MX2008009805A - Nutritional composition for low birth weight infants - Google Patents

Abstract

A nutritional composition for very low birth weight infants which comprises 26 5 to 38 g/l of a source of hypoallergenic hydrolysed whey protein with a degree of hydrolysis between 8 and 20, 37 to 46 g/l of a fat source of which 20 to 50%is medium chain triglycerides and which has an n6:n3 ratio between 6 and 12 and 50 to 100 g/l of a carbohydrate source which composition contains between 3.2 and 4.0 grams of protein per 100kcal.

Description

- - NUTRITIOUS COMPOSITION FOR INFANTS WITH LOW WEIGHT AT BIRTH FIELD OF THE INVENTION This invention relates to a nutritional composition for premature infants with very low birth weight and with a method to satisfy the nutrition requirements of said infants.

BACKGROUND OF THE INVENTION Breast milk is recommended for all infants. However, in some cases, particularly in cases of infants who are born prematurely, breastfeeding may be inadequate or ineffective or may not be advisable for medical reasons or may even be impossible. For these situations formulas for infants have been developed. Preterm infants are infants who are born before the end of the thirty-seventh week of pregnancy. These infants generally show functional immaturity which is more pronounced the higher the degree of premature condition. This immaturity manifests itself in numerous ways. For example, premature infants probably have an immature gastrointestinal tract, in particular regarding the ability to absorb nutrients as well as the development and efficacy of intestinal barrier function. Various techniques have been proposed to improve the function of the intestinal barrier or gastrointestinal health in preterm infants. For example, in the document of E.U.A. 6132710, purified strains of Lactobacillus salivarius and Lactobacillus plantarum are administered to preterm infants to prevent damage caused by infection and inflammation to mucosal tissue, especially by nasogastric administration to avoid damage to the gastrointestinal tissue and reduce the risk of neonatal necrotizing enterocolitis. In addition, premature infants also suffer from a limited capacity to metabolize some amino acids such as phenylalanine which can result in severe amino acid imbalances if the ingestion of proteins exceeds the degradation capacity. On the other hand, the availability of an essential amino acid can be a limiting factor for the synthesis of proteins and therefore for growth. In fact, in the premature infant, some amino acids such as tyrosine and cysteine, which are not essential for a full-term infant, become essential. Recent advances in medical science have allowed infants who are born more prematurely to have a better chance of survival than before.

Currently, the minimum birth weight for survival is considered to be between 500 and 600 g. These infants face particular problems related to their low weight and their degree of immaturity. If these infants with very low birth weight remain in the uterus for a normal period of human pregnancy, in addition to obtaining a normal physiological development at the same time they will have a rapid growth in size. It would be desirable to provide nutrition for such infants adapted to help them obtain a growth rate similar to what they would have if they were in utero. However, the need to avoid tensions in the capacity of the immature metabolism and the excretory functions when overloading them makes the selection of the quality and quantity of proteins of considerable importance when designing infant formulas for babies with a very low weight at birth. BRIEF DESCRIPTION OF THE INVENTION The present invention provides a nutritional composition for infants with a very low birth weight, which comprises 26 to 38 g / 1 of a hypoallergenic hydrolysed whey protein source with a degree of hydrolysis between 8 and 30, 37 to 46 g / 1 of a fat source of which 20 to 50% are medium chain triglycerides and which has a n6: n3 ratio between 6 and 12 and 50 to 100 g / 1 of a carbohydrate source, composition which