerides of which the medium chain triglycerides make up at least 25%. In another aspect, this invention provides the use of a lipid source in the form of a mixture of medium chain triglycerides and long chain triglycerides of which the medium chain triglycerides comprises at least about 25% and having an omega-3 to omega-6 fatty acid ratio of about 4: 1 to about 6: 1 , in the preparation >f an enteral composition for providing nutrition to a paediatric patient. In another aspect, this invention provides the use of a cysteine-rich protein source and a lipid source in the form of a mixture of medium chain triglycerides and long chain triglycerides of which the medium chain triglycerides comprises at least about 25%, in the preparation of an enteral composition for providing nutrition to a paediatric patient suffering from cerebral palsy or recovering from trauma, burns or surgery and having moderate needs for tissue repair. The invention has the advantage that it provides enteral composition that is ready-to-use, nutritionally complete, and contains proteins, lipids, carbohydrates and vitamins and minerals in proportions appropriate for children ages 1-10 years. Moreover, the enteral composition has optimal tolerance and absoφtion in children ages 1-10 years. Also the protein source in a concentration that is adequate to support growth and moderate needs for tissue repair without imposing an undue nitrogen burden on renal function. Embodiments ofthe invention are now described by way of example only. Nutritional support of hospitalised children requires prevention, recognition, and treatment ofthe nutritional depletion that may occur with illness. The goals of nutritional support include stabilising metabolic state, maintaining body mass, and/or facilitating growth and promoting tissue repair in the presence of disease and/or trauma. While diseases relating to nutritional deficiency are unusual in first world countries, other disease states exist that alter intake, absoφtion or metabolism. Certain health conditions can impair the nutrient absoφtion and/or reduce gastrointestinal tolerance for diets which are based on whole proteins, long- chain fatty acids and/or complex carbohydrates. Hence there is a need for an enteral composition which is able to provide adequate nutrition to children. The enteral composition which is suitable for supplying nutrition to paediatric patients is made up of a protein source, a carbohydrate source, and a lipid source. The protein source provides about 10% to 14% ofthe total calories ofthe composition. For example, the protein source may provide about 12% ofthe total calories ofthe composition. This protein concentration is adequate to support growth and moderate needs for tissue repair without imposing an undue nitrogen burden on renal function for children ages 1 to 10 years. The protein source preferably comprises a mixture of casein and whey proteins. The whey protein may be present in whole or in hydrolyzed form. Preferably, the protein source comprises at least about 50% whey protein; for example in the form of hydrolyzed whey. This protein source reduces the incidence of gastric reflux because gastric emptying is faster than with diets containing casein or predominantly casein. Also, whey protein serves as a rich source ofthe amino acid cysteine. Cysteine is a limiting amino acid for the formation of glutathione, and glutathione needs may be higher in children with infectious or inflammatory conditions. Preferably, the enteral composition contains approximately 0.15% of calories as cysteine (approximately 350 mg per 1000 calories). The carbohydrate source provides about 40% to about 60% ofthe caloric content ofthe composition. For example, the carbohydrate source may provide about 51% of the caloric content ofthe composition. A number of carbohydrates can be used including maltodextrin, hydrolyzed corn starch and/or sucrose. The lipid source includes a mixture of medium chain triglycerides (MCT) and long