## 2 Provision of Energy and Macronutrients in Pediatric Patients on PN
### Amino Acids  
In any patient receiving PN, proteins have to be administered in the form of free amino acids. Pediatric amino acid solutions are currently available. Their primary goal is to promote anabolism (protein synthesis and positive nitrogen balance) for cells and tissue building (e.g., muscle, skeleton) consistent with the normal growth and development typical of healthy peers [49]. Due to additional needs for growth, the protein requirements based on weight are higher in newborn infants, infants/toddlers, and children than in adults, and the timely provision of adequate amounts of amino acids with PN is particularly critical [1]. Generally, the total amino acid requirement is lower in parenterally fed newborn infants, infants/toddlers, and children than in entrally fed patients because the intestinal and hepatic \"first-pass\" metabolism is bypassed [50]. The ESPGHAN/ESPEN/ESPR guidelines [50] recommend a minimum parenteral amino acid intake of 1.0 g/kg/d for stable infants and children from 1 month to 3 years to avoid negative balance (LOE 1; moderate quality, RG B, strong recommendation, strong consensus). In stable children aged 3-12 years, an amino acid intake of 1.0-2.0 g/kg per day may be considered (LOE 4, RG GPP, conditional recommendation, strong consensus) [48]. The maximum amino acid intake should not exceed 3.0 g/kg BW/day in term newborn infants and 2.0 g/kg BW/dayin stable children and adolescents [50]. Excessive amino acid intake has been shown to increase oxidation, in turn promoting high blood urea concentrations and metabolic acidosis [51]. Of note, amino acids must always be co-administered with sufficient amounts of energy in the form of glucose and lipid to prevent the wasting of amino acids for endogenous glucose production. The optimal ratio of NPEI in kcal to 1 gr of nitrogen (N) decreases with age, from approximately 250:1 in infants below 1 year of age to 150:1 in adolescents [13]. In the 1960s, in the early phase of PN development, newborn infants received protein hydrolyses as a source of nitrogen [52; 53]. These protein hydrolyses were not only nutritionally unadapted, but raised the risk of severe allergic reactions and were therefore abandoned. With the advent of technology for the production of pure L-amino acids, a second generation of amino acid solution was developed, but was much more adapted for adult than pediatric patients, and especially VLBW newborn infants. Extrapolation from data on oral nutrition was often unsatisfactory for the adequate formulation of such mixtures. The intestinal absorption metabolism of specific amino acids such as branched-chain amino acids (BCAAs), arginine, tyrosine, and methionine [54; 55; 56] is highly variable and may also change with age [50]. Accordingly, the composition of amino acid solutions for pediatric use should ideally be adapted to the specific requirements resulting from the lack of the intestinal \"first-pass\" metabolism. In other words, the composition of amino acid solutions for PN cannot copy the enteral intake. In the 1980s, great attention was given to amino acid supply in very-low-birth-weight infants from the first day of life in order to avoid catabolism, establish anabolism, achieve in utero protein accretion rates, and promote linear growth. Numerous studies have been performed for developing amino acid solutions with the aim of resembling the plasma amino acid patterns of normally growing, breast-fed infants, or resembling the amino acid profile of cord blood and achieving positive nitrogen balance. The direct study of parenterally nourished patients led to the third generation of amino acid solutions, providing all nine essential amino acids and a varying composition of non-essential amino acids. Studies have been published on the clinical efficacy of altered doses of arginine, branched-chain amino acids, cysteine, and taurine supplementation in PN [57; 58; 59; 60; 61; 62; 63; 64; 65; 66]. Today, the most currently used amino acid mixtures contain amino acid amounts that result from this model.