Stress Ulcer Prophylaxis Versus Placebo-A Blinded Pilot Randomized Controlled Trial to Evaluate the Safety of Two Strategies in Critically Ill Infants With Congenital Heart Disease.

OBJECTIVES: The routine use of stress ulcer prophylaxis (SUP) in infants with congenital heart disease (CHD) in the cardiac ICU (CICU) is controversial. We aimed to conduct a pilot study to explore the feasibility of performing a subsequent larger trial to assess the safety and efficacy of withholding SUP in this population (NCT03667703). DESIGN, SETTING, PATIENTS: Single-center, prospective, double-blinded, parallel group (SUP vs. placebo), pilot randomized controlled pilot trial (RCT) in infants with CHD admitted to the CICU and anticipated to require respiratory support for greater than 24 hours. INTERVENTIONS: Patients were randomized 1:1 (stratified by age and admission type) to receive a histamine-2 receptor antagonist or placebo until respiratory support was discontinued, up to 14 days, or transfer from the CICU, if earlier. MEASUREMENTS AND MAIN RESULTS: Feasibility was defined a priori by thresholds of screening rate, consent rate, timely drug allocation, and protocol adherence. The safety outcome was the rate of clinically significant upper gastrointestinal (UGI) bleeding. We screened 1,426 patients from February 2019 to March 2022; of 132 eligible patients, we gained informed consent in 70 (53%). Two patients did not require CICU admission after obtaining consent, and the remaining 68 patients were randomized to SUP (n = 34) or placebo (n = 34). Ten patients were withdrawn early, because of a change in eligibility (n = 3) or open-label SUP use (n = 7, 10%). Study procedures were completed in 58 patients (89% protocol adherence). All feasibility criteria were met. There were no clinically significant episodes of UGI bleeding during the pilot RCT. The percentage of patients with other nonserious adverse events did not differ between groups. CONCLUSIONS: Withholding of SUP in infants with CHD admitted to the CICU was feasible. A larger multicenter RCT designed to confirm the safety of this intervention and its impact on incidence of UGI bleeding, gastrointestinal microbiome, and other clinical outcomes is warranted.

Long-Term Functional Outcomes at 1-Year After Hospital Discharge in Critically Ill Neonates With Congenital Diaphragmatic Hernia.

OBJECTIVES: Congenital diaphragmatic hernia (CDH) is a birth defect associated with long-term morbidity. Our objective was to examine longitudinal change in Functional Status Scale (FSS) after hospital discharge in CDH survivors. DESIGN: Single-center retrospective cohort study. SETTING: Center for comprehensive CDH management at a quaternary, free-standing children's hospital. PATIENTS: Infants with Bochdalek CDH were admitted to the ICU between January 2009 and December 2019 and survived until hospital discharge. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: One hundred forty-two infants (58% male, mean birth weight 3.08 kg, 80% left-sided defects) met inclusion criteria. Relevant clinical data were extracted from the medical record to calculate FSS (primary outcome) at hospital discharge and three subsequent outpatient follow-up time points. The median (interquartile range [IQR]) FSS score at hospital discharge was 8.0 (7.0-9.0); 39 patients (27.5%) had at least moderate impairment (FSS ≥ 9). Median (IQR) FSS at 0- to 6-month ( n = 141), 6- to 12-month ( n = 141), and over 12-month ( n = 140) follow-up visits were 7.0 (7.0-8.0), 7.0 (6.0-8.0), and 6.0 (6.0-7.0), respectively. Twenty-one patients (15%) had at least moderate impairment at over 12-month follow-up; median composite FSS scores in the over 12-month time point decreased by 2.0 points from hospital discharge. Median feeding domain scores improved by 1.0 (1.0-2.0), whereas other domain scores remained without impairment. Multivariable analysis demonstrated right-sided, C- or D-size defects, extracorporeal membrane oxygenation use, cardiopulmonary resuscitation, and chromosomal anomalies were associated with impairment. CONCLUSIONS: The majority of CDH survivors at our center had mild functional status impairment (FSS ≤ 8) at discharge and 1-year follow-up; however, nearly 15% of patients had moderate impairment during this time period. The feeding domain had the highest level of functional impairment. We observed unchanged or improving functional status longitudinally over 1-year follow-up after hospital discharge. Longitudinal outcomes will guide interdisciplinary management strategies in CDH survivors.

