Severe Pediatric Neurological Manifestations With SARS-CoV-2 or MIS-C Hospitalization and New Morbidity.

Importance: Neurological manifestations during acute SARS-CoV-2-related multisystem inflammatory syndrome in children (MIS-C) are common in hospitalized patients younger than 18 years and may increase risk of new neurocognitive or functional morbidity. Objective: To assess the association of severe neurological manifestations during a SARS-CoV-2-related hospital admission with new neurocognitive or functional morbidities at discharge. Design, Setting, and Participants: This prospective cohort study from 46 centers in 10 countries included patients younger than 18 years who were hospitalized for acute SARS-CoV-2 or MIS-C between January 2, 2020, and July 31, 2021. Exposure: Severe neurological manifestations, which included acute encephalopathy, seizures or status epilepticus, meningitis or encephalitis, sympathetic storming or dysautonomia, cardiac arrest, coma, delirium, and stroke. Main Outcomes and Measures: The primary outcome was new neurocognitive (based on the Pediatric Cerebral Performance Category scale) and/or functional (based on the Functional Status Scale) morbidity at hospital discharge. Multivariable logistic regression analyses were performed to examine the association of severe neurological manifestations with new morbidity in each SARS-CoV-2-related condition. Results: Overall, 3568 patients younger than 18 years (median age, 8 years [IQR, 1-14 years]; 54.3% male) were included in this study. Most (2980 [83.5%]) had acute SARS-CoV-2; the remainder (588 [16.5%]) had MIS-C. Among the patients with acute SARS-CoV-2, 536 (18.0%) had a severe neurological manifestation during hospitalization, as did 146 patients with MIS-C (24.8%). Among survivors with acute SARS-CoV-2, those with severe neurological manifestations were more likely to have new neurocognitive or functional morbidity at hospital discharge compared with those without severe neurological manifestations (27.7% [n = 142] vs 14.6% [n = 356]; P < .001). For survivors with MIS-C, 28.0% (n = 39) with severe neurological manifestations had new neurocognitive and/or functional morbidity at hospital discharge compared with 15.5% (n = 68) of those without severe neurological manifestations (P = .002). When adjusting for risk factors in those with severe neurological manifestations, both patients with acute SARS-CoV-2 (odds ratio, 1.85 [95% CI, 1.27-2.70]; P = .001) and those with MIS-C (odds ratio, 2.18 [95% CI, 1.22-3.89]; P = .009) had higher odds of having new neurocognitive and/or functional morbidity at hospital discharge. Conclusions and Relevance: The results of this study suggest that children and adolescents with acute SARS-CoV-2 or MIS-C and severe neurological manifestations may be at high risk for long-term impairment and may benefit from screening and early intervention to assist recovery.

Severe COVID-19 in pregnant women: Analysis of placental features and perinatal outcomes.

OBJECTIVES: Changes in placental features, such as maternal and fetal vascular malperfusion, are associated with SARS-CoV-2 infection. The anatomopathologic study of the placenta is crucial for understanding pregnancy and fetal complications. To that end, this study aimed to describe placental features and analyze the association between placental findings and perinatal outcomes in a cohort of pregnant women with severe COVID-19. METHODS: This nested study within a prospective cohort study consisted of 121 singleton pregnant women with a diagnosis of severe COVID-19. Placental pathologic findings were described, and the associations between severe COVID-19 and clinical parameters and perinatal outcomes were assessed. RESULTS: The prevalence of maternal vascular malperfusion was 52.1%, followed by fetal vascular malperfusion at 21.5%, ascending intrauterine infections at 11.6%, and inflammatory lesions at 11.6%. Other lesions were observed in 39.7% of the placentas examined. Inflammatory lesions were an independent factor (P = .042) in 5-minute Apgar scores below 7. Ascending infection was associated with fetal death (P = .027). CONCLUSIONS: Maternal vascular malperfusion was the most prevalent placental feature in patients with severe COVID-19. Chorangiosis is associated with poor perinatal outcomes.

Executive Summary of the Second International Guidelines for the Diagnosis and Management of Pediatric Acute Respiratory Distress Syndrome (PALICC-2).

OBJECTIVES: We sought to update our 2015 work in the Second Pediatric Acute Lung Injury Consensus Conference (PALICC-2) guidelines for the diagnosis and management of pediatric acute respiratory distress syndrome (PARDS), considering new evidence and topic areas that were not previously addressed. DESIGN: International consensus conference series involving 52 multidisciplinary international content experts in PARDS and four methodology experts from 15 countries, using consensus conference methodology, and implementation science. SETTING: Not applicable. PATIENTS: Patients with or at risk for PARDS. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Eleven subgroups conducted systematic or scoping reviews addressing 11 topic areas: 1) definition, incidence, and epidemiology; 2) pathobiology, severity, and risk stratification; 3) ventilatory support; 4) pulmonary-specific ancillary treatment; 5) nonpulmonary treatment; 6) monitoring; 7) noninvasive respiratory support; 8) extracorporeal support; 9) morbidity and long-term outcomes; 10) clinical informatics and data science; and 11) resource-limited settings. The search included MEDLINE, EMBASE, and CINAHL Complete (EBSCOhost) and was updated in March 2022. Grading of Recommendations, Assessment, Development, and Evaluation methodology was used to summarize evidence and develop the recommendations, which were discussed and voted on by all PALICC-2 experts. There were 146 recommendations and statements, including: 34 recommendations for clinical practice; 112 consensus-based statements with 18 on PARDS definition, 55 on good practice, seven on policy, and 32 on research. All recommendations and statements had agreement greater than 80%. CONCLUSIONS: PALICC-2 recommendations and consensus-based statements should facilitate the implementation and adherence to the best clinical practice in patients with PARDS. These results will also inform the development of future programs of research that are crucially needed to provide stronger evidence to guide the pediatric critical care teams managing these patients.