contains between 3.2 and 4.0 grams of protein per 100 kcal. The invention extends to the use of a hypoallergenic hydrolyzed whey protein source with a degree of hydrolysis between 8 and 20 in an amount corresponding to a protein content of 3.2 to 4.0 grams of protein per 100 kcal in the preparation of a nutritional composition or a medication to promote growth in very low birth weight infants. The invention further extends to a method for promoting growth in an infant with a very low birth weight, in need thereof by administering to the infant a therapeutic amount of a nutritional composition comprising a source of hypoallergenic hydrolysed whey protein with a degree of hydrolysis between 8 and 20 in an amount corresponding to a protein content of 3.2 to 4.0 grams of protein per 100 kcal. DETAILED DESCRIPTION OF THE INVENTION In this specification, the following terms have the following meanings: An "infant with a very low birth weight" or "an infant VLBW" means an infant with a birth weight less than 1500 g. The "degree of hydrolysis" (DH) means the percentage of nitrogen in the form of nitro to free nitrogen examined, in comparison with the total nitrogen, measured by the TNBS method described by Adler-Nissen et al. in "Determination of the Degree of Hydrolysis of Food Protein Hydrolysates by Trinitrobenzcenesulfonic acid" (J. Agrie, Food Chem., 1979, vol.27, no, 6, ppl256-1262). It is a measure of the degree to which a protein has been hydrolyzed. The term "promoting growth in a VLBW infant" means helping the infant VLBW reach a growth rate comparable to that shown by a fetus of the same gestational age in the womb. All references to percentages are percentages by weight, unless otherwise indicated. References to the specific nutrient content in grams per liter refer to a nutrient composition ready for consumption. In the case of pulverized products, this refers to a powder constituted according to the instructions. The nutritional composition of the invention comprises a source of hypoallergenic hydrolyzed whey protein with a DH between 8 and 20, more preferably between 9 and 16. A particularly preferred degree of hydrolysis is 14. Whey protein can be hydrolyzed from any suitable manner known in the art, for example as described in European Patent No. 322,589, the content of which is incorporated herein by reference. If the whey fraction used as the starting material is substantially free of lactose, the protein has been found to have much less lysine blockage during hydrolysis and subsequent thermal processing. This allows the degree of lysine blocking to be reduced from about 15% by weight of total lysine to less than about 10% by weight of lysine. For example, about 7% by weight of lysine block which greatly improves the nutritional quality of the protein source. The whey protein source can be whey acid, whey, whey protein isolate or mixtures thereof. Preferably, however, the protein source is based on whey protein isolate or modified sweet whey. Sweet whey is an easily available by-product of cheesemaking and is often used in the development of infant formulas based on cow's milk. However, the sweet serum includes a component which is undesirably high in concentration of threonine and with low concentration of tryptophan, called caseino-glyco-macropeptide (CGMP). The separation of CGMP from the sweet whey results in a protein with a threonine content closer to that of human milk. This modified sweet whey can be supplemented with those amino acids with respect to which it has a low content (mainly histidine and arginine). A method for separating CGMP from sweet whey is described in EP 880902. If modified whey or whey protein isolate is used as the protein source, it is preferably supplemented by free arginine in an amount of 0.1 to 2% by weight of the protein and / or free histidine in an amount of 0.1 to 3% by weight of the protein. An example of a suitable amino acid profile for a nutritional composition of the present invention is provided as follows: Amino acid (g / 100 g protein) Amount Isoleucine 5.1 Leucine 12.1 