Development and validation of a quantitative choline food frequency questionnaire for use with drinking and non-drinking pregnant women in Cape Town, South Africa.

BACKGROUND: Although animal and human studies have demonstrated interactions between dietary choline and fetal alcohol spectrum disorders, dietary choline deficiency in pregnancy is common in the US and worldwide. We sought to develop and validate a quantitative food frequency questionnaire (QFFQ) to estimate usual daily choline intake in pregnant mothers. METHODS: A panel of nutrition experts developed a Choline-QFFQ food item list, including sources with high choline content and the most commonly consumed choline-containing foods in the target population. A data base for choline content of each item was compiled. For reliability and validity testing in a prospective longitudinal cohort, 123 heavy drinking Cape Coloured pregnant women and 83 abstaining/light-drinking controls were recruited at their first antenatal clinic visit. At 3 prenatal study visits, each gravida was interviewed about alcohol, smoking, and drug use, and administered a 24-hour recall interview and the Choline-QFFQ. RESULTS: Across all visits and assessments, > 78% of heavy drinkers and controls reported choline intake below the Dietary Reference Intakes adequate intake level (450 mg/day). Women reported a decrease in choline intake over time on the QFFQ. Reliability of the QFFQ across visits was good-to-acceptable for 2 of 4 group-level tests and 4 of 5 individual-level tests for both drinkers and controls. When compared with 24-hr recall data, validity of the QFFQ was good-to-acceptable for 3 of 4 individual-level tests and 3 of 5 group-level tests. For controls, validity was good-to-acceptable for all 4 individual-level tests and all 5 group-level tests. CONCLUSIONS: To our knowledge, this is the first quantitative choline food frequency screening questionnaire to be developed and validated for use with both heavy and non-drinking pregnant women and the first to be used in the Cape Coloured community in South Africa. Given the high prevalence of inadequate choline intake and the growing evidence that maternal choline supplementation can mitigate some of the adverse effects of prenatal alcohol exposure, this tool may be useful for both research and future clinical outreach programs.

Body Composition in Children with Chronic Illness: Accuracy of Bedside Assessment Techniques.

OBJECTIVE: To evaluate the accuracy of estimated fat mass and fat-free mass from bedside methods compared with reference methods in children with chronic illnesses. STUDY DESIGN: Fat mass and fat-free mass values were obtained by skinfold, bioelectrical impedance analysis (BIA), dual-energy x-ray absorptiometry (DXA), and deuterium dilution method in children with spinal muscular atrophy, intestinal failure, and post hematopoietic stem cell transplantation (HSCT). Spearman's correlation and agreement analyses were performed between (1) fat mass values estimated by skinfold equations and by DXA and (2) fat-free mass values estimated by BIA equations and by DXA and deuterium dilution methods. Limits of agreement between estimating and reference methods within ±20% were deemed clinically acceptable. RESULTS: Fat mass and fat-free mass values from 90 measurements in 56 patients, 55% male, and median age of 11.6 years were analyzed. Correlation coefficients between the skinfold-estimated fat mass values and DXA were 0.93-0.94 and between BIA-estimated fat-free mass values and DXA were 0.92-0.97. Limits of agreement between estimated and DXA values of fat mass and fat-free mass were greater than ±20% for all equations. Correlation coefficients between estimated fat-free mass values and deuterium dilution method in 35 encounters were 0.87-0.91, and limits of agreement were greater than ±20%. CONCLUSION: Estimated body composition values derived from skinfold and BIA may not be reliable in children with chronic illnesses. An accurate noninvasive method to estimate body composition in this cohort is desirable.

Maternal Alcohol Use and Nutrition During Pregnancy: Diet and Anthropometry.

