Measuring Energy Requirements of Traumatic Brain Injury Patients in Pediatric Intensive Care With Indirect Calorimetry: A Comparison With Empiric Methods.

OBJECTIVES: Energy requirements following moderate or severe pediatric traumatic brain injury (TBI) have not been fully elucidated. Indirect calorimetry (IC) is the gold standard for measuring resting energy expenditure (MREE) in PICU. However, technical complexity limits its use. We aimed to determine whether MREE differs from standard of care energy estimation and delivery in a cohort of pediatric patients following moderate to severe TBI during PICU admission. DESIGN: Retrospective case series study. SETTING: Single-center, 16-bed general PICU in Canada between May 2011 and January 2019. PATIENTS: Children (0-18 yr) admitted to a PICU for moderate (Glasgow Coma Scale [GCS] 9-12) to severe TBI (GCS < 9) and had an IC study performed while mechanically ventilated. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: During the study period, 245 patients were admitted with the diagnosis of trauma with TBI. The study includes a convenience sample of 26 patients with severe ( n = 23) and moderate ( n = 3) TBI who underwent a total of 34 IC measurements. MREE varied considerably from 29% to 144% of predicted energy expenditure. Using Bland-Altman comparative analysis, neither Schofield nor World Health Organization predictive equations were in agreement with MREE. Only one measurement revealed that the patient was appropriately fed (energy provided in nutrition support was within 10% of MREE); 10 (38%) measurements revealed overfeeding and 15 (58%) underfeeding at the time of testing. CONCLUSIONS: The present study adds to the small body of literature highlighting the limitations of predictive equations to evaluate energy requirements following moderate to severe pediatric TBI. IC, when feasible, should be used as the preferred method to orient PICU teams to feed such vulnerable patients.

Effect of Maternal Docosahexaenoic Acid Supplementation on Bronchopulmonary Dysplasia-Free Survival in Breastfed Preterm Infants: A Randomized Clinical Trial.

Importance: Maternal docosahexaenoic acid (DHA) supplementation may prevent bronchopulmonary dysplasia, but evidence remains inconclusive. Objective: To determine whether maternal DHA supplementation during the neonatal period improves bronchopulmonary dysplasia-free survival in breastfed infants born before 29 weeks of gestation. Design, Setting, and Participants: Superiority, placebo-controlled randomized clinical trial at 16 Canadian neonatal intensive care units (June 2015-April 2018 with last infant follow-up in July 2018). Lactating women who delivered before 29 weeks of gestation were enrolled within 72 hours of delivery. The trial intended to enroll 800 mothers, but was stopped earlier. Interventions: There were 232 mothers (273 infants) assigned to oral capsules providing 1.2 g/d of DHA from randomization to 36 weeks' postmenstrual age and 229 mothers (255 infants) assigned to placebo capsules. Main Outcomes and Measures: The primary outcome was bronchopulmonary dysplasia-free survival in infants at 36 weeks' postmenstrual age. There were 22 secondary outcomes, including mortality and bronchopulmonary dysplasia. Results: Enrollment was stopped early due to concern for harm based on interim data from this trial and from another trial that was published during the course of this study. Among 461 mothers and their 528 infants (mean gestational age, 26.6 weeks [SD, 1.6 weeks]; 253 [47.9%] females), 375 mothers (81.3%) and 523 infants (99.1%) completed the trial. Overall, 147 of 268 infants (54.9%) in the DHA group vs 157 of 255 infants (61.6%) in the placebo group survived without bronchopulmonary dysplasia (absolute difference, -5.0% [95% CI, -11.6% to 2.6%]; relative risk, 0.91 [95% CI, 0.80 to 1.04], P = .18). Mortality occurred in 6.0% of infants in the DHA group vs 10.2% of infants in the placebo group (absolute difference, -3.9% [95% CI, -6.8% to 1.4%]; relative risk, 0.61 [95% CI, 0.33 to 1.13], P = .12). Bronchopulmonary dysplasia occurred in 41.7% of surviving infants in the DHA group vs 31.4% in the placebo group (absolute difference, 11.5% [95% CI, 2.3% to 23.2%]; relative risk, 1.36 [95% CI, 1.07 to 1.73], P = .01). Of 22 prespecified secondary outcomes, 19 were not significantly different. Conclusions and Relevance: Among breastfed preterm infants born before 29 weeks of gestation, maternal docosahexaenoic acid supplementation during the neonatal period did not significantly improve bronchopulmonary dysplasia-free survival at 36 weeks' postmenstrual age compared with placebo. Study interpretation is limited by early trial termination. Trial Registration: ClinicalTrials.gov Identifier: NCT02371460.

