Nutritional Intake in Children with Septic Shock: A Retrospective Single-Center Study.

Nutritional practice in children with severe sepsis or septic shock remains poorly described. We aimed to describe nutrition received by children with severe sepsis or septic shock and explore the association of nutritional intake with clinical outcomes. This study was a retrospective study of children who required pediatric intensive care unit (PICU) admission from 2009 to 2016. Outcomes were mortality, ventilator-free days (VFDs), and PICU-free days (IFDs). A total of 74 patients with septic shock or severe sepsis were identified. Forty-one (55.4%) patients received enteral nutrition (EN) only, 6 (8.1%) patients received parental nutrition (PN) only, 15 (20.3%) patients received both EN and PN, and 12 (16.2%) patients received intravenous fluids alone. Eight of 74 (10.8%) and 4 of 74 (5.4%) had adequate energy and protein intake, respectively. Patients who received early EN had lower odds of 28-day mortality (adjusted hazard ratio [HR] = 0.09, 95% confidence interval [CI]: 0.02, 0.45, p = 0.03) more 28-day VFDs (adjusted ß-coefficient = 18.21 [95% CI: 11.11, 25.32], p < 0.001), and IFDs (adjusted ß-coefficient = 16.71 [95% CI: 9.86, 23.56], p < 0.001) than patients who did not receive EN. Late EN was also associated with lower odds of mortality, more VFDs, and IFDs compared with no EN (HR = 0.06, 95% CI: 0.02, 0.23; p < 0.001; adjusted ß coefficient = 15.66, 95% CI: 9.31, 22.02; p < 0.001; and 12.34 [95% CI: 6.22, 18.46], p < 0.001; respectively). Inadequate calories and protein were not associated with mortality. EN in children with septic shock or severe sepsis was associated with improved clinical outcomes. Future prospective studies are required to explore the impact of EN timing and optimal nutritional intake in these children.

Changes in global nutrition practices in critically ill children and the impact of emerging evidence: a secondary analysis of the Pediatric International Nutrition Studies (PINS), 2009-2018.

BACKGROUND: The timeline of the three 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 PINS 1 and 2 (conducted in 2009 and 2011, pre-exposure epoch) versus PINS 3 (conducted in 2018,post-exposure epoch), in relation to the published practice guidelines. DESIGN: This study is a secondary analysis of data from a multi-center prospective cohort study. PARTICIPANTS: /setting. Data from 3650 participants, aged 1 month to 18 years, admitted to 100 unique hospitals that participated in three PINS was used for this study. MAIN OUTCOME MEASURES: The time in days from PICU admission to the initiation of PN and enteral nutrition (EN) 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 EN (88.3% vs. 80.6%, p-value<0.001) was higher, and those receiving PN (20.6% vs. 28.8%, p-value<0.001) was lower in the PINS3 cohort compared to PINS1-2. In the PINS3 cohort, the odds of initiating PN during the 1st 10 days of PICU admission were lower, compared to the PINS1-2 cohort (HR=0.8, CI=[0.67-0.95], p-value=0.013); and prescribed energy goal was lower compared to the PINS1-2 cohort (IRR=0.918, CI=[0.874-0.965], p=0.001). CONCLUSIONS: The likelihood of initiation of PN delivery significantly decreased in the first ten days post-admission in the PINS3 cohort compared to PINS1-2. Energy goal prescription in mechanically ventilated children significantly decreased in the post-guidelines epoch compared to the pre-guidelines epoch.

Strain-resolved metagenomic analysis of the gut as a reservoir for bloodstream infection pathogens among premature infants in Singapore.

