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The bidirectional relationship between nutrition and infection in critically ill infants and children extends well beyond simple caloric sufficiency. When a child develops sepsis or another form of critical illness, inflammatory cytokines alter metabolism, increase protein catabolism, and suppress appetite, while the treatments used to sustain life, including mechanical ventilation, vasoactive infusions, and sedation, frequently interrupt feeding. This creates a cycle in which inflammation worsens nutritional status and nutritional deficits, in turn, weaken the very defenses needed to control infection. Understanding this cycle helps explain why nutritional adequacy in the intensive care unit is not merely a matter of growth but a determinant of infectious morbidity and mortality.

The gastrointestinal tract serves as both a nutrient-processing organ and a frontline immune barrier. Its epithelial lining prevents luminal bacteria from crossing into the bloodstream, while the trillions of commensal microbes that inhabit the gut compete with pathogens, train the immune system, and produce metabolites such as short-chain fatty acids that nourish colonocytes and dampen inflammation. Critical illness undermines these functions through multiple mechanisms: fasting deprives enterocytes of their preferred fuel, antibiotics indiscriminately deplete protective commensals, opioids and sedatives slow motility, and hypoperfusion injures the mucosal barrier. When the barrier fails, bacterial translocation can seed the circulation and distant organs, providing a plausible mechanistic pathway from gut injury to bloodstream infection, ventilator-associated pneumonia, and sepsis progression.

Enteral nutrition is preferred over parenteral nutrition in large part because it sustains these gut-protective functions. Feeding the intestine directly maintains epithelial turnover, stimulates enteroendocrine signaling, and supports a diverse microbiome. In contrast, prolonged reliance on parenteral nutrition is associated with bloodstream infection, in part related to the central venous catheters required for its delivery and in part related to metabolic and gastrointestinal consequences of bypassing the gut. The PEPaNIC trial, a landmark randomized study in critically ill children, demonstrated that delaying supplemental parenteral nutrition until day eight of intensive care admission, rather than initiating it within the first twenty-four hours, reduced the incidence of infection and shortened intensive care unit length of stay. This finding reshaped practice across pediatric intensive care units and informed guidelines that suggest withholding parenteral nutrition for up to seven days when enteral nutrition is not yet feasible or sufficient.

Within the pediatric intensive care unit, sepsis exemplifies the tension between nutritional goals and infectious risk. Sepsis affects roughly 1.3 percent of children in the United States and carries an in-hospital mortality of approximately 10 percent, with gastrointestinal dysfunction common during the course of illness. Bowel wall edema, impaired mesenteric perfusion, vasopressor therapy, and antibiotic exposure combine to produce dysbiosis, barrier dysfunction, and feeding intolerance. Clinicians have historically hesitated to feed children receiving vasoactive medications out of concern for bowel ischemia, but retrospective pediatric studies have not demonstrated increased harm when enteral nutrition is initiated under adequately supported hemodynamic conditions. Current European guidelines support early enteral nutrition across pediatric age groups, including patients on vasoactive support, provided hemodynamic status is stable, while American guidelines recommend initiation within the first forty-eight hours of admission with at least two-thirds of prescribed energy delivered by one week and a minimum protein intake of 1.5 grams per kilogram per day, acknowledging substantial age-related variability in protein requirements.

Nutritional adequacy, however, remains difficult to achieve in practice. Multiple observational studies report that most critically ill children fall short of prescribed energy and protein targets, particularly during the first week of illness when interruptions for procedures, imaging, and extubation trials are frequent. Inadequate protein intake has been associated with increased sixty-day mortality, whereas the relationship between energy adequacy and mortality has been more variable, suggesting that protein delivery may be the more critical target. Early enteral nutrition has also been linked to improved survival, more ventilator-free days, and shorter intensive care unit stays in retrospective pediatric cohorts, and adequate energy and protein intake by day seven has been associated with reduced sixty-day mortality. These associations, while not uniformly causal, reinforce the importance of protocolized feeding pathways that minimize unnecessary interruptions and prioritize protein delivery.

Children with congenital heart disease represent another population in which the nutrition-infection interplay is pronounced. Before and after cardiac surgery, these children exhibit reduced microbial diversity, increased abundance of pro-inflammatory bacteria, and disrupted immune signaling, with medication exposure and physiologic perturbations adding further disruption. Impaired mesenteric perfusion in certain lesions contributes to epithelial barrier dysfunction, and these microbiome alterations have been associated with feeding intolerance, necrotizing enterocolitis, and postoperative complications. Nutritional strategies that target the microbiome, including fiber-containing formulas and physiologic feeding patterns such as bolus feeding, may better support enteroendocrine and metabolic signaling, although the optimal approach to preserving gastrointestinal homeostasis during critical illness remains uncertain and conventional formulas, which are often low in fiber and predominantly bovine-derived, may reduce short-chain fatty acid-producing commensals and foster a pro-inflammatory intestinal environment.

