Research developments in pediatric intensive care nutrition: A research intelligence review.

BACKGROUND & AIMS: Pediatric intensive care nutrition is a growing research field on the intersection of three large research domains: Pediatrics, Critical Care Medicine and Nutrition & Dietetics. This study, using Research Intelligence tools, such as bibliometric network visualization software, was designed to map the developments in research topics and collaboration in the field over the past thirty years, and discuss how these developments align with recent recommendations and guidelines of the active expert groups in the field. METHODS: We searched the Web of Science Core Collection for relevant full articles, reviews, letters and proceedings papers. To describe the research field a search strategy was iteratively designed based on the combinations of relevant key words. The articles the were found were processed using software designed for bibliometric network mapping. Filters were applied to select only the most relevant articles for the field. RESULTS: The resulting visualizations show the network of researchers active in the field of pediatric intensive care nutrition, and the collaborations between them. Using the most frequently used key terms a map was created to show the most prominent research areas within the field, and the development of attention for these topics over time. CONCLUSIONS: The network analyses show a research field that is gaining momentum, with several cores of research activity in different institutions. Some research groups collaborate on specific topics within the field, while others seem to be more isolated. The analyses uncover the potential for future collaborations and emerging topics of attention in the different areas of research in the field. The results are compared to recent recommendations for research priorities by active networks in the field. We discuss similarities and discrepancies.

Pedi-R-MAPP: The development of a nutritional awareness tool for use in remote paediatric consultations using a modified Delphi consensus.

BACKGROUND & AIMS: The Remote Malnutrition Application (R-MAPP) was developed during the COVID-19 pandemic to provide support for health care professionals (HCPs) working in the community to complete remote nutritional assessments, and provide practical guidance for nutritional care. The aim of this study was to modify the R-MAPP into a version suitable for children, Pediatric Remote Malnutrition Application (Pedi-R-MAPP), and provide a structured approach to completing a nutrition focused assessment as part of a technology enabled care service (TECS) consultation. METHODS: A ten-step process was completed: 1) permission to modify adult R-MAPP, 2) literature search to inform the Pedi-R-MAPP content, 3) Pedi-R-MAPP draft, 4) international survey of HCP practice using TECS, 5) nutrition experts invited to participate in a modified Delphi process, 6) first stakeholder meeting to agree purpose/draft of the tool, 7) round-one online survey, 8) statements with consensus removed from survey, 9) round-two online survey for statements with no consensus and 10) second stakeholder meeting with finalisation of the Pedi-R-MAPP nutrition awareness tool. RESULTS: The international survey completed by 463 HCPs, 55% paediatricians, 38% dietitians, 7% nurses/others. When HCPs were asked to look back over the last 12 months, dietitians (n = 110) reported that 5.7 ± 10.6 out of every 10 appointments were completed in person; compared to paediatricians (n = 182) who reported 7.5 ± 7.0 out of every 10 appointments to be in person (p < 0.0001), with the remainder completed as TECS consultations. Overall, 74 articles were identified and used to develop the Pedi-R-MAPP which included colour-coded advice using a traffic light system; green, amber, red and purple. Eighteen participants agreed to participate in the Delphi consensus and completed both rounds of the modified Delphi survey. Agreement was reached at the first meeting on the purpose and draft sections of the proposed tool. In round-one of the online survey, 86% (n = 89/104) of statements reached consensus, whereas in round-two 12.5% (n = 13/104) of statements reached no consensus. At the second expert meeting, contested statements were discussed until agreement was reached and the Pedi-R-MAPP could be finalised. CONCLUSION: The Pedi-R-MAPP nutrition awareness tool was developed using a modified Delphi consensus. This tool aims to support the technological transformation fast-tracked by the COVID-19 pandemic by providing a structured approach to completing a remote nutrition focused assessment, as well as identifying the frequency of follow up along with those children who may require in-person assessment.

Achieving enteral nutrition during the acute phase in critically ill children: Associations with patient characteristics and clinical outcome.

