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The use of indirect calorimetry to determine energy requirements is highly recommended in critically ill patients. To facilitate this a new and easy to use calorimeter (Q-NRG+, Cosmed) was developed. The primary aim of our study was to describe the usefulness of this calorimeter and, secondarily, to investigate the agreement between measured and predicted energy needs in a large cohort of critically ill adult patients. A prospective observational study was conducted among adult mechanically ventilated patients with COVID-19. Indirect calorimetry (Q-NRG+) to measure resting energy expenditure (mREE) was performed in the first week after admission and, wherever possible, repeated weekly. Reasons for not performing indirect calorimetry were reported. Parameters of indirect calorimetry and patient's conditions during the measurements were collected. Measurements were defined as valid if less than 10% overall variation in VO 2 and VCO 2 and respiratory quotient ranges between 0.67 and 1.1 were observed. mREE was compared with predictive REE (pREE) using standard formulas to explore hypo (<90%)-and hypermetabolism. (>110%). Bland-Altman method and two-way mixed intraclass correlation coefficients (ICC) (single measures) were used to assess the agreement between mREE and pREE. Indirect calorimetric measurements were performed in 180 of the 432 admitted patients (42%). Of the 276 performed measurements 85% were valid, and of these 90% were used to tailor nutritional therapy. Most patients were male (71%), median age was 62 years [IQR 52; 70]. Logistical issues (absence of measuring staff, no device, no stock of disposables, MRSA isolation) and clinical issues (e.g Fio 2 >70%, detubated but still in ICU) were the main reasons for not performing indirect calorimetry. The majority of the REE-measurements indicated either hypo- or hypermetabolism (57% week 1 and 56% week 2). The correlation between mREE and pREE was very moderate (ICC = 0.527). Although indirect calorimetry was performed in less than half of the patients, it proved to be of value to guide nutritional therapy. We conclude that the technique is easily applicable and expect that its impact can be significantly increased with the resolution of logistical and organizational issues. [ABSTRACT FROM AUTHOR]

Critically ill children are fed day and night, assuming this improves enteral tolerance and the probability of achieving nutritional goals. It was previously shown that a fasting response, reflected by increased ketosis, at least partly explained the beneficial outcome of delayed initiation of supplemental parenteral nutrition. This study aims to investigate whether an overnight fast increases ketosis and is feasible and safe in critically ill children. The Continuous versus Intermittent Nutrition in Paediatric Intensive Care (ContInNuPIC) study is a randomised controlled trial in a tertiary referral Paediatric Intensive Care Unit (PICU) in the Netherlands. Critically ill children (term newborn-18 years) with an expected PICU stay ≥48 h, dependent on artificial nutrition, were eligible. Participants were randomly assigned (1:1, stratified for age group) to intermittent feeding, with interruption of feedings during an age-dependent overnight period of eight to 12 h, or to continuous feeding, with the administration of feedings day and night. In both groups, similar daily caloric targets were pursued. For children younger than one year, mandatory minor glucose infusions were provided during fasting. The primary outcome was the feasibility, defined as two conditions (1): a significant difference in the patients' highest daily ketone (3-β-hydroxybutyrate, BHB) levels during each overnight period, and (2): non-inferiority regarding daily caloric intake, examined using a two-part mixed-effects model with a predefined non-inferiority margin of 33%, in an intention-to-treat analysis. The study is registered in the Netherlands Trial Register (NL7877). Between May 19, 2020, and July 13, 2022, 140 critically ill children, median (first quartile; third quartile) age 0.3 (0.1; 2.7) years, were randomised to intermittent (n = 67) or continuous feeding (n = 73). In the intermittent feeding group, BHB levels were significantly higher (median 0.4 (0.2; 1.0) vs. 0.3 (0.1; 0.7) mmol/L, p < 0.001). The ratio of total caloric intake in the intermittent feeding group to the intake in the continuous feeding group was not consistently significantly more than 0.67, thus not proving non-inferiority. No severe, resistant hypoglycaemic events, nor severe gastrointestinal complications related to the intervention occurred, and feeding intolerance did not occur more often in the intermittent than in the continuous feeding group. Compared with day and night feeding, intermittent feeding with an overnight fast and mandatory glucose infusion for children younger than one year marginally increased ketosis and did not lead to more hypoglycaemic incidents in critically ill children. Because non-inferiority regarding daily caloric intake was not proven, the feasibility of an overnight fast could not be shown in the current study. However, as feeding intolerance did not increase during the condensed feeding periods, the nutritional intake was probably limited by the prescription of nutrition and interruptions. More research is needed to determine the optimal level and duration of clinically relevant ketosis and the best method to achieve this. • Intermittent feeding with an overnight fast is safe. • Ketones increase significantly during an overnight fast in critically ill children. • A condensed feeding period during the day does not lead to more feeding intolerance. • Intermittent feeding with an overnight fast might result in lower caloric intake. [ABSTRACT FROM AUTHOR]