BACKGROUND: Gut dysbiosis contributes to the high risk of bloodstream infection (BSI) among premature infants. Most prior studies of the premature infant gut microbiota were conducted in Western countries and prior to development of current tools for strain-resolved analysis. METHODS: We performed metagenomic sequencing of weekly fecal samples from 75 premature infants at a single hospital in Singapore. We evaluated associations between clinical factors and gut microbiota composition using PERMANOVA and mixed effects linear regression. We used inStrain to perform strain-level analyses evaluating for gut colonization by BSI-causing strains. RESULTS: Median (interquartile range) gestation was 27 (25, 29) weeks, and 63% of infants were born via Cesarean section. Antibiotic exposures (PERMANOVA; R2 = 0.017, p = 0.001) and postnatal age (R2 = 0.015, p = 0.001) accounted for the largest amount of variability in gut microbiota composition. Increasing postnatal age was associated with higher relative abundances of several common pathogens (Enterococcus faecalis: p < 0.0001; Escherichia coli: p < 0.0001; Klebsiella aerogenes: p < 0.0001; Klebsiella pneumoniae: p < 0.0001). Antibiotic exposures were generally associated with lower relative abundances of both frequently beneficial bacteria (e.g., Bifidobacterium species) and common enteric pathogens (e.g., Enterobacter, Klebsiella species). We identified strains identical to the blood culture isolate in fecal samples from 12 of 16 (75%) infants who developed BSI, including all infections caused by typical enteric bacteria. CONCLUSIONS: Antibiotic exposures were the dominant modifiable factor affecting gut microbiota composition in a large cohort of premature infants from South-East Asia. Strain-resolved analyses indicate that the gut is an important reservoir for organisms causing BSI among premature infants.

Muscle Ultrasound Changes and Physical Function of Critically Ill Children: A Comparison of Rectus Femoris Cross-Sectional Area and Quadriceps Thickness Measurements.

Quadriceps thickness (QT) and rectus femoris cross-sectional area (RFCSA) are both used to evaluate muscle changes in critically ill children. However, their correlation and association with physical function has not been compared. OBJECTIVES: To compare QT with RFCSA changes, and their association with physical function in critically ill children. DESIGN SETTING AND PARTICIPANTS: Secondary analysis of a prospective cohort study of children 0-18 years old admitted to a tertiary mixed PICU between January 2015 and October 2018 with PICU stay greater than 48 hours and greater than or equal to one organ dysfunction. MAIN OUTCOMES AND MEASURES: Ultrasound QT and RFCSA were measured at PICU admission, PICU discharge, hospital discharge, and 6 months post-discharge. QT and RFCSA changes from baseline were compared with each other and with change in motor function, physical ability, and physical health-related quality of life (HRQOL). RESULTS: Two hundred thirty-seven images from 66 subjects were analyzed. RFCSA change was not significantly different from QT change at PICU (-8.07% [interquartile range (IQR), -17.11% to 4.80%] vs -4.55% [IQR, -14.32% to 4.35%]; p = 0.927) or hospital discharge (-5.62% [IQR, -15.00% to 9.42%] vs -8.81% [IQR, -18.67% to 2.39%]; p = 0.238) but was significantly greater than QT change at 6 months (32.7% [IQR, 5.74-109.76%] vs 9.66% [IQR, -8.17% to 25.70%]; p < 0.001). Motor function change at PICU discharge was significantly associated with RFCSA change (adjusted ß coefficient, 0.02 [95% CI, 0.01-0.03]; p = 0.013) but not QT change (adjusted ß coefficient, -0.01 [95% CI, -0.02 to 0.01]; p = 0.415). Similar results were observed for physical HRQOL changes at hospital discharge (adjusted ß coefficient for RFCSA change, 0.51 [95% CI, 0.10-0.92]; p = 0.017 and adjusted ß coefficient for QT change, -0.21 [-0.76 to 0.35]; p = 0.458). Physical ability was not significantly associated with RFCSA or QT changes at 6 months post-discharge. CONCLUSIONS AND RELEVANCE: Ultrasound derived RFCSA is associated with PICU motor function and hospital discharge physical HRQOL changes, unlike QT, and may be more useful for in-hospital muscle monitoring in critically ill children.

Perceptions and acceptance of COVID-19 vaccine among pregnant and lactating women in Singapore: A pre-vaccine rollout cross-sectional study.