Combined effects of microplastics and chemical contaminants on the organ toxicity of zebrafish (Danio rerio).

Microplastics contamination of the aquatic environment is considered a growing problem. The ingestion of microplastics has been documented for a variety of aquatic animals. Studies have shown the potential of microplastics to affect the bioavailability and uptake route of sorbed co-contaminants of different nature in living organisms. Persistent organic pollutants and metals have been the co-contaminants majorly investigated in this field. The combined effect of microplastics and sorbed co-contaminants in aquatic organisms still needs to be properly understood. To address this, we have subjected zebrafish to four different feeds: A) untreated feed; B) feed supplemented with microplastics (LD-PE 125-250µm of diameter); C) feed supplemented with 2% microplastics to which a mixture of PCBs, BFRs, PFCs and methylmercury were sorbed; and D) feed supplemented with the mixture of contaminants only. After 3 weeks of exposure fish were dissected and liver, intestine, muscular tissue and brain were extracted. After visual observation, evaluation of differential gene expression of some selected biomarker genes in liver, intestine and brain were carried out. Additionally, quantification of perfluorinated compounds in liver, brain, muscular tissue and intestine of some selected samples were performed. The feed supplemented with microplastics with sorbed contaminants produced the most evident effects especially on the liver. The results indicate that microplastics alone does not produce relevant effects on zebrafish in the experimental conditions tested; on the contrary, the combined effect of microplastics and sorbed contaminants altered significantly their organs homeostasis in a greater manner than the contaminants alone.

The influence of microplastics and halogenated contaminants in feed on toxicokinetics and gene expression in European seabass (Dicentrarchus labrax).

When microplastics pollute fish habitats, it may be ingested by fish, thereby contaminating fish with sorbed contaminants. The present study investigates how combinations of halogenated contaminants and microplastics associated with feed are able to alter toxicokinetics in European seabass and affect the fish. Microplastic particles (2%) were added to the feed either with sorbed contaminants or as a mixture of clean microplastics and chemical contaminants, and compared to feed containing contaminants without microplastics. For the contaminated microplastic diet, the accumulation of polychlorinated biphenyls (PCBs) and brominated flame retardants (BFRs) in fish was significantly higher, increasing up to 40 days of accumulation and then reversing to values comparable to the other diets at the end of accumulation. The significant gene expression results of liver (cyp1a, il1ß, gstα) after 40 days of exposure indicate that microplastics might indeed exacerbate the toxic effects (liver metabolism, immune system, oxidative stress) of some chemical contaminants sorbed to microplastics. Seabass quickly metabolised BDE99 to BDE47 by debromination, probably mediated by deiodinase enzymes, and unlike other contaminants, this metabolism was unaffected by the presence of microplastics. For the other PCBs and BFRs, the elimination coefficients were significantly lower in fish fed the diet with contaminants sorbed to microplastic compared to the other diets. The results indicate that microplastics affects liver detoxification and lipid distribution, both of which affect the concentration of contaminants.

Reduction of Arachidonate Is Associated With Increase in B-Cell Activation Marker in Infants: A Randomized Trial.

BACKGROUND: Infants who are not breast-fed benefit from formula with both docosahexaenoic acid (C22:6n3) and arachidonic acid (ARA; C20:4n6). The amount of ARA needed to support immune function is unknown. Infants who carry specific fatty acid desaturase (FADS) polymorphisms may require more dietary ARA to maintain adequate ARA status. OBJECTIVE: The aim of the study was to determine whether ARA intake or FADS polymorphisms alter ARA levels of lymphocytes, plasma, and red blood cells in term infants fed infant formula. METHODS: Infants (N = 89) were enrolled in this prospective, double-blind controlled study. Infants were randomized to consume formula containing 17 mg docosahexaenoic acid and 0, 25, or 34 mg ARA/100 kcal for 10 weeks. Fatty acid composition of plasma phosphatidylcholine and phosphatidylethanolamine, total fatty acids of lymphocytes and red blood cells, activation markers of lymphocytes, and polymorphisms in FADS1 and FADS2 were determined. RESULTS: Lymphocyte ARA was higher in the 25-ARA formula group than in the 0- or 34-ARA groups. In plasma, 16:0/20:4 and 18:0/20:4 species of phosphatidylcholine and phosphatidylethanolamine were highest and 16:0/18:2 and 18:0/18:2 were lowest in the 34-ARA formula group. In minor allele carriers of FADS1 and FADS2, plasma ARA content was elevated only at the highest level of ARA consumed. B-cell activation marker CD54 was elevated in infants who consumed formula containing no ARA. CONCLUSIONS: ARA level in plasma is reduced by low ARA consumption and by minor alleles in FADS. Dietary ARA may exert an immunoregulatory role on B-cell activation by decreasing 16:0/18:2 and 18:0/18:2 species of phospholipids. ARA intake from 25 to 34 mg/100 kcal is sufficient to maintain cell ARA level in infants across genotypes.