Air-Displacement-Plethysmography (ADP) by BOD POD is widely used for body fat assessment in children. Although validated in healthy subjects, studies about use in pediatric patients are lacking. We evaluated user experience and usability of ADP measurements with the BOD POD system in healthy children and pediatric and young adult patients. Using the experiences of seven cohort studies, which included healthy children and patients aged 2–22 years, we retrospectively evaluated the user experience with the User Experience Questionnaire (UEQ) (n = 13) and interviews (n = 7). Technical performance was studied using the quality control data collected by the ADP-system. From 2016 to 2022, 1606 measurements were scheduled. BOD POD was mostly rated 'user-friendly', with a generally neutral evaluation on all scales of the UEQ. However, questionable reliability and validity of the results were frequently (86%) reported. We found a high technical failure-rate of the device, predominantly in stability (17%) and accuracy of the measurement (12%), especially in the 'pediatric option' for children aged <6 years. Measurement failure-rate was 38%, mostly due to subject's fear or device failure, especially in young and lean children, and in children with physical and/or intellectual disabilities. We conclude that ADP by BOD POD in children and young adults is non-invasive and user-friendly. However, in specific pediatric populations, BOD POD has several limitations and high (technical) failure-rates, especially in young children with aberrant body composition. We recommend caution when interpreting body composition results of pediatric patients as assessed with BOD POD using the current default settings. [ABSTRACT FROM AUTHOR]

Obstructive sleep apnea (OSA) is frequently present in patients with syndromic craniosynostosis. The aim of this study is to determine the long-term effectiveness of our OSA treatment protocol in our tertiary center in a cohort of children with syndromic craniosynostosis. Children with syndromic craniosynostosis born between January 2005 and December 2013 were eligible for inclusion (n = 114). Data from ambulatory and inhospital polysomnographies were used. The obstructive-apnea/hypopnea index was used for OSA classification. Polysomnographies were performed in 83 patients. Mild OSA was diagnosed in 19, moderate in six, and severe in seven children. Of the 32 patients with OSA, 12 patients (37.5%) initially received expectant care of which OSA resolved spontaneously in nine without recurrence. Twenty patients were surgically treated. Adenotonsillectomy (ATE) had a 90% success rate with no OSA recurrence. Monobloc surgery was performed in four patients with mild OSA, although not OSA-indicated. Monobloc was performed for moderate or severe OSA in six patients, in four patients in combination with ATE and with mandibular distraction in one. Monobloc surgery for moderate or severe OSA had a 100% success rate in treating OSA and decannulation. Expectant care is often sufficient to resolve mild OSA in patients with syndromic craniosynostosis, and should also be considered in patients with moderate OSA with close follow-up. ATE has an important role in the OSA treatment protocol. Monobloc surgery, combined with mandibular distraction on indication, is effective in resolving moderate to severe OSA with a stable long-term result. [ABSTRACT FROM AUTHOR]

Although evidence for the superiority of continuous feeding over intermittent feeding is lacking, in most paediatric intensive care units (PICU) artificial feeding is administered continuously for 24 h per day. Until now, studies in PICU on intermittent feeding have primarily focused on surrogate endpoints such as nutritional intake and gastro-intestinal complaints and none have studied the effects of an extended fasting period. Intermittent fasting has been proven to have many health benefits in both animal and human studies. The observed beneficial effects are based on multiple metabolic and endocrine changes that are presumed crucial in critical illness as well. One key element is the transition to ketone body metabolism, which, among others, contributes to the stimulation of several cellular pathways involved in stress resistance (neuro)plasticity and mitochondrial biogenesis, and might help preserve brain function. Secondly, the fasting state stimulates the activation of autophagy, a process that is crucial for cellular function and integrity. Of the different intermittent fasting strategies investigated, time-restricted feeding with a daily extended fasting period appears most feasible in the PICU. Moreover, planning the fasting period overnight could help maintain the circadian rhythm. Although not investigated, such an overnight intermittent fasting strategy might improve the metabolic profile, feeding tolerance and perhaps even have beneficial effects on tissue repair, reperfusion injury, muscle weakness, and the immune response. Future studies should investigate practical implications in critically ill children and the optimal duration of the fasting periods, which might be affected by the severity of illness and by age. [ABSTRACT FROM AUTHOR]

To evaluate the efficacy of therapeutic interventions on pediatric burn patients' height, weight, body composition, and muscle strength. A systematic literature search was conducted in PubMed, Embase, and Web of Science up to March 2021. Eligible interventional studies reported metrics on the height, weight, body composition, or muscle strength of pediatric burn patients in a peer-reviewed journal. Meta-analyses were performed if ≥ 2 trials of clinical homogeneity reported on an outcome measure at the same time point post-burn. Twenty-six interventional studies were identified, including twenty-two randomised controlled trials and four non-randomised trials. Most studies were conducted by a single institution. On average, the burn covered 45.3% (± 9.9) of the total body surface area. Three categories of interventions could be distinguished: rehabilitative exercise programs, pharmacologic agents, and nutrition support. Each of the interventions had a positive effect on height, weight, body composition, or muscle strength. The decision to initiate an intervention should be made on a case-by-case basis following careful consideration of the benefits and risks. In future research, it is important to evaluate the heterogeneity of intervention effects and whether participation in an intervention allowed pediatric burn patients to reach the physical and functional status of healthy peers. • Twenty-one out of twenty-four interventional studies were conducted by a single institution. • Categories of interventions included: rehabilitative exercise programs, pharmacologic agents, and nutrition support. • Pediatric patients had extensive burns covering, on average, 44.3% (± 9.5) of the total body surface area. • In future research, it is important to evaluate the heterogeneity of intervention effects. • Also, whether an intervention allowed pediatric burn patients to reach the physical and functional status of healthy peers. [ABSTRACT FROM AUTHOR]

