Elemental Diet as a Therapeutic Modality: A Comprehensive Review.

Elemental diets have been employed for the management of various diseases for over 50 years, with several mechanisms mediating their beneficial effects. Yet, they are underutilized due to poor palatability, access, cost, and lack of awareness regarding their clinical efficacy. Therefore, in this review, we aimed to systematically search and review the literature to summarize the formulation variability, mechanisms of action, clinical applications, and tolerability of the elemental diets in gastrointestinal diseases. While large prospective trials are lacking, elemental diets appear to exhibit objective and subjective clinical benefit in several diseases, including eosinophilic esophagitis, eosinophilic gastroenteritis, inflammatory bowel diseases, small intestinal bacterial overgrowth, intestinal methanogen overgrowth, chemoradiotherapy-associated mucositis, and celiac disease. Although some data support the long-term use of elemental diets as an add-on supplement for chronic pancreatitis and Crohn's disease, most of the literature on exclusive elemental diets focuses on inducing remission. Therefore, subsequent treatment strategies for maintaining remission need to be adopted in chronic/relapsing diseases. Several mechanistic pathways were identified to mediate the effects of elemental diets, including food additive and allergen-free content, high passive absorption rate, and anti-inflammatory properties. High rates of intolerance up to 40% are seen in the trials where exclusive elemental diets were administered orally due to poor organoleptic acceptability; however, when tolerated, adverse events were rare. Other limitations of elemental diets are cost, access, and lifestyle/social restrictions. Moreover, judicious use is advised in presence of a concomitant restrictive food intake disorders. Elemental diets offer a potentially highly efficacious dietary intervention with minor side effects. Palatability, cost, access, and social restrictions are common barriers of use. Prospective clinical trials are needed to elucidate the role of elemental formulas in the management of individual diseases.

The impact of low-energy, partially hydrolysed enteral formula on gastrointestinal symptoms and weight in children with neurological impairment: a multicentre retrospective study.

BACKGROUND: Neurological impairment (NI) relates to disorders of the central nervous system. The specific aetiology of NI varies but includes genetic, congenital abnormalities or brain injury. In children with severe NI, feeding impairments can lead to undernutrition, and some children require a feeding tube. Although tube feeding improves overall nutritional status, it has also been associated with excess body fat. Commercially available enteral formulas that are low in energy, hydrolysed and nutritionally adequate for protein and micronutrients are available to mitigate gastrointestinal symptoms and obesity. METHODS: This is a retrospective multicentre study of children who attended NI clinics between January 2022 and July 2023. Data were collected before and 1 month after receiving a low-energy, partially hydrolysed enteral formula (0.6 kcal/mL) on demographic data (age, sex, ethnicity and NI diagnosis), anthropometric measurements (weight, height, weight-for-age Z-score, height-for-age Z-score, body mass index [BMI] Z-score) and feed regimen (feed volume, total fluids and type of formula/supplements). RESULTS: Dietitians collected data on 28 children, the median age was 7 years (interquartile range [IQR] 3, 8). The most frequently recorded NI was cerebral palsy, in 13 of 28 children (48%). Before the formula switch, the most frequently reported gastrointestinal symptom was constipation, in 13 of 28 children. Within 1 month of switching to a low-energy, hydrolysed formula, 10 of the 13 (77%) children reported an improvement in constipation. Before the formula switch, all 28 children were experiencing excessive weight gain. After the formula was switched to low-energy, hydrolysed formula, dietitians reported that 20 of the 28 (76%) children's weight either stabilised or reduced after 1 month. There was no statistically significant difference in weight-for-age Z-score or BMI Z-scores postswitch of formula (p-value 0.1 and 0.09, respectively). Fibre intake increased significantly from 3.3 to 8.1 g/day (p-value < 0.01) after formula switch. The number of children whose feed regimens were simplified after switching to a low-energy, partially hydrolysed formula was 24 of 28 (91%). CONCLUSIONS: Children with an NI who have gastrointestinal symptoms may benefit from a low-energy, hydrolysed enteral formula to maximise feed tolerance and promote healthy weight gain. In addition, changing to a low-energy, hydrolysed formula may simplify feed regimens by eliminating the need for additional electrolytes, multivitamins and fluid boluses. Healthcare professionals should be knowledgeable about the effectiveness and availability of a low-energy, hydrolysed formula.

