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Predicting the patients’ tolerance to enteral nutrition (EN) would help clinicians optimize individual nutritional intake. This study investigated the course of several gastrointestinal (GI) biomarkers and their association with EN advancement (ENA) longitudinally during pediatric intensive care unit (PICU) admission. This is a secondary analysis of the Early versus Late Parenteral Nutrition in the Pediatric Intensive Care Unit randomized controlled trial. EN was started early and increased gradually. The cholecystokinin (CCK), leptin, glucagon, intestinal fatty acid‐binding protein 2 (I‐FABP2), and citrulline plasma concentrations were measured upon PICU admission, day 3 and day 5. ENA was defined as kcal EN provided as % of predicted resting energy expenditure. The course of the biomarkers and ENA was examined in patients with samples on all time points using Friedman and Wilcoxon signed‐rank tests. The association of ENA with the biomarkers was examined using a 2‐part mixed‐effects model with data of the complete population, adjusted for possible confounders. For 172 patients, median age 8.6 years (first quartile; third quartile: 4.2; 13.4), samples were available, of which 55 had samples on all time points. The median ENA was 0 (0; 0) on admission, 14.5 (0.0; 43.8) on day 3, and 28.0 (7.6; 94.8) on day 5. During PICU stay, CCK and I‐FABP2 concentrations decreased significantly, whereas glucagon concentrations increased significantly, and leptin and citrulline remained stable. None of the biomarkers was longitudinally associated with ENA. Based on the current evidence, CCK, leptin, glucagon, I‐FABP2, and citrulline appear to have no added value in predicting ENA in the first 5 days of pediatric critical illness.

Early mobilisation in critically ill children is safe and feasible. However, the effectiveness of early mobilisation on short- and long-term outcomes is understudied. The aim of this scoping review was to generate an overview of outcomes used in previous research regarding early mobilisation in critically ill children.

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Early use of parenteral nutrition in the paediatric intensive care unit (PICU) negatively affects development of executive functions, externalising behaviour, and visual–motor integration 2 years later, compared with omitting parenteral nutrition until PICU day 8 (late parenteral nutrition). The molecular basis of this finding is uncertain. We aimed to test the hypothesis that DNA methylation changes occur during critical illness and that early parenteral nutrition (or a specific macronutrient component hereof) contributes to these changes, which could explain its negative effects on neurocognitive development.

The paediatric early versus late parenteral nutrition in critical illness (PEPaNIC) multicentre, randomised, controlled trial showed that, compared with early parenteral nutrition, withholding supplemental parenteral nutrition for 1 week in the paediatric intensive care unit (PICU; late parenteral nutrition) reduced infections and accelerated recovery from critical illness in children. We aimed to investigate the long-term impact on physical and neurocognitive development of early versus late parenteral nutrition.

Intravenous maintenance fluid therapy (IV-MFT) is one of the most prescribed, yet one of the least studied, interventions in paediatric acute and critical care settings. IV-MFT is not typically treated in the same way as drugs with specific indications, contraindications, compositions, and associated adverse effects. In the last decade, societies in both paediatric and adult medicine have issued evidence-based practice guidelines for the use of intravenous fluids in clinical practice. The main objective of this Viewpoint is to summarise and compare the rationales on which these international expert guidelines were based and how these recommendations affect IV-MFT practices in paediatric acute and critical care. Although these guidelines recommend the use of isotonic fluids as a standard in IV-MFT, some discrepancies and uncertainties remain regarding the systematic use of balanced fluids, glucose and electrolyte requirements, and appropriate fluid volume. IV-MFT should be considered in the same way as any other prescription drug and none of the components of IV-MFT prescription should be overlooked (ie, choice of drug, dosing rate, duration of treatment, and de-escalation). Furthermore, most evidence that was used to inform the guidelines comes from high-income countries. Although some principles of IV-MFT are universal, the direct relevance to and feasibility of implementing the guidelines in low-income and middle-income countries is uncertain.

ABSTRACTCritically ill children requiring intensive care suffer from impaired physical/neurocognitive development 2 y later, partially preventable by omitting early use of parenteral nutrition (early-PN) in the paediatric intensive-care-unit (PICU). Altered methylation of DNA from peripheral blood during PICU-stay provided a molecular basis hereof. Whether DNA-methylation of former PICU patients, assessed 2 y after critical illness, is different from that of healthy children remained unknown. In a pre-planned secondary analysis of the PEPaNIC-RCT (clinicaltrials.gov-NCT01536275) 2-year follow-up, we assessed buccal-mucosal DNA-methylation (Infinium-HumanMethylation-EPIC-BeadChip) of former PICU-patients (N = 406 early-PN; N = 414 late-PN) and matched healthy children (N = 392). CpG-sites differentially methylated between groups were identified with multivariable linear regression and differentially methylated DNA-regions via clustering of differentially methylated CpG-sites using kernel-estimates. Analyses were adjusted for technical variation and baseline risk factors, and corrected for multiple testing (false-discovery-rate <0.05). Differentially methylated genes were functionally annotated (KEGG-pathway database), and allocated to three classes depending on involvement in physical/neurocognitive development, critical illness and intensive medical care, or pre-PICU-admission disorders. As compared with matched healthy children, former PICU-patients showed significantly different DNA-methylation at 4047 CpG-sites (2186 genes) and 494 DNA-regions (468 genes), with most CpG-sites being hypomethylated (90.3%) and with an average absolute 2% effect-size, irrespective of timing of PN initiation. Of the differentially methylated KEGG-pathways, 41.2% were related to physical/neurocognitive development, 32.8% to critical illness and intensive medical care and 26.0% to pre-PICU-admission disorders. Two years after critical illness in children, buccal-mucosal DNA showed abnormal methylation of CpG-sites and DNA-regions located in pathways known to be important for physical/neurocognitive development.

