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.

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.

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.

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.

Time to achieve delivery of nutrition targets is associated with clinical outcomes in critically ill children.

BACKGROUND: Optimal nutrition in critically ill children involves a complex interplay between the doses, route, and timing of macronutrient delivery. OBJECTIVES: We aimed to examine the association between the time to achieve delivery of 60% of the prescribed energy and protein targets and clinical outcomes in mechanically ventilated children. METHODS: We conducted a prospective, observational cohort study of mechanically ventilated children admitted to pediatric intensive care units (PICUs) worldwide. Daily energy and protein delivery were recorded for up to 10 d in the PICU. We calculated "adequacy" as the percentage of the prescribed energy or protein goal delivered by enteral nutrition (EN), parenteral nutrition (PN), and total nutrition (EN + PN). Based on the days required to reach 60% energy or protein adequacy after PICU admission, we categorized patients into 3 groups: early (≤3 d), pragmatic (4 to 7 d), and late (more than 7 d). The primary outcome was 60-d all-cause mortality; secondary outcomes were the incidence of acquired infections and 28-d ventilator-free days (VFDs). RESULTS: From 77 participating PICUs, 1844 patients, with a median age of 1.64 y (IQR, 0.47-7.05), were included; the 60-d mortality rate was 5.3% (n = 97). The average adequacies of delivery via EN + PN was 49% (IQR, 26-70) for energy and 66% (IQR, 44-89) for protein. In multivariable models adjusted for confounders, mortality was significantly lower in patients who achieved targets within 7 d, for energy (adjusted HR, 0.48; 95% CI: 0.28-0.82; P = 0.007) or protein (adjusted HR, 0.55; 95% CI: 0.33-0.94; P = 0.027) delivery. There were no clinically significant differences in infections or VFDs between groups. CONCLUSIONS: Achieving 60% of energy or protein delivery targets within the first 7 d after PICU admission is associated with lower 60-d mortality in mechanically ventilated children, and is not associated with a greater incidence of infections or a reduction in VFDs compared to later achievement of targets. This trial was registered at clinicaltrials.gov as NCT03223038.

Stress ulcer prophylaxis versus placebo-a blinded randomized control trial to evaluate the safety of two strategies in critically ill infants with congenital heart disease (SUPPRESS-CHD).

BACKGROUND: Critically ill infants with congenital heart disease (CHD) are often prescribed stress ulcer prophylaxis (SUP) to prevent upper gastrointestinal bleeding, despite the low incidence of stress ulcers and limited data on the safety and efficacy of SUP in infants. Recently, SUP has been associated with an increased incidence of hospital-acquired infections, community-acquired pneumonia, and necrotizing enterocolitis. The objective of this pilot study is to investigate the feasibility of performing a randomized controlled trial to assess the safety and efficacy of withholding SUP in infants with congenital heart disease admitted to the cardiac intensive care unit. METHODS: A single center, prospective, double-blinded, randomized placebo-controlled pilot feasibility trial will be performed in infants with CHD admitted to the cardiac intensive care unit and anticipated to require respiratory support for > 24 h. Patients will be randomized to receive a histamine-2 receptor antagonist (H2RA) or placebo until they are discontinued from respiratory support. Randomization will be performed within 2 strata defined by admission type (medical or surgical) and age (neonate, age < 30 days, or infant, 1 month to 1 year). Allocation will be a 1:1 ratio using permuted blocks to ensure balanced allocations across the two treatment groups within each stratum. The primary outcomes include feasibility of screening, consent, timely allocation of study drug, and protocol adherence. The primary safety outcome is the rate of clinically significant upper gastrointestinal bleeding. The secondary outcomes are the difference in the relative and absolute abundance of the gut microbiota and functional microbial profiles between the two study groups. We plan to enroll 100 patients in this pilot study. DISCUSSION: Routine use of SUP to prevent upper gastrointestinal bleeding in infants is controversial due to a low incidence of bleeding events and concern for adverse effects. The role of SUP in infants with CHD has not been examined, and there is equipoise on the risks and benefits of withholding this therapy. In addition, this therapy has been discontinued in other neonatal populations due to the concern for hospital-acquired infections and necrotizing enterocolitis. Furthermore, exploring changes to the microbiome after exposure to SUP may highlight the mechanisms by which SUP impacts potential microbial dysbiosis of the gut and its association with hospital-acquired infections. Assessment of the feasibility of a trial of withholding SUP in critically ill infants with CHD will facilitate planning of a larger multicenter trial of safety and efficacy of SUP in this vulnerable population. TRIAL REGISTRATION: ClinicalTrials.gov , NCT03667703. Registered 12 September 2018, https://clinicaltrials.gov/ct2/show/NCT03667703?term=SUPPRESS+CHD&draw=2&rank=1 . All WHO Trial Registration Data Set Criteria are met in this manuscript.