chain triglycerides (LCT). Preferably the lipid source provides about 30% to about 40% ofthe caloric content ofthe composition. For example, the lipid source may provide about 37% ofthe caloric content ofthe composition. The lipid profile is designed to meet essential fatty acid (omega-3 and omega-6) needs of children, and for example comprises about 12.6% of essential fatty acids based on total calories. The lipid source preferably includes at least about 20 to about 30% of medium chain triglycerides. For example, MCTs may make up at least about 25% ofthe lipid source. Suitable sources of long chain triglycerides are canola oil, soy oil, residual milk fat, and soy lecithin. The lipid profile ofthe enteral composition is preferably designed to have a polyunsaturated fatty acid omega-6 (n-6) to omega-3 (n-3) ratio of about 4: 1 to about 6:1. For example, the n-6 to n-3 fatty acid ratio may be about 5:1. Both the omega-6 and omega-3 fatty acids are provided in sufficient quantity to meet tissue growth maintenance needs. To this end, the source of omega-6 fatty acids preferably provides about 4 to about 12% ofthe total calories. The omega-3 fatty acid source is preferably present in the range of approximately 0.8-3.0% ofthe total calories. In addition to the absoφtion/tolerance benefits of a moderate LCT content, the enteral composition less likely to be immunosuppressive due to the low percentage of omega-6 fatty acids. By way of example, and not limitation, an example of a suitable lipid profile that may be used in the enteral composition is as follows: Lipid Profile f42.0 grams/litre^ COMPONENT % of Lipids Grams/Litre C6:0 0.6 0.3 C8:0 14.0 5.9 C10:0 6.7 2.8 C12:0 0.3 0.1 C14:0 0.4 0.2 C16:0 6.4 2.7 C18:0 2.2 0.9 C20:0 0.5 0.2 TOTAL SAT 31.1 13.1 C16:l 0.4 0.2 C18:l 24.1 10.1 C20:l 0.3 0.1 TOTAL MONO 24.8 10.4 C18:2 n6 27.8 11.7 C18:3 n3 5.7 2.35 TOTAL POLY 33.5 14.05 TOTAL, FA'S 89.4 37.55 NON-FA'S 10.6 4.45 TOTAL, ALL 100.0 42.0 Where "FA" means fatty acid, and "Sat" means saturated. P/S Ratio = 1.1; (Saturated includes MCT) N6 = 27.8% of fat (22.7 g/L) 10.5% of total calories N3 = 5.7% of fat (2.35 g/L) 2.1% of total calories N3 to N6 Ratio = 5.0:1. The lipid source may be made up as follows: 1 FAT SOURCE % BY % TOTAL WT KCAL MCT 25% 8.7& CANOLA 24% 9.1% SOY 43% 16.2% MILK* 3% 1.1% SOY LECITHIN 5% 1.9% 1 TOTAL 100% 37.0 ♦ Residual milk fat (with the casein and whey protein) contributes to the total lipid content The enteral composition preferably includes a specialised vitamin and mineral profile. In particular, the composition includes a source of vitamins and minerals providing at least 100% ofthe NAS-NRC Recommended Daily Allowance for children. The vitamin and mineral requirements are met in 1000 kcal per day because this intake is practical, achievable and easily tolerated by children ages 1-10 years, even though it is somewhat less than healthy children normally eat. Unlike prior compositions, the enteral composition meets NAS-NRC RDAs for children ages 1-10 years in 1000 calories. The high vitamin and mineral concentration ofthe enteral composition is of practical benefit because typical feeding regimens (e.g. 50 ml/hour for 20 hours/day) will meet all needs. However, none ofthe vitamin or mineral concentrations are so high that there is any risk of approaching toxic levels, even at 2000-2500 kcal per day. The enteral composition may include a source of beta-carotene. Beta- carotene, formerly considered only as a precursor to vitamin A, is an important nutrient with anti-oxidant properties. For example, the composition may include about 0.5 to about 2.0 mg of beta-carotene per 1000 calories. This amount of beta- carotene is sufficient to maintain plasma beta-carotene concentration in the paediatric patient. The enteral composition may further include certain electrolyte concentrations. The electrolyte concentrations are set to meet needs without providing an undue renal solute burden on kidney function. To this end, sodium is