Embryonic size and growth and adverse birth outcomes: the Rotterdam Periconception Cohort.

STUDY QUESTION: Is early embryonic size and growth in the first trimester of pregnancy associated with adverse birth outcomes? SUMMARY ANSWER: Larger embryonic crown-rump length (CRL) and embryonic volume (EV) are associated with lower odds of adverse birth outcomes, especially small for gestational age (SGA). WHAT IS ALREADY KNOWN: Preterm birth, SGA, and congenital anomalies are the most prevalent adverse birth outcomes with lifelong health consequences as well as high medical and societal costs. In the late first and second trimesters of pregnancy, fetuses at risk for adverse birth outcomes can be identified using 2-dimensional ultrasonography (US). STUDY DESIGN, SIZE, DURATION: Between 2009 and 2018, singleton pregnancies were enrolled in this ongoing prospective Rotterdam Periconception Cohort. PARTICIPANTS/MATERIALS, SETTING, METHODS: This study included 918 pregnant women from a tertiary hospital in the Netherlands. Pregnancy dating was based on either a regular menstrual cycle (for natural pregnancies) or a conception date (for ART pregnancies). CRL and EV were measured using Virtual Reality software on 3-dimensional (3D) ultrasound scans, repeatedly performed around 7, 9, and 11 weeks of gestation. The main outcome measure was adverse birth outcome, defined as the composite of SGA (birth weight <10th percentile), preterm birth (<37th week of gestation), congenital anomalies (Eurocat criteria), stillbirth (>16th week of pregnancy), or early neonatal mortality (≤7 days of life). Reference curves for CRL and EV were constructed. Cross-sectional (CRL/EV <20th percentile at 7, 9, and 11 weeks of gestation) and longitudinal (CRL/EV growth trajectories between 6th and 13th weeks) regression analyses were performed, with adjustments for the participants' educational level, smoking, parity, age, BMI, geographical background, mode of conception, and fetal sex. MAIN RESULTS AND THE ROLE OF CHANCE: Of the 918 pregnant women included, the median age was 32.3 years, and 404 (44%) pregnancies had been conceived via ART. In 199 (22%) pregnancies, there was an adverse birth outcome. Regression analyses showed that at 7 weeks of gestation onwards, embryos with a CRL <20th percentile had an ∼2-fold increased odds of adverse birth outcome (adjusted odds ratio (aOR) 2.03, 95% CI 1.21-3.39, P = 0.007). Similar associations were found for EV <20th percentile but were not statistically significant. These findings were mainly driven by the strong association between embryonic size and SGA (e.g. 7-week CRL: aOR 2.18 (1.16-4.09), P = 0.02; 9-week EV: aOR 2.09 (1.10-3.97, P = 0.02). Longitudinal growth trajectories of CRL, but not of EV, were associated with adverse birth outcomes. Both CRL and EV growth trajectories were associated with SGA. LIMITATIONS, REASONS FOR CAUTION: The tertiary hospital population and the availability of sophisticated 3D-ultrasound techniques limit the generalizability of this study to general populations and settings. WIDER IMPLICATIONS OF THE FINDINGS: Already very early in the first trimester of pregnancy, embryos with increased risks of an adverse birth outcome can be identified by using 3D-US and Virtual Reality. This expands the window of opportunity to enable the development of future interventions to potentially improve pregnancy outcomes and offspring health during their life-course. STUDY FUNDING/COMPETING INTEREST(S): This work was funded by the Department of Obstetrics and Gynecology, Erasmus MC, University Medical Centre, Rotterdam, The Netherlands. The authors declare no conflicts of interest. TRIAL REGISTRATION NUMBER: NL4115.

Early weight measures and long-term neuropsychological outcome of critically ill neonates and infants: a secondary analysis of the PEPaNIC trial.