Nutri-Score: Its Benefits and Limitations in Children's Feeding.

Reducing the burden of noncommunicable diseases (NCDs) is one of the top priorities of public health policies worldwide. One of the recognized means of achieving this objective is to improve the diet quality. The Nutri-Score (N-S) is a [five-color-A, B, C, D, E letters] front-of-pack labeling logo intended to help consumers quickly identify the healthier prepackaged foods within a food category. Available studies have shown that the N-S is an efficient tool to achieve this aim in terms of consumers' awareness, perception, understanding, and purchasing and that its use may help to reduce the prevalence of NCDs. The N-S is currently implemented on a voluntary basis in 7 European countries and a discussion is underway within the European Commission to achieve a harmonized mandatory label. However, no study on the putative impact of the N-S on children's dietary patterns and health is available. The N-S is not applicable to infants' and young children's formulas and to specific baby foods, the compositions of which are already laid down in European Union regulations. The N-S does not replace age-appropriate dietary guidelines. As children consume an increasing number of adult type and processed foods, the relevance of the N-S for children should be evaluated considering the children's high specific requirements, especially in younger children. This is especially necessary for fitting fat and iron requirements, whereas protein-rich foods should be better framed. Moreover, efforts should be made to inform on how to use the N-S and in education on healthy diets.

Early Enteral Nutrition and Gastrointestinal Complications in Pediatric Patients on Extracorporeal Membrane Oxygenation.

OBJECTIVES: To assess the safety of enteral nutrition (EN) in children on extracorporeal membrane oxygenation (ECMO). To describe nutritional status and the characteristics of the nutritional support in this population. METHODS: A retrospective single-center analysis (2006-2016) including children <18 years on ECMO. Demographic data, nutritional status, characteristics of nutritional support, and development of gastrointestinal (GI) complications were recorded. RESULTS: One hundred children, with a median age of 9.7 months (interquartile range [IQR] 3.9-63.1) were enrolled. Undernutrition was prevalent among children on ECMO (33.3%) mainly in patients <2 years (P = 0.042). Most patients (64%) received EN at some point during ECMO therapy. EN was administered in the first 48 hours after ECMO initiation (48HEN) to 60.3% of the children.Mortality rate in the Pediatric Intensive Care Unit was lower in patients who received EN as the initial artificial nutrition support (ANS) (37.7 vs 51%, P = 0.005) and in children on 48HEN (34% vs 50%, P = 0.04). In the logistic regression analysis, duration of ECMO support and low cardiac output indication were the only factors associated with mortality.Although most patients on ECMO (45%) developed digestive complications, they were mostly mild, being constipation the most prevalent. In the logistic regression analysis, EN was not associated with an increase in GI complications (P = 0.09). Only three patients developed intestinal ischemia (one without EN and two on EN). CONCLUSIONS: Undernutrition is prevalent among children on ECMO, mainly in infants <2 years. EN is not associated with severe gastrointestinal complications or higher mortality in these children.

Energy-Dense versus Routine Enteral Nutrition in the Critically Ill.

BACKGROUND: The effect of delivering nutrition at different calorie levels during critical illness is uncertain, and patients typically receive less than the recommended amount. METHODS: We conducted a multicenter, double-blind, randomized trial, involving adults undergoing mechanical ventilation in 46 Australian and New Zealand intensive care units (ICUs), to evaluate energy-dense (1.5 kcal per milliliter) as compared with routine (1.0 kcal per milliliter) enteral nutrition at a dose of 1 ml per kilogram of ideal body weight per hour, commencing at or within 12 hours of the initiation of nutrition support and continuing for up to 28 days while the patient was in the ICU. The primary outcome was all-cause mortality within 90 days. RESULTS: There were 3957 patients included in the modified intention-to-treat analysis (1971 in the 1.5-kcal group and 1986 in the 1.0-kcal group). The volume of enteral nutrition delivered during the trial was similar in the two groups; however, patients in the 1.5-kcal group received a mean (±SD) of 1863±478 kcal per day as compared with 1262±313 kcal per day in the 1.0-kcal group (mean difference, 601 kcal per day; 95% confidence interval [CI], 576 to 626). By day 90, a total of 523 of 1948 patients (26.8%) in the 1.5-kcal group and 505 of 1966 patients (25.7%) in the 1.0-kcal group had died (relative risk, 1.05; 95% CI, 0.94 to 1.16; P=0.41). The results were similar in seven predefined subgroups. Higher calorie delivery did not affect survival time, receipt of organ support, number of days alive and out of the ICU and hospital or free of organ support, or the incidence of infective complications or adverse events. CONCLUSIONS: In patients undergoing mechanical ventilation, the rate of survival at 90 days associated with the use of an energy-dense formulation for enteral delivery of nutrition was not higher than that with routine enteral nutrition. (Funded by National Health and Medical Research Institute of Australia and the Health Research Council of New Zealand; TARGET ClinicalTrials.gov number, NCT02306746 .).