Nutritional support for critically ill children.

BACKGROUND: Nutritional support in the critically ill child has not been well investigated and is a controversial topic within paediatric intensive care. There are no clear guidelines as to the best form or timing of nutrition in critically ill infants and children. This is an update of a review that was originally published in 2009. . OBJECTIVES: The objective of this review was to assess the impact of enteral and parenteral nutrition given in the first week of illness on clinically important outcomes in critically ill children. There were two primary hypotheses:1. the mortality rate of critically ill children fed enterally or parenterally is different to that of children who are given no nutrition;2. the mortality rate of critically ill children fed enterally is different to that of children fed parenterally.We planned to conduct subgroup analyses, pending available data, to examine whether the treatment effect was altered by:a. age (infants less than one year versus children greater than or equal to one year old);b. type of patient (medical, where purpose of admission to intensive care unit (ICU) is for medical illness (without surgical intervention immediately prior to admission), versus surgical, where purpose of admission to ICU is for postoperative care or care after trauma).We also proposed the following secondary hypotheses (a priori), pending other clinical trials becoming available, to examine nutrition more distinctly:3. the mortality rate is different in children who are given enteral nutrition alone versus enteral and parenteral combined;4. the mortality rate is different in children who are given both enteral feeds and parenteral nutrition versus no nutrition. SEARCH METHODS: In this updated review we searched: the Cochrane Central Register of Controlled Trials (CENTRAL 2016, Issue 2); Ovid MEDLINE (1966 to February 2016); Ovid EMBASE (1988 to February 2016); OVID Evidence-Based Medicine Reviews; ISI Web of Science - Science Citation Index Expanded (1965 to February 2016); WebSPIRS Biological Abstracts (1969 to February 2016); and WebSPIRS CAB Abstracts (1972 to February 2016). We also searched trial registries, reviewed reference lists of all potentially relevant studies, handsearched relevant conference proceedings, and contacted experts in the area and manufacturers of enteral and parenteral nutrition products. We did not limit the search by language or publication status. SELECTION CRITERIA: We included studies if they were randomized controlled trials; involved paediatric patients, aged one day to 18 years of age, who were cared for in a paediatric intensive care unit setting (PICU) and had received nutrition within the first seven days of admission; and reported data for at least one of the pre-specified outcomes (30-day or PICU mortality; length of stay in PICU or hospital; number of ventilator days; and morbid complications, such as nosocomial infections). We excluded studies if they only reported nutritional outcomes, quality of life assessments, or economic implications. Furthermore, we did not address other areas of paediatric nutrition, such as immunonutrition and different routes of delivering enteral nutrition, in this review. DATA COLLECTION AND ANALYSIS: Two authors independently screened the searches, applied the inclusion criteria, and performed 'Risk of bias' assessments. We resolved discrepancies through discussion and consensus. One author extracted data and a second checked data for accuracy and completeness. We graded the evidence based on the following domains: study limitations, consistency of effect, imprecision, indirectness, and publication bias. MAIN RESULTS: We identified only one trial as relevant. Seventy-seven children in intensive care with burns involving more than 25% of the total body surface area were randomized to either enteral nutrition within 24 hours or after at least 48 hours. No statistically significant differences were observed for mortality, sepsis, ventilator days, length of stay, unexpected adverse events, resting energy expenditure, nitrogen balance, or albumin levels. We assessed the trial as having unclear risk of bias. We consider the quality of the evidence to be very low due to there being only one small trial. In the most recent search update we identified a protocol for a relevant randomized controlled trial examining the impact of withholding early parenteral nutrition completing enteral nutrition in pediatric critically ill patients; no results have been published. AUTHORS' CONCLUSIONS: There was only one randomized trial relevant to the review question. Research is urgently needed to identify best practices regarding the timing and forms of nutrition for critically ill infants and children.

A Canadian survey of perceived barriers to initiation and continuation of enteral feeding in PICUs.

