## 2 Provision of Energy and Macronutrients in Pediatric Patients on PN
### Lipids  
Intravenous lipid emulsions are an integral component of pediatric PN [23]. ILEs are a low-osmolarity and energy-dense source of calories. In addition, they serve as a source of essential fatty acids (EFAs) and facilitate the delivery of fat-soluble vitamins [24; 25]. According to the ESPGHAN/ESPEN/ESPR guidelines [23], lipid intake should provide 25-50% of non-protein calories in pediatric patients on total PN. As for glucose, the maximal lipid oxidation rate has been established [26]. It decreases with age, from approximately 3 g/kg/day in young children to 1.7-2.5 g/kg/day in adults. According to ESPGHAN/ESPEN/ESPR guidelines [23], parenteral lipid intake in children should be limited to a maximum of 3 g/kg/day. To prevent biochemical evidence of essential fatty acid (EFA) deficiency, parenteral lipid intake should include 0.1 g/kg BW/day of omega-6 polyunsaturated fatty acid (PUFA) linoleic acid in term infants and children [23]. \"Historical\" ILEs, subsequently referred to as \"first generation\", were derived from pure soybean oil (SO) rich in LA. A potential disadvantage with pure SO ILEs is that high contents of omega-6 PUFAs, in particular of LA, have been attributed to pro-inflammatory and immunosuppressive properties [27]. This led to the development of more advanced ILEs containing mixtures of SO with alternative oil sources such as medium-chain triglycerides (MCTs) from coconut/palm kernel oil, olive oil (OO), and/or FO [25; 28]. In particular, FO, representing a source of omega-3 PUFAs with anti-inflammatory properties [29], has become an important component of the last generation of composite ILEs containing FO [27; 28]. Long-chain omega-3 PUFA docosahexaenoic acid (DHA), eicosapentaenoic acid (EPA), and omega-6 PUFA arachidonic acid (ARA) modulate key metabolic pathways, including inflammatory and immune responses, coagulation, and cell signaling [28; 30]. DHA and ARA are also required for an optimal development of the brain, as well as for cognition and visual acuity [31; 32; 33]. In order to prevent EFA deficiency in term infants and children, a lipid emulsion dosage providing a minimum linoleic acid intake of 0.1 g/kg/day can be given, which also provides an adequate intake of linoleic acid (LNA) with all 20% ILEs currently registered for pediatric use. In critically ill pediatric patients, ILE should also be an integral part of PN. Composite ILEs containing FO may be used as the first-choice treatment. Available evidence raises the important question on the best timing to provide PN support in critically ill children, but does not allow us to differentiate potential effects on outcomes of the timing of introducing ILE [21]. The ESPGHAN/ESPEN/ESPR guidelines support that, in newborn infants and older children on short-term PN, pure SO ILEs may provide a less balanced FA profile than composite ILEs [23]. For PN lasting longer than a few days, the use of pure SO-ILE is discouraged and composite ILEs with or without FO are recommended as first-line treatment [23; 34]. Of note, to date there are no quantitative recommendations for the supply of EPA, DHA, or ARA in pediatric patients. Intestinal-failure-associated liver disease (IFALD) is the most prevalent complication affecting children with IF receiving long-term PN [24; 35; 36]. The diagnosis of IFALD is usually based on the onset of cholestasis, generally defined as an elevation in conjugated serum bilirubin (CBil) concentration (\(\geq\)2 mg/dL) [24; 36]. Effects of pure FO-based ILEs (Omegaven(r), Fresenius Kabi, Bad Homburg, Germany) for reversing cholestasis in children receiving an SO-based ILE (Intralipid(r), Fresenius Kabi, Bad Homburg, Germany) were first reported by [PERSON] et al. [37]. Ten years later, the same group reported data on patients treated with pure FO from 2004 to 2014. Most of the time, cholestasis appeared very early during the first year of life. Resolution of cholestasis was defined as sustained direct bilirubin (DBil) < 2 mg/dL, and treatment failure as liver transplantation or death.