BACKGROUND & AIMS: In the absence of methodologically sound randomized controlled trials (RCTs), current recommendations for timing and amount of enteral nutrition (EN) in critically ill children are based on observational studies. These studies have associated achievement of a higher EN intake in critically ill children with improved outcome. Inherent to the observational design of these underlying studies, thorough insight in possible confounding factors to correct for is essential. We evaluated the associations between EN intake and 1) patient and daily clinical characteristics and 2) clinical outcomes adjusted for these patient and clinical characteristics during the first week of critical illness with a multivariable mixed model. METHODS: This secondary analysis of the multicentre PEPaNIC RCT investigated a subgroup of critically ill children with daily prospectively recorded gastrointestinal symptoms and EN intake during the first week with multivariable analyses using two-part mixed effect models, including multiple testing corrections using Holm's method. These models combined a mixed-effects logistic regression for the dichotomous outcome EN versus no EN, and a linear mixed-effects model for the patients who received any EN intake. EN intake per patient was expressed as mean daily EN as % of predicted resting energy expenditure (% of EN/REE). Model 1 included 40 fixed effect baseline patient characteristics, and daily parameters of illness severity, feeding, medication and gastrointestinal symptoms. Model 2 included these patient and daily variables as well as clinical outcomes. RESULTS: Complete data were available for 690 children. EN was provided in 503 (73%) patients with a start after a median of 2 (IQR 2-3) days and a median % of EN/REE of 38.8 (IQR 14.1-79.5) over the first week. Multivariable mixed model analyses including all patients showed that admission after gastrointestinal surgery (-49%EN/REE; p = 0.002), gastric feeding (-31% EN/REE; p < 0.001), treatment with inotropic agents (-22%EN/REE; p = 0.026) and large gastric residual volume (-64%EN/REE; p < 0.001) were independently associated with a low mean EN intake. In univariable analysis, low mean EN intake was associated with new acquired infections, hypoglycaemia, duration of PICU and hospital stay and duration of mechanical ventilation. However, after adjustment for confounders, these associations were no longer present, except for low EN and hypoglycaemia (-39%EN/REE; p = 0.018). CONCLUSIONS: Several patient and clinical characteristics during the first week of critical illness were associated with EN intake. No independent associations were found between EN intake and clinical outcomes such as mortality, new acquired infection and duration of stay. These data emphasize the necessity of adequate multivariable adjustment in nutritional support research and the need for future RCTs investigating optimal EN intake.

Effect of late versus early initiation of parenteral nutrition on weight deterioration during PICU stay: Secondary analysis of the PEPaNIC randomised controlled trial.

BACKGROUND & AIMS: Critically ill children are at increased risk of weight deterioration in the paediatric intensive care unit (PICU). Whether early initiation of parenteral nutrition (PN) prevents weight deterioration is unknown. The aims of this study were to assess the effect of withholding supplemental PN during the first week on weight Z-score change in PICU and to evaluate the association between weight Z-score change in the PICU and clinical outcomes. METHODS: This is a secondary analysis of the Paediatric Early versus Late Parenteral Nutrition in Intensive Care Unit (PEPaNIC) randomised controlled trial (N = 1440), which focused on the subgroup of patients with longitudinal weight Z-scores available on admission and on the last day in PICU. Patients were randomly allocated to initiation of supplemental PN after one week (Late-PN) or within 24 h (Early-PN) when enteral nutrition was insufficient. The effect of Late-PN versus Early-PN on the change in weight Z-score was investigated, adjusted for risk factors. Moreover, the association between weight Z-score change and clinical outcomes was explored, adjusted for risk factors. RESULTS: Longitudinal weight Z-scores were available for 470 patients. Enteral nutrition intake was equal in the Early-PN and Late-PN group. Less weight Z-score deterioration during PICU stay was associated with a lower risk of new infections (adjusted OR per Z-score increase 0.72 [0.55-0.96], p = 0.02), and with a higher likelihood of an earlier discharge from PICU alive (adjusted HR per Z-score increase 1.22 [1.10-1.37], p < 0.001). During PICU-stay, the change in weight Z-score did not differ among both groups (Late-PN median 0.00 [-0.34-0.12] vs Early-PN median -0.03 [-0.48-0.01], adjusted ß = 0.10 [-0.05-0.25], p = 0.18). CONCLUSIONS: Weight deterioration during the PICU stay was associated with worse clinical outcomes. Withholding supplemental PN during the first week did not aggravate weight Z-score deterioration during PICU stay. TRIAL REGISTRATION: clinicaltrials.gov NCT01536275.

Definitions, predictors and outcomes of feeding intolerance in critically ill children: A systematic review.