Lysine 9.1 Methionine 2.2 Cystine 2.6 Phenylalanine 3.7 Tyrosine 3.1 Threonine 5.6 Tryptophan 2.1 Valine 5.2 Arginine 3.5 Histidine 3.6 Alanine 5.0 Aspartic acid 11.0 Glutamic acid 15.8 Glycine 2.2 Proline 4.6 Serine 4.8 The nutritional composition of the present invention contains 3.2 to 4.0 grams of hypoallergenic hydrolyzed whey protein per 100 kcal, more preferably from 3.4 to 3.7 g / 100 kcal. A particularly preferable protein content is 3.6 g / 100 kcal. The nutritional composition of the present invention contains 37 to 46 g / 1 of a fat source of which 20 to 50% are medium chain triglycerides. Preferably, the fat content is from 39 to 43 g / 1. Preferably, the MCT content is between 25 and 45%. The lipids that constitute the source of fat can be suitably fat or a mixture of fat. Vegetable fats are particularly suitable; for example, soybean oil, palm oil, coconut oil, saffron oil, sunflower oil, corn oil, rapeseed oil and the like. Fractionated coconut oil is an adequate source of MCT. However, a major difference between human milk fat and these triglycerides of vegetable origin is that most of the triglycerides of vegetable origin have unsaturated fatty acid residues in the Sn2 position while the residue most commonly found in the Sn2 position In triglycerides of human milk is saturated fatty palmitic acid. It has been shown that fatty acid residues are better absorbed from the Sn2 position and that this is particularly important for the absorption of palmitic acid in preterm infants. Therefore, it is preferable to include in the fat source from 5 to 20% by weight of a structured liquid in which the triglycerides have been subjected to enzymatic or other reesterification such that residues of palmitic acid are present. for the most part in the Sn2 position. An example of a suitable structured lipid is that sold under the trade name Betapol "by Lipid Nutrition, a subsidiary of Loders Croklaan.Preferably, at least 40% of the palmitoic acid residues in the fat source are in the position Sn2, more preferably between 45 and 55% The ratio n6: n3 of the fat source used in the composition of the present invention is between 6 and 12, more preferably between 7 and 10. A ratio n6: n3 particularly preferred is 9: 1. If desired, the fat combination can be supplemented with long chain polyunsaturated fatty acids, preferably those isolated from fungal biomass and algae such as arachidonic and docosahexaenoic acids sold by Martek Inc under the trademarks ArascoMR and DhascoMR, respectively, up to a total amount of 3% of the source of fat.Preferably, the ratio of arachidonic acid to docosahexaenoic acid is approx. approximately 2: 1 The nutritional composition contains 50 to 100 g / 1, preferably 70 to 90 g / 1 of a carbohydrate source. Any suitable carbohydrate can be used, for example lactose, corn syrup solids, maltodextrins and mixtures thereof. Preferred are mixtures of maltose and maltodextrin, preferably in the range of 20% lactose: 80% maltodextrin to 60% lactose: 40% maltodextrin. A particularly preferred mixture is 40% lactose: 60% maltodextrin. Suitable vitamins and minerals can be included in the nutritional composition in an amount to meet the appropriate values with particular attention to the content of sodium, potassium, chloride, calcium, phosphorus, iron, selenium, zinc, vitamin A and vitamin E. For example , the composition may contain, per 100 kcal, 50 to 70 mg of sodium (preferably 55 to 65 mg), 120 to 150 mg of potassium (preferably 130 to 140 mg), 80 to 100 mg of chloride (preferably 90 to 100 mg ), 130 to 170 mg of calcium (preferably 140 to 160 mg), 80 to 105 mg of phosphorus (preferably 85 to 95 mg), 1.6 to 2.5 mg of iron (preferably 1.7 to 2.0 mg), 2.0 to 6.0 g of selenium (preferably 3.0 to 5.0 vg), 1.1 to 1.6 mg of zinc (preferably 1.4 to 1.6 mg), 800 to 1200 IU of vitamin A (preferably 900 to 1100 IU) and 3 to 9 IU of vitamin E (preferably 5 to 7 IU ). The nutrient composition may also contain nucleotides in the following amounts, per 100 kcal: UMP 1.0-4.0 mg, CMP 1.5-5.5 mg AMP 0.3-1.5 mg and GMP 0.1-0.5 mg. The