Personalized nutrition approach in pediatrics: a narrative review.

Dietary habits represent the main determinant of health. Although extensive research has been conducted to modify unhealthy dietary behaviors across the lifespan, obesity and obesity-associated comorbidities are increasingly observed worldwide. Individually tailored interventions are nowadays considered a promising frontier for nutritional research. In this narrative review, the technologies of importance in a pediatric clinical setting are discussed. The first determinant of the dietary balance is represented by energy intakes matching individual needs. Most emerging studies highlight the opportunity to reconsider the widely used prediction equations of resting energy expenditure. Artificial Neural Network approaches may help to disentangle the role of single contributors to energy expenditure. Artificial intelligence is also useful in the prediction of the glycemic response, based on the individual microbiome. Other factors further concurring to define individually tailored nutritional needs are metabolomics and nutrigenomic. Since most available data come from studies in adult groups, new efforts should now be addressed to integrate all these aspects to develop comprehensive and-above all-effective interventions for children. IMPACT: Personalized dietary advice, specific to individuals, should be more effective in the prevention of chronic diseases than general recommendations about diet. Artificial Neural Networks algorithms are technologies of importance in a pediatric setting that may help practitioners to provide personalized nutrition. Other approaches to personalized nutrition, while promising in adults and for basic research, are still far from practical application in pediatrics.

Association Between Anticholinergic Drug Burden and Adequacy of Enteral Nutrition in Critically Ill, Mechanically Ventilated Pediatric Patients.

OBJECTIVES: Enteral nutrition delivery is limited by intolerance and interruptions in critically ill children. Anticholinergic properties of frequently administered medications may contribute to altered gastric motility and enteral nutrition intolerance in this population. We examined the association between the anticholinergic burden of administered medications using the Anticholinergic Drug Scale and adequacy of enteral nutrition delivery. DESIGN: Secondary analysis of data from a previously characterized PICU cohort. SETTING: Multidisciplinary PICU in a quaternary academic medical center. PATIENTS: Younger than or equal to 18 years, on mechanical ventilation and received enteral nutrition within the first 3 days of PICU admission. MEASUREMENTS AND MAIN RESULTS: Daily Anticholinergic Drug Scale score, demographic data, and clinical data were obtained from the primary study. Percent enteral energy adequacy ([kcal delivered ÷ kcal prescribed] × 100) during the first 3 days of PICU admission was calculated. Forty-two patients received enteral nutrition, with median age (interquartile range) 5 years (1.09-12.54 yr), and 62% were male. Median Anticholinergic Drug Scale score was inversely correlated with energy adequacy, with a median 9% decline in energy adequacy per 1-point increase in Anticholinergic Drug Scale score (coefficient, -9.3; 95% CI, -13.43 to -5.27; R2 = 0.35; p < 0.0001). Median hours of enteral nutrition interruptions directly correlated with Anticholinergic Drug Scale score (coefficient, 1.5; 95% CI, 0.531-2.54; R2 = 0.19; p = 0.004). Severity score was greater in patients with less than or equal to 25% enteral energy adequacy and directly correlated with median Anticholinergic Drug Scale score. CONCLUSIONS: Anticholinergic burden from medications administered in the PICU is a potentially modifiable factor for suboptimal enteral nutrition delivery.

The effects of nutritional support baskets on growth parameters of under five years old children with malnutrition and low socio-economic status.

