Clinical, scientific and healthcare system consequences of misdiagnosing neonatal sepsis.

Introduction: Neonatal sepsis remains a major contributor to morbidity and mortality worldwide, with the highest burden in low- and middle-income countries (LMICs). Generating accurate estimates of disease burden is critical for setting research priorities, informing health policy, and resource allocation. However, in many LMICs, limited access to timely and reliable diagnostic tools severely limits case detection, undermines epidemiological surveillance, and impedes efforts to improve clinical outcomes.

RSV Hospital Admissions During the First 2 Seasons Among Children With Chronic Medical Conditions.

Importance: National Immunization Technical Advisory Groups recommend long-acting monoclonal antibody prophylaxis for the prevention of respiratory syncytial virus (RSV) disease for children at high risk in the first season, regardless of RSV vaccination during pregnancy, and for those who remain at increased risk in the second season.

Objective: This study assessed which groups of children with chronic medical conditions (CMCs) are at higher risk of RSV hospitalization during their first and second RSV seasons.

Design, Setting, And Participants: This retrospective, population-based, season-stratified cohort analysis was conducted among children who were born between April 1, 2013, and March 31, 2023, in British Columbia, Canada (population of 5.

Durability of Antibody Responses to SARS-CoV-2 Vaccination over 12 Months in Pediatric Inflammatory Bowel Disease.

Background/objectives: Severe acute respiratory syndrome (SARS-CoV-2) has had a profound global impact and continues to represent a health challenge worldwide. The durability of SARS-CoV-2 vaccine responses in pediatric inflammatory bowel disease (PIBD) patients receiving biologic therapies is unknown. This study aimed to quantify SARS-CoV-2 antibody responses post vaccination in these immunosuppressed patients over 12 months.

Crosstalk with infant-derived Th17 cells, as well as exposure to IL-22 promotes maturation of intestinal epithelial cells in an enteroid model.

Introduction: The intestinal epithelium of human infants is developmentally immature compared to that of adults. Exactly how this immaturity affects key epithelial functions and their interactions with nearby immune cells remains an understudied area of research, partly due to limited access to non-diseased infant gut tissues. Human intestinal organoids, or "mini guts" generated from tissue stem cells, are promising models for investigating intestinal biology and disease mechanisms.

High-dose docosahexaenoic acid for bronchopulmonary dysplasia severity in very preterm infants: a collaborative individual participant data meta-analysis.

Background: Neonatal supplementation with high-dose docosahexaenoic acid (DHA) omega-3 may benefit neurodevelopment in very preterm infants, but concerns remain regarding a potential increased risk and severity of bronchopulmonary dysplasia (BPD). However, the interpretation of evidence on the effect of DHA on severe BPD is challenging because of the heterogeneity in the BPD definitions used across trials.

Objectives: This study aims to determine whether, compared with placebo, neonatal enteral supplementation with high-dose DHA, mimicking placental transfer, is associated with severe BPD in very preterm infants using an individual participant data meta-analysis of randomized controlled trials (RCTs).

Recovery of Antibody Immunity After a Resurgence of Respiratory Syncytial Virus Infections.

Longitudinal measurements of respiratory syncytial virus (RSV) immunity over 4 winter seasons reveal that viral neutralization titers, RSV prefusion F protein (pre-F)-specific immunoglobulin M and immunoglobulin G (IgG) levels, and RSV antibody-dependent cellular phagocytosis function gradually returned to prepandemic levels in female healthcare and school workers of childbearing age after 2 winter seasons, following the resurgence of RSV cases in the Vancouver metropolitan region (British Columbia, Canada). In contrast, pre-F IgG avidity profiles remained unchanged. These findings support the notion that repeated viral infections are necessary to maintain high RSV antibody levels in the population.

Can prenatal conditions impact the effect of omega-3 on bronchopulmonary dysplasia in very preterm infants? A secondary analysis of a randomized controlled trial.

Unlabelled: To explore whether prenatal conditions (i.e. chorioamnionitis, preeclampsia or small-for-gestational age (SGA)) affect the very preterm infant's response to docosahexaenoic acid (DHA) on bronchopulmonary dysplasia (BPD), according to mode of delivery, an independent factor shown to modulate this association.

DNA methylation differences between cord and adult white blood cells reflect postnatal immune cell maturation.

Epigenetic modifications such as DNA methylation are both cell type and developmental age specific. Here, we show that the immunological maturation of blood cell types influences DNA methylation changes from naive cord blood to fully functional adult blood. Lymphoid cells in adult blood showed more variability than in cord blood suggesting an antigen-dependent maturation of DNA methylation in lymphoid cells throughout the lifespan.

Risk of Reinfection and Incidence of Chronic Symptoms After SARS-CoV-2 Infections.

This study showed that a severe acute respiratory syndrome coronavirus 2 infection reduced the risk of reinfection among vaccinated individuals by 0.50 (95% CI, 0.39-0.

The epidemiology and risk factors for postnatal complications among postpartum women and newborns in southwestern Uganda: A prospective cohort study.

Sub-Saharan Africa accounts for two-thirds of the global burden of maternal and newborn deaths. Adverse outcomes among postpartum women and newborns occurring in the first six weeks of life are often related, though data co-examining patients are limited. This study is an exploratory analysis describing the epidemiology of postnatal complications among postpartum women and newborns following facility birth and discharge in Mbarara, Uganda.

Bordetella pertussis infection following relaxation of COVID-19 non-pharmaceutical interventions in 2021-2023 in Vancouver metropolitan area, British Columbia, Canada.