nutritional composition can be prepared in any suitable manner. For example, it can be prepared by combining the hydrolyzed whey protein, the carbohydrate source and the fat source in appropriate proportions. If used, emulsifiers can be included at this point. The vitamins and minerals that can be added at this point but are usually added later to avoid thermal degradation. Any lipophilic vitamin can be dissolved, emulsifiers and the like in the fat source before the combination. Then water, preferably water which has been subjected to reverse osmosis, can be mixed in the form of a liquid mixture. Conveniently, the temperature of the water is from about 50 eC to about 802C to aid in the dispersion of the ingredients. Commercially available liquors can be used to form the liquid mixture. The liquid mixture is then homogenized; for example in two stages. The liquid mixture is then thermally treated to reduce bacterial loads by rapidly heating the liquid mixture to a temperature in the range of about 80 SC to about 150 SC for about 5 seconds to about 5 minutes, for example. This can be carried out by steam injection, autoclave treatment or by heat exchanger; for example, a plate heat exchanger. Then, the liquid mixture can be cooled to about 60 BC to about 85 SC; for example by instantaneous cooling. The liquid mixture can then be homogenized again, for example in two stages at about 10 MPa to about 30 MPa in the first stage and about 2 MPa at about 10 MPa in the second stage. The homogenized mixture can then be further cooled to add any heat sensitive component such as vitamins and minerals. The pH and solids content of the homogenized mixture are conveniently adjusted at this point. If it is desired to produce a powdered nutritional composition, the homogenized mixture is transferred to a suitable drying apparatus such as a spray dryer or a lyophilizer and converted to a powder. The powder should have a moisture content in less than about 5% by weight. If it is desired to produce a liquid composition, the homogenized mixture is preferably filled aseptically in suitable containers by preheating the homogenized mixture (eg at about 75 to 85 aC) and then injecting the vapor into the homogenized mixture to increase the temperature to about 140 to 1602C; for example, at approximately 1502C. The homogenized mixture is then cooled, for example by flash cooling, to a temperature of about 75 to 852C. The mixture can then be homogenized again, further cooled to about room temperature and supplied as a filler in the containers. The suitable apparatuses are available commercially to carry out the aseptic filling of this nature. The liquid composition can be in the form of a ready-to-eat composition with a solids content of about 10 to about 14% by weight or it can be in the form of a concentrate; usually with a solids content of about 20 to about 26% by weight. In another aspect, this invention provides a method for promoting growth in a VLBW infant in need thereof by administering to the infant a therapeutic amount of a nutritional composition comprising a source of hypoallergenic whey protein with a degree of hydrolysis between 8 and 20 in an amount corresponding to the protein content of 3.2 to 4.0 grams of protein per 100 kcal. Protein requirements are not well defined in preterm infants. The American Academy of Pediatrics recommends a protein intake of 2.9 to 3.3 g / 100 kcal [AAPCON, 2003], while The European Society of Pediatric Gastroenterology and Nutrition recommends an intake of 2.2-3.1 g / 100 kcals [ESPGA-CON, 1987a]. In addition, protein intakes in the recommended diet (RDPI) in relation to infants > 26 weeks of gestation and > 800 g and no less mature or smaller infants whose requirements may be higher. The RDPI is also based on needs for normal growth but a supply is not made for an infant to obtain a growth rate comparable to that which has been presented in utero which can be a critical consideration in these infants. Indeed, the IRPD can systematically underestimate the "true" protein needs in these high risk VLBW infants.