Introduction: Vaccination is critical in controlling the coronavirus disease 2019 (COVID-19) pandemic. However, vaccine perception and acceptance among pregnant and lactating women is unknown in Singapore. We aimed to determine the acceptance of COVID-19 vaccination among these two groups of women in Singapore and the factors associated with vaccine acceptance. Methods: We conducted an anonymous, online survey on the perceptions of the COVID-19 vaccine and its acceptance by pregnant and lactating women at a tertiary maternal and child hospital in Singapore from 1 March to 31 May 2021. Information on their demographics and knowledge was collected. These factors were assessed for their relationship with vaccine acceptance. Results: A total of 201 pregnant and 207 lactating women participated. Vaccine acceptance rates in pregnant and lactating women were 30.3% and 16.9%, respectively. Pregnant women who were unsure or unwilling to take the vaccine cited concerns about safety of the vaccine during pregnancy (92.9%), while lactating women were concerned about its potential long-term negative effects on the breastfeeding child (75.6%). Factors that were positively associated with vaccine acceptance included a lower monthly household income or education level, appropriate knowledge regarding vaccine mechanism and higher perceived maternal risk of COVID-19. Most pregnant (70.0%) and lactating women (83.7%) were willing to take the vaccine only when more safety data during pregnancy and breastfeeding were available. Conclusion: COVID-19 vaccine acceptance was low among pregnant and lactating women in Singapore. Addressing the safety concerns when more data are available and education on the mechanism of vaccine action will likely improve acceptance among these women.

Protein supplementation versus standard feeds in underweight critically ill children: a pilot dual-centre randomised controlled trial protocol.

INTRODUCTION: Protein-energy malnutrition, increased catabolism and inadequate nutritional support leads to loss of lean body mass with muscle wasting and delayed recovery in critical illness. However, there remains clinical equipoise regarding the risks and benefits of protein supplementation. This pilot trial will determine the feasibility of performing a larger multicentre trial to determine if a strategy of protein supplementation in critically ill children with body mass index (BMI) z-score ≤-2 is superior to standard enteral nutrition in reducing the length of stay in the paediatric intensive care unit (PICU). METHODS AND ANALYSIS: This is a randomised controlled trial of 70 children in two PICUs in Singapore. Children with BMI z-score ≤-2 on PICU admission, who are expected to require invasive mechanical ventilation for more than 48 hours, will be randomised (1:1 allocation) to protein supplementation of ≥1.5 g/kg/day in addition to standard nutrition, or standard nutrition alone for 7 days after enrolment or until PICU discharge, whichever is earlier. Feasibility outcomes for the trial include effective screening, satisfactory enrolment rate, timely protocol implementation (within first 72 hours) and protocol adherence. Secondary outcomes include mortality, PICU length of stay, muscle mass, anthropometric measurements and functional outcomes. ETHICS AND DISSEMINATION: The trial protocol was approved by the institutional review board of both participating centres (Singhealth Centralised Institutional Review Board and National Healthcare Group Domain Specific Review Board) under the reference number 2020/2742. Findings of the trial will be disseminated through peer-reviewed journals and scientific conferences. TRIAL REGISTRATION NUMBER: NCT04565613.

A narrative review of skeletal muscle atrophy in critically ill children: pathogenesis and chronic sequelae.

Muscle wasting is now recognized as a growing, debilitating problem in critically ill adults, resulting in long-term deficits in function and an impaired quality of life. Ultrasonography has demonstrated decreases in skeletal muscle size during pediatric critical illness, although variations exist. However, muscle protein turnover patterns during pediatric critical illness are unclear. Understanding muscle protein turnover during critical illness is important in guiding interventions to reduce muscle wasting. The aim of this review was to explore the possible protein synthesis and breakdown patterns in pediatric critical illness. Muscle protein turnover studies in critically ill children are lacking, with the exception of those with burn injuries. Children with burn injuries demonstrate an elevation in both muscle protein breakdown (MPB) and synthesis during critical illness. Extrapolations from animal models and whole-body protein turnover studies in children suggest that children may be more dependent on anabolic factors (e.g., nutrition and growth factors), and may experience greater muscle degradation in response to insults than adults. Yet, children, particularly the younger ones, are more responsive to anabolic agents, suggesting modifiable muscle wasting during critical illness. There is a lack of evidence for muscle wasting in critically ill children and its correlation with outcomes, possibly due to current available methods to study muscle protein turnover in children-most of which are invasive or tedious. In summary, children may experience muscle wasting during critical illness, which may be more reversible by the appropriate anabolic agents than adults. Age appears an important determinant of skeletal muscle turnover. Less invasive methods to study muscle protein turnover and associations with long-term outcome would strengthen the evidence for muscle wasting in critically ill children.

