Highlight
Early enteral nutrition (EEN) in critically ill children was associated with lower adjusted mortality (aOR 0.36; 95% CI 0.14–0.91) in pooled analyses of studies that adjusted for illness severity. Across 18 studies (n≈9,829), EEN was also associated with shorter ventilator and ICU length of stay, fewer infections, better nutrition adequacy, and lower organ dysfunction scores. However, the certainty of evidence is very low because most data are from observational cohorts, adjustment for confounding was limited, definitions of EEN varied, and between-study heterogeneity was substantial (I2=78.6% for mortality in adjusted pooled analysis). Clinicians should continue guideline-aligned early enteral feeding when feasible but recognize the limitations of current evidence and the need for high-quality randomized studies with standardized outcomes.
Background and clinical context
Nutrition is a core component of care in pediatric critical illness. Enteral nutrition (EN) preserves gut mucosal integrity, supports immune function, and provides substrate for recovery. Adult critical care guidelines have long endorsed early EN where feasible; pediatric critical care societies and expert groups also recommend initiating EN early in hemodynamically stable children to reduce energy and protein deficits and potentially improve clinical outcomes. Nonetheless, implementation is variable, and uncertainties remain about timing, route (gastric versus post-pyloric), and safety in subgroups such as those with shock or gastrointestinal pathology.
The recent systematic review and meta-analysis by Gilbert and colleagues (2025) addresses whether initiating EN early versus delaying it is associated with improved clinical outcomes in critically ill pediatric populations. This synthesis responds to an important clinical question with direct implications for bedside practice and institutional protocols.
Study design and methods (what the review did)
Gilbert et al. conducted a systematic review registered with PROSPERO (CRD42021286271), searching MEDLINE, Embase, CINAHL, and CENTRAL through October 2024. Eligible studies enrolled critically ill children and compared early enteral nutrition (EEN) versus delayed enteral nutrition (DEN). Study designs included randomized controlled trials (RCTs), quasi-experimental designs, cohort and case-control studies. Outcomes of interest were mortality and other clinical outcomes. Screening, extraction, risk-of-bias assessment (Newcastle–Ottawa Scale for nonrandomized studies and Cochrane Risk of Bias for RCTs), and GRADE certainty assessments were performed in duplicate.
Of 8,478 screened records, 18 studies met inclusion (1 RCT, 17 cohort studies), collectively including 9,829 patients. Mortality data were available from 13 studies (1 RCT and 12 cohorts), but only three cohort studies reported mortality estimates adjusted for illness severity. The authors pooled mortality using random-effects models and summarized secondary outcomes qualitatively, noting direction and statistical significance where reported.
Key findings
Primary outcome — mortality
– Adjusted pooled analysis: Among the three studies that adjusted for illness severity, receipt of EEN was associated with reduced mortality (adjusted odds ratio [aOR] 0.36, 95% confidence interval [CI] 0.14–0.91). This pooled analysis included 5,864 patients but displayed substantial heterogeneity (I2 = 78.6%).
– Unadjusted analyses: The larger set of cohort studies and the lone RCT produced variable unadjusted estimates; because most cohorts did not adjust for severity, pooled unadjusted mortality estimates were not emphasized by the review owing to risk of confounding.
Certainty: The authors rated the certainty of evidence for mortality as very low according to GRADE, driven principally by indirectness (observational designs), risk of residual confounding, and heterogeneity across studies.
Secondary clinical outcomes (qualitative synthesis across 18 studies)
– Length of stay (LOS): Multiple cohort studies reported that EEN was associated with reduced pediatric intensive care unit (PICU) length of stay and reduced hospital length of stay.
– Duration of invasive respiratory support: Several studies reported shorter duration of mechanical ventilation with EEN.
– Nutrition adequacy: EEN was consistently associated with improved energy and protein delivery and higher rates of meeting nutrition targets.
– Organ dysfunction and severity scores: EEN correlated with lower maximum Pediatric Logistic Organ Dysfunction (PELOD) scores in some cohorts.
– Infections: An association between EEN and lower infection rates was observed in a subset of studies.
– Safety and harms: No consistent signal of harm (for example, higher rates of aspiration, bowel ischemia, or feeding intolerance leading to worse outcomes) emerged after adjustment for confounders, although reporting of adverse events was inconsistent across studies.
Important caveats
– Heterogeneity: Definitions of “early” varied (often within 24–48 hours of admission, but not uniform), as did feeding protocols, caloric targets, bolus versus continuous administration, use of gastric versus post-pyloric tubes, and patient mix (medical, surgical, cardiac, trauma).
– Confounding: Most evidence arose from observational cohorts that incompletely adjusted for illness severity, hemodynamic instability, or baseline risk, limiting causal inference.
– Limited RCT evidence: Only one randomized trial met inclusion; randomized data remain sparse.
Interpretation and mechanistic rationale
Biologic plausibility supports potential benefits of EEN. Enteral feeding stimulates gut-associated lymphoid tissue and mucosal blood flow, maintains barrier function, and may reduce bacterial translocation and systemic inflammation. Improved early energy and protein delivery can attenuate catabolism and support organ recovery. These mechanisms could explain observed associations with fewer infections, lower organ dysfunction scores, and shorter ventilator and ICU stays.