BACKGROUND & AIMS: Clinicians and researchers often use feeding intolerance (FI) as main cause for insufficient enteral nutrition (EN). However, there is no uniform definition for FI. A uniform definition is essential for future studies focusing on predictors and outcomes of FI and enteral nutrition. A systematic review was performed to investigate the definitions, prevalence, predictors and outcomes of FI in critically ill children. METHODS: The databases Medline, Embase, Cochrane CENTRAL, Web of Science were searched. Inclusion criteria were interventional, observational or case-control studies (>10 patients) in which a definition of FI was reported in critically ill children (0-21 years). RESULTS: FI was defined in 31 unique studies performed in 2973 critically ill children. FI was most commonly defined as presence of gastrointestinal (GI) symptoms and/or large gastric residual volume (GRV) (n = 21), followed by discontinuation of EN due to GI symptoms (n = 7) and inadequate delivery of EN (n = 3). Median prevalence of FI was 20.0% [IQR 7.4%-33.0%]. Large GRV, abdominal distention, diarrhoea and vomiting/emesis, were the predominantly reported GI symptoms to define FI. FI was associated with severity of illness, mortality and nosocomial infections. CONCLUSIONS: Feeding intolerance is inconsistently defined in the current literature, but appears to be a prevalent concern in critically ill children. FI is most frequently defined by the presence of GI symptoms. A standardized definition is needed for both clinical and research purpose to determine the consequences of FI in relation to short-term and long-term outcomes. The new proposed definition for FI entails the inability to achieve enteral nutrition target intakes in combination with the presence of GI symptoms indicating GI dysfunction. PROTOCOL REGISTRATION: PROSPERO registration number: CRD42018092967. Registered on 07 June 2018.

Weight improvement with the use of protein and energy enriched nutritional formula in infants with a prolonged PICU stay.

BACKGROUND: Reaching an optimal nutritional intake is challenging in critically ill infants. One possible way to minimise nutritional deficits is the use of protein and energy-enriched (PE)-formulas. We aimed to describe weight achievement and gastrointestinal symptoms in infants admitted to the paediatric intensive care unit (PICU) while receiving PE-formula for a prolonged period. METHODS: Records from infants admitted to a multidisciplinary PICU and using PE-formula were analysed retrospectively. Infants were eligible if they received PE-formula daily for at least 2 weeks. Weight achievement was determined as the difference between weight-for-age (WFA) Z-scores at the start and end of PE-formula use. Gastrointestinal symptoms, including gastric residual volume, constipation and vomiting, were evaluated as tolerance parameters. RESULTS: Seventy infants with a median [interquartile range (IQR)] age of 76 (30-182) days were eligible. The PICU duration was 50 (35-83) days during which they received PE-formula for 30 (21-54) days. Predominant admission diagnoses were post-cardiac surgery, respiratory and cardiac diagnosis. A significant mean (SD) WFA Z-score increase of 0.48 (1.10) (P < 0.001) and a median (IQR) weight gain of 5.80 (3.28-9.04) g kg-1 day-1 was observed. Multivariate regression showed that a lower WFA Z-score at start was associated with a higher WFA Z-score increase during PE-formula use (ß -0.35 (95% confidence interval =  -0.50 to -0.19); P < 0.001). The maximum 24-h gastric residual volume was 8.1 mL (IQR = 2.2-14.3) for each 1 kg in bodyweight. Three (4%) infants were treated for diarrhoea and three infants were treated for vomiting. CONCLUSIONS: The majority of infants with a prolonged PICU stay showed weight improvement when using PE-formula. PE-formula was well tolerated because gastrointestinal symptoms only occurred in few infants.

Current clinical trials in paediatrics: Report of the ESPEN special interest group in paediatrics.