Neonates and infants surviving critical illness show impaired growth during critical illness and are at risk for later neuropsychological impairments. Early identification of individuals most at risk is needed to provide tailored long-term follow-up and care. The research question is whether early growth during hospitalization is associated with growth and neuropsychological outcomes in neonates and infants after pediatric intensive care unit admission (PICU). This is a secondary analysis of the PEPaNIC trial. Weight measurements upon PICU admission, at PICU discharge, at hospital discharge, at 2- and 4-year follow-up, and of different subgroups were compared using (paired) t-tests. Multiple linear regression analyses were performed to investigate the association between early growth in weight measures and neuropsychological outcomes at 4-year follow-up. One hundred twenty-one infants were included, and median age upon admission was 21 days. Growth in weight per week was less than the age-appropriate norm, resulting in a decrease in weight-for-age Z-score during hospitalization. Weight is normalized at 2- and 4-year follow-up. Weight gain in kilograms per week and change in weight Z-score were not associated with neurodevelopmental outcome measures at 4-year follow-up. Lower weight-for-age Z-score at PICU admission and at hospital discharge was associated only with lower weight and height Z-scores at 4-year follow-up. CONCLUSION: Growth in weight during hospital stay of young survivors of critical illness is impaired. Worse early growth in weight is associated with lower weight and height but not with neuropsychological outcomes at 4-year follow-up. WHAT IS KNOWN: • Critically ill neonates and infants show impaired early growth during admission and are at risk for later neuropsychological impairments. • Unraveling the association between early growth and later neuropsychological impairments is crucial since the first year of life is critical for brain development. WHAT IS NEW: • Critically ill neonates and infants had age appropriate weight measures at 4-year follow-up. • Poor growth in weight during hospital stay was not associated with poorer cognitive, emotional, or behavioral functioning four years after critical illness.

Factors associated with laryngeal injury after intubation in children: a systematic review.

PURPOSE: The purpose of this study is to evaluate all potential factors associated with laryngeal injury after endotracheal intubation in the pediatric population. METHODS: A systematic literature search was conducted in Medline, Embase, Cochrane, web of science and Google scholar up to 20th of March 2023. We included all unique articles focusing on factors possibly associated with intubation-injury in pediatric patients. Two independent reviewers determined which articles were relevant by coming to a consensus, quality of evidence was rated using GRADE criteria. All articles were critically appraised according to the PRISMA guidelines. The articles were categorized in four outcome measures: post-extubation stridor, post-extubation upper airway obstruction (UAO) necessitating treatment, laryngeal injury found at laryngoscopy and a diagnosed laryngotracheal stenosis (LTS). RESULTS: A total of 24 articles with a total of 15.520 patients were included. The incidence of post-extubation stridor varied between 1.0 and 30.3%, of post-extubation UAO necessitating treatment between 1.2 and 39.6%, of laryngeal injury found at laryngoscopy between 34.9 to 97.0% and of a diagnosed LTS between 0 and 11.1%. Although the literature is limited and quality of evidence very low, the level of sedation and gastro-esophageal reflux are the only confirmed associated factors with post-extubation laryngeal injury. The relation with age, weight, gender, duration of intubation, multiple intubations, traumatic intubation, tube size, absence of air leak and infection remain unresolved. The remaining factors are not associated with intubation injury. CONCLUSION: We clarify the role of the potential factors associated with laryngeal injury after endotracheal intubation in the pediatric population.

The impact of obstructive sleep apnea on growth in patients with syndromic and complex craniosynostosis: a retrospective study.