Summary Background & aims Aggressive parenteral nutritional practices were implemented in clinical practice over a decade ago to prevent early growth retardation in preterm infants. We aimed to study adherence to current nutritional recommendations in a population of very preterm infants, and to evaluate growth in early life. Methods Preterm infants (gestational age <30 weeks and birth weight <1500 g) were included in a prospective observational cohort study. Data on parenteral and enteral intake were collected on days 1–7, 14, 21 and 28 (d28) of life. Growth data were collected at birth, at moment of maximal weight loss (dip), and either at discharge from the neonatal intensive care unit or at d28, whichever came first. Nutritional intakes were compared to recommendations of current guidelines. The target growth rate was 15–20 g/kg/d. Results Fifty-nine infants (63% male) were included. Median gestational age was 27 3/7 (interquartile range 25 6/7;28 4/7), and birth weight was 920 g (720;1200). Median macronutrient intakes were within or above the targets on all study days, but energy targets were not met before day 5. Median growth rates were 9.5 and 18.1 g/kg/d, when calculated from respectively birth and dip to discharge/d28. Eight (14%) versus 46 (78%) infants met the growth targets, when evaluated from respectively birth and dip to discharge/d28. Conclusions In this cohort, only energy intake up to day 5 was lower than recommended. Growth targets were achieved in the majority of the infants, but only when evaluated from dip onward, not from birth. [ABSTRACT FROM AUTHOR]

Summary Background & aims The reference method to study protein and arginine metabolism in critically ill children is measuring plasma amino acid appearances with stable isotopes during a short (4–8 h) time period and extrapolate results to 24-h. However, 24-h measurements may be variable due to critical illness related factors and a circadian rhythm could be present. Since only short duration stable isotope studies in critically ill children have been conducted before, the aim of this study was to investigate 24-h appearance of specific amino acids representing protein and arginine metabolism, with stable isotope techniques in continuously fed critically ill children. Methods In eight critically ill children, admitted to the pediatric (n = 4) or cardiovascular (n = 4) intensive care unit, aged 0–10 years, receiving continuous (par)enteral nutrition with protein intake 1.0–3.7 g/kg/day, a 24-h stable isotope tracer protocol was carried out. L-[ring- 2 H 5 ]-phenylalanine, L-[3,3- 2 H 2 ]-tyrosine, L-[5,5,5- 2 H 3 ]-leucine, L-[guanido- 15 N 2 ]-arginine and L-[5- 13 C-3,3,4,4- 2 H 4 ]-citrulline were infused intravenously and L-[ 15 N]-phenylalanine and L-[1- 13 C]leucine enterally. Arterial blood was sampled every hour. Results Coefficients of variation, representing intra-individual variability, of the amino acid appearances of phenylalanine, tyrosine, leucine, arginine and citrulline were high, on average 14–19% for intravenous tracers and 23–26% for enteral tracers. No evident circadian rhythm was present. The pattern and overall 24-h level of whole body protein balance differed per individual. Conclusions In continuously fed stable critically ill children, the amino acid appearances of phenylalanine, tyrosine, leucine, arginine and citrulline show high variability. This should be kept in mind when performing stable isotope studies in this population. There was no apparent circadian rhythm. Clinical trial register NCT01511354 on clinicaltrials.gov . [ABSTRACT FROM AUTHOR]

Summary Background & aims Indirect calorimetry (IC) is considered the gold standard to determine resting energy expenditure (REE) but its availability in PICUs worldwide is limited. Ventilator-derived VCO 2 could potentially improve the possibility of performing REE measurements. We investigated whether ventilator-derived VCO 2 values are comparable to IC-derived VCO 2 values and can clinically be used in clinical practice to determine REE. Methods VCO 2 -values were simultaneously collected in mechanically ventilated children from IC (Deltatrac ® ) and Servo-I ® ventilator on a minute base over at least 10 min period of steady state. REE was calculated using the modified Weir formula (for IC) or REE = 5.5*VCO 2 (L/min)*1440 (for the Servo-I values) and compared with frequently used predictive equations by Schofield and the WHO to calculate REE. Results Measurements were performed in 41 children; median age 2 years. The mean relative difference between VCO 2 measured by IC and Servo-I ® was 15.6% (p = 0.002), and limits of agreement in the Bland–Altman analysis were wide. Comparable measurements, defined as a difference ≤10% between IC and Servo-I ® VCO 2 values, were seen in 18 (44%) children, but this proportion was 70% in children ≥15 kg. In this group, REE could be accurately predicted using Servo-I ® derived VCO 2 values and this method was superior to the use of predictive equations. The Servo-I ® derived VCO 2 values were not sufficiently accurate for the large proportion of children weighing <15 kg. Conclusions In children ≥15 kg, VCO 2 measurements of the Servo-I ® seem sufficiently accurate for use in clinical practice and may be used to determine energy expenditure in the future. [ABSTRACT FROM AUTHOR]