OBJECTIVE: Clinicians believe nutrition support is important; however, delivery of enteral nutrition may be delayed or interrupted due to a lack of guidelines or perceived contraindications to administration. The aim of this national survey was to examine the knowledge and perceived barriers among clinicians which prevent enteral nutrition administration to PICU patients. DESIGN: The survey consisted of 23 questions (19 primary and four branching). The survey was validated using a semistructured pilot test by three pediatric critical care intensivists and two pediatric critical care registered dietitians external to the study team. SETTING: The survey was electronically distributed to clinicians in all PICUs across Canada. POPULATION: One hundred sixty-two PICU clinicians, including 96 staff intensivists, eight clinical assistants, 36 fellows, and 22 registered dietitians from PICUs across Canada. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The survey was administered from January to March 2013. The response rate was 50% (55 staff intensivists, two clinical assistants, nine fellows, and 15 registered dietitians). There was high variability among clinicians regarding reasons to delay the onset of enteral nutrition or interrupt enteral nutrition administration. High variability (> 70% agreement and < 10% disagreement or vice versa) was found for some reasons to delay or interrupt enteral nutrition, including lactates (rising or > 2 or > 4 mmol/L), high gastric residual volumes, CT/MRI scans, and hypoplastic left heart syndrome. Sixty-eight percent of PICU clinicians reported no written feeding protocol to be in place. CONCLUSIONS: Overall, there is high variability among clinicians regarding acceptable procedural and clinical barriers to enteral nutrition administration; this may be improved by a standardized feeding protocol. Therefore, further research must be conducted to provide clinicians with evidence to support their practices for enteral nutrition administration.

Indicators of Pediatric Malnutrition in a Tertiary Care Hospital.

PURPOSE: This study was conducted to determine the prevalence of malnutrition at a Canadian children's hospital based on medical records and to identify gaps in current practices and rates/reasons for dietitian consult. METHODS: A retrospective chart audit of patients admitted during a winter season was completed. Patients with length of stay <4 days were excluded, as were those with fluid retention diseases. Outcome variables included anthropometrics, diet order, rates and reasons for dietitian consult, and biochemical data. RESULTS: Of the 83 charts reviewed (mean ± SD age 7.3 ± 5.6 years of age), weights were recorded less frequently than recommended (45% of patients ≤2 years of age and 85% of patients >2 years of age met or exceeded recommendations). Twenty-nine (36%) patients were identified at potential increased nutrition risk for overweight, 10 (12%) for underweight, and 31 (38%) patients had nutrition-related chart notes. Only 23 patients (28%) received a dietitian consult and, of those, 21 had a nutrition related chart note. Consultation occurred an average 5.4 ± 4.96 days after admission. CONCLUSIONS: These data emphasize the need for development of standardized screening and assessment tools to better identify pediatric patients at risk for malnutrition and to improve access to optimal nutrition care.

Microplastics in feed affect the toxicokinetics of persistent halogenated pollutants in Atlantic salmon.

Microplastics (MPs) are carriers of persistent organic pollutants (POPs). The influence of MPs on the toxicokinetics of POPs was investigated in a feeding experiment on Atlantic salmon (Salmo salar), in which fish were fed similar contaminant concentrations in feed with contaminants sorbed to MPs (Cont. MPs); feed with virgin MPs and contaminated feed (1:1), and feed with contaminants without MPs (Cont.). The results showed that the salmon fillets accumulated more POPs when fed with a diet where contaminants were sorbed to the MPs, despite the 125-250 µm size MPs themselves passing the intestines without absorption. Furthermore, depuration was significantly slower for several contaminants in fish fed the diet with POPs sorbed to the MPs. Modelled elimination coefficients and assimilation efficiencies of lipophilic chlorinated and brominated contaminants correlated with contaminant hydrophobicity (log Kow) within the diets and halogen classes. The more lipophilic the contaminant was, the higher was the transfer from feed to salmon fillet. The assimilation efficiency for the diet without MPs was 50-71% compared to 54-89% for the contaminated MPs diet. In addition, MPs caused a greater proportional uptake of higher molecular weight brominated congeners. In the present study, higher assimilation efficiencies and a significantly higher slope of assimilation efficiencies vs log Kow were found for the Cont. MPs diet (p = 0.029), indicating a proportionally higher uptake of higher-brominated congeners compared to the Cont. diet. Multiple variance analyses of elimination coefficients and assimilation efficiencies showed highly significant differences between the three diets for the chlorinated (p = 2E-06; 6E-04) and brominated (p = 5E-04; 4E-03) congeners and within their congeners. The perfluorinated POPs showed low assimilation efficiencies of <12%, which can be explained by faster eliminations corresponding to half-lives of 11-39 days, as well as a lower proportional distribution to the fillet, compared to e.g. the liver.

