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ABSTRACT:Background and Objectives:Neurological involvement associated with SARS-CoV-2 infection is increasingly recognized. However, the specific characteristics and prevalence in pediatric patients remain unclear. The objective of this study was to describe the neurological involvement in a multinational cohort of hospitalized pediatric patients with SARS-CoV-2.Methods:This was a multicenter observational study of children <18 years of age with confirmed SARS-CoV-2 infection or multisystemic inflammatory syndrome (MIS-C) and laboratory evidence of SARS-CoV-2 infection in children, admitted to 15 tertiary hospitals/healthcare centers in Canada, Costa Rica, and Iran February 2020–May 2021. Descriptive statistical analyses were performed and logistic regression was used to identify factors associated with neurological involvement.Results:One-hundred forty-seven (21%) of 697 hospitalized children with SARS-CoV-2 infection had neurological signs/symptoms. Headache (n= 103), encephalopathy (n= 28), and seizures (n= 30) were the most reported. Neurological signs/symptoms were significantly associated with ICU admission (OR: 1.71, 95% CI: 1.15–2.55; p= 0.008), satisfaction of MIS-C criteria (OR: 3.71, 95% CI: 2.46–5.59; p< 0.001), fever during hospitalization (OR: 2.15, 95% CI: 1.46–3.15; p< 0.001), and gastrointestinal involvement (OR: 2.31, 95% CI: 1.58–3.40; p< 0.001). Non-headache neurological manifestations were significantly associated with ICU admission (OR: 1.92, 95% CI: 1.08–3.42; p= 0.026), underlying neurological disorders (OR: 2.98, 95% CI: 1.49–5.97, p= 0.002), and a history of fever prior to hospital admission (OR: 2.76, 95% CI: 1.58–4.82; p< 0.001).Discussion:In this study, approximately 21% of hospitalized children with SARS-CoV-2 infection had neurological signs/symptoms. Future studies should focus on pathogenesis and long-term outcomes in these children.

People with inflammatory or autoimmune diseases are recommended to continue immunomodulatory biologic agents throughout pregnancy. However, concerns regarding potential immunosuppression in infants exposed to biologic agents have led to recommendations to avoid live vaccines in the first 6–12 months of life. We aimed to examine whether live rotavirus vaccine could be administered safely to infants exposed to biologic agents, assessed in the Canadian Special Immunization Clinic (SIC) Network.

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Background:SARS-CoV-2 infection can lead to multisystem inflammatory syndrome in children (MIS-C). We sought to investigate risk factors for admission to the intensive care unit (ICU) and explored changes in disease severity over time.Methods:We obtained data from chart reviews of children younger than 18 years with confirmed or probable MIS-C who were admitted to 15 hospitals in Canada, Iran and Costa Rica between Mar. 1, 2020, and Mar. 7, 2021. Using multivariable analyses, we evaluated whether admission date and other characteristics were associated with ICU admission or cardiac involvement.Results:Of 232 children with MIS-C (median age 5.8 yr), 130 (56.0%) were male and 50 (21.6%) had comorbidities. Seventy-three (31.5%) patients were admitted to the ICU but none died. We observed an increased risk of ICU admission among children aged 13–17 years (adjusted risk difference 27.7%, 95% confidence interval [CI] 8.3% to 47.2%), those aged 6–12 years (adjusted risk difference 25.2%, 95% CI 13.6% to 36.9%) or those with initial ferritin levels greater than 500 μg/L (adjusted risk difference 18.4%, 95% CI 5.6% to 31.3%). Children admitted to hospital after Oct. 31, 2020, had numerically higher rates of ICU admission (adjusted risk difference 12.3%, 95% CI −0.3% to 25.0%) and significantly higher rates of cardiac involvement (adjusted risk difference 30.9%, 95% CI 17.3% to 44.4%). At Canadian sites, the risk of ICU admission was significantly higher for children admitted to hospital between December 2020 and March 2021 than those admitted between March and May 2020 (adjusted risk difference 25.3%, 95% CI 6.5% to 44.0%).Interpretation:We observed that age and higher ferritin levels were associated with more severe MIS-C. We observed greater severity of MIS-C later in the study period. Whether emerging SARS-CoV-2 variants pose different risks of severe MIS-C needs to be determined.