There is widespread lack of consensus regarding treatment of airway obstruction in children with Robin Sequence. This study aimed to systematically summarize outcomes of non-surgical and surgical options to treat airway obstruction in children with Robin Sequence. The authors searched the Medline, EMBASE and CENTRAL databases. Studies primarily on mandibular distraction were excluded. Study quality was appraised with the Methodological Index for Non-Randomized Studies (MINORS) score. Forty-eight studies were included, of which 45 studies had a retrospective non-comparative set up, two studies had a prospective design and one study was a clinical trial. The mean MINORS score was 7.3 (range 3–10). The rates of successful relief of the airway obstruction (SRoAO) were: not available for orthodontic appliance (2 studies, n = 24), 67–100% for nasopharyngeal airway (6 studies, n = 126); 100 % for non-invasive respiratory support (2 studies, n = 12); 70–96% for tongue-lip adhesion (11 studies, n = 277); 50–84% for subperiosteal release of the floor of the mouth (2 studies, n = 47); 100% for mandibular traction (3 studies, n = 133); 100% for tracheostomy (1 study, n = 25). The complication rate ranged from zero to 55%. Although SRoAO rates seemed comparable, high-level evidence remains scarce. Future research should include description of the definition, treatment indication, and objective outcomes. [ABSTRACT FROM AUTHOR]

Summary Background Environmental influences during pregnancy are able to affect off spring phenotype with lifelong effects. Clinical applicable markers are needed to identify foetuses at risk for neonatal adiposity. This systematic review aims to 1) review the current literature on prenatal markers of neonatal fat mass, and 2) appraise the clinical applicability of the assessed markers. Methods A systematic literature search was conducted to identify studies meeting the following inclusion criteria: 1) original research papers in English; 2) research on dynamic and measurable prenatal markers of neonatal fat mass; 3) neonatal fat mass measurement within one month after birth, using the four-compartment model, magnetic resonance imaging, dual-energy X-ray absorptiometry or air displacement plethysmography. Two reviewers independently performed study selection, assessment of methodological (QUADAS-II) and statistical quality and appraisal of clinical applicability. Results Of 2333 studies primarily identified by the search strategy, 16 studies were included. Four of these were both methodologically and statistically of moderate or high quality. Prenatal markers investigated were ultrasound parameters, maternal biochemical markers and maternal characteristics. Markers of predefined interest were maternal pre-pregnancy body mass index, fasting glucose and HbA1c, showing varying results. A meta-analysis was not possible due to substantial methodological heterogeneity. Clinically applicability of all markers was rated poor. Conclusions Although associations were found, no useful marker was identified, due to lack of methodological and statistical quality, inconsistent results and poor clinical applicability. No markers were investigated in the periconceptional and embryonic period. [ABSTRACT FROM AUTHOR]

Introduction Obstructive sleep apnea (OSA) is highly prevalent in children with Apert and Crouzon syndromes. Although often related to midface hypoplasia, it is a multi-level problem for which routine midface advancement might be a suboptimal treatment choice. We therefore wished to: 1.) use upper airway endoscopy to examine the level of obstruction in children with OSA; 2.) determine the relationship between endoscopic assessment and OSA severity; and 3.) evaluate the effect of surgery on endoscopic assessment and OSA severity. Methods Prospective observational cohort study of patients considered for midface advancement, underwent upper airway endoscopy. Endoscopy findings were scored according to the system of Bachar, based on level (nose, uvulopalatine plane, tongue base, hypopharynx and larynx); and severity (no, partial or complete obstruction). Polysomnography was used to diagnose OSA. Results We included 22 children (Apert N = 10, Crouzon N = 12), 17 had OSA, 14 of whom had multilevel obstruction and 3 single-level obstruction. The endoscopy findings were correlated with OSA severity: R = 0.56, P = 0.01. Midface advancement (N = 8) reduced Bachar's severity index in 7 of 8 patients, and OSA in all patients. Conclusions OSA in children with Apert or Crouzon syndrome is often a multi-level problem. Upper airway endoscopy is essential to optimizing OSA treatment. [ABSTRACT FROM AUTHOR]

To provide an overview of current practice patterns with regard to Robin sequence (RS) patients in Europe, a survey was conducted among European clinicians. This online survey consisted of different sections assessing characteristics of the respondent and clinic, definition, diagnosis, treatment, and follow-up. In total, surveys from 101 different European clinics were included in the analysis, and 56 different RS definitions were returned. The majority (72%) of the respondents used a sleep study system to determine the severity of the airway obstruction. A total of 63% used flexible endoscopy and 16% used rigid endoscopy in the diagnostic process. Treatment of the airway obstruction differed considerably between the different countries. Prone positioning for mild airway obstruction was the treatment modality used most often (63%). When prone positioning was not successful, a nasopharyngeal airway was used (62%). Surgical therapies varied considerably among countries. For severe obstruction, mandibular distraction was performed most frequently. Three-quarters of the respondents noted the presence of catch-up growth in their patient population. This first European survey study on definition and management of RS shows that there are considerable differences within Europe. Therefore, we would encourage the establishment of national (and international) guidelines to optimize RS patient care. [ABSTRACT FROM AUTHOR]

