Early Versus Late Initiation of Parenteral Nutrition in Critically Ill Children: A Meta-Analysis of Randomized Controlled Trials

Abstract

Introduction: Optimal timing of parenteral nutrition (PN) in pediatric critical illness is controversial. Early PN (within 24 hours of admission) may prevent nutritional deficits but could suppress autophagy and increase infections. Late PN (day 8 or later) allows time for enteral tolerance but risks cumulative energy deficit. This review compares clinical outcomes.

Methods: We searched MEDLINE, Embase, and Cochrane for RCTs comparing early vs. late PN initiation in critically ill children (1 month–18 years) expected to require ICU stay ≥3 days. Primary outcome: new nosocomial infection. Secondary: ICU mortality, duration of mechanical ventilation. Random-effects meta-analysis.

Results: Five RCTs (n=1,449 children) were included. The largest (PEPaNIC trial) contributed 71% of patients. Late PN significantly reduced new infections (OR 0.65, 95% CI 0.48–0.88, p=0.005). ICU mortality was unchanged (OR 0.88, 95% CI 0.62–1.25). Duration of mechanical ventilation was shorter in late PN group (mean difference –1.8 days, 95% CI –2.9 to –0.7). Hypoglycemia episodes were more frequent with early PN (12% vs. 7%, p=0.03).

Discussion: Delaying PN until day 8 reduces infections and ventilator days without increasing mortality. The mechanism likely involves preserved autophagy and reduced hyperglycemia. Exclusion of children with pre-existing malnutrition limits generalizability to that subgroup. Late PN requires adequate enteral nutrition provision.

Conclusions: Late initiation of parenteral nutrition (day 8) is superior to early PN in critically ill children without prior malnutrition. Guidelines should recommend tolerance of enteral feeding attempts before PN.