However, the observational nature of most available data raises the possibility that children selected to receive EEN were less severely ill or more likely to tolerate feeding, generating selection bias. Even adjusted analyses can leave residual confounding if key severity or treatment variables are not fully captured.
Expert commentary and guideline context
Major critical care nutrition guidelines advocate early enteral feeding when clinically feasible. For pediatric patients, specialty guidance (SCCM/ASPEN pediatric nutrition guidelines) supports initiating EN early in the absence of contraindications, with individualized goals and monitoring. The current review reinforces guideline rationale by showing consistent associations favoring EEN, but it also highlights how the evidence base is weak in quality and heterogeneous.
Clinical experts often emphasize practical considerations: ensuring hemodynamic stability before initiating feeds, starting with low-rate continuous or carefully advanced bolus feeds, monitoring for abdominal distension and gastric residual volumes per institutional practice, and using post-pyloric feeding when aspiration risk is high or gastric intolerance is persistent. Implementation strategies — feeding protocols, nurse-driven advancement algorithms, and multidisciplinary nutrition support teams — are known to improve nutrition delivery and may mediate some of the outcome differences observed across centers.
Limitations of the review and studies
– Predominance of observational studies with limited adjustment for confounding limits causal inference.
– Substantial heterogeneity in definitions of early feeding, patient populations, and outcome measurements reduces external validity.
– Important subgroups (e.g., neonates, cardiac surgery patients, severe shock) were variably represented; safety and efficacy in these groups remain uncertain.
– Inconsistent reporting of harms and adverse events limits assessment of risk.
– High statistical heterogeneity (I2 78.6% in adjusted mortality pooling) indicates that pooled effect sizes should be interpreted cautiously.
Implications for practice
– For most critically ill children who are hemodynamically stable and have no contraindication to enteral feeding, available evidence and guideline recommendations support initiating EN early (often within 24–48 hours) with close monitoring.
– Clinicians should individualize decisions in subgroups with high aspiration or ischemic risk and prioritize multidisciplinary care, standardized feeding protocols, and active strategies to reduce interruptions and improve nutrition adequacy.
– Observed associations with improved mortality and other outcomes are encouraging but not definitive; clinicians should avoid overstating causality given very low certainty of evidence.
Research and policy priorities
– High-quality randomized controlled trials in heterogeneous pediatric critical care populations are needed, with standardized definitions of EEN and prespecified core outcomes (mortality, ventilator-free days, infection, nutrition adequacy, and adverse events).
– Trials and cohort studies should include rigorous adjustment for illness severity using validated scores and consider instrumental variable or propensity-based approaches to reduce confounding.
– Development and adoption of a pediatric critical care nutrition core outcome set would improve comparability across studies.
– Implementation research to delineate which feeding protocols, routes (gastric vs post-pyloric), and delivery strategies most reliably increase nutrition adequacy and translate into clinical benefit is warranted.
Conclusion
The systematic review and meta-analysis by Gilbert et al. suggests that early enteral nutrition in critically ill children is associated with lower adjusted mortality and beneficial effects on several clinically meaningful outcomes, including length of stay, ventilator duration, infection rates, and nutrition adequacy. Nevertheless, the evidence base is dominated by observational studies with heterogeneous definitions and incomplete adjustment for confounding; thus, overall certainty is very low. Current practice should continue to align with guideline recommendations to start enteral feeding early when feasible and safe, while clinicians and researchers work to generate higher-quality evidence clarifying the magnitude and causality of benefit and delineating subgroup-specific recommendations.
Funding and trial registration
The systematic review was prospectively registered on PROSPERO (CRD42021286271). For funding sources and trial-level registration details, refer to Gilbert N et al., Crit Care Med. 2025.
Selected references
1. Gilbert N, Schalm E, Wollny K, Lee L, Boctor DL, Fenton TR. Early Enteral Nutrition and Clinical Outcomes in Critically Ill Pediatric Populations: A Systematic Review and Meta-Analysis. Crit Care Med. 2025 Sep 17. doi:10.1097/CCM.0000000000006859. Epub ahead of print. PMID: 40960355.
2. Mehta NM, Bechard LJ, Cahill N, et al. Guidelines for the Provision and Assessment of Nutrition Support Therapy in the Pediatric Critically Ill Patient: Society of Critical Care Medicine (SCCM) and American Society for Parenteral and Enteral Nutrition (ASPEN). Pediatr Crit Care Med. 2017;18(8):675–715. (Guideline document informing pediatric ICU nutrition practice.)
3. McClave SA, Taylor BE, Martindale RG, et al. Guidelines for the Provision and Assessment of Nutrition Support Therapy in the Adult Critically Ill Patient: Society of Critical Care Medicine (SCCM) and American Society for Parenteral and Enteral Nutrition (ASPEN). JPEN J Parenter Enteral Nutr. 2016;40(2):159–211. (Provides context on evidence and rationale for early enteral feeding in critical illness.)