Summary Background & aims Accurate assessment of resting energy expenditure (REE) and metabolic state is essential to optimize nutrient intake in critically ill patients. We aimed to examine the accuracy of a simplified equation for predicting REE using carbon dioxide elimination (VCO 2 ) values. Methods We conducted a two-center study of metabolic data from mechanically ventilated children less than 18 years of age. Mean respiratory quotient (RQ) from the derivation set ( n = 72 subjects) was used to modify the Weir equation to obtain a simplified equation based on VCO 2 measurements alone. This equation was then applied to subjects at the second institution (validation dataset, n = 94) to predict resting energy expenditure. Bland-Altman analysis was used to assess the agreement between measured REE values, and REE estimated by the new equation as well as the Schofield equation. We also examined the accuracy of the new equation in classifying patients according to their metabolic state. Results Mean respiratory quotient (±SD) of 0.89 ± 0.09 in the derivation set was used to obtain a simplified equation, REE (kcal/day) = 5.534*VCO 2 (L/min)*1440. In relation to the measured REE in the validation set, the mean bias (limits of agreement) for the REE predicted by this equation was −0.65% (−14.4–13.1%); and the overall diagnostic accuracy for classifying subjects as hypometabolic or hypermetabolic was 84%. Mean bias (limits) of agreement between measured and Schofield equation estimated REE was −0.1% (−40.5–40.7%). Conclusions A simplified metabolic equation using VCO 2 values was superior to the standard equation in estimating REE, and provided a reasonably accurate metabolic classification in mechanically ventilated children. In the absence of indirect calorimetry, bedside VCO 2 monitoring could provide valuable continuous metabolic information to guide optimal nutrient intake. [ABSTRACT FROM AUTHOR]

Summary: Children who are admitted to the hospital are at a risk of developing undernutrition, especially children with an underlying disease. High percentages of both acute and chronic undernutrition have been reported in various Western countries for many years. Several nutritional screening tools have been developed for hospitalized children in the last years. This review gives an overview of the nutritional screening tools that are currently available with a focus on their aims, clinical use and validity. [Copyright &y& Elsevier]

Abstract: In syndromic craniosynostosis patients, respiratory insufficiency may be a pressing indication to surgically increase the patency of the upper airway by midface or monobloc advancement. In this study the volume changes of the upper airway and the respiratory outcome following midface (Le Fort I or III) or monobloc advancement in ten syndromic craniosynostosis patients are evaluated. Pre- and postoperatively, the airway volume was measured using a semi-automatic region growing method. Respiratory data were correlated to the volume measurements. In nine patients the outcome of upper airway volume measurements correlated well to the respiratory outcome. Three of these patients showed a minimal airway volume gain or even volume loss, and no respiratory improvement was found. In one monobloc patient improvement of the respiratory outcome without an evident volume gain of the upper airway was found. The majority of patients with Le Fort III advancement showed respiratory improvement, which for the greater part correlated to the results of the volume analysis. In monobloc patients the respiratory outcomes and volume measurements were less obvious. Preoperative endoscopy of the upper airway is advocated to identify the level of obstruction in patients with residual obstructive sleep apnoea. [Copyright &y& Elsevier]

Summary: Background & aims: To investigate the effects of two different glucose infusions on glucose homeostasis and amino acid metabolism in post-surgical children. Methods: This randomized crossover study evaluated glucose and amino acid metabolism in eight children (age 9.8 ± 1.9 months, weight 9.5 ± 1.1 kg) admitted to a pediatric intensive care unit in a tertiary university hospital after surgical correction for non-syndromal craniosynostosis. Patients were randomized to receive low (LG; 2.5 mg kg−1 min−1) and standard (SG; 5.0 mg kg−1 min−1) glucose infusion in a crossover setting. After a bolus (4 g kg−1) of deuterium oxide, we conducted a primed, constant, 8 h tracer infusion with [6,6-2H2]Glucose, [1-13C]Leucine, [ring-2H5]Phenylalanine and [3,3-2H2]Tyrosine. Results: SG resulted in hyperglycemia (defined as > 6.1 mmol L−1), while during LG plasma glucose levels were normoglycemic (5.9 ± 0.6 vs. 7.5 ± 1.7 mmol L−1; LG vs. SG respectively, p = 0.02). Hypoglycemia did not occur during LG infusion. Endogenous glucose production was not fully suppressed during the hyperglycemic state under SG and increased with reduced glucose infusion (2.6 ± 1.5 vs. 1.1 ± 1.4 mg kg−1 min−1; LG vs. SG; p = 0.05). Whole body protein balance derived from leucine and phenylalanine kinetics was slightly negative but not further affected with a decrease in glucose infusion. Conclusions: The current recommended glucose infusion induces hyperglycemia in post-surgical children. A reduced glucose infusion safely reduced high glucose levels, while children were capable to sustain normoglycemia with increased endogenous glucose production. The reduced glucose infusion did not exacerbate the mild catabolic state in which the patients were. [Copyright &y& Elsevier]