BACKGROUND AND OBJECTIVES: Although malnutrition is globally widespread among children, there is no consensus on the most effective intervention for improving a child's growth. The present study is designed to investigate the effects of nutritional support basketson growth indices of malnourished children. METHODS: This is a field trial conducted on 3667 malnourished children (0-60 months) for 9months, between 2017 and 2018, in Fars province of Iran. Weight-for-age, height-for-age, weight-for-height and body mass index-for age indices were assessed before and after the intervention with nutritional support baskets, which contains 600 kcal/day. RESULTS: The baseline prevalence of moderate/severeunderweight, stunting and wasting were 31.5%, 33.3% and 28.9%, respectively. After the intervention, the prevalence non-significantly reduced to 25.5%, 31.7% and 20.35%, respectively (p > 0.05). The intervention is associated with a non-significant reduction in the prevalence of underweight and wasting in 0-23 months children, and a non-significant reduction in the prevalence of underweight, stunting and wasting in 24-60 months children. Furthermore, the intervention is associated with a non-significant reduction in the prevalence of underweight, stunting and wasting in girls, and a non-significant reduction in the prevalence of underweight and wasting in boys. CONCLUSIONS: Nutrition support was effective in improving malnutrition indices of children; however, the results were non-significant. Further studies with longer period and control group areneeded to support the effectiveness of nutrition support in children.

The influence of nutrition on clinical outcomes in children with cancer.

Adequate and appropriate nutrition is essential for growth and development in children; all put at risk in those with cancer. Overnutrition and undernutrition at diagnosis raise the risk of increased morbidity and mortality during therapy and beyond. All treatment modalities can jeopardize nutritional status with potentially adverse effects on clinical outcomes. Accurate assessment of nutritional status and nutrient balance is essential, with remedial interventions delivered promptly when required. Children with cancer in low- and middle-income countries (LMICs) are especially disadvantaged with concomitant challenges in the provision of nutritional support. Cost-effective advances in the form of ready-to-use therapeutic foods (RUTF) may offer solutions. Studies in LMICs have defined a critical role for the gut microbiome in the causation of undernutrition in children and have demonstrated a beneficial effect of selected RUTF in redressing the imbalanced microbiota and improving nutritional status. Challenges in high-income countries relate both to concerns about the potential disadvantage of preexisting obesity in those newly diagnosed and to undernutrition identified at diagnosis and during treatment. Much remains to be understood but the prospects are bright for offsetting malnutrition in children with cancer, resulting in enhanced opportunity for healthy survival.

The relevance of nutrition to pediatric oncology: A cancer control perspective.

It is indisputable that adequate and appropriate nutrition is fundamental to the health, growth, and development of infants, children, and adolescents, including those with cancer. Nutrition has a role in most of the accepted components of the cancer control spectrum, from prevention through to palliation. The science of nutrigenomics, nutrigenetics, and bioactive foods (phytochemicals), and how nutrition affects cancer biology and cancer treatment, is growing. Nutritional epigenetics is giving us an understanding that there are possible primary prevention strategies for pediatric cancers, especially during conception and pregnancy, which need to be studied. Primary prevention of cancer in adults, such as colorectal cancer, should commence early in childhood, given the long gestation of nutritionally related cancers. Obesity avoidance is definitely a target for both pediatric and adult cancer prevention, commencing in childhood. There is now compelling evidence that the nutritional status of children with cancer, both overweight and underweight, does affect cancer outcomes. This is a potentially modifiable prognostic factor. Consistent longitudinal nutritional assessment of patients from diagnosis through treatment and long-term follow-up is required so that interventions can be implemented and evaluated. While improving, there remains a dearth of basic and clinical nutritional research in pediatric oncology. The perspective of evaluating nutrition as a cancer control factor is discussed in this article.

Environmental exposures and child and maternal gut microbiota in rural Malawi.