Nutrition in Pediatric Extracorporeal Membrane Oxygenation: A Narrative Review.

Extracorporeal membrane oxygenation (ECMO) support is increasingly utilized in quaternary pediatric intensive care units. Metabolic derangements and altered nutritional requirements are common in critically ill children supported on ECMO. However, there remains no consensus on the optimal approach to the prescription of nutrition in these patients. This narrative review aims to summarize the current medical literature on various aspects of nutrition support in pediatric patients on ECMO. These include: (1) nutritional adequacy, (2) pros and cons of feeding on ECMO, (3) enteral vs. parenteral nutrition, and (4) proposed recommendations and future directions for research in this area.

High burden of acquired morbidity in survivors of pediatric acute respiratory distress syndrome.

INTRODUCTION: With improving mortality rates in pediatric acute respiratory distress syndrome (PARDS), functional outcomes in survivors are increasingly important. We aim to describe the change in functional status score (FSS) from baseline to discharge and to identify risk factors associated with poor functional outcomes. METHODS: We examined clinical records of patients with PARDS admitted to our pediatric intensive care unit (PICU) from 2009 to 2016. Our primary outcome was acquired morbidity at PICU and hospital discharge (defined by an increase in FSS ≥3 points above baseline). We included severity of illness scores and severity of PARDS in our bivariate analysis for risk factors for acquired morbidity. RESULTS: There were 181 patients with PARDS, of which 90 (49.7%) survived. Median pediatric index of mortality 2 score was 4.05 (1.22, 8.70) and 21 (23.3%) survivors had severe PARDS. A total of 59 (65.6%) and 14 (15.6%) patients had acquired morbidity at PICU and hospital discharge, respectively. Median baseline FSS was 6.00 (6.00, 6.25), which increased to 11.00 (8.75, 12.00) at PICU discharge before decreasing to 7.50 (6.00, 9.25) at hospital discharge. All patients had significantly higher FSS at both PICU and hospital discharge median compared to baseline. Feeding and respiratory were the most affected domains. After adjusting for severity of illness, severity categories of PARDS were not a risk factor for acquired morbidity. CONCLUSION: Acquired morbidity in respiratory and feeding domains was common in PARDS survivors. Specific attention should be given to these two domains of functional outcomes in these children.

Association between admission body mass index and outcomes in critically ill children: A systematic review and meta-analysis.

BACKGROUND & AIMS: The association between nutritional status at pediatric intensive care unit (PICU) admission with clinical outcomes remains unclear. We conducted this systematic review to summarize the overall impact of PICU admission body mass index (BMI) on clinical outcomes. METHODS: We searched the following medical databases from inception through May 2020: PubMed, Excerpta Medica database (Embase), Cumulative Index of Nursing and Allied Health Literature (CINAHL), Cochrane Library, and Web of Science. We included studies on patients ≤18 years old admitted to a PICU that investigated the effect of BMI on mortality, PICU or hospital length of stay (LOS), or duration of mechanical ventilation (MV). Classification of underweight, overweight, and obese were based on each study's criteria. RESULTS: There was a total of 21,558 patients from 20 included studies. 12,936 (60.0%), 2965 (13.8%), 2182 (10.1%), 3348 (15.5%) were normal weight, underweight, overweight, and obese patients, respectively. Relative to normal weight patients, underweight (OR 1.32, 95% CI 0.89-1.98; p = 0.171) and overweight/obese patients (OR 1.10, 95% CI 0.86-1.42; p = 0.446) did not have an increase risk in mortality. There was also no difference in duration of MV, PICU and hospital LOS between all three weight categories. Included studies were heterogeneous and lacked standardized nutritional categorization. Sensitivity analysis including only studies that used BMI z-scores as nutritional classification (n = 5) revealed that underweight patients had higher odds of mortality compared to patients with normal weight (OR 1.61, 95% CI 1.35-1.92; p < 0.001); studies that used percentiles as classification did not reveal any differences in mortality. Sensitivity analysis including only studies containing mixed PICU cohorts (i.e., excluding specialized cohorts e.g., congenital heart surgeries, burns) revealed higher mortality odds in underweight patients (OR 1.53, 95% CI 1.25-1.87; p < 0.001) and overweight/obese patients (OR 1.51, 95% CI 1.14-2.01; p = 0.004) relative to normal weight patients. CONCLUSIONS: Our systematic review did not reveal any association between PICU admission BMI status and outcomes in critically ill children. Further investigation with standardized nutrition status classification on admission, stratified by patient subgroups, is needed to clarify the association between nutritional status and clinical outcomes of PICU patients.

