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Enteral nutrient supply for preterm infants

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Enteral nutrient supply for preterm infants

Enteral nutrient supply for preterm infants. A comment of the ESPGHAN

    Committee on Nutrition.

    123ESPGHAN Committee on Nutrition and invited expert guests: C. Agostoni; Buonocore G, Carnielli VP

    45678910M. De Curtis, Darmaun D, T. Decsi; M. Domellöf, N.D. Embleton, C. Fusch, Genzel-Boroviczeny O,

    11121314* #1516175 O. Goulet;Kalhan S.C. S. Kolacek; B. Koletzko, A. Lapillonne, W. Mihatsch, L. Moreno;

    1819202122*2324252627?Neu J, Poindexter B, J. Puntis, Putet G , J.Rigo, Riskin A, Salle B, Sauer P, R. Shamir; H.

    282930*31Szajewska; Thureen P, D. Turck, J.B. van Goudoever, Ziegler E.

    *Project steering committee, # Committee on Nutrition Chair, ?Committee on Nutrition Secretary

1210 Department of Paediatrics, San Paolo Hospital, University of Milan, Italy; Pediactrics, Obstetrics and

    3Reproductive Medicine, University of Siena, Italy; Division of Neonatology, Salesi Hospital,

    45Polytechnical University of Marche, Ancona, Italy; University of Rome, Italy; Centre Hospitalier,

    67Universitaire de Nantes, France; Department of Paediatrics, University of Pecs, Hungary; Department of

    8paediatrics Umeå University, Sweden; Royal Victoria Infirmary, Newcastle upon Tyne, United Kingdom; 91015 Ernst-Moritz-Arndt-University, Greifswald, Germany; Neonatologie Klinikum der Universität München,

    1112Germany; Hôpital Necker Enfants-Malades, University of Paris Descartes, Paris, France; Cleveland

    13Clinic Lerner College of Medicine, Case Western Reserve University, USA; Children’s Hospital, Zagreb

    14Medical University, Croatia; Dr von Hauner Children’s Hospital, University of Munich, Germany;

    1516Hôpital Saint-Vincent de Paul, Paris, France; Deaconry Hospital, Schwaebisch Hall, Germany; 171820 Escuela Universitaria de Ciencias de la Salud, Zaragoza, Spain; Department of paediatrics, University

    19of Florida, Gainesville, USA; Section of neonatal, Indiana University, School of Medicine, Indianapolis,

    2021USA; Leeds General Infirmary, Leeds, UK; Service de Néonatologie Réanimation néonatale, Hôspital

    2223de la Croix Rousse, Lyon, France; CHR Citadelle, University of Liege, Belgium; Bnai Zion Medical

    24Center, Haifa, Israel; Service de Medicine de la Reproduction, Hôspital Edouard Herriot, Lyon, France; 2526 25 Department of paediatrics, University Medical Centre Groningen, The Netherlands; Schneider

    27Children's Medical Center, Tel-Aviv University, Tel Aviv, Israel; The Medical University of Warsaw,

    2829Poland; University of CO Health Sciences Center, Denver, USA; Jeanne de Flandre Children’s

    30Hospital/University of Lille, France; Erasmus MC - Sophia Children's Hospital, Rotterdam, the

    31Netherlands; Fomon Infant Nutrition Unit, Children’s Hospital, University of Iow, USA

    30

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Acknowledgements: A scientific workshop held to discuss the draft recommendations with invited expert

guests was financially supported by unrestricted educational grants donated by Danone Baby Nutrition

(then Nutricia Baby Foods), Mead Johnson Nutritionals, and Nestlé Nutrition to and administered by the

Charitable Child Health Foundation, Munich, Germany (www.kindergesundheit.de). All meetings and the

    35 writings of the manuscripts were performed without any participation of representatives or employees of commercial enterprises, and subjects and contents of the guideline were in no way influenced by the supporting companies.