BACKGROUND: Despite known risks of prenatal nutritional deficiencies and studies documenting increased prevalence of poor dietary intake among nonpregnant alcohol abusers, the nutritional status of heavy drinking pregnant women remains largely unstudied. Animal models have found interactions between prenatal ethanol exposure and micronutrients, such as choline, folate, B12, and iron, and human studies have reported that lower maternal weight and body mass confer increased fetal alcohol-related risk. METHODS: One hundred and twenty-three heavy drinking Cape Coloured pregnant women and 83 abstaining controls were recruited at their first antenatal clinic visit. At 3 prenatal study visits, each gravida was interviewed about alcohol, smoking, and drug use and weight, height, and arm skinfolds were measured. Dietary intakes of energy, protein, fat, and major micronutrients were assessed from three 24-hour recall interviews. RESULTS: The majority of women gained less than the recommended 0.42 kg/wk during pregnancy. Whereas methamphetamine use was associated with smaller biceps skinfolds, an indicator of body fat, alcohol consumption was not related to any anthropometric indicator. Alcohol was related to higher intake of phosphorus, choline, and vitamins B12 and D. Alcohol, cigarette, and methamphetamine use were related to lower vitamin C intake. Insufficient intake was reported by >85% of women for 10 of 22 key nutrients, and >50% for an additional 3 nutrients. CONCLUSIONS: Alcohol consumption during pregnancy was not associated with meaningful changes in diet or anthropometric measures in this population, suggesting that poor nutrition among drinkers does not confound the extensively reported effects of prenatal alcohol exposure on growth and neurobehavior. The poor gestational weight gain and high rates of insufficient intake for several nutrients in both the alcohol-exposed and control groups are also of public health importance.

Nutritional Status Based on Body Mass Index Is Associated With Morbidity and Mortality in Mechanically Ventilated Critically Ill Children in the PICU.

OBJECTIVE: To determine the influence of admission anthropometry on clinical outcomes in mechanically ventilated children in the PICU. DESIGN: Data from two multicenter cohort studies were compiled to examine the unique contribution of nutritional status, defined by body mass index z score, to 60-day mortality, hospital-acquired infections, length of hospital stay, and ventilator-free days, using multivariate analysis. SETTING: Ninety PICUs from 16 countries with eight or more beds. PATIENTS: Children aged 1 month to 18 years, admitted to each participating PICU and requiring mechanical ventilation for more than 48 hours. MEASUREMENTS AND MAIN RESULTS: Data from 1,622 eligible patients, 54.8% men and mean (SD) age 4.5 years (5.1), were analyzed. Subjects were classified as underweight (17.9%), normal weight (54.2%), overweight (14.5%), and obese (13.4%) based on body mass index z score at admission. After adjusting for severity of illness and site, the odds of 60-day mortality were higher in underweight (odds ratio, 1.53; p < 0.001) children. The odds of hospital-acquired infections were higher in underweight (odds ratio, 1.88; p = 0.008) and obese (odds ratio, 1.64; p < 0.001) children. Hazard ratios for hospital discharge were lower among underweight (hazard ratio, 0.71; p < 0.001) and obese (hazard ratio, 0.82; p = 0.04) children. Underweight was associated with 1.3 (p = 0.001) and 1.6 (p < 0.001) fewer ventilator-free days than normal weight and overweight, respectively. CONCLUSIONS: Malnutrition is prevalent in mechanically ventilated children on admission to PICUs worldwide. Classification as underweight or obese was associated with higher risk of hospital-acquired infections and lower likelihood of hospital discharge. Underweight children had a higher risk of mortality and fewer ventilator-free days.

Enteral Nutrition and Acid-Suppressive Therapy in the PICU: Impact on the Risk of Ventilator-Associated Pneumonia.

OBJECTIVE: Enteral nutrition has been implicated as a risk factor for ventilator-associated pneumonia. We explored the prevalence of ventilator-associated pneumonia and its association with clinical and nutrition-related therapies in mechanically ventilated children. DESIGN: Prospective, multicenter, cohort study. SETTING: Fifty-nine PICU in 15 countries. PATIENTS: Children less than 18 years old, mechanically ventilated for more than 48 hours. INTERVENTIONS: None. Multivariable logistic regression to determine factors associated with ventilator-associated pneumonia. MEASUREMENTS AND MAJOR RESULTS: Data are presented as median (interquartile range) or counts (%). We enrolled 1,245 subjects (45% women; 42% surgical), age 20 months (4-84 mo), and duration of mechanical ventilation 7 days (3-13 d). Culture-positive ventilator-associated pneumonia was diagnosed in 80 patients (6.4%); duration of mechanical ventilation for this subgroup was 17 days (8-39 d). Enteral nutrition was delivered in 985 patients (79%), initiated within 48 hours in 592 patients (60%), and via postpyloric route in 354 patients (36%). Acid-suppressive agents were used in 763 patients (61%). The duration of enteral nutrition (p = 0.21), route (gastric vs postpyloric) of delivery (p = 0.94), severity of illness (p = 0.17), and diagnostic category on admission (p = 0.31) were not associated with ventilator-associated pneumonia. After adjusting for enteral nutrition days, illness severity, and site, ventilator-associated pneumonia was significantly associated with mechanical ventilation more than 10 days (odds ratio, 3.7; 95% CI, 2.2-6.5; p < 0.001), PICU length of stay more than 10 days (odds ratio, 1.8; 95% CI, 1.1-3.1; p = 0.029), and the use of acid-suppressive medication (odds ratio, 2.0; 95% CI, 1.2-3.6; p = 0.011). CONCLUSIONS: Ventilator-associated pneumonia was diagnosed in 6.5% of mechanically ventilated children in a heterogeneous multicenter cohort. We did not find a link between enteral nutrition duration or route of delivery and ventilator-associated pneumonia. In addition to duration of mechanical ventilation and length of PICU stay, the use of acid-suppressive therapy independently increased the likelihood of developing ventilator-associated pneumonia in this population. This association must be further explored in clinical trials.