Skeletal Muscle Changes, Function, and Health-Related Quality of Life in Survivors of Pediatric Critical Illness.

OBJECTIVES: To describe functional and skeletal muscle changes observed during pediatric critical illness and recovery and their association with health-related quality of life. DESIGN: Prospective cohort study. SETTING: Single multidisciplinary PICU. PATIENTS: Children with greater than or equal to 1 organ dysfunction, expected PICU stay greater than or equal to 48 hours, expected survival to discharge, and without progressive neuromuscular disease or malignancies were followed from admission to approximately 6.7 months postdischarge. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Functional status was measured using the Functional Status Scale score and Pediatric Evaluation of Disability Inventory-Computer Adaptive Test. Patient and parental health-related quality of life were measured using the Pediatric Quality of Life Inventory and Short Form-36 questionnaires, respectively. Quadriceps muscle size, echogenicity, and fat thickness were measured using ultrasonography during PICU stay, at hospital discharge, and follow-up. Factors affecting change in muscle were explored. Associations between functional, muscle, and health-related quality of life changes were compared using regression analysis. Seventy-three survivors were recruited, of which 44 completed follow-ups. Functional impairment persisted in four of 44 (9.1%) at 6.7 months (interquartile range, 6-7.7 mo) after discharge. Muscle size decreased during PICU stay and was associated with inadequate energy intake (adjusted ß, 0.15; 95% CI, 0.02-0.28; p = 0.030). No change in echogenicity or fat thickness was observed. Muscle growth postdischarge correlated with mobility function scores (adjusted ß, 0.05; 95% CI, 0.01-0.09; p = 0.046). Improvements in mobility scores were associated with improved physical health-related quality of life at follow-up (adjusted ß, 1.02; 95% CI, 0.23-1.81; p = 0.013). Child physical health-related quality of life at hospital discharge was associated with parental physical health-related quality of life (adjusted ß, 0.09; 95% CI, 0.01-0.17; p = 0.027). CONCLUSIONS: Muscle decreased in critically ill children, which was associated with energy inadequacy and impaired muscle growth postdischarge. Muscle changes correlated with change in mobility, which was associated with child health-related quality of life. Mobility, child health-related quality of life, and parental health-related quality of life appeared to be interlinked.

A Cross-Sectional Study of the Clinical Metrics of Functional Status Tools in Pediatric Critical Illness.

OBJECTIVES: To determine the clinical metrics of functional assessments in pediatric critical illness survivors. DESIGN: Cross-sectional observational study. SETTING: PICU follow-up clinic. PATIENTS: Forty-four PICU survivors 6-12 months post PICU stay, and 52 healthy controls 0-18 years old. INTERVENTIONS: Nil. MEASUREMENTS AND MAIN RESULTS: Function was assessed using the Pediatric Quality of Life Inventory 4.0 generic scales and infant scales, the Pediatric Evaluation of Disability Inventory-Computer Adaptive Test, and the Functional Status Scale. Muscle strength was assessed by hand grip strength in children greater than or equal to 6 years. Clinical metrics assessed included floor and ceiling effects, known-group, and convergent validity. Floor and ceiling effects were present if the participants achieving the worst or best scores exceeded 15%, respectively. Known-group validity was assessed by comparing scores between those with and without complex chronic conditions and abnormal versus good baseline function. Convergent validity was assessed using partial correlation between two tools. Functional Status Scale and Pediatric Quality of Life Inventory physical domain scores showed significant ceiling effects in PICU survivors (69.2% and 15.4%, respectively, achieved the highest possible score). Functional scores were not significantly different between children with or without complex chronic conditions or children with good versus abnormal baseline function. In healthy children, Pediatric Quality of Life Inventory physical correlated moderately with hand grip strength (partial r = 0.66; p < 0.001), whereas Pediatric Quality of Life Inventory psychosocial correlated moderately with Pediatric Evaluation of Disability Inventory-Computer Adaptive Test social/cognitive score (partial r = 0.53; p < 0.001). In PICU survivors, only Pediatric Quality of Life Inventory physical and Pediatric Evaluation of Disability Inventory-Computer Adaptive Test mobility scores were correlated (partial r = 0.55; p < 0.001). CONCLUSIONS: PICU functional assessment tools have varying clinical metrics. Considering ceiling effects, Pediatric Evaluation of Disability Inventory-Computer Adaptive Test may be more suitable in survivors than Functional Status Scale. Differences in scores between children with or without complex chronic conditions, and with or without baseline functional impairment, were not observed. Functional assessments likely require a combination of tools to measure the spectrum of pediatric critical illness and recovery.