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.

Feasibility of Enteral Protein Supplementation in Critically Ill Children.

BACKGROUND: We describe the protein type and concentration in standard enteral nutrition (EN) formulas and the effect of protein supplementation on the osmolality of standard formulas. We also aimed to examine factors associated with optimal protein delivery in critically ill children. METHODS: Protein content and other characteristics of pediatric EN formulas used worldwide were recorded. Factors associated with achievement of recommended protein delivery and tolerance of protein-supplemented formulas were recorded prospectively in a cohort of critically ill children. A range of protein supplement doses was added to 2 standard formulas and water, and the osmolality was recorded by cryoscopy in a bench experiment. RESULTS: We reviewed 125 formulas used in a multicenter study including sites from >13 countries. A majority of the EN formulas (73.6%) were polymeric, with a nonprotein calorie/nitrogen ratio of 182 ± 66 and protein content of 3.53 ± 2.00 g/100 mL. In the cohort of critically ill children, 28.5% achieved protein intake goal within 4 days, with no intolerance. In addition to optimal protein prescription (P < 0.001), protein supplementation (P = 0.018) and early EN initiation (P = 0.006) were associated with significantly higher odds of achieving goal protein intake. Formulas supplemented with up to 8 g/100 mL polymeric protein had osmolality <450 mOsm/kg. CONCLUSIONS: The protein content of current pediatric formulas may be inadequate to meet the needs of critically ill children. Protein supplementation of formulas allows early achievement of goal and is likely to be safe.).

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.

Importance of Dietary Sources of Iron in Infants and Toddlers: Lessons from the FITS Study.

Iron deficiency (ID) affects 13.5% of 1-2 years old children in the US and may have a negative impact on neurodevelopment and behavior. Iron-fortified infant cereal is the primary non-heme iron source among infants aged 6-11.9 months. The objective of this study was to compare iron intakes of infant cereal users with non-users. Data from the Feeding Infants and Toddlers Study 2008 were used for this analysis. Based on a 24-h recall, children between the ages of 4-17.9 months were classified as 'cereal users' if they consumed any amount or type of infant cereal and 'non-users' if they did not. Infant cereal was the top source of dietary iron among infants aged 6-11.9 months. The majority of infants (74.6%) aged 6-8.9 months consumed infant cereal, but this declined to 51.5% between 9-11.9 months and 14.8% among 12-17.9 months old toddlers. Infant cereal users consumed significantly more iron than non-users across all age groups. Infants and toddlers who consume infant cereal have higher iron intakes compared to non-users. Given the high prevalence of ID, the appropriate use of infant cereals in a balanced diet should be encouraged to reduce the incidence of ID and ID anemia.

Nutrient delivery in mechanically ventilated surgical patients in the pediatric critical care unit.

PURPOSE: Inadequate nutrient intake is associated with poor outcomes in critically ill children. We examined macronutrient delivery in surgical patients in the pediatric intensive care unit (PICU). METHODS: In a prospective international cohort study of mechanically ventilated children (1month to 18years), we recorded adequacy of cumulative nutrient delivery in the PICU. Surgical patients enrolled in this study were included in the current analysis. Protein intake <60% of the prescribed goal was deemed inadequate. RESULTS: Five hundred nineteen surgical patients, 45% female, median age 2years (IQR 0.5, 8), BMI z score -0.26, with 9-day median PICU stay and 60-day mortality 5.8% were enrolled. Three hundred forty-one (66%) patients received enteral nutrition (EN), and median time of initiation was PICU day 2. EN delivery was interrupted in 68% of these patients for a median duration of 9hours. Median enteral protein delivery was <15% of the prescribed goal and was <60% in two-thirds of the cohort. Patients with inadequate enteral protein delivery had longer time to EN initiation (p<0.001) and longer duration of EN interruptions (p<0.001) compared to those with adequate delivery. CONCLUSION: Enteral protein delivery in critically ill pediatric surgical patients is inadequate. Early EN initiation and minimizing interruptions may increase protein delivery and potentially improve outcomes in this population. LEVEL OF EVIDENCE: I. TYPE OF STUDY: Prospective study.

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.

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.