The profile of inflammatory and metabolic response in children undergoing heart transplantation.

Inflammatory and metabolic response is an important factor to determine clinical outcomes. However, it remains unknown in children undergoing heart transplantation (HTx). We examined the perioperative changes in the inflammatory and metabolic response markers C-reactive protein (CRP) and prealbumin (PA) in 38 heart-transplanted children. Data obtained prior to and within one month after HTx included CRP, PA, total and differential white blood cell counts, doses of inotropes and immunosuppressants, cultures of blood and body fluids, duration of cardiopulmonary bypass (CPB), aortic cross clamp and donor heart ischemia, and days in the intensive care unit (ICU) and hospital. CRP was 32±49 mg/L before HTx, increased to 130±55 mg/L on postoperative day 1-2, and decreased to 21±31 mg/L by one month after HTx. PA was 0.15±0.06 g/L before HTx, decreased to 0.12±0.03 g/L on postoperative day 1-2, and then gradually increased to 0.21±0.10 g/L by one month after HTx. Postoperative CRP positively correlated with epinephrine dosage and CPB duration. PA positively correlated with age. In conclusion, inflammatory and metabolic response is present before HTx and acutely intensified after HTx. It may be mainly influenced by CPB duration and cardiovascular function status.

An estrogen-responsive plasma protein expression signature in Atlantic cod (Gadus morhua) revealed by SELDI-TOF MS.

Compound-specific protein expression signatures (PESs) can be revealed by proteomic techniques. The SELDI-TOF MS approach is advantageous due to its simplicity and high-throughput capacity, however, there are concerns regarding the reproducibility of this method. The aim of this study was to define an estrogen-responsive PES in plasma of Atlantic cod (Gadus morhua) using the SELDI-TOF MS technique. Protein expression analysis of male cod exposed to 17ß-estradiol (E2) showed that 27 plasma peaks were differentially expressed following exposure. The reproducibility of this result was evaluated by reanalyzing the samples six months later, and a significant change in expression was confirmed for 13 of the 27 peaks detected in the first analysis. The performance of the reproducible E2-responsive PES, constituting these 13 peaks, was then tested on samples from juvenile cod exposed to 4-nonylphenol, North Sea oil, or North Sea oil spiked with alkylphenols. Principal component analysis revealed that nonylphenol-exposed cod could be separated from unexposed cod based on the E2-responsive PES, indicating that the PES can be used to assess estrogenic exposure of both juvenile and adult specimens of cod. A targeted antibody-assisted SELDI-TOF MS approach was carried out in an attempt to identify the E2-responsive peaks. Results indicated that 2 peaks were fragments of the well-known biomarkers VTG and/or ZRP. In this study, the SELDI-TOF MS technology has shown its potential for defining compound-specific PESs in fish. Nevertheless, thorough validation of reproducibility, specificity and sensitivity of a PES is required before it can be applied in environmental monitoring.

Growth performance, bioavailability of toxic and essential elements and nutrients, and biofortification of iodine of rainbow trout (Onchorynchus mykiss) fed blends with sugar kelp (Saccharina latissima).

Aquaculture production is demanding novel feed ingredients that reflect natural marine nutrient levels, that are also essential to humans. In this regard, biofortification through addition of iodine-rich sugar kelp in feed formulations was assessed in a 12 week rainbow trout trial. Yttrium inclusion in feed allowed determinations of apparent absorption coefficients of essential and potentially toxic elements and apparent digestibility coefficient of nutrients. E.g. apparent absorption coefficients in trouts fortified feed with 1-4% dw kelp were 67-61% As, 32-40% Cd, <5% Fe; 80-83% I; 66-58% Se. Iodine concentrations in feed up to 239 mg/kg (~4% kelp) was proportional to iodine accumulation in trout fillets (R2 = 1.00) with 0.5% transfer ratio. Feed iodine concentrations up to 117 mg/kg (~2% kelp) did not affect growth performance negatively, but increased significantly protein efficiency ratio after eight weeks feeding. However, 4% kelp meal inclusion affected final growth and hepato somatic index, and caused histomorphological changes in the intestine. All fillets had low toxic element concentrations (As, Cd, Hg, Pb). The potential applicability of Saccharina latissima as feed ingredient to tailor iodine concentration in farmed fish is evident. Consuming of a 160 g fillet (2% kelp) contributes ~60% of recommended daily iodine intake for adults.