Implementation of a nutrition screening tool to improve nutritional status of children with cancer in Singapore's largest paediatric hospital.

Poor nutritional status in children with cancer can impact treatment outcomes and mortality. Nutrition screening is a simple yet effective approach to identify malnutrition risk for early intervention. We aim to improve the identification of children with cancer at high risk of malnutrition, so that nutritional intervention and rehabilitation can commence early for these children. Our multidisciplinary team conducted a root cause analysis and concluded that the generic screening tool did not differentiate malnutrition risk for different cancer types, stage and intensity of treatment. Hence, a screening tool that considered the identified factors was tested for reliability and validity first. Subsequently, we used the Plan, Do, Study, Act model with two improvement cycles to put in place a systematic process to facilitate the implementation. The interventions included (1) instituting the tool in the electronic medical records and (2) direct referral to dietitian based on screening score.We compared pre- and post-implementation cohorts and demonstrated better identification of nutritionally at-risk patients (36.4%-85.7%, p<0.001) with the new tool as well as improved timeliness of nutritional intervention (3 days to 1 day from admission, p=0.010). A lower malnutrition rate (17.4%-6.5%, p<0.001) in the postimplementation cohort was also demonstrated. Nutritional intervention within 48 hours of admission led to an overall positive weight change at 3 months (+2.68%, IQR: -1.14 to 9.09 vs -0.43%, -6.60 to 2.29; p=0.036) in the malnourished patients from both cohorts. Further studies will be conducted to evaluate the scale of the effectiveness of early intervention and close nutritional monitoring, in improving the nutritional status of children with cancer. The collaborative partnership among the doctors, nurses and dietitians has helped to streamline and simplify nutrition screening, making it an efficient and sustainable system in our hospital.

Neutralizing Activity and SARS-CoV-2 Vaccine mRNA Persistence in Serum and Breastmilk After BNT162b2 Vaccination in Lactating Women.

Background: There is limited information on the functional neutralizing capabilities of breastmilk SARS-CoV-2-specific antibodies and the potential adulteration of breastmilk with vaccine mRNA after SARS-CoV-2 mRNA vaccination. Methods: We conducted a prospective cohort study of lactating healthcare workers who received the BNT162b2 vaccine and their infants. The presence of SARS-CoV-2 neutralizing antibodies, antibody isotypes (IgG, IgA, IgM) and intact mRNA in serum and breastmilk was evaluated at multiple time points using a surrogate neutralizing assay, ELISA, and PCR, over a 6 week period of the two-dose vaccination given 21 days apart. Results: Thirty-five lactating mothers, median age 34 years (IQR 32-36), were included. All had detectable neutralizing antibodies in the serum immediately before dose 2, with significant increase in neutralizing antibody levels 7 days after this dose [median 168.4 IU/ml (IQR 100.7-288.5) compared to 2753.0 IU/ml (IQR 1627.0-4712.0), p <0.001]. Through the two vaccine doses, all mothers had detectable IgG1, IgA and IgM isotypes in their serum, with a notable increase in all three antibody isotypes after dose 2, especially IgG1 levels. Neutralizing antibodies were detected in majority of breastmilk samples a week after dose 2 [median 13.4 IU/ml (IQR 7.0-28.7)], with persistence of these antibodies up to 3 weeks after. Post the second vaccine dose, all (35/35, 100%) mothers had detectable breastmilk SARS-CoV-2 spike RBD-specific IgG1 and IgA antibody and 32/35 (88.6%) mothers with IgM. Transient, low intact vaccine mRNA levels was detected in 20/74 (27%) serum samples from 21 mothers, and 5/309 (2%) breastmilk samples from 4 mothers within 1 weeks of vaccine dose. Five infants, median age 8 months (IQR 7-16), were also recruited - none had detectable neutralizing antibodies or vaccine mRNA in their serum. Conclusion: Majority of lactating mothers had detectable SARS-CoV-2 antibody isotypes and neutralizing antibodies in serum and breastmilk, especially after dose 2 of BNT162b2 vaccination. Transient, low levels of vaccine mRNA were detected in the serum of vaccinated mothers with occasional transfer to their breastmilk, but we did not detect evidence of infant sensitization. Importantly, the presence of breastmilk neutralising antibodies likely provides a foundation for passive immunisation of the breastmilk-fed infant.