Metabolic assessment and individualized nutrition in children dependent on mechanical ventilation at home.

OBJECTIVE: To evaluate the nutritional and metabolic status and body composition of children on long-term mechanical ventilation using a home-based model. STUDY DESIGN: Children on home mechanical ventilation, for at least 12 hours a day, were eligible. We performed anthropometry, bioelectrical impedance analysis (BIA), actual energy intake (AEI), and indirect calorimetry in the subject's home. Agreement between measured energy expenditure (MEE) from indirect calorimetry, and estimated energy expenditure by the Schofield equation and a novel volumetric carbon dioxide production-based equation was examined. Agreement between fat mass estimates from anthropometry and BIA was examined and compared with population norms. RESULTS: We enrolled 20 children, 11 (55%) male; mean age 8.4 years (SD 4.8). Mean weight for age z-score was -0.26 (SD 1.48); 9/20 had z-scores <-1 or >+1. Thirteen were underfed (AEI:MEE <90%) or overfed (AEI:MEE >110%); 11 of 19 had protein intake that was less than recommended by guidelines. Fifteen subjects were hypo- or hypermetabolic. Mean (SD) fat mass % was 33.6% (8.6) by anthropometry, which was significantly greater than matched population norms (mean 23.0%, SD 6.1, P < .001). The estimated energy expenditure by a volumetric carbon dioxide production-based equation was in stronger agreement with the MEE than the Schofield equation (mean bias 0.06%, limits -15.98% to 16.16% vs mean bias -1.31%, limits -74.3% to 72%, respectively). BIA and anthropometric fat mass values were not in agreement. CONCLUSION: A majority of children on home ventilation are characterized by malnutrition, altered metabolic status, and suboptimal macronutrient intake, in particular low protein intake. A multidisciplinary home-based model facilitates individualized energy and protein delivery and may improve outcomes in this cohort.

Bone loss and vitamin D deficiency in children undergoing hematopoietic cell transplantation.

BACKGROUND: Hematopoietic cell transplantation (HCT) may be detrimental to bone health and vitamin D status in children. PROCEDURE: We conducted a prospective, multicenter cohort study to identify changes in bone health markers during the first 100 days after allogeneic HCT in 26 children. Bone mineral density (BMD), bone mineral content (BMC), and serum 25-hydroxyvitamin D (25OHD) concentrations were measured at baseline, 30 days, and 100 days after HCT. RESULTS: Mean (SD) BMD and BMC Z-scores (-0.48 ± 1.09 and -0.98 ± 1.26, respectively) were normal at baseline. Repeated-measures analysis revealed significant declines in BMD and BMC Z-scores over the 100 day study period, when adjusted for age, sex, Tanner stage, lean mass, fat mass, resting energy expenditure, total energy intake, insulin sensitivity, serum phosphorus, and inpatient steroid intake. Adjusted mean (SE) 25OHD concentrations declined from 29.2 (3.1) ng/ml at baseline, to 17.7 (1.8) ng/ml at 100 days after HCT. Vitamin D deficiency (25OHD <20 ng/ml) was present in 50% of patients 100 days after HCT. CONCLUSIONS: Significant bone loss and vitamin D deficiency occur in children in the first 100 days following allogeneic HCT. Strategies to diminish acute bone loss during HCT in children are needed.

Impact of Individualized Diet Intervention on Body Composition and Respiratory Variables in Children With Respiratory Insufficiency: A Pilot Intervention Study.