Diets supplemented with Saccharina latissima influence the expression of genes related to lipid metabolism and oxidative stress modulating rainbow trout (Oncorhynchus mykiss) fillet composition.

This study aimed to evaluate the impact of diets including increasing amounts (1, 2 and 4%) of an iodine-rich macroalgae, Saccharina latissima, on gene expression and fillet composition of commercial-sized rainbow trout. Liver and muscle expression of genes related to growth, iodine, oxidative stress, and lipid metabolism, and the fillet content of fatty acids, cholesterol, and vitamin D3 were assessed. The highest kelp inclusion led to lower final body weight and HSI, without significant differences in mRNA transcription of genes involved in growth (ghr1, ghr2 and igf1) or iodine metabolism (dio1, thra, and thrb). A significant downregulation of an oxidative stress marker, gpx1b2, was observed in fish fed 2% S. latissima, which might suggest the need for less endogenous antioxidants. Dietary inclusion of kelp impacted lipid metabolism, with a downregulation of fatty acid synthase, accompanied by a general decrease of fatty acids in fillet. The present study demonstrated that supplementation of diets with 1 or 2% S. latissima can be achieved without detrimental effects on rainbow trout final weight. Evidence suggest a lipid-lowering effect of diets that did not compromise fillet EPA and DHA concentrations, being 3.7 times above the recommended levels for human consumption.

Gangliosides protect bowel in an infant model of necrotizing enterocolitis by suppressing proinflammatory signals.

OBJECTIVES: Necrotizing enterocolitis (NEC) has high morbidity in premature infants. Hypoxia-ischemia, infection, and enteral feeding are risk factors associated with NEC, whereas feeding human milk is protective. Vasoactive and inflammatory mediators in NEC remain elusive. Gangliosides are found in human milk and enterocyte membranes. An infant bowel model of NEC was developed to test the hypothesis that gangliosides modulate the inflammatory response to infection and hypoxia. PATIENTS AND METHODS: Viable, noninflamed bowel was obtained from 9 infants between 26 and 40 weeks' gestational age. Infant bowel was treated in culture with Escherichia coli lipopolysaccharide (LPS) and hypoxia in the presence or absence of preexposure to gangliosides. Bowel necrosis and production of nitric oxide, endothelin-1, serotonin, eicosanoids, hydrogen peroxide, and proinflammatory cytokines were measured. RESULTS: Ganglioside preexposure reduced bowel necrosis and endothelin-1 production in response to LPS. Gangliosides suppressed infant bowel production of nitric oxide, leukotriene B4, prostaglandin E2, hydrogen peroxide, interleukin-1beta, interleukin-6, and interleukin-8 in response to LPS exposure and hypoxia. CONCLUSIONS: A bowel protective effect of gangliosides is indicated by modulation of vasoactive mediators and proinflammatory signal suppression.

Nutritional support for critically ill children.

BACKGROUND: Nutritional support in the critically ill child has not been well investigated and is a controversial topic within paediatric intensive care. There are no clear guidelines as to the best form or timing of nutrition in critically ill infants and children. OBJECTIVES: To assess the impact of enteral and total parenteral nutrition on clinically important outcomes for critically ill children. SEARCH STRATEGY: We searched: the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2007, Issue 1); Ovid MEDLINE (1966 to February 2007); Ovid EMBASE (1988 to February 2007); OVID Evidence-Based Medicine Reviews; ISI Web of Science - Science Citation Index Expanded (1965 to February 2007); WebSPIRS Biological Abstracts (1969 to February 2007); and WebSPIRS CAB Abstracts (1972 to February 2007). We also searched trial registries; reviewed reference lists of all potentially relevant studies; handsearched relevant conference proceedings; and contacted experts in the area and manufacturers of enteral and parenteral nutrition products. We did not limit the search by language or publication status. SELECTION CRITERIA: We included studies if they were randomized controlled trials; involved paediatric patients, aged one day to 18 years of age, cared for in a paediatric intensive care unit setting (PICU) and received nutrition within the first seven days of admission; and reported data for at least one of the pre-specified outcomes (30-day or PICU mortality; length of stay in PICU or hospital; number of ventilator days; and morbid complications, such as nosocomial infections). We excluded studies if they only reported nutritional outcomes, quality of life assessments, or economic implications. Furthermore, other areas of paediatric nutrition, such as immunonutrition and different routes of delivering enteral nutrition, were not addressed in this review. DATA COLLECTION AND ANALYSIS: Two authors independently screened searches, applied inclusion criteria, and performed quality assessments. We resolved discrepancies through discussion and consensus. One author extracted data and a second checked data for accuracy and completeness. MAIN RESULTS: Only one trial was identified as relevant. Seventy-seven children in intensive care with burns involving > 25% of the total body surface area were randomized to either enteral nutrition within 24 hours or after at least 48 hours. No statistically significant differences were observed for mortality, sepsis, ventilator days, length of stay, unexpected adverse events, resting energy expenditure, nitrogen balance, or albumin levels. The trial was assessed as of low methodological quality (based on the Jadad scale) with an unclear risk of bias. AUTHORS' CONCLUSIONS: There was only one randomized trial relevant to the review question. Research is urgently needed to identify best practices regarding the timing and forms of nutrition for critically ill infants and children.