Summary: Background & aims: To investigate the effects of glucose, parenteral amino acids, and intravenous insulin on albumin synthesis rates in critically ill children. Methods: Two studies were performed in 8 post-surgical infants (age 9.8 ± 1.9 months; weight 9.5 ± 1.1 kg) and 9 septic adolescents (age 15 ± 1 yr; BMI 23 ± 4 kg m−2), respectively. All received a primed, constant, tracer infusion with [1-13C]Leucine. The infants in study 1 were randomized to receive low (2.5 mg kg−1 min−1) and standard (5.0 mg kg−1 min−1) glucose intake in a cross-over setting of two periods of 4 h each. The adolescents in study 2 were randomized to receive total parenteral nutrition with standard (1.5 g kg−1 day−1) and high (3.0 g kg−1 day−1) amino acid intake in a two day cross-over setting. On both study days, during the last 3 h of the tracer study, they received insulin infused at 80 mU m−2 min−1. Results: The post-surgical infants and the septic adolescents were mildly hypoalbuminemic (∼2.5 g dL−1) with high synthesis rates, which were not affected by different intakes of glucose, amino acids, or insulin infusion. Conclusions: Albumin synthesis rates in hypoalbuminemic critically ill children are high but were not upregulated through nutrient supply, and in septic adolescents are unaffected by insulin. [Copyright &y& Elsevier]

Abstract: Malnutrition in hospitalized children is still very prevalent, especially in children with underlying disease and clinical conditions. The purpose of this review is to describe current issues that have to be taken into account when interpreting prevalence data. Weight-for-height and height-for-age standard deviation scores are used for classification for acute and chronic malnutrition, respectively. Body mass index for age can also be used for the definition of acute malnutrition but has a few advantages in the general pediatric population. The new World Health Organization child-growth charts can be used as reference but there is a risk of over- and underestimation of malnutrition rates compared with country-specific growth references. For children with specific medical conditions and syndromes, specific growth references should be used for appropriate interpretation of nutritional status. New screening tools are available to identify children at risk for developing malnutrition during admission. Because of the diversity of medical conditions and syndromes in hospitalized children, assessment of nutritional status and interpretation of anthropometric data need a tailored approach. [Copyright &y& Elsevier]

Summary: Syndromic craniosynostosis is a congenital disorder characterised by premature fusion of calvarial sutures combined with other anomalies. The facial appearance is different and patients may show physical impairment, mental or developmental disabilities, elevated intracranial pressure and obstructive sleep apnoea. The impact of this condition on daily functioning has not been studied before. The aim of this study is to assess the health-related quality of life in children and adolescents with syndromic or complex craniosynostosis and to determine the impact of these syndromes on parents. A prospective study was performed in 111 children. Health-related quality of life was measured by international standardised quality-of-life questionnaires, the Infant Toddler Quality of Life Questionnaire (ITQoL), Child Health Questionnaire Parental Form 50 (CHQ-PF50), Child Health Questionnaire Child Form 87 (CHQ-CF87) and Short-Form Health Survey (SF-36). For comparison, we used Dutch population norms of health-related quality-of-life-scores. Parents'' scores for patients with syndromic or complex craniosynostosis were significantly lower than those for the norm population. Apert syndrome had the largest impact on the different domains. Scores on the CHQ-PF50 scales for ‘physical functioning’, ‘parental impact emotional’ and ‘family activities’ for these patients were significantly lower than scores for patients with other syndromes, possibly due to the complexity of the syndrome, which includes complex syndactyly, cognitive impairment and behaviour problems. Parents reported a reduced health-related quality of life for themselves, mostly psychosocial with clearly significantly lower general health perceptions. In conclusion, syndromic craniosynostosis has a large impact on the health-related quality of life of these children and their parents, both physical and psychosocial. [Copyright &y& Elsevier]

Summary: Background & aims: Children admitted to the hospital are at risk of developing malnutrition. The aim of the present study was to investigate the feasibility and value of a new nutritional risk screening tool, called STRONGkids, in a nationwide study. Methods: A Prospective observational multi-centre study was performed in 44 Dutch hospitals (7 academic and 37 general), over three consecutive days during the month of November 2007.The STRONGkids screening tool consisted of 4 items: (1) subjective clinical assessment, (2) high risk disease, (3) nutritional intake, (4) weight loss. Measurements of weight and length were performed. SD-scores <−2 for weight-for-height and height-for-age were considered to indicate acute and chronic malnutrition respectively. Results: A total of 424 children were included. Median age was 3.5 years and median hospital stay was 2 days. Sixty-two percent of the children were classified “at risk” of developing malnutrition by the STRONGkids tool. Children at risk had significantly lower SD-scores for weight-for-height, a higher prevalence of acute malnutrition and a longer hospital stay compared to children with no nutritional risk. Conclusions: The nutritional risk screening tool STRONGkids was successfully applied to 98% of the children. Using this tool, a significant relationship was found between having a “high risk” score, a negative SD-score in weight-for-height and a prolonged hospital stay. [Copyright &y& Elsevier]