BACKGROUND: Gut microbiota composition is associated with child health, but the effect of the environment on microbiota composition is not well understood. Few studies have been conducted in low-income settings where childhood malnutrition is common and possibly related to microbiota composition. OBJECTIVES: To investigate whether gut microbiota composition in young children and their mothers is associated with different environmental exposures in rural Malawi. We hypothesized that more adverse environmental exposures would be associated with lower levels of microbiota maturity and diversity. METHODS: Faecal samples from up to 631 children and mothers participating in a nutrition intervention trial were collected at 1, 6, 12, 18, and 30 months (children) and at 1 month (mothers) after birth and analysed for microbiota composition with 16S rRNA sequencing. Bacterial OTU and genus abundances, measures of microbiota maturity and diversity, and UniFrac distances were compared between participants with different environmental exposures. The exposure variables included socio-economic status, water source, sanitary facility, domestic animals, maternal characteristics, season, antibiotic use, and delivery mode. RESULTS: Measures of microbiota maturity and diversity in children were inversely associated with maternal education at 6, 18, and 30 months and did not otherwise differ consistently between participants with different environmental exposures. Phylogenetic distance was related to season of stool sample collection at all time points. At the level of individual OTUs and genera, season of stool sample collection, type of water source, and maternal education showed most associations with child gut microbiota, while HIV status was the most important predictor of relative OTU and genus abundances in mothers. CONCLUSION: The results do not support the hypothesis that adverse environmental exposures are broadly associated with lower microbiota maturity and diversity but suggest that environmental exposures influence the abundance of several bacterial OTUs and genera and that low maternal education is associated with higher microbiota maturity and diversity.

Review of nutritional status, body composition, and effects of antineoplastic drug disposition.

The overall survival for children with cancer in high income countries is excellent. However, there are many disparities that may negatively affect survival, which are particularly problematic in low income countries, such as nutritional status at diagnosis and throughout therapy. Nutritional status as well as concomitant foods, supplements, and medications may play a role in overall exposure and response to chemotherapy. Emerging science around the microbiome may also play a role and should be further explored as a contributor to disease progression and therapeutic response. This article highlights some of these issues and proposes additional areas of research relevant to nutritional status and pharmacology that are needed in pediatric oncology.

Energy and protein requirements for children with CKD stages 2-5 and on dialysis-clinical practice recommendations from the Pediatric Renal Nutrition Taskforce.

Dietary management in pediatric chronic kidney disease (CKD) is an area fraught with uncertainties and wide variations in practice. Even in tertiary pediatric nephrology centers, expert dietetic input is often lacking. The Pediatric Renal Nutrition Taskforce (PRNT), an international team of pediatric renal dietitians and pediatric nephrologists, was established to develop clinical practice recommendations (CPRs) to address these challenges and to serve as a resource for nutritional care. We present CPRs for energy and protein requirements for children with CKD stages 2-5 and those on dialysis (CKD2-5D). We address energy requirements in the context of poor growth, obesity, and different levels of physical activity, together with the additional protein needs to compensate for dialysate losses. We describe how to achieve the dietary prescription for energy and protein using breastmilk, formulas, food, and dietary supplements, which can be incorporated into everyday practice. Statements with a low grade of evidence, or based on opinion, must be considered and adapted for the individual patient by the treating physician and dietitian according to their clinical judgment. Research recommendations have been suggested. The CPRs will be regularly audited and updated by the PRNT.

Early versus late parenteral nutrition for critically ill term and late preterm infants.

BACKGROUND: Recently conducted randomised controlled trials (RCTs) suggest that late commencement of parenteral nutrition (PN) may have clinical benefits in critically ill adults and children. However, there is currently limited evidence regarding the optimal timing of commencement of PN in critically ill term and late preterm infants. OBJECTIVES: To evaluate the benefits and safety of early versus late PN in critically ill term and late preterm infants. SEARCH METHODS: We used the standard search strategy of Cochrane Neonatal to search the Cochrane Central Register of Controlled Trials (5 April 2019), MEDLINE Ovid (1966 to 5 April 2019), Embase Ovid (1980 to 5 April 2019), EMCare (1995 to 5 April 2019) and MEDLINE via PubMed (1966 to 5 April 2019). We searched for ongoing or recently completed clinical trials, and also searched the grey literature and reference lists of relevant publications. SELECTION CRITERIA: We included RCTs comparing early versus late initiation of PN in term and late preterm infants. We defined early PN as commencing within 72 hours of admission, and late PN as commencing after 72 hours of admission. Infants born at 37 weeks' gestation or more were defined as term, and infants born between 34 and 36+6 weeks' gestation were defined as late preterm. DATA COLLECTION AND ANALYSIS: Two review authors independently selected the trials, extracted the data and assessed the risk of bias. Treatment effects were expressed using risk ratio (RR) and risk difference (RD) for dichotomous outcomes and mean difference (MD) for continuous data. The quality of the evidence was assessed using the GRADE approach. MAIN RESULTS: Two RCTs were eligible for inclusion. Data were only available from a subgroup (including 209 term infants) from one RCT in children (aged from birth to 17 years) conducted in Belgium, the Netherlands and Canada. In that RCT, children with medium to high risk of malnutrition were included if a stay of 24 hours or more in the paediatric intensive care unit (PICU) was expected. Early PN and late PN were defined as initiation of PN within 24 hours and after day 7 of admission to PICU, respectively. The risk of bias for the study was considered to be low for five domains and high for two domains. The subgroup of term infants that received late PN had significantly lower risk of in-hospital all-cause mortality (RR 0.35, 95% confidence interval (CI) 0.14 to 0.87; RD -0.10, 95% CI -0.18 to -0.02; number needed to treat for an additional beneficial outcome (NNTB) = 10; 1 trial, 209 participants) and neonatal mortality (death from any cause in the first 28 days since birth) (RR 0.29, 95% CI 0.10 to 0.88; RD -0.09, 95% CI -0.16 to -0.01; NNTB = 11; 1 trial, 209 participants). There were no significant differences in rates of healthcare-associated blood stream infections, growth parameters and duration of hospital stay between the two groups. Neurodevelopmental outcomes were not reported. The quality of evidence was considered to be low for all outcomes, due to imprecision (owing to the small sample size and wide confidence intervals) and high risk of bias in the included studies. AUTHORS' CONCLUSIONS: Whilst late commencement of PN in term and late preterm infants may have some benefits, the quality of the evidence was low and hence our confidence in the results is limited. Adequately powered RCTs, which evaluate short-term as well as long-term neurodevelopmental outcomes, are needed.