Leveraging Clinical Informatics and Data Science to Improve Care and Facilitate Research in Pediatric Acute Respiratory Distress Syndrome: From the Second Pediatric Acute Lung Injury Consensus Conference.

OBJECTIVES: The use of electronic algorithms, clinical decision support systems, and other clinical informatics interventions is increasing in critical care. Pediatric acute respiratory distress syndrome (PARDS) is a complex, dynamic condition associated with large amounts of clinical data and frequent decisions at the bedside. Novel data-driven technologies that can help screen, prompt, and support clinician decision-making could have a significant impact on patient outcomes. We sought to identify and summarize relevant evidence related to clinical informatics interventions in both PARDS and adult respiratory distress syndrome (ARDS), for the second Pediatric Acute Lung Injury Consensus Conference. DATA SOURCES: MEDLINE (Ovid), Embase (Elsevier), and CINAHL Complete (EBSCOhost). STUDY SELECTION: We included studies of pediatric or adult critically ill patients with or at risk of ARDS that examined automated screening tools, electronic algorithms, or clinical decision support systems. DATA EXTRACTION: Title/abstract review, full text review, and data extraction using a standardized data extraction form. DATA SYNTHESIS: The Grading of Recommendations Assessment, Development and Evaluation approach was used to identify and summarize evidence and develop recommendations. Twenty-six studies were identified for full text extraction to address the Patient/Intervention/Comparator/Outcome questions, and 14 were used for the recommendations/statements. Two clinical recommendations were generated, related to the use of electronic screening tools and automated monitoring of compliance with best practice guidelines. Two research statements were generated, related to the development of multicenter data collaborations and the design of generalizable algorithms and electronic tools. One policy statement was generated, related to the provision of material and human resources by healthcare organizations to empower clinicians to develop clinical informatics interventions to improve the care of patients with PARDS. CONCLUSIONS: We present two clinical recommendations and three statements (two research one policy) for the use of electronic algorithms and clinical informatics tools for patients with PARDS based on a systematic review of the literature and expert consensus.

Diagnostic, Management, and Research Considerations for Pediatric Acute Respiratory Distress Syndrome in Resource-Limited Settings: From the Second Pediatric Acute Lung Injury Consensus Conference.

OBJECTIVES: Diagnosis of pediatric acute respiratory distress syndrome (PARDS) in resource-limited settings (RLS) is challenging and remains poorly described. We conducted a review of the literature to optimize recognition of PARDS in RLS and to provide recommendations/statements for clinical practice and future research in these settings as part of the Second Pediatric Acute Lung Injury Consensus Conference (PALICC-2). DATA SOURCES: MEDLINE (Ovid), Embase (Elsevier), and CINAHL Complete (EBSCOhost). STUDY SELECTION: We included studies related to precipitating factors for PARDS, mechanical ventilation (MV), pulmonary and nonpulmonary ancillary treatments, and long-term outcomes in children who survive PARDS in RLS. DATA EXTRACTION: Title/abstract review, full-text review, and data extraction using a standardized data collection form. DATA SYNTHESIS: The Grading of Recommendations Assessment, Development, and Evaluation approach was used to identify and summarize evidence and develop recommendations. Seventy-seven studies were identified for full-text extraction. We were unable to identify any literature on which to base recommendations. We gained consensus on six clinical statements (good practice, definition, and policy) and five research statements. Clinicians should be aware of diseases and comorbidities, uncommon in most high-income settings, that predispose to the development of PARDS in RLS. Because of difficulties in recognizing PARDS and to avoid underdiagnosis, the PALICC-2 possible PARDS definition allows exclusion of imaging criteria when all other criteria are met, including noninvasive metrics of hypoxemia. The availability of MV support, regular MV training and education, as well as accessibility and costs of pulmonary and nonpulmonary ancillary therapies are other concerns related to management of PARDS in RLS. Data on long-term outcomes and feasibility of follow-up in PARDS survivors from RLS are also lacking. CONCLUSIONS: To date, PARDS remains poorly described in RLS. Clinicians working in these settings should be aware of common precipitating factors for PARDS in their patients. Future studies utilizing the PALICC-2 definitions are urgently needed to describe the epidemiology, management, and outcomes of PARDS in RLS.

Prevalence and Risk Factors of Neurologic Manifestations in Hospitalized Children Diagnosed with Acute SARS-CoV-2 or MIS-C.