Reassessing the Use of Proton Pump Inhibitors and Histamine-2 Antagonists in Critically Ill Children: A Systematic Review and Meta-Analysis.

OBJECTIVE: To determine the associations of stress ulcer prophylaxis with gastrointestinal (GI) bleeding, nosocomial pneumonia (NP), mortality, and length of stay in the pediatric intensive care unit (PICU). STUDY DESIGN: We conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) and observational studies in the English language assessing the effects of proton pump inhibitors and histamine-2 receptor antagonists on patients in the PICU published before October 2018 from the PubMed, Embase, CINAHL, and Cochrane Central Register of Controlled Trials databases. A random-effects Mantel-Haenszel risk difference (MHRD) model was used to pool all the selected studies for meta-analysis. Primary outcomes were the incidences of GI bleeding and NP. Secondary outcomes included mortality and length of PICU stay. RESULTS: Seventeen studies (4 RCTs and 13 observational studies) with a total of 340 763 patients were included. The overall incidence of GI bleeding was 15.2%. There was no difference in the risk of GI bleeding based on stress ulcer prophylaxis status (MHRD, 5.0%; 95% CI, -1.0% to 11.0%; I2 = 62%). There was an increased risk of NP in patients who received stress ulcer prophylaxis compared with those who did not (MHRD, 5.3%; 95% CI, 3.5%-7.0%; I2 = 0%). An increased risk of mortality was seen in patients receiving stress ulcer prophylaxis (MHRD, 2.1%; 95% CI, 2.0%-2.2%; I2 = 0%), although this association was no longer found when 1 large study was removed in a sensitivity analysis. There was no statistically significant difference in length of PICU stay between the groups (standardized mean difference, 0.42 days; 95% CI, -0.16 to 1.01 days; I2 = 89.8%). CONCLUSIONS: Stress ulcer prophylaxis does not show a clear benefit in reducing GI bleeding or length of PICU stay. Observational studies suggest an increased risk of NP and mortality with stress ulcer prophylaxis, which remains to be validated in clinical trials.

How to Feed the Critically Ill-A Review.

INTRODUCTION: Number of recently published studies on nutritional support in the intensive care unit (ICU) have resulted in a paradigm shift of clinical practices. This review summarises the latest evidence in four main topics in the ICU, namely: (1) function of validated nutrition screening/assessment tools, (2) types and validity of body composition measurements, (3) optimal energy and protein goals, and (4) delivery methods. METHODS: Recent studies that investigated the above aims were outlined and discussed. In addition, recent guidelines were also compared to highlight the similarities and differences in their approach to the nutrition support of critically ill patients. RESULTS: Regardless of nutritional status and body composition, all patients with >48 hours of ICU stay are at nutrition risk and should receive individualised nutrition support. Although a recent trial did not demonstrate an advantage of indirect calorimetry over predictive equations, it was recommended that indirect calorimetry be used to set energy targets with better accuracy. Initiation of enteral nutrition (EN) within 24-48 hours was shown to be associated with improved clinical outcomes. The energy and protein goals should be achieved gradually over the first week of ICU stay. This practice should be protocolised and regularly audited as critically ill patients receive only part of their energy and protein goals. CONCLUSIONS: Metabolic demands of critically ill patients can be variable and nutrition support should be tailored to each patient. Given that many nutrition studies are on-going, we anticipate improvements in the individualisation of nutrition support in the near future.