Correspondence:

    40 Prof. Dr. J.B. van Goudoever, MD PhD

    Division of Neonatology, Department of Peadiatrics, Sophia Children’s Hospital Erasmus Medical Center,

    Rotterdam, The Netherlands, Tel: +31-10-7036077, Fax:+31-10-7036811

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45

    Abstract ....................................................................................................................................... 4

    Introduction ................................................................................................................................. 4

    Fluid ............................................................................................................................................ 5

    Energy ......................................................................................................................................... 6 50 Protein ........................................................................................................................................ 8

    Lipids ......................................................................................................................................... 9

    Carbohydrates<.......................................................................................................................... 12

    Minerals .................................................................................................................................... 14

    Trace elements ........................................................................................................................... 20 55 Vitamins .................................................................................................................................... 24

    Pre- and Probiotics ..................................................................................................................... 32

    Nucleotides ................................................................................................................................ 34

    Choline ...................................................................................................................................... 35

    References ................................................................................................................................. 37 60 Tables ........................................................................................................................................ 50

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    Abstract (235 words)

    The number of surviving children born prematurely have increased substantially over the last two decades. 65 The major goal of enteral nutrient supply to these infants is to achieve growth similar to foetal growth

    coupled with satisfactory functional development. The accumulation of knowledge since the previous

    guideline on nutrition of preterm infants from the Committee on Nutrition of the European Society of

    Paediatric Gastroenterology and Nutrition in 1987, has made a new guideline necessary. Thus, an ad hoc

    Expert Panel was convened by the Committee on Nutrition of the European Society of Paediatric 70 Gastroenterology, Hepatology and Nutrition in 2007 to make appropriate recommendations. The present

    guideline is consistent with, but not identical to, recent guidelines from the Life Sciences Research Office

    of the American Society for Nutritional Sciences published in 2002 and recommendations from the

    handbook "Nutrition of the preterm infant. Scientific basis and practical application", edited by Tsang et al,

    nd ed. published in 2005. The preferred food for premature infants is fortified human milk from the infant's 2

    75 own mother, or alternatively formula designed for premature infants. This guideline aims provides

    proposed advisable ranges for nutrient intakes for stable growing preterm infants up to a weight of

    approximately 1800 gram, since most data are available for these infants. These recommendations are

    based on a considered review of available scientific reports on the subject, and on expert consensus where

    the available scientific data is considered inadequate.

    80

    Key words: Child Development, Embryonic and Fetal Development, *Premature infant feeding,

    *Nutritional Requirements

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85 Introduction

    In 1987 the European Society of Paediatric Gastroenterology and Nutrition published recommendations on

    nutrition and feeding of preterm infants [1] to provide guidance on feeding of preterm infants. Even though

    extensive reviews on the topic have recently been published [2, 3], the ESPGHAN Committee on Nutrition

    considered it necessary to review the recommendations on nutrient needs of preterm infants. 90 An expert group reviewed the existing evidence and prepared draft manuscripts on advisable intakes of

    macro- and micro-nutrients for preterm infants. These proposals were reviewed and discussed in detail at a

    scientific workshop organised by the charitable Child Health Foundation (www.kindergesundheit.de) in

    March 2007. This meeting was attended by observing experts in infant formula design and manufacturing

    (listed in footnote 1) who were asked to provide advice on the feasibility of producing food products based 95 on the recommendations made.

    The aim of this report is to provide guidance on quantity and quality of nutrients needed for preterm infants,

    so as to achieve growth similar to foetal growth coupled with satisfactory functional development. The

    recommendations relate to ranges of enteral intakes for stable growing preterm infants up to a weight of

    approximately 1800 gram, since most data are available for these infants. No specific recommendations are 100 provided for infants with a weight below 1000 gram as data is lacking for this group for most nutrients,

    except for protein needs. The needs of infants with specific diseases (e.g. bronchopulmonary dysplasia,

    congenital heart disease or short bowel syndrome) and those receiving parenteral nutrition have been

    reviewed recently [4] and are not specifically addressed in this report.

    The Committee advocates the use of human milk for preterm infants as standard practice, provided it is 105 fortified with added nutrients where necessary to meet requirements. Parents and health care providers

    should be aware that human milk composition may vary over the duration of lactation, within the day and

    even during one expression. Also the treatment following expression, e.g. storage or pasteurisation, may

    influence composition. Alternatively to human milk, preterm formula may be used. This comment focuses

    on providing guidance on appropriate nutrient intakes with fortified human milk or formula. 110

    Footnote 1: Observers from the dietetic industry at the scientific workshop held to discuss the draft

    recommendations with invited expert guests (in alphabetical order): H. Böckler, G. Boehm, C. Garcia F.