BACKGROUND: Our objective was to characterize the frequency, early impact, and risk factors for neurological manifestations in hospitalized children with acute severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection or multisystem inflammatory syndrome in children (MIS-C). METHODS: Multicenter, cross-sectional study of neurological manifestations in children aged <18 years hospitalized with positive SARS-CoV-2 test or clinical diagnosis of a SARS-CoV-2-related condition between January 2020 and April 2021. Multivariable logistic regression to identify risk factors for neurological manifestations was performed. RESULTS: Of 1493 children, 1278 (86%) were diagnosed with acute SARS-CoV-2 and 215 (14%) with MIS-C. Overall, 44% of the cohort (40% acute SARS-CoV-2 and 66% MIS-C) had at least one neurological manifestation. The most common neurological findings in children with acute SARS-CoV-2 and MIS-C diagnosis were headache (16% and 47%) and acute encephalopathy (15% and 22%), both P < 0.05. Children with neurological manifestations were more likely to require intensive care unit (ICU) care (51% vs 22%), P < 0.001. In multivariable logistic regression, children with neurological manifestations were older (odds ratio [OR] 1.1 and 95% confidence interval [CI] 1.07 to 1.13) and more likely to have MIS-C versus acute SARS-CoV-2 (OR 2.16, 95% CI 1.45 to 3.24), pre-existing neurological and metabolic conditions (OR 3.48, 95% CI 2.37 to 5.15; and OR 1.65, 95% CI 1.04 to 2.66, respectively), and pharyngeal (OR 1.74, 95% CI 1.16 to 2.64) or abdominal pain (OR 1.43, 95% CI 1.03 to 2.00); all P < 0.05. CONCLUSIONS: In this multicenter study, 44% of children hospitalized with SARS-CoV-2-related conditions experienced neurological manifestations, which were associated with ICU admission and pre-existing neurological condition. Posthospital assessment for, and support of, functional impairment and neuroprotective strategies are vitally needed.

A Core Outcome Set for Pediatric Critical Care.

OBJECTIVES: More children are surviving critical illness but are at risk of residual or new health conditions. An evidence-informed and stakeholder-recommended core outcome set is lacking for pediatric critical care outcomes. Our objective was to create a multinational, multistakeholder-recommended pediatric critical care core outcome set for inclusion in clinical and research programs. DESIGN: A two-round modified Delphi electronic survey was conducted with 333 invited research, clinical, and family/advocate stakeholders. Stakeholders completing the first round were invited to participate in the second. Outcomes scoring greater than 69% "critical" and less than 15% "not important" advanced to round 2 with write-in outcomes considered. The Steering Committee held a virtual consensus conference to determine the final components. SETTING: Multinational survey. PATIENTS: Stakeholder participants from six continents representing clinicians, researchers, and family/advocates. MEASUREMENTS AND MAIN RESULTS: Overall response rates were 75% and 82% for each round. Participants voted on seven Global Domains and 45 Specific Outcomes in round 1, and six Global Domains and 30 Specific Outcomes in round 2. Using overall (three stakeholder groups combined) results, consensus was defined as outcomes scoring greater than 90% "critical" and less than 15% "not important" and were included in the final PICU core outcome set: four Global Domains (Cognitive, Emotional, Physical, and Overall Health) and four Specific Outcomes (Child Health-Related Quality of Life, Pain, Survival, and Communication). Families (n = 21) suggested additional critically important outcomes that did not meet consensus, which were included in the PICU core outcome set-extended. CONCLUSIONS: The PICU core outcome set and PICU core outcome set-extended are multistakeholder-recommended resources for clinical and research programs that seek to improve outcomes for children with critical illness and their families.

Bioelectrical Impedance Phase Angle and Morbidity and Mortality in Critically Ill Children.

BACKGROUND: Nutrition markers may be useful for diagnosis and monitoring and, also, as additional indicators of estimating death risk. We tested the association of body composition indicators (mid-upper arm circumference and phase angle) with pediatric intensive care unit (PICU) length of stay and mortality in critically ill pediatric patients. METHODS: Data from children aged 2 months-18 years were collected, and bioelectrical impedance was performed to obtain phase angle. Severity was evaluated by scoring the Pediatric Index of Mortality. Descriptive statistics were reported for nominal variables. Receiver operating characteristic curve was used to analyze the association of phase angle with 30-day mortality and to find the best cutoff. Survival probabilities and PICU length of stay were estimated using the Kaplan-Meier method. RESULTS: We evaluated 247 children with a median age of 4.8 years whose main cause of admission was sepsis. Survival curves showed higher survival in patients with phase angle >2.8° compared with patients with phase angle ≤2.8° (P < .0001). Kaplan-Meier time-to-event analysis showed that children with lower phase angle values were more likely to remain in the PICU (hazard ratio, 1.84; P = .003). Lower survival was also observed in patients who presented mid-upper arm circumference values ≤5th percentile (P < .03). CONCLUSIONS: Mid-upper arm circumference and phase angle were associated with mortality and morbidity in critically ill children, suggesting that these parameters may be useful not only for nutrition diagnosis and monitoring, but also as an additional indicator in estimating prognosis.