Objectives: In many jurisdictions, routine medical care was reduced in response to the COVID-19 pandemic. The objective of this study was to determine whether the frequency of on-time routine childhood vaccinations among children age 0–2 years was lower following the COVID-19 declaration of emergency in Ontario, Canada, on March 17, 2020, compared to prior to the pandemic. Methods: We conducted a longitudinal cohort study of healthy children aged 0–2 years participating in the TARGet Kids! primary care research network in Toronto, Canada. A logistic mixed effects regression model was used to determine odds ratios (ORs) for delayed vaccination (> 30 days vs. ≤ 30 days from the recommended date) before and after the COVID-19 declaration of emergency, adjusted for confounding variables. A Cox proportional hazards model was used to explore the relationship between the declaration of emergency and time to vaccination. Results: Among 1277 children, the proportion of on-time vaccinations was 81.8% prior to the COVID-19 declaration of emergency and 62.1% after (p&lt; 0.001). The odds of delayed vaccination increased (odds ratio = 3.77, 95% CI: 2.86–4.96), and the hazard of administration of recommended vaccinations decreased after the declaration of emergency (hazard ratio = 0.75, 95% CI: 0.60–0.92). The median vaccination delay time was 5 days (95% CI: 4–5 days) prior to the declaration of emergency and 17 days (95% CI: 12–22 days) after. Conclusion: The frequency of on-time routine childhood vaccinations was lower during the first wave of the COVID-19 pandemic. Sustained delays in routine vaccinations may lead to an increase in rates of vaccine-preventable diseases.

BackgroundThe composition of the infant gastrointestinal (GI) microbiome has been linked to adverse long-term health outcomes and neonatal sepsis. Several factors are known to impact the composition of the microbiome, including mode of delivery, gestational age, feeding method and exposure to antibiotics. The impact of intrapartum antibiotics (IPAs) on the infant microbiome requires further research.ObjectiveWe aimed to evaluate the impact of IPAs on the infant GI microbiome.MethodsWe searched Ovid MEDLINE and Embase Classic+Embase for articles in English reporting on the microbiome of infants exposed to IPAs from the date of inception to 3 January 2021. Primary outcomes included abundance and colonisation of Bifidobacteriumand Lactobacillus, as well as alpha and beta diversity.Results30 papers were included in this review. In the first year of life, following exposure to IPAs, 30% (6/20) of infant cohorts displayed significantly reduced Bifidobacterium, 89% (17/19) did not display any significant differences in Lactobacilluscolonisation, 21% (7/34) displayed significantly reduced alpha diversity and 35% (12/34) displayed alterations in beta diversity. Results were further stratified by delivery, gestational age (preterm or full term) and feeding method.ConclusionsIPAs impact the composition of the infant GI microbiome, resulting in possible reductions Bifidobacteriumand alpha diversity, and possible alterations in beta diversity. Our findings may have implications for maternal and neonatal health, including interventions to prevent reductions in health-promoting bacteria (eg, probiotics) and IPA class selection.

AbstractObjective:In this study, we aimed to capture perspectives of healthcare workers (HCWs) on coronavirus disease 2019 (COVID-19) and infection prevention and control (IPAC) measures implemented during the early phase of the COVID-19 pandemic.Design:A cross-sectional survey of HCWs.Participants:HCWs from the Hospital for Sick Children, Toronto, Canada.Intervention:A self-administered survey was distributed to HCWs. We analyzed factors influencing HCW knowledge and self-reported use of personal protective equipment (PPE), concerns about contracting COVID-19 and acceptance of the recommended IPAC precautions for COVID-19.Results:In total, 175 HCWs completed the survey between March 6 and March 10: 35 staff physicians (20%), 24 residents or fellows (14%), 72 nurses (41%), 14 respiratory therapists (8%), 14 administration staff (8%), and 14 other employees (8%). Most of the respondents were from the emergency department (n = 58, 33%) and the intensive care unit (n = 58, 33%). Only 86 respondents (50%) identified the correct donning order; only 60 (35%) identified the correct doffing order; but the majority (n = 113, 70%) indicated the need to wash their hands immediately prior to removal of their mask and eye protection. Also, 91 (54%) respondents felt comfortable with recommendations for droplet and/or contact precautions for routine care of patients with COVID-19. HCW occupation and concerns about contracting COVID-19 outside work were associated with nonacceptance of the recommendations (P= .016 and P= .036 respectively).Conclusion:As part of their pandemic response plans, healthcare institutions should have ongoing training for HCWs that focus on appropriate PPE doffing and discussions around modes of transmission of COVID-19.