    Haschke, J. Wallingford

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    115 Recent extensive reports on this topic [2, 3] as well as recommendations on nutrient supply for term infants

    [5] have been taken into account in preparing this report. A Medline search was performed for publications

    on preterm nutrition. For several nutrients, however, there is insufficient evidence on which to base

    definitions of lower and upper intake levels. When no sufficient data were available, intakes provided with

    human milk feeding and currently available human milk fortifiers and with preterm infant formulae were 120 considered.

    Ranges of advisable nutrient intakes are expressed both per kg bodyweight per day and per 100 kcal (table

    1). Calculation of the latter values was based on the minimum energy intake of 110 kcal/kg/d that we chose

    to recommend. Thereby, the ranges of nutrient intakes per 100 kcal will ensure the infant receives the

    minimum or maximum of each specific nutrient at an intake of 110 kcal/kg/d. One should be aware that at 125 higher energy intakes, the individual nutrient should not exceed an acceptable maximum level of intake.

    While the recommended ranges of nutrient intakes are considered reasonable, a high degree of uncertainty

    remains and hence the provision of nutrient intakes outside of the specified ranges is not discouraged if

    justified by good reasons. Nevertheless, it must be noted that using levels found in available commercial

    products without apparent problems as the basis for providing guidelines is less than satisfactory, since 130 subtle adverse affects may not be detected without conducting adequate randomised controlled trials. Such

    trials can also be aimed at obtaining data on suitability and safety of intakes that are outside the specified

    ranges.

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135 Fluid

    Ad libitum feeding studies as in healthy breastfed infants have not been performed in very low birth weight

    infants in view of their lack of autonomy with respect to fluid intake. Randomized controlled trials on

    enteral fluid intake of preterm infants are also lacking as are studies comparing different fluid volumes (e.g.

    140 vs. 200 ml/kg/d) providing identical nutrient intakes. Measured values of fluid intake established by 140 dietary protocols or stable isotopes are available for 6-week-old healthy ex preterm neonates (140 180

    ml/kg/d) [6], term infants (160 ml/kg/d) [7-9] and non-ad libitum fed preterm infants (160 +/- 30 ml/kg/d)

    [10, 11].

    Extrapolation from measured enteral intake at term to preterm needs in addition to a factorial approach

    should account for higher preterm growth rates with storage of intra- and extra cellular water and 145 electrolytes, and for higher losses via more immature skin and reduced renal concentration capacity. Thus,

    the preterm infant’s enteral fluid needs are about 15 – 25 % higher than that of the term infant. [6-11]

    From data of combined parenteral/enteral regimens, and assuming full enteral absorption, it follows a) that

    fluid volumes between 96 to 200 ml/kg/d are tolerated and that these values may serve as lower and upper

    limits [12]; b) that postnatal intakes at the lower range is likely to minimise risk of long-term morbidity 150 such as BPD and PDA. It is important to note that fluid volumes needed for enteral nutrition are influenced

    by osmolarity, renal solute load and are not synonymous with actual water needs.

    On the basis of these data sources, recommendations made in this comment and based upon final

    osmolarity and previous recommendations [3, 4] we regard 135 ml/kg/d as the minimum fluid volume

    and 200 ml/kg/d as a reasonable upper limit. For routine feeding, rates of 150 - 180 ml/kg/d nutrient

    155 intakes when standard formula or breast milk is used are likely to achieve meeting nutrient requirements.

    Some infants may need higher volumes in order to meet requirements of substrates other than fluid.

    Energy

    Recommendations for energy intake are based on the assumption that growth and nutrient retention similar

    160 to intrauterine references are appropriate. Yet we must make allowances for extra uterine environment and

    differences in nutrient supply and metabolism (e.g. the foetus receives only a small proportion of energy as

    fat). Using intrauterine growth as a standard should involve not only achieving similar weight gain but also

    body composition, even though a higher extra uterine fat deposition may be needed to provide thermal and

    mechanical protection.