OBJECTIVES: Diet modification may improve body composition and respiratory variables in children with respiratory insufficiency. Our objective was to examine the effect of an individualized diet intervention on changes in weight, lean body mass, minute ventilation, and volumetric CO2 production in children dependent on long-term mechanical ventilatory support. DESIGN: Prospective, open-labeled interventional study. SETTING: Study subjects' homes. PATIENTS: Children, 1 month to 17 years old, dependent on at least 12 hr/d of transtracheal mechanical ventilatory support. INTERVENTIONS: Twelve weeks of an individualized diet modified to deliver energy at 90-110% of measured energy expenditure and protein intake per age-based guidelines. MEASUREMENTS AND MAIN RESULTS: During a multidisciplinary home visit, we obtained baseline values of height and weight, lean body mass percent by bioelectrical impedance analysis, actual energy and protein intake by food record, and measured energy expenditure by indirect calorimetry. An individualized diet was then prescribed to optimize energy and protein intake. After 12 weeks on this interventional diet, we evaluated changes in weight, height, lean body mass percent, minute ventilation, and volumetric CO2 production. Sixteen subjects, mean age 9.3 years (SD, 4.9), eight male, completed the study. For the diet intervention, a majority of subjects required a change in energy and protein prescription. The mean percentage of energy delivered as carbohydrate was significantly decreased, 51.7% at baseline versus 48.2% at follow-up, p = 0.009. Mean height and weight increased on the modified diet. Mean lean body mass percent increased from 58.3% to 61.8%. Minute ventilation was significantly lower (0.18 L/min/kg vs 0.15 L/min/kg; p = 0.04), and we observed a trend toward lower volumetric CO2 production (5.4 mL/min/kg vs 5.3 mL/min/kg; p = 0.06) after 12 weeks on the interventional diet. CONCLUSIONS: Individualized diet modification is feasible and associated with a significant decrease in minute ventilation, a trend toward significant reduction in CO2 production, and improved body composition in children on long-term mechanical ventilation. Optimization of respiratory variables and lean body mass by diet modification may benefit children with respiratory insufficiency in the ICU.

Variability of resting energy expenditure in infants and young children with intestinal failure-associated liver disease.

OBJECTIVE: The aim of the study was to determine, in a cohort of young children with intestinal failure (IF), whether the estimates of basal metabolic rate (BMR) by standard equations can approximate measured resting energy expenditure (REE) by indirect calorimetry (IC). METHODS: IC was performed using the dilutional canopy technique. REE measurements were compared with standard, age-based estimation equations (World Health Organization) for BMR. Subjects were classified as hypermetabolic (REE > 110% BMR), hypometabolic (REE < 90% BMR), or normal (REE = 90%-110% BMR). RESULTS: Twenty-eight IF patients (11 girls, 17 boys) had an underlying diagnosis of necrotizing enterocolitis (n = 10) or a congenital gastrointestinal defect (n = 18). Median age was 5.3 months. Median interquartile range (IQR) REE was 46 (42-58) kcal · kg · day. Median (IQR) total energy intake provided 209% (172%-257%) of REE, with parenteral nutrition providing 76% (23%) of total energy intake. REE was variable, with 39% (n = 11) of measurements hypermetabolic, 39% (n = 11) hypometabolic, and the remaining 21% (n = 6) normal. Although REE was well correlated with estimated BMR (r = 0.82, P < 0.0001), estimated BMR was not consistently an adequate predictor of REE. BMR over- or underestimated REE by >10 kcal · kg · day in 15 of 28 (54%) patients. REE was not significantly correlated with severity of liver disease, nutritional status, total energy intake, or gestational age. CONCLUSIONS: Energy expenditure is variable among children with IF and IF-associated liver disease, with approximately 80% of our cohort exhibiting either hypo- or hypermetabolism. Standard estimation equations frequently do not correctly predict individual REE. Longitudinal studies of energy expenditure and body composition may be needed to guide provision of nutrition regimens.

Serum citrulline as a biomarker of gastrointestinal function during hematopoietic cell transplantation in children.