The amount of the nutritional composition to be administered will vary depending on the state of maturation or growth of the infant but, assuming that it is the only source of nutrition for the infant, it can be provided either as required or, if the infant is incapable. to control the intake itself, in accordance with the hopes of professional health care experts who are caring for VLBW infants. The invention is now further illustrated with reference to the following examples: EXAMPLE 1 An example of a nutritional composition according to the present invention is as follows: Cal. Density (kcal / 100 ml) 80 g protein / 100 kcal 3.6 Protein Hydrolyzed whey protein hypoallergenic DH14 1.4% (protein) free from 1.9% arginine (protein) free of histidine g fat / 100 kcal 5.2 of which: MCT 40% interesterified palm oil 11% (56% palmitic acid in Sn2 position) ARA 0.6% DHA 0.3% n6: n3 8.2 : 1 ARA: DHA 2.1 g / carbohydrate / 100 kcal Lactose / maltodextrin 40/60 Electrolytes and minerals, per 100 kcal Na (mg) 64 K (mg) 136 Cl (mg) 95 Ca (mg) 150 P (mg) 88 Ca / P 1.7 Mg (mg) 10 Mn ^ g) 7.0 Vitamins and trace elements per 100 kcal A (UI) 1000 D (UI) 150 E (UI) 6.0 Kl (g) 8.0 C (mg) 30 Bl (mg) 0.2 B2 (mg) 0.3 Niacin (mg) 4.0 B6 (mg) 0.2 Folic acid (ig) 70 Pantothenic acid (mg) 1.4 B12 (yg) 0.25 Biotin (yg) 5.0 Hill (mg) 15 Inositol (mg) 6.5 Taurine (mg) 8.0 Carnitine (mg) 2.0 Fe (mg) 1.8 i (yg) 35 Cu (mg) 0.15 Zn (mg) 1.5 It is (g) 4.0 Nucleotides, per 100 kcal UMP (mg) 3.0 CMP (mg) 4. 6 A P (mg) 0. 5 GMP (mg) 0. 3 EXAMPLE 2 This example compared the effect of a nutritional composition according to the present invention used as the sole source of nutrition for a group of preterm infants, compared to the effect of a nutritional control composition on the use of protein, the metabolic state and growth. The compositions of the formulas are given in the following table: TABLE 1 . COMPOSITION OF STUDY FORMULAS (/ 100 kcal) * Experimental Control Formula Caloric density (kcal / 100 ml) 80 80 Protein 3.0 3.6 Quality of the protein Hydrolyzed whey protein Fat (g) 5.2 5.2 MCT (%) 25 30 Carbohydrates (g) 10.5 9.9 Lactose / maltodextrin 40/60 20/80 Minerals Sodium (mg) 55 64 Potassium (mg) 120 136 chloride (mg) 85 95 calcium (mg) 131 131 Phosphorus (mg) 75 75 Iron (mg) 1.5 0 Copper (mg) 0.1 0.1 Zinc (mg) 1.2 1.2 The formulas differ mainly with respect to protein content (3.0 versus 3.6 g / 100 kcal). Other differences were noted in carbohydrates (10.5 versus 9.9 g), electrolytes (see above), vitamin A (350 versus 500 IU) and iron content (1.5 mg versus 0). The study is prospective, double-blind, randomized and cross-linked in which each infant is fed with the two formulas. The sequence of feeding with the formulas is predetermined in a random and balanced manner. Infants are randomly distributed to sequence A and fed first with the experimental protein formula, and secondly with the control protein formula. Infants randomized in sequence B are fed first with the control protein formula and then with the experimental protein formula. Infants of two centers are included in the study; the Special Care Baby Unit, Royal Victoria Infirmary, Newcastle in Tyne, United Kingdom and Service Universitaire de Neonatologie Liege, Liège, Belgium. The study is approved by the local Ethics Committee at each site. Informed and written consent is obtained from parents / guardians. Preterm infants (< 1500 g, gestation < 32 weeks) are considered eligible in the study. Pregnancy is determined using maternal dates and intra uterine ultrasound. Only those who are clinically stable and have established a complete enteral intake (>; 130 mls / kg / d) are included in the study. Infants who require oxygen treatment are considered eligible but are withdrawn if oxygen treatment is needed when the first nutrient balance is performed. Infants receiving diuretics or steroids were not included in the study. When an eligible infant is identified, a contact is made with the responsible physician. After contact is made with the tutors, the study is explained and a written outline is provided. After