Background:Risk factors for severe outcomes of SARS-CoV-2 infection are not well established in children. We sought to describe pediatric hospital admissions associated with SARS-CoV-2 infection in Canada and identify risk factors for more severe disease.Methods:We conducted a national prospective study using the infrastructure of the Canadian Paediatric Surveillance Program (CPSP). Cases involving children who were admitted to hospital with microbiologically confirmed SARS-CoV-2 infection were reported from Apr. 8 to Dec. 31 2020, through weekly online questionnaires distributed to the CPSP network of more than 2800 pediatricians. We categorized hospital admissions as related to COVID-19, incidental, or for social or infection control reasons and determined risk factors for disease severity in hospital.Results:Among 264 hospital admissions involving children with SARS-CoV-2 infection during the 9-month study period, 150 (56.8%) admissions were related to COVID-19 and 100 (37.9%) were incidental infections (admissions for other reasons and found to be positive for SARS-CoV-2 on screening). Infants (37.3%) and adolescents (29.6%) represented most cases. Among hospital admissions related to COVID-19, 52 (34.7%) had critical disease, 42 (28.0%) of whom required any form of respiratory or hemodynamic support, and 59 (39.3%) had at least 1 underlying comorbidity. Children with obesity, chronic neurologic conditions or chronic lung disease other than asthma were more likely to have severe or critical COVID-19.Interpretation:Among children who were admitted to hospital with SARS-CoV-2 infection in Canada during the early COVID-19 pandemic period, incidental SARS-CoV-2 infection was common. In children admitted with acute COVID-19, obesity and neurologic and respiratory comorbidities were associated with more severe disease.

RésuméContexte:Les facteurs de risque de complications graves de l’infection par le SRAS-CoV-2 n’ont pas été bien établis chez les enfants. Nous avons voulu décrire les hospitalisations pédiatriques associées au SRAS-CoV-2 au Canada et identifier les facteurs de risque de maladie grave.Méthodes:Nous avons procédé à une étude prospective nationale en utilisant l’infrastructure du Programme canadien de surveillance pédiatrique (PCSP). Les hospitalisations d’enfants ayant contracté une infection par le SRAS-CoV-2 confirmée en laboratoire de microbiologie ont été rapportées du 8 avril au 31 décembre 2020 au moyen de questionnaires hebdomadaires en ligne distribués au réseau du PCSP, qui compte plus de 2800 pédiatres. Nous avons catégorisé les hospitalisations comme suit : liées à la COVID-19, infections découvertes fortuitement, ou hospitalisations pour des raisons sociales ou de contrôle des infections, et dégagé les facteurs de risque associés à la gravité de la maladie chez les patients hospitalisés.Résultats:Sur les 264 hospitalisations d’enfants ayant contracté le SRAS-CoV-2 au cours de la période de l’étude de 9 mois, 150 (56,8 %) ont été associées à la COVID-19 et 100 (37,9 %) étaient des cas découverts fortuitement (admission pour d’autres raisons et découverte fortuite du SRAS-CoV-2 par dépistage positif). Les nourrissons (37,3 %) et les adolescents (29,6 %) représentaient la majorité des cas. Parmi les hospitalisations liées à la COVID-19, 52 patients (34,7 %) étaient atteints d’une forme grave de la maladie, dont 42 (28,0 % des cas liés à la COVID-19) ont eu besoin d’une forme d’assistance respiratoire ou hémodynamique, et 59 (39,3 %) présentaient au moins 1 comorbidité sous-jacente. Les enfants atteints d’obésité, de maladies neurologiques chroniques ou de maladies pulmonaires chroniques, à l’exclusion de l’asthme, étaient plus susceptibles de présenter une forme grave ou critique de la COVID-19.Interprétation:Parmi les enfants hospitalisés au Canada chez lesquels on a diagnostiqué une infection par le SRAS-CoV-2 au début de la pandémie de COVID-19, la découverte fortuite du SRAS-CoV-2 a été fréquente. Chez les enfants hospitalisés pour une COVID-19 aiguë, l’obésité et les comorbidités neurologiques et respiratoires ont été associées à une gravité accrue.