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    165 Studies in the two decades since the last ESPGHAN recommendations[13] have provided data on longer

    term outcomes, and there are indications that rapid infant weight gain in term infants may be associated

    with adverse outcomes [14], adding to the uncertainty regarding optimal energy provision for preterm

    infants.

    Energy requirements for otherwise healthy preterm infants will depend on the post conceptional age (higher 170 per kg body weight at 24 than at 36 weeks post conceptional age), accumulated nutrient deficits (both pre-

    and postnatal growth restriction), alterations in body composition, and differences in resting energy

    expenditure (REE). As REE is affected by sleep state and activity levels, environment (thermoregulation),

    genetic differences in basal metabolic rate and demands for tissue synthesis, energy needs may vary

    considerably amongst populations of healthy preterm infants. Synthesis of new tissue is energy intense and 175 strongly affected by the intake of protein and other nutrients, thus achieving an adequate energy:protein

    ratio is as important as providing adequate energy intake.[15]

    Energy required for protein deposition approaching intrauterine dimensions is approximately 5.5-7.75

    kcal/g protein deposited, and for fat deposition 1.55-1.6 kcal/g fat deposited, excluding the amount of

    energy which is stored in the process.[16, 17] REE is approximately 45 kcal/kg/d and does not seem to vary 180 much with gestational age, but may be lower in some babies[18]. Estimated average energy requirements

    for depositing new tissue (13% protein, 20 to 30% fat) are 3.3-4.7 kcal/g,[16, 19], so achieving an

    intrauterine weight gain of 17 g/kg/d[20] will require about 56-80 kcal/kg/day on top of REE (~45

    kcal/kg/d). Thus, a total metabolizable energy intake (including protein) of approximately 100-125

    kcal/kg/d is needed, corresponding to 110-140 kcal intake for an energy absorption rate of 85% with human 185 milk and 90% with a well-absorbed formula.

    Clinical studies suggest that energy intakes ?100 kcal/kg/d will not meet the needs of some preterm infants

    prior to discharge. Where protein:energy ratios are adequate (>3-3.6g/100kcal) in a formula providing well

    absorbed nutrients, an energy intake >100 kcal/kg/day is generally appropriate[21] and may result in a fat

    mass (FM) percentage closer to both intrauterine references and normal term infants. SGA infants might 190 need a higher energy intake than AGA infants [21], however, a focus on achieving an optimal lean mass

    (LM) accretion rather than FM may be more appropriate. Whilst higher intakes (140-150 kcal/kg/d) appear

    generally safe in the short term, there is limited evidence of improved linear growth (as a proxy for LM

    accretion) but FM deposition appears excessive.[21-24]

    Nitrogen retention is affected by source of non-protein energy. Carbohydrate appears more effective at 195 sparing protein oxidation and may result in faster linear growth, but studies at energy intakes of 155

    kcal/kg/d with high carbohydrate:fat ratios showed substantially greater fat deposition than intrauterine

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references.[24] A reasonable range of energy intake for healthy growing preterm infants with

    adequate protein intake is 110-135 kcal/kg/d. Increasing energy intake may not be appropriate for infants

    whose growth appears inadequate (without evidence of fat malabsorption) as it is more likely that other nutrients (e.g. protein) are rate limiting. 200

    When considering other nutrient intakes it is important that recommended minimum intakes meet needs. At an intake of 110 kcal/kg/day, formula compositions should ensure that basic minimum intakes of other nutrients are met, and this figure should then be used in determining nutrient ratios of enteral feeds. Protein

    205 There is a lack of data on long-term outcome effects of different protein intakes from randomized controlled trials, but there are some indications that a suboptimal intake of protein, energy and other nutrients may lead to lower cognitive achievements. [25] Dietary protein requirements can be estimated by the factorial method or by empirical approach. The factorial method estimates requirements from the sum of obligatory losses with urine, faeces and skin and the amount deposited in newly formed tissue. However,