written informed consent is obtained, the infant is included. Then the anthropometric and biochemical baseline investigations are obtained and the infant is randomly distributed in one of the two sequences of the study. During the first balance, infants are usually fed by continuous nasogastric infusion. During the second balance the infants are fed by bolus infusion or orally as they show appetite. Each sequence is designed to last a week. When an enteral intake of > 135 ml / kg / d of the first study formula is tolerated during > 48 hours anthropometry is performed, a blood sample is drawn and the first balance is started. At the end of the first balance, anthropometry is repeated and a second blood sample is obtained. The formula of the second study is then supplied and the procedure repeated. When the second balance ends, the study also ends. During the first balance, the nutrient intake of the study formula is measured daily and maintained at 135-150 ml / kg / d. During the second balance it is not always possible given that some infants are fed according to their appetite. Body weight, serum urea, serum electrolytes, blood pH and excess base are measured at the beginning of the study, at the end of the first balance and at the end of the second collection balance. The concentrations of retinol binding protein (RBP) and serum transferrin are measured at the end of each balance. Blood samples are taken every morning and synchronized to coincide with the end of each feeding cycle (continuous feeding) or immediately after feeding. The blood gas analysis is performed immediately. The plasma is also separated immediately. An aliquot is sent to the main laboratory for the determination of electrolytes, urea nitrogen, total protein and albumin analysis. The second aliquot is stored at -302C and is subsequently sent for analysis of RBP and transferrin. Anthropometry is performed as previously described [Cooke, 1988a]. The electrolytes, urea nitrogens, total protein and albumin are analyzed using systematic laboratory methodology. Transferrin is measured by immunoturbidimetry using the Tina-quant transferrin kit (Roche No. 1 931 628, Switzerland) [Kreutzer, 1976; Lievens, 1994]. RBP is measured by immunoturbidimetry using rabbit retinol binding protein against human [Gulamali, 1985] with N Protein Standard SL (human) used as the calibrator (Dade Behring, Germany). Determinations are made using the BM / Hitachi 917 analyzer (Roche, Switzerland). Nutrient balance collections are performed as previously described [Cooke, 1988a]. Formula bottles are weighed before and after each feeding; Differences in weight are used to calculate the ingestion of each formula. The bottles are also supplied until their completion; the differences in weight between full and empty bottles are used as an additional verification for the accuracy of cumulative weights between feeds. Splashes are collected in pre-weighed diapers placed around the infant. Weight differences between clean and "soiled" diapers are used to calculate losses. Urine and feces (girls) and feces are collected (children) in a Pyrex container placed under the infants. Urine in children is collected by means of a urine collection bag. Urine, faeces and formulas are analyzed for nutrient content in the Samuel J Fomon Infant Nutrition Unit, University of Iowa, Iowa, USA and the Services Universitaire de Neonatologie Liege, Lieu, Belgium. Nitrogen is determined by micro-Kj eldahl digestion followed by a modified microdiffusion analysis [Fomon, 1973]. The content of calcium, magnesium, iron, copper and zinc is made by atomic absorption spectrometry (Perkin-Elmer model 560). Fat is determined by a modification of the method of Van de Kamer et al [Van de Kamer, 1949], phosphorus using the phosphomolybdate method as described by Leloir and Cardini [Leloir, 1957]. The volume of ingestion is calculated by dividing the differences in weight between the specific gravity of the formula. The ingestion of nutrients is calculated from the volume supplied and the content of the formula. Excretion of faeces is calculated