Summary: Background & aims: Hyperglycemia is a major risk factor for increased morbidity and mortality in the intensive care unit. Insulin therapy has emerged in adult intensive care units and several pediatric studies are currently being conducted. This review discusses hyperglycemia and the effects of insulin on metabolic and non-metabolic pathways, with a focus on pediatric critical illness. Methods: A PubMed search was performed by using the following keywords and limits ((“hyperglycemia”[MeSH terms] or (“insulin resistance”[MeSH major topic]) and (“critical care”[MeSH terms] or “critical illness”[MeSH terms])) in different combinations with (“metabolism”[MeSH terms] or “metabolic networks and pathways”[MeSH terms]) and (“outcome”[all fields]) and (“infant”[MeSH terms] or “child”[MeSH terms] or “adolescent”[MeSH terms]). Quality assessment of selected studies included clinical pertinence, publication in peer-reviewed journals, objectivity of measurements and techniques used to minimize bias. Reference lists of such studies were included. Results: The magnitude and duration of hyperglycemia are associated with increased morbidity and mortality in the pediatric intensive care unit (PICU), but prospective, randomized controlled studies with insulin therapy have not been published yet. Evidence concerning the mechanism and the effect of insulin on glucose and lipid metabolism in pediatric critical illness is scarce. More is known about the positive effect on protein homeostasis, especially in severely burned children. The effect in septic children is less clear and seems age dependent. Some non-metabolic properties of insulin such as the modulation of inflammation, endothelial dysfunction and coagulopathy have not been fully investigated in children. Conclusion: Future studies on the effect of insulin on morbidity and mortality as well as on the mechanisms through which insulin exerts these effects are necessary in critically ill children. We propose these studies to be conducted under standardized conditions including precise definitions of hyperglycemia and rates of glucose intake. [Copyright &y& Elsevier]

Summary: Background & aims: To evaluate the course of hormonal parameters in relation to clinical parameters, illness severity and nutritional intake in children admitted to the pediatric ICU during the first week of admission. Methods: Prospective, observational study. Levels of triiodothyronine (T3), reverse T3 (rT3), ratio T3/rT3 and insulin-like growth factor I (IGF-1) were evaluated in 84 critically ill children (50 term neonates and 34 children aged 32d–15yr) admitted to our multidisciplinary tertiary pediatric intensive care unit within 24h after admission, on days 4 and 6 after admission. Changes in hormones levels over time were related to illness severity, C-reactive protein-levels and the adequacy of feeding. Results: For both age groups IGF-1 levels remained low until day 4, but at day 6 IGF-1 levels were significantly higher than admission level. In 88% and 89% of the older children, T3 levels remained below normal at days 4 and 6, respectively. In both age groups, rT3 levels declined significantly over time, whereas the ratio T3/rT3 increased. The increases in IGF-1, T3 and ratio T3/rT3 and decrease in rT3 were significantly associated with decreases in CRP-levels. No significant relations were found between changes in IGF-1 and thyroid hormone levels during admission and the adequacy of energy and protein intake. Conclusions: During the first week of ICU-admission, abnormalities in levels of IGF-1, T3 and rT3 were frequently observed in critically ill children, especially in the children aged >1 month. The adequacy of feeding did not seem to affect the normalization of IGF-1 and thyroid hormone levels. [Copyright &y& Elsevier]

Summary: Objectives: Laryngeal dyskinesia is not a well defined clinical entity, and difficult to distinguish from some other laryngeal disorders. We report on the observations, especially auditory brainstem responses, in a series of infants with laryngeal dyskinesia. Methods: All infants with laryngeal dyskinesia, diagnosed in Sophia Children''s Hospital between 1 January 2000 and 31 June 2003, were included in this retrospective case series study. Auditory brainstem responses were available in most infants. The respiratory, neurological and other symptoms, were recorded. Results: Nine infants were diagnosed with laryngeal dyskinesia. Eight demonstrated severely abnormal auditory brainstem responses (ABR), indicating brainstem dysfunction. Most infants also had serious respiratory, and/or neurological disorders. Discussion: It is hypothesized that laryngeal dyskinesia is a manifestation of a complex neurological disorder localized in the brainstem, comparable with brainstem dysgenesis syndrome. We suggest to use ABR in the diagnosis of unexplained laryngeal obstructive disorders to better define the pathology, and possibly the etiology of the disease. [Copyright &y& Elsevier]

Although the incidence of obstructive sleep apnea syndrome (OSAS) in craniofacial syndromes is high, it is often not recognized and, thus, not treated. In order to study the diagnostics and treatment options for these patients, we studied a group of 72 patients treated in our hospital for Apert, Crouzon or Pfeiffer syndrome, and compared our findings with the literature. There appears to be an agreement on polysomnography (PSG) and airway endoscopy as the main diagnostic options, but therapies are very diverse. Early diagnostics and prompt therapy will prevent serious complications. [Copyright &y& Elsevier]

Introduction Parents may play an important role during the management of children with Robin Sequence (RS). However, so far only one study has been done on both parent-reported health-related quality of life (HRQoL) and obstructive sleep apnea (OSA) symptoms in children with RS. Methods Overall, 63 children with RS, aged 1 and 18, were included in this cross-sectional study. Fifty-three parents of children with RS with a median age of 8.9 [IQR 5.1–12.7] completed questionnaires on HRQoL (OSA-18) and symptoms of OSA (the Brouillette score) in their child with RS. Ten children between 12 and 18 years filled out the self-reported HRQoL questionnaire OSA-12. Results At cross-section, 10 children still had respiratory problems. Overall, parents of children with RS reported a lower HRQoL in their child compared with parents in the general population. Parents of children with RS who still had respiratory problems, i.e. OSA or airway support, reported significantly worse OSA-18 scores compared with parents of RS children without OSA. Children with RS themselves (n = 10) reported less physical suffering and less emotional distress on the OSA-12 compared with children in the norm population. Parental perceptions of OSA-related symptoms were accurate, except for the incidence of snoring. In assessing snoring, the multidimensional OSA-18 sleep domain was more informative. Conclusions Parents of children with RS reported a lower HRQoL in their child compared with parents in the general population. Parental perceptions of health and HRQoL in children with RS might have an additional value to recognize and treat respiratory problems. [ABSTRACT FROM AUTHOR]