OBJECTIVES: We sought to determine whether serum citrulline (CIT), an amino acid produced by small bowel enterocytes, was associated with clinical and biochemical markers of gastrointestinal function in children undergoing hematopoietic cell transplantation (HCT). METHODS: We conducted a multicenter, prospective cohort study of 26 children to define time-related changes in serum CIT during the course of HCT. Markers of gastrointestinal function including oral energy intake, emesis, stool volume, presence of graft-versus-host disease (GVHD), oral mucositis severity, and cytokine and neurohormone levels were measured. Weekly serum CIT concentrations were obtained from 10 days prior until 30 days after HCT. RESULTS: Mean baseline CIT concentration was 22.7 µmol/L (95% confidence interval [CI] 17.7-27.6) on day -10, which decreased to a nadir of 7.5 µmol/L (95% CI 3.1-18.0, P = 0.017) on day 8 following HCT before returning to baseline by day 30. After adjustment for IL-6 level (1.0% lower CIT per 10% increase in interleukin-6, P = 0.004), presence of acute GVHD (27% lower CIT, P = 0.025), and oral energy intake (2.1% lower CIT per 10% decrease in energy intake, P = 0.018), the nadir shifted to day 10, when mean CIT concentration was lower in patients with severe oral mucositis (6.7 µmol/L, 95% CI 3.4-13.1) than in those without severe mucositis (11.9 µmol/L, 95% CI 5.8-24.4, P = 0.003). Change in CIT was not correlated with stool volume, C-reactive protein, tumor necrosis factor-α, leptin, or ghrelin. CONCLUSIONS: In children undergoing HCT, serum CIT correlates with measures of gastrointestinal function (oral mucositis severity, dietary intake, acute GVHD) and may reflect mucosal injury to the gastrointestinal tract.

Changes in Global Nutrition Practices in Critically Ill Children and the Influence of Emerging Evidence: A Secondary Analysis of the Pediatric International Nutrition Studies, 2009-2018.

BACKGROUND: The timeline of the 3 Pediatric International Nutrition Studies (PINS) coincided with the publication of 2 major guidelines for the timing of parenteral nutrition (PN) and recommended energy and protein delivery dose. OBJECTIVE: The study's main objective was to describe changes in the nutrition delivery practice recorded in PINS1 and PINS2 (PINS1-2) (conducted in 2009 and 2011, preexposure epoch) vs PINS3 (conducted in 2018, postexposure epoch), in relation to the published practice guidelines. DESIGN: This study is a secondary analysis of data from a multicenter prospective cohort study. PARTICIPANTS/SETTING: Data from 3650 participants, aged 1 month to 18 years, admitted to 100 unique hospitals that participated in 3 PINS was used for this study. MAIN OUTCOME MEASURES: The time in days from pediatric intensive care unit admission to the initiation of PN and enteral nutrition delivery were the primary outcomes. Prescribed energy and protein goals were the secondary outcomes. STATISTICAL ANALYSES PERFORMED: A frailty model with a random intercept per hospital with stratified baseline hazard function by region for the primary outcomes and a mixed-effects negative binomial regression with random intercept per hospital for the secondary outcomes. RESULTS: The proportion of patients receiving enteral nutrition (88.3% vs 80.6%; P < .001) was higher, and those receiving PN (20.6% vs 28.8%; P < .001) was lower in the PINS3 cohort compared with PINS1-2. In the PINS3 cohort, the odds of initiating PN during the first 10 days of pediatric intensive care unit admission were lower, compared with the PINS1-2 cohort (hazard ratio 0.8, 95% CI 0.67 to 0.95; P = .013); and prescribed energy goal was lower compared with the PINS1-2 cohort (incident rate ratio 0.918, 95% CI 0.874 to 0.965; P = .001). CONCLUSIONS: The likelihood of initiation of PN delivery significantly decreased during the first 10 days after admission in the PINS3 cohort compared with PINS1-2. Energy goal prescription in children receiving mechanical ventilation significantly decreased in the postguidelines epoch compared with the preguidelines epoch.

Nutritional practices and their relationship to clinical outcomes in critically ill children--an international multicenter cohort study*.