PurposeTo estimate the minimum incidence of congenital Zika syndrome (CZS) and severe microcephaly in Canada and describe key clinical, epidemiological, aetiological and outcome features of these conditions.MethodsTwo separate national surveillance studies were conducted on CZS and severe microcephaly using the well-established Canadian Paediatric Surveillance Program from 2016 to 2019. Over 2700 paediatricians across Canada were surveyed monthly and asked to report demographic details, pregnancy and travel history, infant anthropometry, clinical features and laboratory findings of newly identified cases. Reports were reviewed to assign an underlying aetiology of severe microcephaly. Incidence rates were estimated using monthly live birth denominators.ResultsThirty-four infants met the case definition for severe microcephaly and <5 met the case definition for CZS. The associated minimum incidence rates were 4.5 per 100 000 live births for severe microcephaly and 0.1–0.5 per 100 000 live births for CZS. Of severe microcephaly cases, 53% were attributed to genetic causes, 15% to infectious or ischaemic causes and 32% to unknown causes. The median head circumference-for-age Z-score at birth was −3.2 (IQR −3.8 to −2.6), and catch-up growth was often not achieved. Common clinical features included intracranial abnormalities (n=23), dysmorphology (n=19) and developmental delays (n=14). Mothers of infants with non-genetic aetiologies travelled during pregnancy more often (10/16) than mothers of infants with genetic aetiologies (<5/18; p<0.01).ConclusionSevere microcephaly and CZS are both rare in Canada. Minimum incidence rates can be used as a baseline against which novel or re-emergent causes of severe microcephaly or CZS can be compared.

PurposeChildhood tuberculosis disease is difficult to diagnose and manage and is an under-recognised cause of morbidity and mortality. Reported data from Canada do not focus on childhood tuberculosis or capture key epidemiologic, clinical and microbiologic details. The purpose of this study was to assess demographics, presentation and clinical features of childhood tuberculosis in Canada.MethodsWe conducted prospective surveillance from 2013 to 2016 of over 2700 paediatricians plus vertical tuberculosis programmes for incident tuberculosis disease in children younger than 15 years in Canada using the Canadian Paediatric Surveillance Program (CPSP).ResultsIn total, 200 cases are included in this study. Tuberculosis was intrathoracic in 183 patients of whom 86% had exclusively intrathoracic involvement. Central nervous system tuberculosis occurred in 16 cases (8%). Fifty-one per cent of cases were hospitalised and 11 (5.5%) admitted to an intensive care unit. Adverse drug reactions were reported in 9% of cases. The source case, most often a first-degree relative, was known in 73% of cases. Fifty-eight per cent of reported cases were Canadian-born Indigenous children. Estimated study rates of reported cases (per 100 000 children per year) were 1.2 overall, 8.6 for all Indigenous children and 54.3 for Inuit children.ConclusionChildhood tuberculosis may cause significant morbidity and resource utilisation. Key geographies and groups have very high incidence rates. Elimination of childhood tuberculosis in Canada will require well-resourced community-based efforts that focus on these highest risk groups.

Liver abscesses occur in up to one-third of patients with chronic granulomatous disease (CGD). Surgery has traditionally been considered the cornerstone of management. Emerging reports in older children and adults, however, have demonstrated successful treatment of CGD-related liver abscesses with corticosteroids and antibiotics alone. We describe the safe and effective use of corticosteroids and antibiotics for CGD-related liver abscesses in an infant with X-linked CGD who had high surgical risk for hepatic resection. Medical management was started at 11 months of age and the abscesses resolved without requiring any subsequent invasive surgical procedures. This case report highlights that corticosteroids and antibiotics may be considered in the management of CGD-related liver abscesses in the infant age group, especially when surgical management is not an option.

Documentation of the demographic and geographical details of changes in cause-specific neonatal (younger than 1 month) and 1–59-month mortality in India can guide further progress in reduction of child mortality. In this study we report the changes in cause-specific child mortality between 2000 and 2015 in India.

Lack of success in achieving considerable reductions in neonatal mortality is a contributory factor in failing to achieve Millennium Development Goal 4.2.6 million neonates still die each year, with preterm birth and infections the two leading causes. Maternal infections and environmental and infant factors influence acquisition of viral and bacterial infections in the perinatal and neonatal period. Scaling up evidence-based interventions addressing maternal risk factors and underlying causes could reduce neonatal infections by 84%. The emergence of new infections and increasing antimicrobial resistance present public health challenges that must be addressed to achieve substantial reductions in neonatal mortality.

We undertook a 28-year review of enteric fever at a large tertiary care pediatric center. Most cases occurred in children who visited friends and relatives in the Indian subcontinent, and there was significant antibiotic resistance. Documented vaccination rates were low, and many cases also had evidence of delays in diagnosis and treatment.