Given the high prevalence of OSA in children with syndromic and complex craniosynostosis (SCC) and the consequences of untreated OSA, it is important to assess their nutritional status and growth. Yet, literature regarding growth in children with SCC remain scarce. Therefore, this study aimed to (1) illustrate the growth pattern in SCC, (2) determine the impact of OSA on this growth pattern, and (3) evaluate the effect of surgical treatment of OSA on growth over time. A retrospective study was performed in children with SCC, who were treated at the Dutch Craniofacial Center (Rotterdam, Netherlands). Growth variables (height, weight, weight-for-age standard-deviation-score (SDS), weight-for-height SDS, and height-for-age SDS) and degree of OSA (obstructive apnea-hypopnea index) were assessed. Of the 153 children with SCC, 38 (25%) were acutely malnourished at some point during follow-up, of whom 21 had disease-related acute malnutrition. Children with moderate-severe OSA had significant lower weight-for-height SDS compared to children without OSA (p = 0.0063). Growth parameters (weight-for-age SDS, weight-for-height SDS, height-for-age SDS) in children with SCC without OSA were not impaired as they did not differ from the normal healthy population, with exception of the patients with Saethre-Chotzen syndrome (SCS) who had a significantly lower SDS for height-for-age.   Conclusion: Children with SCC have a substantial chance of developing acute malnutrition at some point during growth. Additionally, in children with moderate-severe OSA, a significant lower SDS for weight-for-height is present, indicating the importance of assessing the weight and growth pattern in children who are clinically suspected for OSA. What is Known: • Obstructive sleep apnea is seen in up to two-thirds of the children with syndromic and complex craniosynostosis. • Presence of obstructive sleep apnea is associated with intracranial hypertension and an increased risk of metabolic, cardiovascular, and neurocognitive consequences later in life. Untreated obstructive sleep apnea may lead to impaired growth and weight gain, which can result in growth failure. What is New: • Craniosynostosis patients with moderate-severe obstructive sleep apnea had significant lower weight-for-height standard deviation scores (SDS), compared to children without obstructive sleep apnea.  • Children with syndromic and complex craniosynostosis without OSA did not significantly differ from the normal healthy population in regard to weight-for-age SDS, weight-for-height SDS, and height-for-age SDS.

Post-extubation stridor after prolonged intubation in the pediatric intensive care unit (PICU): a prospective observational cohort study.

PURPOSE: Prolonged endotracheal intubation may lead to laryngeal damage, with stridor being the most relevant clinical symptom. Our objective was to determine the incidence of post-extubation stridor and their clinical consequences in children within a tertiary referral center and to identify contributing factors. METHODS: 150 children, aged 0-16 years, intubated for more than 24 h were prospectively enrolled until discharge of the hospital. Potential relevant factors, thought to mediate the risk of laryngeal damage, were recorded and analyzed. RESULTS: The median duration of intubation was 4 days, ranging from 1 to 31 days. Stridor following extubation occurred in 28 patients (18.7%); 3 of them required reintubation due to respiratory distress and in 1 child stridor persisted for which a surgical intervention was necessary. In multivariate analyses, we found the following independent predictors of stridor: intubation on the scene, the use of cuffed tubes and lower age. CONCLUSION: Despite a high incidence for post-extubation stridor, only few children need reintubation or surgical intervention as a result of post-extubation lesions. Intubation on the scene, the use of cuffed tubes and young age are associated with a significant increased risk of post-extubation stridor. Awareness of these factors gives the possibility to anticipate on the situation and to minimize laryngeal injury and its possible future consequences.

Peptide nutrient-energy dense enteral feeding in critically ill infants: an observational study.

BACKGROUND: Enteral feeding is challenging in critically ill infants. Target intakes are often not achieved as a result of fluid restriction, procedural interruptions and perceived enteral feeding intolerance. In those infants perceived to have poor feeding tolerance, the use of a peptide nutrient-energy dense enteral feed (PEF) may improve nutritional intake and minimise feeding interruptions as a result of gastrointestinal symptoms. The aim of this observational study was to characterise the use of a PEF amongst critically ill infants in two paediatric intensive care units (PICUs). METHODS: Records from critically ill infants aged <12 months admitted to two PICUs were retrospectively reviewed with a PICU length of stay (LOS) ≥ 7 days. Achievement of nutritional targets for the duration of PEF was reviewed. Gastrointestinal symptoms, including gastric residual volume, constipation and vomiting, were evaluated as tolerance parameters. RESULTS: In total, 53 infants were included, with a median age on admission of 2.6 months. Median admission weight was 3.9 kg in PICU-1 and 4.7 kg in PICU-2. Median (interquatile range) energy intake in PICU-1 and PICU-2 was 68 (47-92) and 90 (63-124) kcal kg-1 , respectively, and median (interquatile range) protein intake 1.7 (1.1-2.4) g kg-1 and 2.5 (1.6-3.2) g kg-1 , respectively. Feeding was withheld because of feeding intolerance in one infant (4%) on two occasions in PICU-1 for 2.5 h and in two infants (7%) on two occasions in PICU-2 for 19.5 h. Gastric residual mean (SD) volumes were 3.5 (5.4) mL kg-1 in PICU-1 and 16.9 (15.6) mL kg-1 in PICU-2. CONCLUSIONS: Peptide nutrient-energy dense feeding in infants admitted to the PICU is feasible, well tolerated and nutritional targets are met. However, with this study design, it is not possible to draw any conclusions regarding the benefit of PEF over standard PE feed in critically ill children and future work is required to clarify this further.