from the weight and content of the faeces, the excretion of urine from the volume and content of the urine. Absorption is calculated by subtracting stool output from ingestion, retention by subtracting urinary excretion from absorption. During the collections of balances, the care of the infants in the study is provided by nurses responsible only for the infant under study. These nurses are specially trained in the care of the preterm infant and in the performance of nutrient balance collection. The general care of infants is under the direction of a responsible physician. All routine nursing procedures are performed as indicated. The determination of sample size is related to nitrogen retention and is based on a standard deviation of 20 mg / kg / d, a significant difference of 30 mg / kg / d, energy = 0.80 and = 0.05. Center-to-center variation is allowed and it is estimated that 16 infants are required to complete the study. The data is analyzed in an intention advance for trait using ANOVA. The results are considered significant at p < 0.05. Eighteen infants (9 girls, 9 boys) were studied, the mean (± standard deviation) of weights at birth and the gestational age are 1226 ± 204 g and 29.5 ± 1.5 weeks. No infant received supplemental oxygen or medications during the study. Nine infants were fed the experimental formula and 9 infants with the control formula first. Upon entering the study, the postnatal age (18 ± 8 <25 ± 9 d; p <0.05) but not the corrected age (229 ± 5 versus 229 ± 6 d), body weight (1473 ± 262 versus 1470) ± 197 g), crown-heel length (40 ± 2.7 versus 40 ± 1.7 cm) and occipitofrontal circumference (29 ± 2.2 versus 29 ± 1.6 cm) differ between infants fed the experimental formula and those fed first with the control formula . Thirty-six balances were performed on 18 infants. The absorption and retention of nitrogen is a linear function of the intake (figure 1). Intake (743 ± 71> 604 ± 35 mg / kg / d, p <0.001), absorption (624 ± 84> 500 ± 49, p <0.001) and retention (514 ± 85> 426 ± 45) , p <0.001) are higher with the experimental protein formula. No differences were detected in the percentage of absorption (83 ± 6 versus ± 6) or percentage of retention (71 ± 6 versus 70 ± 6) between the formulas. The results of the remaining balance are presented in Table 2 below. Fat intake is similar but faecal excretion is lower, while absorption is higher with the experimental formula (p <0.05). Although minor differences were detected in the ingestion of magnesium and zinc, no differences were observed in the balance of calcium, phosphorus, magnesium or zinc between formulas. However, copper intake and absorption are greater with the control formula (p <; 0.05). No differences were detected in the postnatal age when the blood samples were taken (33 ± 10 versus 31 ± 7 d for the experimental and control formulas). No infant developed uraemia (urea> 7.0 mmol) or metabolic acidosis (base deficiency> -8.0) [Schwartz, 1979] but serum urea is higher with the experimental formula (3.5 ± 1.3> 2.1 ± 0.8 mmol, p <0.001). There were no differences in blood pH (7.38 ± 0.04 versus 7.37 ± 0.04), or excess of base (-1.2 ± 1.7 versus -1.4 ± 2.1 mmol / 1) between the formulas. No differences were detected in creatinine (44 ± 5 versus 46 ± 12), total protein (44 ± 3 versus 45 ± 3 g / 1), albumin (31 ± 3 versus 31 ± 3 g / 1) or transferrin (20 ± 3) versus 21 ± 4) but RBP is greater with the experimental formula (12.4 ± 3.3> 11.0 ± 2.6, p <0.05). The gain in weight is also greater (measured differences = 11 ± 12 g / d, p <0.05), an effect which is more marked in boys than in girls (figure 2). Consensus recommendations on protein intakes for infants who weigh < 100 g at birth are ~ 3.0 g / 100 kcals. However, these recommendations imply a tissue increase for growth of ~ 2.3 g / kg / d. Recent data suggest that tissue requirements are closer to 2.5 g / kg / d. Assuming that the obligatory protein losses in urine and skin [Snyderman, 1969] are 1.0 g / kg / d and an absorption rate by fractions of 90% then the requirements can be closer to 3.6 g / 100 kcals.