preferably present in a range of about 420 to about 500 mg/L, potassium is preferably present in a range of about 1260 to about 1380 mg/L and chloride is preferably present in a range of about 1040 to about 1120 mg/L. The renal solute load is, for example, present in a range of about 200 to about 210 Mosm. In a preferred example, the electrolyte concentrations are as follows: sodium is present at about 460 mg/L; potassium is present at about 1320 mg/L; chloride is present at about 1080 mg/L; and the renal solute load is at about 205 Mosm. The enteral composition is in the form of a ready-to-use enteral formulation. The composition can be used as a supplement or for total enteral nutritional support. The composition can be tube-fed to a patient, or fed by having the patient drink it. Preferably, the caloric density of the composition is 1.0 kcal/ml. Various flavorants, fibres and other additives may also be present. The enteral composition may be used for providing nutrition to paediatric patients of ages of 1 to 10 years. Likewise, the composition can be used for providing nutrition to a paediatric patient recovering from surgery, burns or trauma. The diet utilises a significant amount of whey protein, medium chain triglycerides and maltodextrin to enhance absoφtion and reduce intolerance. By way of example, and not limitation, suitable compositions that may be used are as follows: Examples 1 - 2 The enteral nutritional compositions comprise the following ingredients: protein: casein and whey; carbohydrate: maltodextrin and sucrose; lipid: canola oil, soy oil, coconut oil (MCT), residual milk fat, soy lecithin; water; vitamin A (retinol); beta-carotene; vitamin D, vitamin E; vitamin K; vitamin C; thiamine B| ; riboflavin B 2 ; niacin; vitamin B 6 ; folic acid; pantothenic acid; vitamin B 12 ; biotin; choline; taurine; L-carnitine; inositol; calcium; phosphorus; magnesium; zinc; iron; copper; manganese; iodine; sodium; potassium; chloride; chromium; molybdenum; and selenium. The enteral of example 1 includes dietary fibre while that of example 2 does not. The composition have the following nutrient composition (per 1000 calories): Paediatric Enteral Nutritional Compositions COMPOSITION (Per Litre) UNITS Example 1 Example 2 Cal. Density Kcal/ml 1.0 1.0 CalsJCan Calories 250 250 PROTEIN g L (% Kcal) 30.0 (12%) 30.0 (12%) Casein 50% 50% Whey 50% 50% CARBOHYDRATE g/L (% Kcal) 127.5 (51%) 127.5 (51%) Maltodextrin 66% 66% Sucrose 34% 34% FIBER g/L 0.0 6.0 LACTOSE CONTENT g L 1.5 1.5 FAT g/L (% Kcal) 42.0 (37%) 42.0 (37%) % by weight Soy oil 43% 25% MCT 25% 25% Canola oil 24% 24% Soy Lecithin 5% 5% Residual milk fat 3% 3% MCT g/L (% Kcal) 10.5 (8.7%) 10.5 (8.7%) Linolenic (N6) 11.7 10.5%) 11.7 (10.5%) Linoleic (N3) 2.35 (2.1%) 2.35 (2.1%) N6:N3 ratio 5.0:1 5.0:1 OSMOLALITY MOSM 350 350 RENAL SOLUTE LOAD MOSM/L 205 205 MCT.LCT RATIO 25:75 25:75 volume to meet or exceed 1.0 L 1.0 L NAS-NRC RDA DENSITY g/ml 1.057 1.060 WATER ml/L 850 (85%) 840 (84%) CAL/gN Ratio 210:1 210:1 NPC/gN Ratio 185:1 185:1 1 Examples 3-4 The enteral compositions may be provided in storage stable, ready to use, liquid form in cans or in retort processed, screw-topped containers. Examples 3-4 show the formulations for 250 ml cans and one litre containers with respect to NAS-NRC recommended dietary allowances for children 7-10 years of age as follows: Paediatric Nutritional Formulations in 250 ml and 1 L Containers Calcium mg 800 250 31 1000 125 Phosphorus mg 800 200 25 800 100 Magnesium mg 170 50 29 200 118 Zinc mg 10 3.8 38 15 150 Iron mg 10 3.5 35 14 140 Copper mg φ 0.25 ΦΦ 1.0 ΦΦ Manganese mg φφ 0.4 ΦΦ 1.5 ΦΦ Iodine μg 120 30 25 120 100 Sodium mg ΦΦ 115 ΦΦ 460 φφ Potassium mg φφ 330 ΦΦ 1320 φφ 1 Chloride mg φ 270 ΦΦ 1080 φφ Chromium μg φφ 7.5 Φ Φ 30 φ φ Molybdenum μg φφ 7.5 ΦΦ 30 φφ J Selenium μg 30 7.5 25 30 100 ** NAS-NRC RDA not established *** 26% from Vit. A plus a max. of 416 l.U. from conversion of beta- carotene (Total=44% NAS-NRC RDA) Example 5 Another enteral