OBJECTIVES: To examine factors influencing the adequacy of energy and protein intake in the pediatric intensive care unit and to describe their relationship to clinical outcomes in mechanically ventilated children. DESIGN, SETTING, PATIENTS: We conducted an international prospective cohort study of consecutive children (ages 1 month to 18 yrs) requiring mechanical ventilation longer than 48 hrs in the pediatric intensive care unit. Nutritional practices were recorded during the pediatric intensive care unit stay for a maximum of 10 days, and patients were followed up for 60 days or until hospital discharge. Multivariate analysis, accounting for pediatric intensive care unit clustering and important confounding variables, was used to examine the impact of nutritional variables and pediatric intensive care unit characteristics on 60-day mortality and the prevalence of acquired infections. MAIN RESULTS: 31 pediatric intensive care units in academic hospitals in eight countries participated in this study. Five hundred patients with mean (SD) age 4.5 (5.1) yrs were enrolled and included in the analysis. Mortality at 60 days was 8.4%, and 107 of 500 (22%) patients acquired at least one infection during their pediatric intensive care unit stay. Over 30% of patients had severe malnutrition on admission, with body mass index z-score >2 (13.2%) or <-2 (17.1%) on admission. Mean prescribed goals for daily energy and protein intake were 64 kcals/kg and 1.7 g/kg respectively. Enteral nutrition was used in 67% of the patients and was initiated within 48 hrs of admission in the majority of patients. Enteral nutrition was subsequently interrupted on average for at least 2 days in 357 of 500 (71%) patients. Mean (SD) percentage daily nutritional intake (enteral nutrition) compared to prescribed goals was 38% for energy and 43% (44) for protein. A higher percentage of goal energy intake via enteral nutrition route was significantly associated with lower 60-day mortality (Odds ratio for increasing energy intake from 33.3% to 66.6% is 0.27 [0.11, 0.67], p = .002). Mortality was higher in patients who received parenteral nutrition (odds ratio 2.61 [1.3, 5.3], p = .008). Patients admitted to units that utilized a feeding protocol had a lower prevalence of acquired infections (odds ratio 0.18 [0.05, 0.64], p = .008), and this association was independent of the amount of energy or protein intake. CONCLUSIONS: Nutrition delivery is generally inadequate in mechanically ventilated children across the world. Intake of a higher percentage of prescribed dietary energy goal via enteral route was associated with improved 60-day survival; conversely, parenteral nutrition use was associated with higher mortality. Pediatric intensive care units that utilized protocols for the initiation and advancement of enteral nutrient intake had a lower prevalence of acquired infections. Optimizing nutrition therapy is a potential avenue for improving clinical outcomes in critically ill children.

Systematic review of the influence of energy and protein intake on protein balance in critically ill children.

OBJECTIVE: To examine the influence of protein and energy intakes on protein balance in children receiving mechanical ventilation in the pediatric intensive care unit. STUDY DESIGN: We hypothesized that higher energy and protein intakes are correlated with positive protein balance. We performed a systematic literature search to identify studies reporting protein balance in children requiring mechanical ventilation. Factors contributing to protein balance, including protein and energy intake, age, illness severity, study design, and feeding routes, were analyzed using a qualitative approach. RESULTS: Nine studies met the entry criteria and were included in the final analysis. Positive nitrogen balance was reported in 6 of the studies, with a wide range of associated energy and protein intakes. Measures of central tendency for daily energy and protein intakes were significantly correlated with positive protein balance. A minimum intake of 57 kcal/kg/day and 1.5 g protein/kg/day were required to achieve positive protein balance. CONCLUSION: We found a correlation between higher energy and protein intakes and achievement of positive protein balance in children receiving mechanical ventilation in the pediatric intensive care unit. However, there is a paucity of interventional studies, and a variety of protocols have been used to determine nitrogen balance. Larger clinical trials with uniform methodology are needed to further examine the effect of energy and protein intake on protein balance, lean body mass, and clinical outcomes in children on mechanical ventilation.

Bio-impedance spectroscopy for total body water assessment in pediatric surgical patients: A single center pilot cohort study.

BACKGROUND: Excess peri­operative fluid administration is associated with higher morbidity and mortality. We aimed to examine the feasibility of bio-impedance spectroscopy (BIS) to record serial peri­operative fluid volumes in the pediatric surgical population. METHODS: Children who underwent major elective general surgery from March 2019 to March 2020 were included. Total body water (TBW) assessment by BIS was recorded prior to surgery and on subsequent post-operative days (POD). We recorded the duration, tolerance and completion of each BIS assessment. We used Spearman coefficient and Bland Altman analysis to examine correlation and agreement between fluid balance (FB) in ml/kg calculated from intake/output (IO) recording and measured by BIS. RESULTS: 20 (87%) of 23 consented patients, median age 2.5 (1-17) years and 13 (65%) male, completed pre-operative and post-operative measurements, and were included in the analysis. Median time required for BIS assessments was 10 (5-15) minutes, and there were no recorded side effects or intolerance. The correlation coefficient for fluid balance measurements on POD 1 between BIS and IO methods was 0.59 (p = 0.01); mean bias (limits) of agreement was 26 (111 to 163) mL/kg. The trend in TBW measured by BIS declined from POD 1-3, while the recorded FB increased. CONCLUSION: Bedside BIS is feasible and well-tolerated. Despite moderate correlation between fluid balance assessment by BIS and IO on POD 1, the wide limits of agreement between values from these methods preclude their use interchangeably. The role of BIS in assessment of fluid status in the pediatric surgical population should be further examined. LEVEL OF EVIDENCE: Level III.

