Considerations for nutrition support in critically ill children with COVID-19 and paediatric inflammatory multisystem syndrome temporally associated with COVID-19

The aim of this editorial is to provide an adaptation of nutrition support recommendations for the overall population of critically ill children, to provide further refined recommendations for critically ill children presenting with COVID-19 or paediatric hyper-inflammatory syndrome temporally associated with COVID-19. They are based on the ESPNIC-MEN section recommendations published in January 2020 (6) and Surviving Sepsis Campaign recommendations from February 2020 (7). These recommendations cover the acute, stable and rehabilitation phases (Table 1, Table 2)

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.</p

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

Background &amp; 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 (&lt;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.</p

Megacystis-microcolon-intestinal hypoperistalsis syndrome:A case report

Megacystis-microcolon-intestinal hypoperistalsis syndrome (MMIHS) is a rare congenital disorder characterized by a dilated, non-obstructive urinary bladder and hypoperistalsis of the gastrointestinal tract, which is considered lethal. About 90 patients have been reported, predominantly female. We present the case of a female newborn with MMIHS in whom antenatal ultrasound was suggestive for the diagnosis, which was confirmed after delivery. Diagnostic features by antenatal ultrasound are described.</p

Intermittent versus continuous enteral nutrition in critically ill children: A pre-planned secondary analysis of an international prospective cohort study

Background & aims: Intermittent enteral nutrition (EN) may have physiologic benefits over continuous feeding in critical illness. We aimed to compare nutrition and infection outcomes in critically ill children receiving intermittent or continuous EN. Methods: International, multi-center prospective observational study of mechanically ventilated children, 1 month to 18 years of age, receiving EN. Percent energy or protein adequacy (energy or protein delivered/prescribed × 100) and acquired infection rates were compared between intermittent and continuous EN groups using adjusted-multivariable and 4:1 propensity-score matched (PSM) analyses. Sensitivity analyses were performed after excluding patients who crossed over between intermittent and continuous EN. Results: 1375 eligible patients from 66 PICUs were included. Patients receiving continuous EN (N = 1093) had a higher prevalence of respiratory illness and obesity, and lower prevalence of neurologic illness and underweight status on admission, compared to those on intermittent EN (N = 282). Percent energy or protein adequacy, proportion of patients who achieved 60% of energy or protein adequacy in the first 7 days of admission, and rates of acquired infection were not different between the 2 groups in adjusted-multivariable and propensity score matching analyses (P > 0.05). Conclusion: Intermittent versus continuous EN strategy is not associated with differences in energy or protein adequacy, or acquired infections, in mechanically ventilated, critically ill children. Until further evidence is available, an individualized feeding strategy rather than a universal approach may be appropriate

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 (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