Can broad-spectrum multinutrients treat symptoms of antenatal depression and anxiety and improve infant development? Study protocol of a double blind, randomized, controlled trial (the 'NUTRIMUM' trial).

BACKGROUND: Untreated antenatal depression and anxiety can be associated with short and long term health impacts on the pregnant woman, her infant and the rest of the family. Alternative interventions to those currently available are needed. This clinical trial aims to investigate the efficacy and safety of a broad-spectrum multinutrient formula as a treatment for symptoms of depression and anxiety in pregnant women and to determine the impact supplementation has on the general health and development of the infant. METHODS: This randomised, controlled trial will be conducted in Canterbury, New Zealand between April 2017 and June 2022. One hundred and twenty women aged over 16 years, between 12 and 24 weeks gestation and who score ≥ 13 on the Edinburgh Postnatal Depression Scale (EPDS) will be randomly assigned to take the intervention (n = 60) or an active control formula containing iodine and riboflavin (n = 60) for 12 weeks. After 12 weeks, participants can enter an open-label phase until the birth of their infant and naturalistically followed for the first 12 months postpartum. Infants will be followed until 12 months of age. Randomisation will be computer-generated, with allocation concealment by opaque sequentially numbered envelopes. Participants and the research team including data analysts will be blinded to group assignment. The EPDS and the Clinical Global Impressions Scale of Improvement (CGI-I) will be the maternal primary outcome measures of this study and will assess the incidence of depression and anxiety and the improvement of symptomatology respectively. Generalized linear mixed effects regression models will analyse statistical differences between the multinutrient and active control group on an intent-to-treat basis. A minimum of a three-point difference in EPDS scores between the groups will identify clinical significance. Pregnancy outcomes, adverse events and side effects will also be monitored and reported. DISCUSSION: Should the multinutrient formula be shown to be beneficial for both the mother and the infant, then an alternative treatment option that may also improve the biopsychosocial development of their infants can be provided for pregnant women experiencing symptoms of depression and anxiety. TRIAL REGISTRATION: Trial ID: ACTRN12617000354381 ; prospectively registered at Australian New Zealand Clinical Trials Registry on 08/03/2017.

Early Enteral Nutrition Is Associated With Improved Clinical Outcomes in Critically Ill Children: A Secondary Analysis of Nutrition Support in the Heart and Lung Failure-Pediatric Insulin Titration Trial.