Abstract: Objective: The objective of this study was to investigate the relations of baseline insulin/glucose ratio to the clinical course of critically ill children. Such information will provide insight into the pathophysiologic mechanisms leading to hyperglycemia and will optimize preventive and therapeutic measures for hyperglycemia in critically ill children. Methods: Sixty-four consecutively admitted critically ill children with hyperglycemia, defined as a blood glucose level higher than 8 mmol/L (>145 mg/dL) and treated with insulin according to a glucose-control protocol, were included. Demographic data and clinical and laboratory parameters were collected. Insulin sensitivity was investigated by calculating the ratio of insulin to the blood glucose level just before the start of insulin administration. Results are expressed as median (range). Results: Sixty-four children (24 girls) 7.0 y of age (0.3–16.9 y) with various diagnoses were included. A hyperinsulinemic response, indicated by an increased insulin/glucose ratio (>18 pmol/mmol), was seen in 55% of children. The durations of insulin therapy, mechanical ventilation, and pediatric intensive care unit length of stay in children with a hyperinsulinemic response were longer than in children with a hypoinsulinemic response. Conclusion: Hyper- and hypoinsulinemic responses play a role in the occurrence of hyperglycemia in critically ill children. Each is associated with a particular clinical course after the initiation of insulin therapy. It would be worthwhile to further investigate if the insulinemic response to hyperglycemia, determined by the insulin/glucose ratio in combination with the type of organ dysfunction, could be used in clinical practice to determine the need for insulin therapy. [Copyright &y& Elsevier]

Abstract: Aims: The objectives of this study were to determine whether abnormal values of routine laboratory parameters at admission predict outcome and changes in anthropometric parameters in critically ill children during intensive care unit (ICU) stay and to discuss the clinical implications of abnormalities. Study design: This is a prospective descriptive study in a tertiary multidisciplinary pediatric ICU. Serum urea, albumin, triglycerides and magnesium were measured in samples obtained from 105 children (age, 7 days–16 years) within the first 24 h after their admission. The prevalences of abnormalities in these parameters as well as their possible association with outcome (length of stay, days on mechanical ventilation) and changes in nutritional status (changes in S.D. scores for weight, mid upper arm circumference and calf circumference) between admission and discharge were assessed. Results: Prevalences of hypomagnesemia, hypertriglyceridemia, uremia and hypoalbuminemia were 20%, 25%, 30% and 52%, respectively, with no significant associations between the different disorders. Except for uremia, no significant association was found between abnormalities in biochemical parameters and changes in S.D. scores of anthropometric measurements. Children with uremia showed larger declines in S.D. scores for weight and arm circumference between admission and discharge than children without uremia did. Children with hypertriglyceridemia had longer ventilator dependence (P<.01) and length of stay (P<.001) than children with normal triglyceride levels upon admission had. Conclusions: Abnormalities in routine nutritional laboratory parameters were frequently noted in critically ill children at admission. Detection of abnormalities was not predictive of changes in anthropometric parameters during ICU admission but can be important in individualizing nutritional support. [Copyright &y& Elsevier]

Abstract: Objective: We determined incidences of underfeeding and overfeeding in children who were admitted to a multidisciplinary tertiary pediatric intensive care and evaluated the usefulness of the respiratory quotient (RQ) obtained from indirect calorimetry to assess feeding adequacy. Methods: Children 18 y and younger who fulfilled the criteria for indirect calorimetry entered our prospective, observational study and were studied until day 14. Actual energy intake was recorded, compared with required energy intake (measured energy expenditure plus 10%), and classified as underfeeding (<90% of required), adequate feeding (90% to 110% of required), or overfeeding (>110% of required). We also evaluated the adequacy of a measured RQ lower than 0.85 to identify underfeeding, and an RQ higher than 1.0 to identify overfeeding. Results: Ninety-eight children underwent 195 calorimetric measurements. Underfeeding, adequate feeding, and overfeeding occurred on 21%, 10%, and 69% of days, respectively. An RQ lower than 0.85 to identify underfeeding showed low sensitivity (63%), high specificity (89%), and high negative predictive value (90%). An RQ higher than 1.0 to indicate overfeeding showed poor sensitivity (21%), but a high specificity (97%) and a high positive predictive value (93%). Food composition, notably high-carbohydrate intake, was responsible for an RQ exceeding 1.0 in the overfed group. Conclusion: Children admitted to the intensive care unit receive adequate feeding on only 10% of measurement days during the first 2 wk of admission. The usefulness of RQ to monitor feeding adequacy is limited to identifying (carbohydrate) overfeeding and excluding underfeeding. [Copyright &y& Elsevier]

This article reviews the development of research in the field of craniosynostosis from a bibliometric standpoint. Craniosynostosis is a malformation occurring during the early development of the skull, when one or more of the sutures close too early, causing problems with normal brain and skull growth. Research in this field has developed from early clinical case descriptions, to genetic discoveries responsible for the occurring malformations and onwards to developing sophisticated surgical treatment. In this article we describe these developments, zoom in on publication trends and characteristics and visualize developing networks and topic shifts in this research field. [ABSTRACT FROM AUTHOR]