Relating biomarkers to whole-organism effects using species sensitivity distributions: a pilot study for marine species exposed to oil.

Biomarkers are widely used to measure environmental impacts on marine species. For many biomarkers, it is not clear how the signal levels relate to effects on the whole organism. This paper shows how species sensitivity distributions (SSDs) can be applied to evaluate multiple biomarker responses in species assemblages. To our knowledge, the present study compared for the first time SSDs based on biomarker response levels for marine species to a SSD for whole-organism responses. The comparison indicates that for exposure to dispersed oil in the marine environment, the selected biomarkers were, on average, 35- to 50-fold more sensitive than the whole-organism effect. At the 5% hazardous concentration derived from the SSD for whole-organism effects, which is a conservative threshold level, the potentially affected fraction of species showing biomarker response corresponds to approximately 80%. Variation in species sensitivity, expressed either as biomarker or as whole-organism response levels, were similar. Although uncertainties exist, the link between biomarkers and risk assessment presented here provides a preliminary guideline for deciding when biomarker responses likely are hazardous and, therefore, require further investigation.

Priorities for Nutrition Research in Pediatric Critical Care.

BACKGROUND: Widespread variation exists in pediatric critical care nutrition practices, largely because of the scarcity of evidence to guide best practice recommendations. OBJECTIVE: The objective of this paper was to develop a list of topics to be prioritized for nutrition research in pediatric critical care in the next 10 years. METHODS: A modified 3-round Delphi process was undertaken by a newly established multidisciplinary group comprising 11 international researchers in the field of pediatric critical care nutrition. Items were ranked on a 5-point Likert scale. RESULTS: Forty-five research topics (with a mean priority score >3(0-5) were identified within the following 10 domains: the pathophysiology and impact of malnutrition in critical illness; nutrition assessment: nutrition risk assessment and biomarkers; accurate assessment of energy requirements in all phases of critical illness; the role of protein intake; the role of pharmaco-nutrition; effective and safe delivery of enteral nutrition; enteral feeding intolerance: assessment and management; the role of parenteral nutrition; the impact of nutrition status and nutrition therapies on long-term patient outcomes; and nutrition therapies for specific populations. Ten top research topics (that received a mean score >4(0-5) were identified as the highest priority for research. CONCLUSIONS: This paper has identified important consensus-derived priorities for clinical research in pediatric critical care nutrition. Future studies should determine topics that are a priority for patients and parents. Research funding should target these priority areas and promote an international collaborative approach to research in this field, with a focus on improving relevant patient outcomes.

Optimizing Nutrition in Pediatric Heart Failure: The Crisis Is Over and Now It's Time to Feed.

Pediatric heart failure is a complex disease occurring when cardiac output is unable to meet the metabolic demands of the body. With improved surgical interventions and medical therapies, survival rates have improved, and care has shifted from focusing on survival to optimizing quality of life and health outcomes. Based on current literature, this review addresses the nutrition needs of infants and children in heart failure and describes the pathophysiology and metabolic implications of this disease. The prevalence of wasting in pediatric heart failure has been reported to be as high as 86%, highlighting the importance of nutrition assessment through all stages of treatment to provide appropriate intake of energy, protein, and micronutrients. The etiology of malnutrition in pediatric heart failure is multifactorial and involves hypermetabolism, decreased intake, increased nutrient losses, inefficient utilization of nutrients, and malabsorption. Children in heart failure often present with tachypnea, tachycardia, fatigue, nausea, and vomiting and consequently may not be able to meet their nutrition requirements through oral intake alone. Nutrition support, including enteral nutrition and parenteral nutrition, should be considered an essential part of routine care. The involvement of multiple allied health professionals may be needed to create a feeding therapy plan to support patients and their families. With appropriate nutrition interventions, clinical outcomes and quality of life can be significantly improved.