OBJECTIVES: The impact of early enteral nutrition on clinical outcomes in critically ill children has not been adequately described. We hypothesized that early enteral nutrition is associated with improved clinical outcomes in critically ill children. DESIGN: Secondary analysis of the Heart and Lung Failure-Pediatric Insulin Titration randomized controlled trial. SETTING: Thirty-five PICUs. PATIENTS: Critically ill children with hyperglycemia requiring inotropic support and/or invasive mechanical ventilation who were enrolled for at least 48 hours with complete nutrition data. INTERVENTIONS: Subjects received nutrition via guidelines that emphasized enteral nutrition and were classified into early enteral nutrition (enteral nutrition within 48 hr of study randomization) and no early enteral nutrition (enteral nutrition after 48 hr of study randomization, or no enteral nutrition at any time). MEASUREMENTS AND MAIN RESULTS: Of 608 eligible subjects, 331 (54%) received early enteral nutrition. Both early enteral nutrition and no early enteral nutrition groups had similar daily caloric intake over the first 8 study days (median, 36 vs 36 kcal/kg/d; p = 0.93). After controlling for age, body mass index z scores, primary reason for ICU admission, severity of illness, and mean Vasopressor-Inotrope Score at the time of randomization, and adjusting for site, early enteral nutrition was associated with lower 90-day hospital mortality (8% vs 17%; p = 0.007), more ICU-free days (median, 20 vs 17 d; p = 0.02), more hospital-free days (median, 8 vs 0 d; p = 0.003), more ventilator-free days (median, 21 vs 19 d; p = 0.003), and less organ dysfunction (median maximum Pediatric Logistic Organ Dysfunction, 11 vs 12; p < 0.001). CONCLUSIONS: In critically ill children with hyperglycemia requiring inotropic support and/or mechanical ventilation, early enteral nutrition was independently associated with better clinical outcomes.

Stress Ulcer Prophylaxis in Critically Ill Children: A Multicenter Observational Study.

OBJECTIVE: To describe current stress ulcer prophylaxis practice in Canadian PICUs. DESIGN: Multicenter cohort study. We defined stress ulcer prophylaxis as the use of a proton-pump inhibitor, histamine-2 receptor antagonist, or sucralfate within the first 2 PICU days among children who had not been on these medications at home and had no evidence of gastrointestinal bleeding. SETTING: Seven PICUs in Canada. PATIENTS: Three hundred seventy-eight children requiring mechanical ventilation. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Children were ventilated for a median (interquartile range) of 2 days (1-6 d) and stayed in the PICU for a median (interquartile range) of 4 days (2-10 d). The median (interquartile range) age was 1.3 years (0.3-6.7 yr). Seventy percent of all children received acid suppression during their PICU stay. One hundred sixty-seven (54%) of the 309 children eligible for stress ulcer prophylaxis received it. Histamine-2 receptor antagonists were the most frequently used class (66%), followed by proton-pump inhibitors (47%) and sucralfate (4%), and 20% received more than one class. Stress ulcer prophylaxis was continued on the PICU transfer orders for 34% of these children. Children who received prophylaxis were older and had a higher Pediatric Risk of Mortality III score, more often received nonsteroidal anti-inflammatory drugs and systemic corticosteroids and received less enteral nutrition. In multivariate analysis, age and invasive mechanical ventilation were independently associated with an increased likelihood of receiving stress ulcer prophylaxis and receiving feeds was independently associated with a decreased likelihood of receiving stress ulcer prophylaxis. Gastrointestinal bleeding was reported in 21 (6%) of 378 children; three (0.8%) were clinically important. Eighteen percent were treated for a new respiratory tract infection, and 1% developed Clostridium difficile-associated diarrhea. CONCLUSIONS: Stress ulcer prophylaxis is common in Canadian PICUs. Clinically important gastrointestinal bleeding and C. difficile-associated diarrhea are rare, and the utility of routine prophylaxis should be examined.

Developing a national research agenda to reduce consumption of sugar-sweetened beverages and increase safe water access and consumption among 0- to 5-year-olds: a mixed methods approach.