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.

Atypical presentation of a newborn with Apert syndrome.

INTRODUCTION: Apert syndrome is a rare syndrome characterized by a consistent phenotype including bilateral coronal suture synostosis with an enlarged anterior fontanel, midface hypoplasia, and complex symmetric syndactyly of hands and feet. CASE REPORT: We present a boy with Apert syndrome caused by the pathogenic c.755C > G p.Ser252Trp mutation in the FGFR2 gene with atypical characteristics, including premature fusion of the metopic suture with a small anterior fontanel, hypotelorism, and a massive posterior fontanel. Directly after birth, he showed papilledema, epilepsy, and central apneas. CONCLUSION: We present a newborn with Apert syndrome with atypical craniofacial presentation.

Plasma and red blood cell concentrations of zinc, copper, selenium and magnesium in the first week of paediatric critical illness.

BACKGROUND & AIMS: Critically ill children are at risk of micronutrient deficiencies, which might lead to poor clinical outcomes. However, the interpretation of micronutrient concentrations in plasma is complicated due to age-dependent and critical illness-dependent changes. Certain red blood cell (RBC) concentrations might reflect the overall body status more reliably than plasma levels in the presence of systemic inflammatory response. This study longitudinally examined micronutrient concentrations in both plasma and RBC in critically ill children. METHODS: This secondary analysis of the PEPaNIC RCT investigated the impact of early versus late initiation of parenteral macronutrient supplementation in critically ill children. All children received micronutrients when EN was insufficient (<80 % energy requirements). Blood samples were obtained on days 1, 3, 5 and 7 of Paediatric Intensive Care Unit (PICU) admission. Inductively coupled plasma mass spectrometry was used to measure zinc, selenium, and copper in plasma and selenium, copper, and magnesium in RBCs. Plasma magnesium was measured with colorimetric detection. Micronutrient concentrations were compared with age-specific reference values in healthy children and expressed using Z-scores. Changes in micronutrient concentrations over time were examined using the Friedman and post hoc Wilcoxon signed-rank tests. RESULTS: For 67 critically ill children, median (Q1; Q3) age 9.5 (5.5; 13.2) years, PIM3 score -2.3 (-3.1; -0.8), samples were available at various time points during their PICU stay. For 22 patients, longitudinal samples were available. On day 1, the median plasma Z-score for zinc was -5.2 (-5.2; -2.9), copper -1.6 (-2.9; -0.2), selenium -2.6 (-3.8; -1.0), magnesium -0.2 (-1.6; 1.3), and median RBC Z-score for copper was 0.5 (-0.1; 1.3), selenium -0.3 (-1.1; 0.7), magnesium 0.2 (-0.4; 1.3). In the longitudinal analysis, plasma zinc was significantly higher on day 5 (Z-score -3.2 (-4.6; -1.4)) than on day 1 (Z-score -5.2 (-5.2; -3.0), p = 0.032), and plasma magnesium was significantly higher on day 3 (Z-score 1.1 (-0.7; 4.0)) than on day 1 (Z-score -0.3 (-1.6; 0.5), p = 0.018). Plasma copper and selenium remained stable, and the RBC concentrations of all micronutrients remained stable during the first five days. CONCLUSIONS: Most patients had low plasma zinc, copper and selenium concentrations in the first week of their PICU stay, whereas they had normal to high RBC concentrations. More research is needed to examine the relationships between micronutrients and clinical outcome.

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.

Nutritional intake and gastro-intestinal symptoms in critically ill COVID-19 patients.