Formula Intake Absorption% Retention% Absorption retention Fat 3.6 g 6.6 ± 0.6 5.1 ± 0.8 77 ± 9 (g / kg / d) 3.0 g 6.6 ± 0.4 4.8 ± 0.7 * 73 ± 11 * Calcium 3.6 g 181 ± 17 85 ± 32 46 ± 17 83 ± 32 46 ± 14 (mg / kg / d) 3.0 g 181 + 12 82 ± 36 45 ± 19 81 ± 35 45 ± 19 Phosphorus 3.6 g 101 ± 10 88 ± 10 87 ± 5.2 71 ± 13 70 ± 11 (mg / kg / d) 3.0 g 103 ± 6 91 ± 7.1 89 ± 4.2 66 ± 11 64 ± 10 Magnesium 3.6 g 12.6 ± 1.2 6.0 ± 2.1 48 ± 15 5.6 ± 2.0 45 ± 12 (mg / kg / d) 3.0 g 11.1 ± 0.8 * 5.3 ± 1.7 48 ± 15 5.0 ± 1.8 45 ± 15 Zinc 3.6 g 1819 ± 175 574 ± 358 31 ± 18 556 ± 354 31 ± 15 (Mg / kg / d) 3.0 g 1964 ± 137 * 563 ± 361 28 ± 18 544 ± 370 28 ± 18 Copper 3.6 g 166 ± 16 43 ± 49 25 ± 29 (Mg / kg / d) 3.0 g 205 ± 18 * 83 ± 41 * 40 ± 19 * The current recommendations are related to the needs for normal growth but it takes time to establish the RDPI in an unstable untreated preterm infant. Therefore, infants accumulate a deficiency of nutrients, the more immature the infant is, the greater the deficiency. In this study, the average protein deficiency at the start of the study is ~ 10 g / kg, additionally increasing the requirements in these high-risk infants. In this study, since protein intake increased from 3.4 to 5.2 g / kg / d, the same happened with absorption and retention. No infant became uremic or developed metabolic acidosis and no differences in acid-base status were detected between the experimental and control formulas. At the same time, growth is better, suggesting that the experimental formula better meets the needs of high-risk infants. The findings in this study are important. There is concern about the potential adverse effects of higher concentrations of dietary protein intake. Recent recommendations have suggested an upper limit of 4 to 4.5 g / kg / d. The data from this study show that an intake of up to 5.2 g / kg / d of protein is not only well tolerated but also related to better growth.

Claims (12)

1. - -
2. CLAIMS 1. Nutritional composition for infants with very low birth weight (VLBW) comprising 26 to 38 g / 1 of a hypoallergenic hydrolysed whey protein source with a degree of hydrolysis between 8 and 30, 37 to 46 g / 1 from a source of fat of which 20 to 50% are medium chain triglycerides and which has a n6: n3 ratio between 6 and 12 and 50 to 100 g / 1 of a carbohydrate source, which composition contains between 3.2 and 4.0 grams of protein per 100 kcal. 2. Composition as described in claim 1, wherein the degree of hydrolysis is between 9 and 16.
3. 3. Composition as described in claim 1 or 2, wherein the whey protein source is sweet whey of which has separated the caseino-gluco-macropeptide or the isolate of whey protein.
4. 4. Composition as described in claim 3, which additionally includes free arginine in an amount of 0.1 to 2.0% by weight of protein and / or free histidine in an amount of 0.1 to 3% by weight of protein.
5. 5. Composition as described in any preceding claim, which comprises 3.4 to 3.7 grams of protein per 100 kcal.
6. 6. Composition as described in any preceding claim, wherein the source of fat comprises from 25 to 45% of medium chain triglycerides. Composition as described in any preceding claim, wherein the source of fat comprises from 5 to 20% of a structured lipid in which at least 50% of the palmitic acid residues contained in the structured lipid are esterified in the Sn2 position. 8. Use of a hypoallergenic hydrolyzed whey protein source with a degree of hydrolysis between 8 and 20 in an amount corresponding to a protein content of 3.2 to 4.0 grams of protein per 100 kcal in the preparation of a nutritional composition or medication to promote growth in VLBW infants. 9. Use as described in claim 8, wherein the degree of hydrolysis is between 9 and 16. Use as described in claim 8 or 9, wherein the source of whey protein is sweet whey which is has separated the caseino-gluco-macropeptide or the isolate of whey protein. 11. Use as described in claim 10, wherein the composition additionally includes free arginine in an amount of 0.1 to 2% by weight of protein and / or free histidine in an amount of 0.1 to 3% by weight of protein. 12. Use as described in any of claims 8 to 11, wherein the protein content of the nutritional composition is 3.4 to 3.7 g / 100 kcal.