The goal of nutritional support during critical illness is to provide the appropriate amount of nutrition accounting for the acute, stable and recovery phase in order to accelerate recovery and to improve short-term and long-term outcomes. Although the preferred route to provide nutritional support during paediatric critical illness is via enteral route, reaching target intakes is often difficult due to (perceived) feeding intolerance, fluid restriction, and interruptions around procedures. Because undernourishment in these children has been associated with impaired outcome, parenteral nutrition (PN) has therefore been viewed as an optimal alternative for reaching early and high nutritional targets. However, PN recommendations regarding timing, dose and composition varied widely and were based on studies using intermediate or surrogate endpoints and observational studies. It was not until the paediatric early versus late PN in critically ill children (PEPaNIC) randomized controlled trial (RCT) that the advice to reach high and early macronutrient goals via PN was challenged. The PEPaNIC study showed that omitting supplemental PN during the first week of paediatric intensive care unit (PICU) admission as compared with early initiation of PN (<24 hours) reduced new acquired infections and accelerated recovery. The provision of amino acids in particular was negatively associated with short-term outcomes, probably explained by the suppression of the activation of autophagy. Autophagy is an evolutionary conserved intracellular degradation process and it is crucial for maintaining cellular integrity and function, which becomes even more important during acute stress. Results of the long-term PEPaNIC follow-up study showed that withholding early PN did not negatively affect anthropometrics and health status but improved neurocognitive and psychosocial development 2 and 4 years later. Current guidelines therefore advise to consider withholding parenteral macronutrients for the first week of PICU admission, while providing micronutrients. Although parenteral restriction during the first week of critical illness has been found beneficial, further research beyond the acute phase is warranted to determine the best role of PN in terms of optimal timing, dose and composition in order to improve short-term recovery and long-term developmental outcomes.
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Conflicts of Interest: The authors have completed the ICMJE uniform disclosure form (available at http://dx.doi. org/10.21037/pm-20-88). The series “Nutrition in the Critically Ill Child” was commissioned by the editorial office without any funding or sponsorship. Dr. SCATV served as the unpaid Guest Editor of the series, and serves as an unpaid editorial board member of Pediatric Medicine from Oct 2019 to Sep 2021. Dr. RDE reports grants from ESPEN Research Grant, outside the submitted work. Dr. SCATV reports grants from ESPEN Research Grant, grants from Sophia Research Foundation, grants from Nutricia Research BV, outside the submitted work. Dr. KFMJ reports grants from Fonds NutshOhra, grants from Erasmus Trustfonds, grants from Nutricia Research BV, grants from AGIS Zorginnovatie, during the conduct of the study; grants from ESPEN Research Grant, grants from
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