High-density enteral formula in critically ill pediatric patients: A systematic review and meta-analysis

Background and aims: Critically ill pediatric patients, particularly infants, require sufficient nutrition even in the acute phase because they are at a high risk of malnutrition. Water restrictions are frequently required to avoid the adverse effects of fluid overload. Administration of energy or protein-dense enteral formulas is considered a potential therapeutic strategy to achieve these requirements simultaneously. This study aimed to assess efficacy and safety of energy or protein-dense enteral formula through a systematic review and meta-analysis. Methods: We searched MEDLINE via PubMed, Cochrane Central Register of Controlled Trials, and Igaku-Chuo-Zasshi in April 2023 for randomized controlled trials comparing high-density formulas (more than 0.9 kcal/mL) to standard-density formulas (0.67 to less than 0.9 kcal/mL) in critically ill pediatric patients undergoing enteral nutrition by artificial formula. The primary outcome was mortality, and secondary outcomes included length of stay in the intensive care unit (ICU), duration of mechanical ventilation, adverse events (emesis, diarrhea, and gastrointestinal bleeding), and weight-for-age Z score (WAZ). Data extraction and risk of bias assessment were performed by two independent reviewers using the Cochrane risk-of-bias tool. A meta-analysis was conducted using a random-effects model, and the certainty of the findings was assessed using the Grading of Recommendations Assessment, Development, and Evaluation methodology. Results: Seven studies involving 542 patients were included in the meta-analysis. Six of these seven studies included patients with congenital heart disease, and the remaining study included infants with acute respiratory failure due to viral infection. The effects on mortality were not significant (risk ratio: 2.05, 95 % confidence interval: [CI] 0.76–5.50, P = 0.16, low certainty). No significant effects were observed on length of ICU stay, length of hospital stay, duration of mechanical ventilation, or adverse events. High-density formulas had a significant effect on increasing WAZ (mean difference: 0.61, 95 % CI: 0.28–0.94, P < 0.001, low certainty). Conclusion: Our results showed that the administration of high-density formulas was effective in increasing WAZ. Further investigation will contribute to improving the certainty of this evidence.