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Previous randomised studies showed that withholding parenteral nutrition for 1 week of critical illness was superior to early initiation (<24–48 h) of parenteral nutrition in children and adults. However, neonates are considered more susceptible to macronutrient deficits. We investigated the effect of withholding parenteral nutrition for 1 week in critically ill, term neonates.

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Large randomised controlled trials have shown that early supplemental parenteral nutrition in patients admitted to adult and paediatric intensive care units (PICUs) is harmful. Overdosing of energy with too little protein was suggested as a potential reason for this. This study analysed which macronutrient was associated with harm caused by early supplemental parenteral nutrition in the Paediatric Early versus Late Parenteral Nutrition In Critical Illness (PEPaNIC) randomised trial.

Overfeeding during critical illness is associated with adverse effects such as metabolic disturbances and increased risk of infection. Because of the lack of sound studies with clinical endpoints, overfeeding is arbitrarily defined as the ratio caloric intake/measured resting energy expenditure (mREE) or alternatively as a comparison of measured respiratory quotient (RQ) to the predicted RQ based on the macronutrient intake (RQmacr). We aimed to compare definitions of overfeeding in critically ill mechanically ventilated children based on mREE, RQ, and caloric intake to find an appropriate definition. Indirect calorimetry measurements were performed in 78 mechanically ventilated children, median age 6.3 months. Enteral and/or parenteral nutrition was provided according to the local guidelines. Definitions used to indicate overfeeding were the ratio caloric intake/mREE of >110% and >120% and by the measured RQ > RQmacr+ 0.05. The proportion of patients identified as overfed varied widely depending on the definition used, ranging from 22% (RQ > RQmacr+ 0.05), to 40% and 50% (caloric intake/mREE of >120% and >110%, respectively). Linear regression analysis showed that all patients would be identified as overfed with the definition RQ > RQmacr+ 0.05 when the ratio caloric intake/mREE exceeded 165%. Caloric intake was higher in children with a standard deviation-score weight for age <-2. The proportion of mechanically ventilated patients identified as overfed ranged widely depending on the definition applied. These currently used definitions fail to take into account several relevant factors affecting metabolism during critical illness and are therefore not generally applicable to the pediatric intensive care unit population.

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Iron deficiency (ID) and iron deficiency anemia (IDA), during the first years of life, are associated with delayed motor and neurological development. Many studies evaluated iron status without an assessment of an acute-phase protein to identify infection. Because most indicators of iron status are influenced by infection, these data may underestimate the ID prevalence. A food consumption survey in the Netherlands showed that the mean iron intake of children ages 2 to 3 years was below the advised adequate intake of 7 mgday. The aim of the study was to investigate iron status in a well-defined, healthy population of young children in the southwestern region of the Netherlands and to identify risk factors for ID.

Iron deficiency (ID) and iron deficiency anemia (IDA), during the first years of life, are associated with delayed motor and neurological development. Many studies evaluated iron status without an assessment of an acute-phase protein to identify infection. Because most indicators of iron status are influenced by infection, these data may underestimate the ID prevalence. A food consumption survey in the Netherlands showed that the mean iron intake of children ages 2 to 3 years was below the advised adequate intake of 7 mg/day. The aim of the study was to investigate iron status in a well-defined, healthy population of young children in the southwestern region of the Netherlands and to identify risk factors for ID. We conducted a multicenter, observational study in healthy children ages 0.5 to 3 years. We defined ID as ferritin <12 µg/L and IDA when, in addition, hemoglobin was <110 g/L. Children with elevated C-reactive protein levels (>5 mg/L) or underlying causes for anemia were excluded. Parents filled in a questionnaire to identify risk factors for ID. We included 400 children in the study. ID and IDA were detected in 18.8% and 8.5% of the children, respectively. The present use of formula and the visit of preschool/day care were associated with a lower prevalence of ID, and a high intake of cow's milk was associated with a higher prevalence of ID, after adjustment for age. ID is present in 18.8% of healthy children ages 0.5 to 3 years and living in the southwestern region of the Netherlands. The present visit of preschool/day care and the use of formula are associated with a reduced risk of ID, whereas a high intake of cow's milk is associated with an increased risk of ID.