composition is shown in the following Example 5. The following table shows a comparison ofthe composition of Example 5 with the NAS-NRC RDAs and with a prior paediatric formulation, PEDIASURE® available from Ross Laboratories, as follows: 11- Comparison of Composition of Example 5 with PEDIASURE® and NAS-NRC RDAs fPer 1000 Calories^ NAS-NRC RDAs Nutrient Units Pediasure® 1-3 4-6 7-10 Example 5 composition Yrs Yrs Yrs CAL. Density Kcal/ 1.0 ΦΦ ΦΦ ΦΦ 1.0 ml Protein g (%) 30.0 (12%) 16 24 28 30.0 (12%) Casein 82% 50% Whey 18% 50% Carbohydrate g (%) 109.7 ΦΦ Φ Φ Φ Φ 127.5 (44%) (51%) FAT g %) 49.7 (44%) ΦΦ ΦΦ ΦΦ 42.0 (37%) Safflower Oil 50% — Canola Oil — 24% Soy Oil 30% 43% MCT 20% 25% Residual Milk — 3% Fat Soy Lecithin 5% 5% N6:N3 Ratio 9:1 5:1 Fibre g 5.0 Φ Φ ΦΦ Φ Φ 6.0 or 0.0 Water ml 844 Φ Φ ΦΦ Φ Φ 840 or 850 Vitamin A (retinol) IU 2570 1325 1665 2330 2400 Beta-carotene mg 0 Φ Φ Φ Φ Φ Φ 1.0 Vitamin D IU 510 400 400 400 560 Vitamin E IU 23 6 7 7 28 Vitamin K ΦΦ ΦΦ μg 38 Φ Φ 30 Vitamin C mg 100 40 45 45 100 Thiamine Bi mg 2.7 0.7 0.9 1.0 2.4 Riboflavin B 2 mg 2.1 0.8 1.1 1.2 2.0 Niacin mg 17 9 12 13 20 Vitamin B 6 mg 2.6 1.0 1.1 1.4 2.4 Folic acid μg 370 50 75 100 400 ** NAS-NRC RDA not established. It will be understood that various modifications to the presently preferred embodiments described herein will be apparent to those skilled in the art. Such changes and modifications can be made without departing from the spirit and scope ofthe present invention and without diminishing its attendant advantages. It is therefore intended that such changes and modifications be covered by the appended claims.

Claims: cjaims 1. An enteral composition for paediatric patients comprising: a protein source providing 10% to 14% ofthe total calories and comprising casein and whey in whole or hydrolysed form; a carbohydrate source; and a lipid source comprising a mixture of medium and long chain triglycerides, at least 20% ofthe lipid source being medium chain triglycerides. 2. A composition of Claim 1 in which the protein source comprises about 50% casein and about 50% intact or hydrolyzed whey. 3. A composition of Claim 1 in which the carbohydrate component is sucrose, maltodextrin or corn starch, and mixtures thereof. 4. A composition of Claim 1 in which the long chain triglycerides are selected from soy oil, canola oil, residual milk fat, and soy lecithin. 5. A composition of Claim 1 in which the lipid source has an omega-6 to omega-3 fatty acid ratio of 4: 1 to 6: 1. 6. A composition of Claim 5 in which the omega-6 fatty acids provide about 10.5% of total calories and the omega-3 fatty acids provide about 2.1% of total calories. 7. A composition of Claim 1 further comprising at least 100% ofthe NAS- NRC RDA of all vitamins and minerals in 1000 calories. 8. A composition of any of claims 1 to 7 in which the protein source provides cysteine in an amount of about 0.15% of calories ofthe composition. 9. The use of a lipid source in the form of a mixture of medium chain triglycerides and long chain triglycerides of which the medium chain triglycerides comprises at least about 25% and having an omega-3 to omega-6 fatty acid ratio of about 4: 1 to about 6: 1, in the preparation of an enteral composition for providing nutrition to a paediatric patient. -14- 10. The use of a cysteine-rich protein source and a lipid source in the form of a mixture of medium chain triglycerides and long chain triglycerides of which the medium chain triglycerides comprises at least about 25%, in the preparation of an enteral composition for providing nutrition to a paediatric patient suffering from cerebral palsy or recovering from trauma, burns or surgery and having moderate needs for tissue repair.

Inventors: KRUSEMAN JAN, KRUZEL CHRIS, MARK DAVID A, REDDY SEKHAR, TRIMBO SUSAN L, KRUSEMAN, JAN, KRUZEL, CHRIS, MARK, DAVID, A., REDDY, SEKHAR, TRIMBO, SUSAN, L.
Applicants: NESTLE SA, SOCIETE DES PRODUITS NESTLE S.A.
Application year: 1996
Main classification: A23L1
IPC codes: A23L1