Can energy intake alter clinical and hospital outcomes in PICU?

BACKGROUND & AIMS: Energy is essential for the treatment and recovery of children admitted to Pediatric Intensive Care Units (PICU). There are significant immediate and long-term health consequences of both under- and over-feeding in this population. Energy requirements of critically ill children vary depending on age, nutritional status, sepsis, fever, pharmacotherapy, and duration and stage of critical illness. This study aimed to determine the incidence of over- and under-feeding and to compare hospital outcomes between these feeding categories. Secondary outcomes were collected to describe the association between feeding categories and biochemistries (serum lactate, triglycerides, C-reactive protein). METHODS: An ethics approved retrospective study of children admitted to PICU was performed. All intubated patients admitted to PICU (2008-2013) were included, except those in which an IC test was not feasible. Data collection included demographics, the primary outcome variable reported as under feeding (<90%MREE), appropriate (MREE ±10%) or overfeeding (>110% MREE) determined through comparison of measured resting energy expenditure (MREE) using indirect calorimetry (IC) to actual energy intake based on predicted basal metabolic rate (PBMR) and clinical outcomes mechanical ventilation and PICU length of stay (LOS). Data were analysed with descriptive methods, ANOVA and linear regression models. RESULTS: A total of 139 patients aged 10 (range 0.03-204) months were included. Sixty (43%) were female and 77 (55%) were admitted after a surgical procedure. A total of 210 IC tests were conducted showing a statistically significant difference between MREE measurements and PBMR (p = 0.019). Of the 210 measurements, only 26 measures (12.4%) demonstrated appropriate feeding, while 72 (34.3) were underfed and 112 (53.3%) were overfed. Children who were overfed had significantly longer PICU LOS (median 45.5, IQR 47.8 days) compared to those children in the appropriately fed (median 21.0, IQR 54.5 days), and underfed groups (median 16.5, IQR 21.3 days). There was a mean difference between the over and under feeding category and ventilation days after adjusting for age and PRISM score (p = 0.026), suggesting decreased mechanical ventilation days for underfed. Children who were underfed had significantly higher CRP (median 75.5, IQR 152.8 mg/L) compared to those children in the appropriately fed (median 57.8, IQR 90.9 mg/L) and overfed groups (median 22.4, IQR 56.2 mg/L). CONCLUSIONS: This retrospective study confirms that estimations of energy expenditure in critically ill children are inaccurate leading to unintended under and overfeeding. Importantly under feeding seems to be associated with fewer mechanical ventilation days and PICU LOS. Further research is required to elucidate the role of optimal nutrition in altering clinical variables in this population.

Adherence to a Nurse-Driven Feeding Protocol in a Pediatric Intensive Care Unit.

BACKGROUND: Patients admitted to pediatric intensive care units (PICUs) often experience prolonged periods without nutrition support, which may result in hospital-induced malnutrition and longer length of stay. Nurse-driven feeding protocols have been developed to prevent unnecessary interruptions or delays to nutrition support. The primary objective of this study was to identify compliance and reasons for noncompliance to a feeding protocol at a tertiary care hospital PICU in Canada. The secondary aim was to determine the mean time (hours) spent without any form of nutrition and to identify reasons for time spent without nutrition. MATERIALS AND METHODS: This was a prospective cohort audit, consisting of 150 consecutive PICU admissions (January-February 2016). Exclusion criteria consisted of patient mortality within 48 hours (n = 1) and patients who were still admitted at the end of the data collection timeframe (n = 7). The remaining cohort consisted of 142 consecutive admissions. Data collection took place in real time and included patient demographics, diagnostic categories, time spent without nutrition, reasons for interruptions to nutrition support, and reasons for noncompliance to the protocol. Observations were obtained through paper and computer charts and conversing with clinicians. RESULTS: There was a 95% compliance rate to the protocol and an average of 25.6 hours spent without nutrition per patient. The most prevalent reason for noncompliance was an avoidable delay to restart feeds before/after procedures or after surgery. CONCLUSIONS: A nurse-driven feeding protocol may reduce time spent without nutrition. Future research is required to examine the relationship between adherence to feeding protocols and clinical outcomes.