    210 this method is subject to misinterpretation since losses might be underestimated and the exact composition of the newly formed tissue is not known. The empirical approach measures biochemical or physiological responses to graded intakes. Individual amino acid requirements can also be determined by both these methods, but the use of indicator amino acid methodology may be more accurate.[26]

    Compositional analysis of foetal tissues has been a valuable data source for our understanding of the

    215 nutrient needs of the foetus, and by analogy, those of the growing preterm infant. Protein accretion has been estimated at approximately 1.7 g/kg/d for foetuses throughout the second half of gestation but is lower at the end of gestation.[27] Obligatory protein losses are at least 0.7 g/kg/d but may be higher if nitrogen losses from skin and breath could be measured. Nevertheless, this value is close to that found necessary to reach a nitrogen equilibrium.[28] Clinical practice, however, regularly shows deficits in protein supply

    220 relative to estimated requirements in the first few weeks of life, particularly in more immature preterm infants, depending on feeding policy, tolerance and illness. [29]

    Faecal nitrogen loss is related to the protein source fed and to feeding effects on endogenous nitrogen losses. Net absorption equals nitrogen intake minus faecal loss (either secreted or non-absorbed). The highest nitrogen absorption rate (% of intake) is observed with powder whey predominant formula (90%).

    225 Absorption rate with ready-to-use liquid whey predominant premature formulae (86.0 %) is slightly higher than with human milk supplemented with fortifiers (82.7 %) or hydrolysed preterm formula (84.3%) Table 1.[30] Some hydrolysed proteins in preterm formulae tend to shorten gastrointestinal transit time, which might accelerate feeding advancement [31, 32] but could also reduce utilisation.

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    Compared to current preterm formulae, human milk contains a higher proportion of non-protein nitrogen

    230 (20-25% of total nitrogen). The degree of utilisation of non-protein nitrogen in preterms is not entirely

    known and may vary considerably, contributing to the lower nitrogen absorption rate of human milk.

    Furthermore, the quality of the provided protein might interfere with the recommended intake, since the

    infant does not require proteins but specific amino acids. Little is known about optimal intakes of specific

    amino acids. A different composition of the proteins administered might change the quantity of proteins

    235 required.

    However, based on the above figures for protein needs and nitrogen utilisation, the protein intake should at

    be at least 3.0 g/kg/d. Empirical data show that weight gain approximating to that in utero can be achieved

    at approximately 3 g/kg/d protein intake [3, 28, 33, 34], and that weight gain rates are linearly related to

    protein intakes up to 4.5 g/kg/d. Intrauterine weight gain can be matched at protein intakes less than 3 - 3.5

    g/kg/d accompanied by a very high energy intake, but body fat percentage will then be much higher than 240

    observed in the foetus.

    Protein supply needs to compensate for the accumulated protein deficit observed in almost all small

    preterm infants, and can be increased to a maximum of 4.5 g/kg/d, depending on the magnitude of the

    accumulated protein deficit. Intakes in the range of 3-4.5 g/kg/d will achieve acceptable plasma albumin

    245 and transthyretin concentrations [35]. Some excess of protein intake over requirements was not shown to

    cause detrimental effects in preterms, but, on the other hand, a small deficit will impair growth. We

    therefore recommend to aim at 4.0 - 4.5 g/kg/d protein intake for infants up to 1000 g, and 3.5 - 4.0 g

    for infants from 1000-1800 g which will meet the needs of most very preterm infants. Protein intake

    can be reduced towards discharge if the infant’s growth pattern allows for this. The recommended

    250 range of protein intake is therefore 3.6-4.1 g/100 kcal for infants weighing less than 1000 g and 3.2-3.6

    g/100 kcal for infants from 1000-1800 g.

    Lipids

    Dietary lipids provide the preterm infant with much of its energy needs, essential polyunsaturated fatty

    255 acids and lipid soluble vitamins [3]. Amount and composition of dietary lipids affect both growth pattern

    and body composition. The availability and metabolism of long-chain polyunsaturated fatty acids (LC-

    PUFA) have direct implications for cell membrane functions and the formation of bioactive eicosanoids.

    Brain grey matter and the retina are particularly rich in LC-PUFA, and complex neural functions are related

    to energy supply and the composition of dietary fatty acids.

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