OBJECTIVE: Sugar-sweetened beverage (SSB) consumption in early childhood is a public health concern. Adequate hydration in early childhood is also important. We developed a national research agenda to improve beverage consumption patterns among 0-5-year-olds. This article focuses on the process used to develop this research agenda. DESIGN: A mixed methods, multi-step process was used to develop the research agenda, including: (i) a scientific advisory committee; (ii) systematic reviews on strategies to reduce SSB consumption and increase water access and consumption; (iii) two stakeholder surveys to first identify and then rank strategies to reduce SSB consumption and increase water access and consumption; (iv) key informant interviews to better understand determinants of beverage consumption and strategies to improve beverage consumption patterns among high-risk groups; (v) an in-person convening with experts; and (vi) developing the final research agenda. SETTING: This process included research and stakeholders from across the United States. PARTICIPANTS: A total of 276 participants completed survey 1 and 182 participants completed survey 2. Key informant interviews were conducted with 12 stakeholders. Thirty experts attended the convening, representing academia, government, and non-profit sectors. RESULTS: Thirteen key issue areas and 59 research questions were developed. Priority topics were beverage consumption recommendations, fruit-flavoured drink consumption, interventions tailored to high-risk groups, and family engagement in childcare. CONCLUSIONS: This research agenda lays the groundwork for research efforts to improve beverage patterns of young children. The methods used can be a template to develop research agendas for other public health issues.

Diet and nutrition information and support needs in pelvic radiotherapy: A systematic, mixed-methods review.

INTRODUCTION: This study aimed to review diet and nutrition information and support needs of cancer patients who receive pelvic radiotherapy to inform the development of interventions to improve this area of care. METHODS: The systematic review followed the PRISMA guidelines. Six electronic databases were searched for peer-reviewed studies of any design that assessed diet and nutrition needs after a pelvic cancer diagnosis. Narrative synthesis was used to integrate findings. RESULTS: Thirty studies (12 quantitative, 15 qualitative, 3 mixed-methods) were included. Four themes, "content of dietary information"; "sources of information"; "sustaining dietary change"; and "views on the role of diet post-treatment," summarised evidence about provision of nutritional guidance following diagnosis, but also contrasting views about the role of diet post-diagnosis. Qualitative studies contributed considerably more to the synthesis, compared to quantitative studies. Included studies were of moderate to good quality; selection bias in quantitative studies and poor evidence of credibility and dependability in qualitative studies were highlighted. CONCLUSION: There is some evidence of lack of nutrition support in pelvic cancer survivors, but methodological limitations of included studies may have had an impact on the findings. Future, prospective studies that focus on diet and nutrition needs post-diagnosis are warranted to improve care.

Proof-of-concept study of the efficacy of a microbiota-directed complementary food formulation (MDCF) for treating moderate acute malnutrition.

BACKGROUND: Childhood undernutrition remains a significant global health challenge accounting for over half of all under 5 child mortality. Moderate acute malnutrition (MAM), which leads to wasting [weight-for-length z-scores (WLZ) between - 2 and - 3], affects 33 million children under 5 globally and more than 2 million in Bangladesh alone. We have previously reported that acute malnutrition in this population is associated with gut microbiota immaturity, and in a small, 1-month pre-proof-of-concept (POC) study demonstrated that a microbiota-directed complementary food formulation (MDCF-2) was able to repair this immaturity, promote weight gain and increase plasma biomarkers and mediators of healthy growth. Here we describe the design controlled feeding study that tests whether MDCF-2 exhibits superior efficacy (ponderal growth, host biomarkers of a biological state) than a conventional Ready-to-use Supplementary Food (RUSF) in children with MAM over intervention period of 3 months. METHODS: Two separate cohorts of 12-18-month-old children will be enrolled: 124 with primary MAM, and 124 with MAM after having been treated for severe acute malnutrition (post-SAM MAM). We have established several field sites in an urban slum located in the Mirpur district of Dhaka, Bangladesh and at a rural site, Kurigram in the north of Bangladesh. The two groups of children receiving MDCF-2 and RUSF will be compared at baseline (pre-intervention), after 1 month, at the end of intervention (3 months), 1 month after cessation of intervention, and every 6 months thereafter for 4 years. DISCUSSION: This study will determine whether daily, controlled administration of MDCF-2 for 3 months provides superior improvements in weight gain, microbiota repair, and elevated levels of key plasma biomarkers/mediators of healthy growth compared to the control RUSF formulation. The pathogenesis of MAM is poorly defined and there are currently no WHO-approved treatments; results from the current study of children with primary MAM and post-SAM MAM will shed light on the effects of the gut microbiota on childhood growth/development and will provide a knowledge base that may help improve complementary feeding practices. TRIAL REGISTRATION: The primary MAM and post-SAM MAM trials are registered in Clintrials.gov (NCT04015999 and NCT04015986, registered on July 11, 2019, retrospectively registered).