Background: We recently reported a near disappearance of B. pertussis and a decline in anti-B. pertussis antibodies during the peak implementation of Coronavirus disease 2019 (COVID-19) non-pharmaceutical interventions (NPI) in 2021 in British Columbia (BC), Canada.

Angiogenesis-associated pathways play critical roles in neonatal sepsis outcomes.

Neonatal sepsis is a major cause of childhood mortality. Limited diagnostic tools and mechanistic insights have hampered our abilities to develop prophylactic or therapeutic interventions. Biomarkers in human neonatal sepsis have been repeatedly identified as associated with dysregulation of angiopoietin signaling and altered arachidonic acid metabolism.

Prediction models for post-discharge mortality among under-five children with suspected sepsis in Uganda: A multicohort analysis.

In many low-income countries, over five percent of hospitalized children die following hospital discharge. The lack of available tools to identify those at risk of post-discharge mortality has limited the ability to make progress towards improving outcomes. We aimed to develop algorithms designed to predict post-discharge mortality among children admitted with suspected sepsis.

Prognostic algorithms for post-discharge readmission and mortality among mother-infant dyads: an observational study protocol.

Introduction: In low-income country settings, the first six weeks after birth remain a critical period of vulnerability for both mother and newborn. Despite recommendations for routine follow-up after delivery and facility discharge, few mothers and newborns receive guideline recommended care during this period. Prediction modelling of post-delivery outcomes has the potential to improve outcomes for both mother and newborn by identifying high-risk dyads, improving risk communication, and informing a patient-centered approach to postnatal care interventions.

A Novel Anti-nucleocapsid Antibody Avidity Method for Identifying SARS-CoV-2 Reinfections.

Detecting severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) reinfections is challenging with current serology assays and is further complicated by the marked decrease in routine viral testing practices as viral transmission increased during Omicron. Here, we provide proof-of-principle that high-avidity anti-nucleocapsid (N) antibodies detects reinfections after a single infection with higher specificity (85%; 95% confidence interval [95% CI], 80%-90%) compared to anti-N antibody levels (72%; 95% CI, 66%-79%) in a vaccinated cohort. This method could be used to retroactively investigate the epidemiology and incremental long-term health consequences of SARS-CoV-2 reinfections.

Decreased β-catenin Protein in Lungs From Human Congenital Diaphragmatic Hernia Archival Pathology Specimens: A Case-control Study.

Background: Lung hypoplasia contributes to congenital diaphragmatic hernia (CDH) associated morbidity and mortality. Changes in lung wingless-type MMTV integration site family member (Wnt)-signalling and its downstream effector beta-catenin (CTNNB1), which acts as a transcription coactivator, exist in animal CDH models but are not well characterized in humans. We aim to identify changes to Wnt-signalling gene expression in human CDH lungs and hypothesize that pathway expression will be lower than controls.

DDIT4L regulates mitochondrial and innate immune activities in early life.

Pattern recognition receptor responses are profoundly attenuated before the third trimester of gestation in the relatively low-oxygen human fetal environment. However, the mechanisms regulating these responses are uncharacterized. Herein, genome-wide transcription and functional metabolic experiments in primary neonatal monocytes linked the negative mTOR regulator DDIT4L to metabolic stress, cellular bioenergetics, and innate immune activity.

Efficacy of Palivizumab Immunoprophylaxis for Reducing Severe RSV Outcomes in Children with Immunodeficiencies: A Systematic Review.

Background: Palivizumab is recommended for prevention of severe respiratory syncytial virus (RSV) disease in immunocompromised children, despite a lack of strong supporting evidence. The recent approval of substitute RSV-neutralizing monoclonal antibodies against RSV, offers an opportunity to synthesize the most current evidence supporting the palivizumab standard of care.

Objective: To evaluate the efficacy of palivizumab in preventing acute respiratory tract infection- or RSV-related hospitalization, or mortality in immunocompromised children.

World Health Organization Danger Signs to predict bacterial sepsis in young infants: A pragmatic cohort study.

Bacterial sepsis is generally a major concern in ill infants. To help triaging decisions by front-line health workers in these situations, the World Health Organization (WHO) has developed danger signs (DS). The objective of this study was to evaluate the extent to which nine DS predict bacterial sepsis in young infants presenting with suspected sepsis in a low-income country setting.

Loss of Respiratory Syncytial Virus Antibody Functions During the Peak of the COVID-19 Pandemic Mitigation Measures.

Studies have linked respiratory syncytial virus (RSV) antibody-mediated phagocytosis and complement deposition to severe RSV infection in humans. This study shows waning of these antibody functions in women of childbearing age in 2020-2021 during the implementation of COVID-19 mitigation measures, in absence of RSV circulation. These functions could be explored as correlates of protection against severe RSV disease.

Total liquid ventilation in an ovine model of extreme prematurity: a randomized study.

Background: This study aimed at comparing cardiorespiratory stability during total liquid ventilation (TLV)-prior to lung aeration-with conventional mechanical ventilation (CMV) in extremely preterm lambs during the first 6 h of life.

Methods: 23 lambs (11 females) were born by c-section at 118-120 days of gestational age (term = 147 days) to receive 6 h of TLV or CMV from birth. Lung samples were collected for RNA and histology analyses.

Verbal Autopsy to Assess Postdischarge Mortality in Children With Suspected Sepsis in Uganda.

Background: Reducing child mortality in low-income countries is constrained by a lack of vital statistics. In the absence of such data, verbal autopsies provide an acceptable method to determining attributable causes of death. The objective was to assess potential causes of pediatric postdischarge mortality in children younger than age 5 years (under-5) originally admitted for suspected sepsis using verbal autopsies.