Synthesize the available evidence on the immunogenicity, safety, and effectiveness of live-attenuated varicella vaccine in solid organ transplant (SOT) recipients.

Children living with chronic comorbid conditions are at increased risk for severe COVID-19, though there is limited evidence regarding the risks associated with specific conditions and which children may benefit from targeted COVID-19 therapies. The objective of this study was to identify factors associated with severe disease among hospitalized children with COVID-19 in Canada.

Although often regarded as a foreign disease, latent tuberculosis or tuberculosis disease will be encountered in many clinical situations by the Canadian child health practitioner. There are key differences between tuberculosis in children and adults. In the present article, the changing epidemiology of tuberculosis in children in Canada and around the world, the pathogenesis of infection, diagnostic tests, and clinical management of childhood latent tuberculosis and tuberculosis disease are reviewed.

The COVID-19 pandemic resulted in unprecedented implementation of wide-ranging public health measures globally. During the pandemic, dramatic decreases in seasonal influenza virus detection have been reported worldwide. Information on the impact on paediatric influenza-related hospitalisations is limited. We describe influenza-related hospitalisation in children in Canada following the onset of the COVID-19 pandemic.

The ongoing coronavirus disease 2019 (COVID-19) pandemic has resulted in implementation of public health measures worldwide to mitigate disease spread, including; travel restrictions, lockdowns, messaging on handwashing, use of face coverings and physical distancing. As the pandemic progresses, exceptional decreases in seasonal respiratory viruses are increasingly reported. We aimed to evaluate the impact of the pandemic on laboratory confirmed detection of seasonal non-SARS-CoV-2 respiratory viruses in Canada.

(Abstracted from N Engl J Med2018;379:535–546)It is unclear whether maternal vitamin D supplementation during pregnancy and lactation improves fetal and infant growth in regions where vitamin D deficiency is common.

ABSTRACTBackgroundIn 2018, Pakistan had the world’s highest neonatal mortality rate. Within Pakistan, most neonatal deaths occur in rural areas where access to health facilities is limited, and robust vital registration systems are lacking. To improve newborn survival, there is a need to better understand the causes of neonatal death in high burden settings and engage caregivers in the promotion of newborn health.ObjectiveTo describe the causes of neonatal death in a rural area in Pakistan and to estimate the effect of an integrated neonatal care kit (iNCK) on cause-specific neonatal mortality.MethodsWe analyzed data from a community-based, cluster-randomized controlled trial of 5286 neonates in Rahim Yar Khan (RYK), Punjab, Pakistan between April 2014 and August 2015. In intervention clusters, Lady Health Workers (LHW) delivered the iNCK and education on its use to pregnant women while control clusters received the local standard of care. The iNCK included interventions to prevent and identify signs of infection, identify low birthweight (LBW), and identify and manage hypothermia. Verbal autopsies were attempted for all deaths. The primary outcome was cause-specific neonatal mortality.ResultsVerbal autopsies were conducted for 84 (57%) of the 147 reported neonatal deaths. The leading causes of death were infection (44%), intrapartum-related complications (26%) and prematurity/LBW (20%). There were no significant differences in neonatal mortality due to prematurity/LBW (RR 0.43; 95% CI 0.15–1.24), infection (RR 1.10; 95% CI 0.58–2.10) or intrapartum-related complications (RR 1.04; 95% CI 0.0.45–2.41) among neonates who died in the intervention arm compared to those who died in the control arm.ConclusionThe major causes of neonatal deaths in RYK, Pakistan mirror the global landscape of neonatal deaths. The iNCK did not significantly reduce any cause-specific neonatal mortality.

ABSTRACTLyme neuroborreliosis is a tick-borne illness with central and peripheral nervous system manifestations. Clinical features and methods for accurate diagnosis differ across world regions owing to different causative Borreliaspecies. The importance of these distinctions is highlighted by a 12-year-old Canadian girl who acquired Lyme neuroborreliosis in Europe.

Blastomycosis is an uncommon life-threatening disease caused by the dimorphic fungus Blastomyces dermatitidis. Estimates of the percentage of cases occurring in children range from 2% to 11%, and it is exceedingly rare in individuals less than 1 year of age. We present the case of an otherwise healthy infant with disseminated blastomycosis acquired in Northern Ontario and a brief review of the pediatric literature.