BACKGROUND & AIMS: Critically ill COVID-19 patients seem hypermetabolic and difficult to feed enterally, due to gastro-intestinal (GI) symptoms such as high gastric residual volumes (GRV) and diarrhea. Our aim was to describe the association of nutritional intake and GI symptoms during first 14 days of ICU admission. METHODS: Observational study including critically ill adult COVID-19 patients. Data on nutritional intake [enteral nutrition (EN) or parenteral nutrition] and GI symptoms were collected during 14 days after ICU admission. Target energy and protein feeding goals were calculated conform ESPEN guidelines. GI symptoms included GRV (ml/d), vomiting, abdominal distension, and faeces (ml/d). High GRV's were classified as ≥2 times ≥150 ml/d and diarrhea as Bristol stool chart ≥6. GI symptoms were defined as mild if at least one symptom occurred and as moderate when ≥2 symptoms occurred. Acute gastrointestinal injury (AGI) grades of III were classified as GI dysfunction and grades of IV were considered as GI failure with severe impact on distant organs. Linear mixed model analysis was performed to explore the development of nutritional intake and GI symptoms over time at day (D) 0, 4, 10, and 14. RESULTS: One hundred and fifty patients were included [75% male; median age 64 years (IQR 54-70)]. BMI upon admission was 28 kg/m2 (IQR 25-33), of which 43% obese (BMI > 30 kg/m2). Most patients received EN during admission (98% D4; 96% D10-14). Mean energy goals increased from 87% at D4 to 93% D10-14 and protein goals (g/kg) were increasingly achieved during admission (84% D4; 93% D10-14). Presence of moderate GI symptoms decreased (10% D0; 6% D4-10; 5% D14), reversely mild GI symptoms increased. Occurrence of GI dysfunction fluctuated (1% D0; 18% D4; 12% D10; 8% D14) and none of patients developed grade IV GI failure. Development of high GRV fluctuated (5% D0; 23% D4; 14% D10; 8% D14) and occurrence of diarrhea slightly increased during admission (5% D0; 22% D4; 25% D10; 27% D14). Linear mixed models showed only an association between AGI grades III and lower protein intake at day 10 (p = 0.020). CONCLUSION: Occurrence of GI symptoms was limited and seems no major barrier for EN in our group of critically COVID-19 patients. Nutritional intake was just below requirements during the first 14 days of ICU admission. The effect on nutritional status remains to be studied.

Feeding and swallowing outcomes following mandibular distraction osteogenesis: an analysis of 22 non-isolated paediatric cases.

Patients with mandibular hypoplasia and upper airway obstruction are at an increased risk of feeding and swallowing difficulties. Little has been described regarding these outcomes following mandibular distraction. The aim of this study was to evaluate the effect of mandibular distraction on feeding and swallowing function. A retrospective study was performed on 22 patients with non-isolated mandibular hypoplasia and severe upper airway obstruction treated with mandibular distraction. Median age at first mandibular distraction was 3.1 years (interquartile range 2.3-6.0 years) and the median follow-up time was 3.5 years (interquartile range 2.0-9.4 years). Prior to mandibular distraction, feeding difficulties were present in 18 patients. Swallowing difficulties were present in 20 patients, all of whom had problems in the oral phase of swallowing, while 11 patients had additional problems in the pharyngeal phase. Following mandibular distraction, at the time of follow-up, feeding difficulties persisted in 13 patients. Swallowing difficulties in the oral phase remained present in all 20 patients, while pharyngeal phase problems persisted in seven patients. In conclusion, feeding and swallowing difficulties are highly prevalent in non-isolated patients and often persist following mandibular distraction. Moreover, these can be the reason that decannulation cannot be accomplished. Hence, awareness and close follow-up by a specialized speech therapist is of paramount importance.

Early Ultrasonic Monitoring of Brain Growth and Later Neurodevelopmental Outcome in Very Preterm Infants.