Use of an Electronic Feeds Calorie Calculator in the Pediatric Intensive Care Unit.

Strategies to improve nutritional management are associated with better outcomes in pediatric intensive care units. We implemented a calorie-based protocol that integrated an electronic feeds calculator and stepwise feeds increment algorithm. METHODS: Using a pretest-posttest design, we compared the effectiveness of the calorie-based protocol with an existing fluid-based protocol in a quality improvement project. The main outcome measure was the proportion of patients prescribed with the appropriate amount of calories (defined as 90%-110% of calculated energy requirements). Nurses were surveyed on their satisfaction with the new calorie-based protocol. We compared consecutive patients enrolled in the calorie-based protocol over 21 months with retrospective data of patients in the fluid-based protocol. χ 2 and Mann-Whitney U tests were used to compare categorical and continuous variables, respectively. RESULTS: We enrolled 75 and 92 patients in the fluid-based (pre) and calorie-based (post) protocols, respectively. Both groups did not differ in their age, reasons for pediatric intensive care units admissions, length of stay, duration of mechanical ventilation, and risks of mortality. The frequency of appropriate feeds prescription increased (16.0% versus 33.7%, P = 0.002). The new protocol significantly reduced the time from protocol initiation to full feeds (median: 18.0 hours, interquartile range = 18.0-27.5 versus median: 12.8 hours, interquartile range = 12.0-16.0, P < 0.001). The satisfaction surveys (n = 63) revealed favorable nursing perceptions. CONCLUSIONS: The use of a calorie-based protocol with an electronic calculator led to an improvement in the accuracy of the prescribed feeds and the time required to attain full enteral feeding. Nursing perceptions regarding the protocol were positive.

Prediction of Acquired Morbidity Using Illness Severity Indices in Pediatric Intensive Care Patients.

OBJECTIVES: To assess the ability of two illness severity scores, Pediatric Logistic Organ Dysfunction Score 2 and Pediatric Index of Mortality 3, in predicting PICU-acquired morbidity. DESIGN: Retrospective chart review conducted from April 2015 to March 2016. SETTING: Single-center study in a multidisciplinary PICU in a tertiary pediatric hospital in Singapore. PATIENTS: The study included all index admissions of patients 0-18 years old to the PICU during the study period. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Three outcomes were assessed at hospital discharge: mortality, survival with new morbidity defined as an increase in the Functional Status Scale score of greater than or equal to 3 points from baseline, and survival without morbidity. Of 577 consecutive admissions, 95 were excluded: 82 readmissions, 10 patients greater than or equal to 18 years old, two patients with missing baseline data, and one transferred to another PICU. Of 482 patients, there were 37 hospital deaths (7.7%) and 39 (8.1%) with acquired new morbidity. Median admission Pediatric Logistic Organ Dysfunction Score 2 and Pediatric Index of Mortality 3 scores differed among the three outcome groups. In addition, differences were found in emergency admission and neurologic diagnosis rates, PICU mechanical ventilation usage rates, and PICU length of stay. The highest proportion of neurologic diagnoses was observed in the new morbidity group. The final model simultaneously predicted risks of mortality, survival with new morbidity and survival without morbidity using admission Pediatric Logistic Organ Dysfunction Score 2 score, admission type, neurologic diagnosis, and preexisting chronic disease. Pediatric Logistic Organ Dysfunction Score 2 was superior to Pediatric Index of Mortality 3 in predicting risks of mortality and new morbidity, as indicated by volume under surface values of 0.483 and 0.362, respectively. CONCLUSIONS: Risk of mortality, survival with new morbidity, and survival without morbidity can be predicted simultaneously using admission Pediatric Logistic Organ Dysfunction Score 2, admission type, admission diagnosis, and preexisting chronic disease. Future independent studies will be required to validate the proposed model before clinical implementation.