In neonatal intensive care, the stakes are heightened by intestinal immaturity in premature infants, whose epithelial barrier, digestive capacity, and immune systems are still developing. Necrotizing enterocolitis, a devastating inflammatory intestinal disease of prematurity, illustrates how feeding practices, microbiome composition, and barrier integrity converge on clinical outcomes. Human milk, with its immunoglobulins, oligosaccharides, and bioactive factors, supports microbial diversity and epithelial maturation in ways that infant formulas do not fully replicate, and dysbiosis preceding necrotizing enterocolitis has been described in multiple cohorts. Feeding advancement strategies, antibiotic stewardship, and microbiome-targeted interventions are active areas of investigation aimed at reducing both necrotizing enterocolitis and late-onset sepsis in this vulnerable population.

Children undergoing hematopoietic stem cell transplant face compounded nutritional and infectious risks. Mucositis from conditioning chemotherapy, graft-versus-host disease, and profound immunosuppression impair both nutrient absorption and host defense, while prolonged neutropenia heightens susceptibility to bacterial, fungal, and viral infections. Nutritional support in this population must balance the need for adequate protein and energy against the risks of central venous catheter infection and fluid overload, and the timing of parenteral nutrition initiation remains a key consideration given the PEPaNIC findings. Individualized feeding plans that preserve enteral nutrition whenever feasible, even at trophic volumes, may help maintain barrier function during periods of maximal immunosuppression.

Feeding route and pattern may matter as much as feeding volume. Bolus feeding, which mimics physiologic meal patterns, may better support enteroendocrine and metabolic signaling than continuous drip feeding, though direct comparative evidence in critically ill children is limited. Gastric feeding is generally preferred over post-pyloric delivery when tolerated, simplifying care and supporting gut hormone responses, while post-pyloric feeding is reserved for children with intolerance or aspiration risk. The Surviving Sepsis Campaign guidelines could not determine whether trophic feeding followed by gradual advancement is preferable to early full enteral nutrition, highlighting an important evidence gap that prospective studies are needed to address.

Measurement of energy expenditure through indirect calorimetry, rather than predictive equations, is recommended by American guidelines because predictive formulas frequently overestimate or underestimate actual needs in critically ill children, leading to unintended underfeeding or overfeeding. Overfeeding carries its own risks, including hyperglycemia, hepatic steatosis, carbon dioxide production that prolongs ventilation, and dysbiosis, whereas underfeeding contributes to catabolism, impaired wound healing, and weakened immunity. Achieving the right balance requires attention not only to macronutrient targets but also to micronutrients, including zinc, selenium, and vitamins that support immune function, though evidence for specific micronutrient supplementation in pediatric critical illness remains limited.

Antibiotic stewardship intersects closely with nutritional strategy. Broad-spectrum antibiotics, while lifesaving, deplete protective commensal bacteria and select for resistant organisms, compounding the dysbiosis already induced by fasting and critical illness. Minimizing unnecessary antibiotic exposure, de-escalating when cultures permit, and considering microbiome-protective strategies may complement nutritional interventions in reducing infectious complications. Similarly, minimizing fasting time around procedures, using protocols that allow enteral nutrition to continue during common intensive care interventions, and coordinating surgical and medical teams around feeding plans can substantially improve nutritional adequacy without added risk.

Collectively, the evidence synthesized across neonatal and pediatric intensive care settings suggests that nutritional management is inseparable from infection prevention. Early enteral nutrition under stable hemodynamic conditions, delayed supplemental parenteral nutrition when enteral intake is insufficient, adequate protein delivery, microbiome-conscious formula selection, and careful attention to feeding interruptions form a coherent strategy to reduce infectious morbidity. The narrative review by Kerstein and colleagues, drawing on clinical and research expertise across the neonatal, pediatric, and cardiac intensive care units at Boston Children’s Hospital, emphasizes that the optimal timing, composition, and advancement of nutrition during critical illness remain active questions, and that prospective studies are needed to define approaches that minimize both malnutrition and infectious complications in this vulnerable population.

Subject of Research: …

Article Title: Impact of malnutrition and nutritional support on infectious complications in critically ill infants and children

Article References: Kerstein, J. S., Weld, J. K., Mulhall, D. T., Lee, J. J., Allfather, A. E., Morton, S. U., Martinez, E. E., & Mills, K. I. (2026). Impact of malnutrition and nutritional support on infectious complications in critically ill infants and children. Frontiers in Pediatrics, 14, Article 1913382. https://doi.org/10.3389/fped.2026.1913382

Image Credits: AI Generated

DOI: 10.3389/fped.2026.1913382

Keywords: Impact, malnutrition, nutritional, support, infectious, complications, critically, infants, children, scientific research