BACKGROUND AND PURPOSE: In infants born very preterm, monitoring of early brain growth could contribute to prediction of later neurodevelopment. Therefore, our aim was to investigate associations between 2 early cranial ultrasound markers (corpus callosum-fastigium and corpus callosum length) and neurodevelopmental outcome and the added value of both markers in the prediction of neurodevelopmental outcome based on neonatal risk factors and head circumference in very preterm infants. MATERIALS AND METHODS: This prospective observational study included 225 infants born at <30 weeks' gestational age, of whom 153 were without any brain injury on cranial ultrasound. Corpus callosum-fastigium and corpus callosum length and head circumference were measured at birth, 29 weeks' gestational age, transfer from the neonatal intensive care unit to a level II hospital, and 2 months' corrected age. We analyzed associations of brain markers and their growth with cognitive, motor, language, and behavioral outcome at 2 years' corrected age. RESULTS: In infants without brain injury, greater corpus callosum-fastigium length at 2 months was associated with better cognitive outcome. Corpus callosum length at 2 months was positively associated with cognitive, motor, and language outcome. Faster growth of the corpus callosum length between birth and 2 months was associated with better cognitive and motor function. Prediction of neurodevelopmental outcome based on neonatal risk factors with or without head circumference was significantly improved by adding corpus callosum length. CONCLUSIONS: Both corpus callosum-fastigium and corpus callosum length on cranial ultrasound are associated with neurodevelopmental outcome of very preterm infants without brain injury at 2 years, but only corpus callosum length shows the added clinical utility in predicting neurodevelopmental outcome.

Early hypophosphatemia in critically ill children and the effect of parenteral nutrition: A secondary analysis of the PEPaNIC RCT.

BACKGROUND & AIMS: Hypophosphatemia during critical illness has been associated with adverse outcome. The reintroduction of enteral or parenteral nutrition, leading to refeeding hypophosphatemia (RFH), has been presented as potential risk factor. We investigated the occurrence of early RFH, its association with clinical outcome, and the impact of early parenteral nutrition (PN) on the development of early RFH in pediatric critical illness. METHODS: This is a secondary analysis of the PEPaNIC randomized controlled trial (N = 1440), which showed that withholding supplemental parenteral nutrition (PN) for 1 week (late-PN) in the pediatric intensive care unit (PICU) accelerated recovery and reduced new infections compared to early-PN (<24 h). Patients with renal replacement therapy or unavailable phosphate concentrations were excluded from this analysis. Early RFH was defined as serum/plasma phosphate <0.65 mmol/L and a drop of >0.16 mmol/L within 3 days of admission to the PICU. The association between baseline characteristics and early RFH, and the association of early RFH with clinical outcome were investigated using logistic and linear regression models, both uncorrected and corrected for possible confounders. To examine the impact of nutritional intake on phosphate concentrations, structural nested mean models with propensity score and censoring models were used. RESULTS: A total of 1247 patients were eligible (618 early-PN, 629 late-PN). Early RFH occurred in 40 patients (3%) in total, significantly more in the early-PN group (n = 31, within-group occurrence 5%) than in the late-PN-group (n = 9, within-group occurrence 1%, p < 0.001). Patients who were older (OR 1.14 (95% CI 1.08; 1.21) per year added, p < 0.001) and who had a higher Pediatric Risk of Mortality (PIM3) score had a higher risk of developing early RFH (OR 1.36 (95% CI 1.15; 1.59) per unit added, p < 0.001), whereas patients in the late-PN group had a lower risk of early RFH (OR 0.24 (95% CI 0.10; 0.49), p < 0.001). Early RFH was significantly associated with a 56% longer PICU stay (p = 0.003) and 42% longer hospital stay (p = 0.007), but not with new infections (OR 2.01 (95% CI 0.90; 4.30), p = 0.08) or length of mechanical ventilatory support (OR 1.05 (95% CI -3.92; 6.03), p = 0.68), when adjusted for possible confounders. Increase of parenteral nutrition intake (in % kcal of predicted resting energy expenditure) decreased phosphate concentrations (c = -0.002 (95% CI -0.002; -0.001). CONCLUSIONS: Early RFH occurred in 3% of critically ill children. Patients randomized to late-PN had a lower chance of developing early RFH, which may be explained by the more gradual build-up of nutrition. As early RFH might impact recovery, it is important to closely monitor phosphate concentrations in patients, especially of those at risk for early RFH.

Indications and clinical outcome in pediatric tracheostomy: Lessons learned.

