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Chris HP van den Akker
Frans WJ te Braake
Johannes B van Goudoever
Professor of Paediatrics/Neonatology
Chief of Neonatology
Department of Paediatrics
Division of Neonatology
Sophia Children’s Hospital
In growing neonates, an adequate nutritional strategy should focus on both energy generation and anabolism. Thus, it should involve a balanced amount of nutrients. Although micronutrients such as vitamins and trace elements are crucial, this article will review only macronutrients: carbohydrates, lipids and proteins. Preterm infants constitute an important category in the neonatal intensive care unit (NICU), and their specific needs are challenging for neonatologists. Current nutritional standards and developments for preterm infants in the NICU are reviewed here.
Both immaturity and clinical problems in the early postnatal phase complicate the provision of adequate nutrition in preterm infants. Problems occur when enteral feedings are given, due to the fact that coordination of breathing, sucking and swallowing are not yet totally developed; this results in aspiration pneumonias. Full gastric feeding leads to other complications because of the immaturity of the gastrointestinal tract; this results in gastric residuals and necrotising enterocolitis.(1) Thus, parenteral nutrition seems the only suitable and relatively safe way to provide a significant amount of nutrients to preterm infants in the direct postnatal phase. However, clinical problems such as pulmonary disease and patent ductus arteriosus often result in restricted fluid administration and, therefore, in diminished administration of calories and protein. After the umbilical cord has been cut, the very low birth weight (VLBW) infant is almost immediately dependent on externally administered nutrients, as hardly any stored energy is at their disposal. Fat tissue and glycogen levels are scarce and of minimal importance for this matter, especially for the small-for-gestational-age infant. Although their use is undesirable, proteins could constitute a source of energy in these infants.
To provide adequate nutrition, paediatricians should supply preterm infants with sufficient amounts of intravenously administered glucose, amino acids and lipids, which will provide both calories and substrates for growth.
Unfortunately, this theoretical approach has not been implemented in clinical practice. In the first few days of life, these infants are often dependent on glucose only, because of bad experiences, in the 1960s and 1970s, with hydrolysed L-amino acid mixtures, which resulted in hyperammonaemia and metabolic acidosis. This was due to the immaturity of metabolic pathways and the suboptimal composition of the solutions.(2,3) However, in utero, amino acids are supplied in large amounts and function both as building blocks for growth and a source of fuel. Commercial crystalline solutions are now widely available, with none of the negative side-effects of early infusion. Therefore, it seems rational to deliver an adequate amount of energy and protein immediately after birth to meet energy requirements – and preferably more in order to promote protein accretion.
During the past decades, evidence has accumulated that both quantity and quality of early nutrition is correlated with outcome in adult life. This fetal origins hypothesis states that even a brief period of malnutrition in utero or in the early postnatal phase is associated with long-term metabolic changes, potentially resulting in hypertension, cardiovascular disease and adult-onset diabetes.(4) The postnatal weight loss contrasts with the fetus average weight gain of 15–17g/kg/day between 26 and 36 weeks of gestation – a higher rate than at any other time in life thereafter. The current consensus in feeding the preterm infant is to achieve a weight gain – with the same body composition – similar to the gain the fetus would have had in utero.
Use of amino acids
At approximately 7 months, amino acids are taken up at rates far beyond those of protein accretion and are, therefore, oxidised.(5,6) On the other hand, there is little lipid uptake, let alone a role for lipids in the current process of oxidation.(7) This contrasts with the nutritional regimens for preterm infants, especially in the first week of life. Relatively low amounts of amino acids are administered, with, gradually, a surplus of lipids.
Many nutritional studies have been performed especially focusing on amino acids. Table 1 summarises some of the research published on early infusions of amino acids to preterm infants. Although these studies differ with respect to time of introduction of the amino acids and birth weight of the included infants, they all suggest early amino acid tolerance with increased nitrogen balances.(8–12) So far, no study has combined a high amino acid intake directly postpartum with a large group of VLBW infants. Therefore, during the last two years, we set up a clinical trial in 135 preterm infants with a birth weight of less than 1,500g. Half of them solely received glucose after birth, whereas the other half received 2.4g of amino acids/(kg.d) in addition to glucose. No signs of metabolic acidosis were observed, whereas blood urea nitrogen levels were increased. The latter observation can be interpreted as a sign of increased amino acid oxidation rather than intolerance. Whereas infants dependent on glucose were catabolic – nitrogen balance of –90mg N/(kg.d) – the group receiving amino acids obtained a positive nitrogen balance of 140mg N/(kg.d) on postnatal day 2. In a subset of infants, we determined the specific metabolism of leucine with the use of stable isotopes. We demonstrated that half of the administered leucine was used for oxidation and the other half for protein synthesis. Leucine release resulting from protein breakdown was not altered.
Due to clinical problems, preterm infants do not tolerate full enteral feedings in the direct postnatal phase and are, therefore, dependent on parenteral nutrition. Often, only glucose is administered during the first day(s) because of the dogmatic view of intolerance. Lipids and amino acids are only gradually given over days. As a consequence, infants are placed in a catabolic state, and clinical problems are made worse in these nutritionally deprived infants. The fact that suboptimal nutrition results in impaired growth,(13) impaired neurodevelopment(14) and altered metabolism(4) implies that future research should focus on the specific nutritional needs of the preterm infant. The absolute needs of all macronutrients have to be defined, both for growth and energy generation. Regarding the quality of nutritional solutions, there is still scope for improvement. In particular, contents of all individual amino acids should be investigated.