Feasibility of bioimpedance spectroscopy and long-term functional assessment in critically ill children.

BACKGROUND & AIMS: Lean body mass loss due to critical illness in childhood could be detrimental to long term outcomes, including functional status and quality of life. We describe the feasibility of body composition assessment by bioimpedance spectroscopy (BIS) in the pediatric intensive care unit (PICU), and functional status and quality of life assessments up to 6 months following admission in a cohort of mechanically ventilated, critically ill children. METHODS: We conducted a prospective, observational pilot study in a multidisciplinary PICU. Children aged 1 month to 18 years who required mechanical ventilation, with expected stay in the PICU of at least 5 days were included. We examined the feasibility of consenting, enrolling, and completing baseline and 6-month assessments of BIS variables, Functional Status Scale (FSS), and Pediatric Quality of Life (Peds QL), in eligible patients. RESULTS: Of 32 patients approached, 23 (72%) completed baseline assessments [median (IQR) age 3.4 (1.0, 7.8) years, 14 (61%) male]; 6-month assessments were completed in 15 (65%) enrolled patients. Mean (SD) phase angle at study enrollment was 2.95 (0.93) and the impedance ratio was 0.90 (0.03). Phase angle (rs = -0.58, p = 0.03) and impedance ratio (rs = 0.61, p = 0.02) by BIS were significantly correlated with total FSS at PICU discharge. Median total FSS and FSS tech (feeding and respiratory domains of FSS) scores improved from enrollment [16 (13, 26) and 8 (7, 10)] to 6 months [6 (6, 9) and 2 (2, 4), respectively, p < 0.001]. Median Peds QL total, physical summary and psychosocial summary scores were not significantly different between PICU discharge and 6 months after PICU admission. Correlations between the total 6-month FSS and a) phase angle (-0.45, p = 0.197) and b) impedance ratio (0.56, p = 0.096) at PICU discharge were not significant. CONCLUSIONS: We have demonstrated the feasibility of obtaining bedside BIS measurements in the PICU, and functional and quality of life assessments remotely following PICU discharge. Body composition and long-term assessment of functional outcomes and quality of life must be incorporated in nutrition trials in critically ill children.

Intermittent versus continuous enteral nutrition in critically ill children: A pre-planned secondary analysis of an international prospective cohort study.

BACKGROUND & AIMS: Intermittent enteral nutrition (EN) may have physiologic benefits over continuous feeding in critical illness. We aimed to compare nutrition and infection outcomes in critically ill children receiving intermittent or continuous EN. METHODS: International, multi-center prospective observational study of mechanically ventilated children, 1 month to 18 years of age, receiving EN. Percent energy or protein adequacy (energy or protein delivered/prescribed × 100) and acquired infection rates were compared between intermittent and continuous EN groups using adjusted-multivariable and 4:1 propensity-score matched (PSM) analyses. Sensitivity analyses were performed after excluding patients who crossed over between intermittent and continuous EN. RESULTS: 1375 eligible patients from 66 PICUs were included. Patients receiving continuous EN (N = 1093) had a higher prevalence of respiratory illness and obesity, and lower prevalence of neurologic illness and underweight status on admission, compared to those on intermittent EN (N = 282). Percent energy or protein adequacy, proportion of patients who achieved 60% of energy or protein adequacy in the first 7 days of admission, and rates of acquired infection were not different between the 2 groups in adjusted-multivariable and propensity score matching analyses (P > 0.05). CONCLUSION: Intermittent versus continuous EN strategy is not associated with differences in energy or protein adequacy, or acquired infections, in mechanically ventilated, critically ill children. Until further evidence is available, an individualized feeding strategy rather than a universal approach may be appropriate.