OBJECTIVE: Indications for tracheostomy have changed over the last decades and clinical outcome varies depending on the indication for tracheostomy. By gaining more insight in the characteristics and outcome of the tracheostomized pediatric population, clinical care can be improved and a better individual prognosis can be given. Therefore, we studied the outcome of our pediatric tracheostomy population in relation to the primary indication over the last 16 years. METHODS: We retrospectively included children younger than 18 years of age with a tracheostomy tube in the Erasmus Medical Center, Sophia children's hospital. The primary indication for tracheostomy, gender, age at tracheostomy, age at decannulation, comorbidity, mortality, closure of a persisting tracheocutaneous fistula after decannulation, surgery prior to decannulation and the use of polysomnography were recorded and analyzed. RESULTS: Our research group consisted of 225 children. Reasons for a tracheostomy were first divided in two major diagnostic groups: 1) airway obstruction group (subgroups: laryngotracheal obstruction and craniofacial anomalies) and 2) pulmonary support group (subgroups: cardio-pulmonary diseases and neurological diseases). Children in the airway obstruction group were younger when receiving a tracheostomy (3.0 months vs. 31.0 months, p < 0.05), they were tracheostomy dependent for a longer time (median 21.5 months vs. 2.0 months, p < 0.05) and they required surgery more often (74.5% vs. 8.3%, p < 0.05) than the children in the pulmonary support group. The decannulation rate of children with a laryngotracheal obstruction is high (74.8%), but low in all other subgroups (craniofacial anomalies; 38.5%, cardio-pulmonary diseases; 34.6% and neurological diseases; 52.9%). Significantly more children (36.7%) died in the pulmonary support group due to underlying comorbidity, mainly in the cardio-pulmonary diseases subgroup. Surgery for a persisting tracheocutaneous fistula was performed in 34 (37.8%) children, with a significant relationship between the duration of the tracheostomy and the persistence of a tracheocutaneous fistula. No cannula related death occurred during this study period. CONCLUSION: Main indications for a tracheostomy were airway obstruction and pulmonary support. Children in the airway obstruction group were younger when receiving a tracheostomy and they were tracheostomy dependent for a longer period. Within the airway obstruction group, the decannulation rate for children with laryngotracheal stenosis was high, but low for children with craniofacial anomalies. In the pulmonary support group, the decannulation rate was low and the mortality rate was high. Surgery for a persisting tracheocutaneous fistula was frequently needed.

Energy expenditure and feeding practices and tolerance during the acute and late phase of critically ill COVID-19 patients.

BACKGROUND & AIMS: Different metabolic phases can be distinguished in critical illness, which influences nutritional treatment. Achieving optimal nutritional treatment during these phases in critically ill patients is challenging. COVID-19 patients seem particularly difficult to feed due to gastrointestinal problems. Our aim was to describe measured resting energy expenditure (mREE) and feeding practices and tolerance during the acute and late phases of critical illness in COVID-19 patients. METHODS: Observational study including critically ill mechanically ventilated adult COVID-19 patients. Indirect calorimetry (Q-NRG+, Cosmed) was used to determine mREE during the acute (day 0-7) and late phase (>day 7) of critical illness. Data on nutritional intake, feeding tolerance and urinary nitrogen loss were collected simultaneously. A paired sample t-test was performed for mREE in both phases. RESULTS: We enrolled 21 patients with a median age of 59 years [44-66], 67% male and median BMI of 31.5 kg/m2 [25.7-37.8]. Patients were predominantly fed with EN in both phases. No significant difference in mREE was observed between phases (p = 0.529). Sixty-five percent of the patients were hypermetabolic in both phases. Median delivery of energy as percentage of mREE was higher in the late phase (94%) compared to the acute phase (70%) (p = 0.001). Urinary nitrogen losses were significant higher in the late phase (p = 0.003). CONCLUSION: In both the acute and late phase, the majority of the patients were hypermetabolic and fed enterally. In the acute phase patients were fed hypocaloric whereas in the late phase this was almost normocaloric, conform ESPEN guidelines. No significant difference in mREE was observed between phases. Hypermetabolism in both phases in conjunction with an increasing loss of urinary nitrogen may indicate that COVID-19 patients remain in a prolonged acute, catabolic phase.

Radar-based sleep stage classification in children undergoing polysomnography: a pilot-study.