BACKGROUND & AIMS: At the 38th annual ESPEN congress in The Hague, the Netherlands, the Special Interest Group (SIG) in Paediatrics presented data about current research activities in the field of paediatric nutrition which are performed worldwide and translated this to future research perspectives. METHODS: Extensive search of all registered observational and interventional clinical trials in the database ClinicalTrials.gov using the search terms: children nutrition, paediatrics nutrition and children feeding. RESULTS: A total of 717 studies were found; 173 were duplicates and 114 included adult participants and were therefore excluded. Hence, 430 remained for analysis, of which 69% were randomized controlled trials. The most investigated research topic was nutrition in specific diseases (n = 98), followed by obesity (n = 92), and studies including premature infants (n = 48). The overall median estimated enrolment of children in the trials was 150 children [IQR 50-365]. There were 44 studies in which >1000 participants will be enrolled and six studies with >10,000 participants. Studies including >1000 participants were primarily performed in North America (39%), Africa (27%), and Europe (16%). CONCLUSIONS: This SIG report showed that 430 clinical nutrition trials in paediatrics are registered and current research focusses primarily on specific diseases and obesity. The SIG paediatrics encourages future research to invest in well-controlled interventional trials.

Promoting intestinal adaptation by nutrition and medication.

The ultimate goal in the treatment of short bowel syndrome is to wean patients off parenteral nutrition, by promoting intestinal adaptation. Intestinal adaptation is the natural compensatory process that occurs after small bowel resection. Stimulating the remaining bowel with enteral nutrition can enhance this process. Additionally, medication can be used to either reduce factors that complicate the adaptation process or to stimulate intestinal adaptation, such as antisecretory drugs and several growth factors. The aim of this review was to provide an overview of the best nutritional strategies and medication that best promote intestinal adaptation.

Achieving energy goals at day 4 after admission in critically ill children; predictive for outcome?

BACKGROUND & AIMS: Adequate nutritional intake is essential during pediatric intensive care admission. We investigated whether achievement of energy intake goals at day 4 after admission and route of nutrition were associated with improved outcome. METHODS: Observational study using prospectively acquired data. Patients receiving enteral and/or parenteral nutrition were included. The energy intake target range at day 4 after admission was 90-110% of resting energy expenditure +10%. Acute malnutrition was defined as weight-for-age <-2 SD. Clinical outcome measures were length of stay, days on ventilator, duration of antibiotics and number of new infections. Data as median (min-max). RESULTS: Of 325 subjects (age 0.14 (0.0-18.0) year), 19% were acutely malnourished upon admission. Median 86% of energy goals were administered via the enteral route. With enteral energy intake, 7% of patients were fed within the target range, 50% were fed below and 43% were fed above the target range. In a subgroup (n = 223) the acutely malnourished proportion at discharge (26%) was not significantly different from that upon admission (22%). Whether the energy intake was below, within or above the target range did not affect changes in clinical outcome, nor did the route of nutrition. CONCLUSIONS: Acute malnutrition was highly prevalent upon admission and at discharge. With our nutritional protocol we achieved high rates of (enteral) energy intake. A high percentage of our population received enteral energy above the target energy range. However, there was no association between the amount of energy intake or route of nutrition and clinical outcome.

National malnutrition screening days in hospitalised children in The Netherlands.

OBJECTIVE: Nationwide prevalence studies on malnutrition in hospitalised children have not been done. This study aimed to investigate the prevalence of malnutrition of all newly admitted children in The Netherlands during 3 consecutive days. DESIGN: Prospective observational study. SETTING: Paediatric wards of 44 hospitals (7 academic and 37 general). PARTICIPANTS: A total of 424 children aged > or = 30 days and hospitalised for > or = 1 day were included, 63% male, 86% non-white. Median age was 3.5 years and median hospital stay was 2 days. MAIN OUTCOME MEASURES: SD scores ,22 for weight for height and height for age were considered to indicate acute and chronic malnutrition, respectively. RESULTS: Overall 19% of the children had acute and/or chronic malnutrition at admission (academic 22% and general 17%). The proportion of children with chronic malnutrition was significantly higher in academic hospitals (14% vs 6%). Logistic regression analysis allowing for age, underlying disease, ethnicity, surgery and type of centre showed a significant relation between the presence of malnutrition at admission and underlying disease (odds ratio (OR) 2.2). For chronic malnutrition both underlying disease and non-white ethnicity were significantly related to a higher prevalence (OR 3.7 and OR 2.8, respectively). Multiple regression analysis showed that children with acute malnutrition stayed on average 45% longer (95% CI 7% to 95%) in the hospital than children without such malnutrition. CONCLUSIONS: This unique nationwide study shows that 19% of children admitted to Dutch hospitals are malnourished at admission. This high prevalence underlines the need for routine screening and treatment of malnutrition in hospitalised children.