STUDY OBJECTIVES: Unobtrusive monitoring of sleep and sleep disorders in children presents challenges. We investigated the possibility of using Ultra-Wide band (UWB) radar to measure sleep in children. METHODS: Thirty-two children scheduled to undergo a clinical polysomnography participated; their ages ranged from 2 months to 14 years. During the polysomnography, the children's body movements and breathing rate were measured by an UWB-radar. A total of 38 features were calculated from the motion signals and breathing rate obtained from the raw radar signals. Adaptive boosting was used as machine learning classifier to estimate sleep stages, with polysomnography as gold standard method for comparison. RESULTS: Data of all participants combined, this study achieved a Cohen's Kappa coefficient of 0.67 and an overall accuracy of 89.8% for wake and sleep classification, a Kappa of 0.47 and an accuracy of 72.9% for wake, rapid-eye-movement (REM) sleep, and non-REM sleep classification, and a Kappa of 0.43 and an accuracy of 58.0% for wake, REM sleep, light sleep and deep sleep classification. CONCLUSION: Although the current performance is not sufficient for clinical use yet, UWB radar is a promising method for non-contact sleep analysis in children.

Functional outcomes in patients with facial dysostosis and severe upper airway obstruction.

An increased risk of upper airway obstruction (UAO) is seen in up to 95% of patients with facial dysostosis. Secondary to respiratory problems are feeding difficulties and increased nutritional requirements. Little has been described regarding these outcomes in this patient population. Hence, a retrospective cohort study was performed to gather data on functional outcomes. Eighteen patients with facial dysostosis and severe UAO were included. The median follow-up time was 3.42 years. A tracheostomy tube was placed in 13 patients, of whom 10 subsequently underwent mandibular distraction. Three of the five patients without a tracheostomy underwent mandibular distraction as the primary surgical treatment; the remaining two patients were treated conservatively with oxygen supplementation. At presentation, 13 patients had feeding difficulties. Overall malnutrition was present in 16 patients during follow-up. At the end of follow-up, severe UAO was present in 12 patients, feeding difficulties in seven patients, and malnutrition in four patients, while two patients died. In conclusion, patients with facial dysostosis have a high prevalence of severe UAO, feeding difficulties, and malnutrition. Importantly, mandibular distraction has limited success in treating severe UAO in these patients. Close follow-up by a specialized craniofacial team is of paramount importance to manage the long-term consequences.

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.

Cervical Spinal Cord Compression and Sleep-Disordered Breathing in Syndromic Craniosynostosis.

BACKGROUND AND PURPOSE: Cerebellar tonsillar herniation arises frequently in syndromic craniosynostosis and causes central and obstructive apneas in other diseases through spinal cord compression. The purposes of this study were the following: 1) to determine the prevalence of cervical spinal cord compression in syndromic craniosynostosis, and 2) to evaluate its connection with sleep-disordered breathing. MATERIALS AND METHODS: This was a cross-sectional study including patients with syndromic craniosynostosis who underwent MR imaging and polysomnography. Measures encompassed the compression ratio at the level of the odontoid process and foramen magnum and the cervicomedullary angle. MR imaging studies of controls were included. Linear mixed models were developed to compare patients with syndromic craniosynostosis with controls and to evaluate the association between obstructive and central sleep apneas and MR imaging parameters. RESULTS: One hundred twenty-two MR imaging scans and polysomnographies in 89 patients were paired; 131 MR imaging scans in controls were included. The mean age at polysomnography was 5.7 years (range, 0.02-18.9 years). The compression ratio at the level of the odontoid process was comparable with that in controls; the compression ratio at the level of the foramen magnum was significantly higher in patients with Crouzon syndrome (+27.1, P < .001). The cervicomedullary angle was significantly smaller in Apert, Crouzon, and Saethre-Chotzen syndromes (-4.4°, P = .01; -10.2°, P < .001; -5.2°, P = .049). The compression ratios at the level of the odontoid process and the foramen magnum, the cervicomedullary angle, and age were not associated with obstructive apneas (P > .05). Only age was associated with central apneas (P = .02). CONCLUSIONS: The prevalence of cervical spinal cord compression in syndromic craniosynostosis is low and is not correlated to sleep disturbances. However, considering the high prevalence of obstructive sleep apnea in syndromic craniosynostosis and the low prevalence of compression and central sleep apnea in our study, we would, nevertheless, recommend a polysomnography in case of compression on MR imaging studies.