Early preschool wheeze trajectories are predominantly non-allergic with distinct biologic and microbiome traits.

Background: Disentangling preschool wheezing heterogeneity in terms of clinical traits, temporal patterns, and collective healthcare burden is critical for precise and effective interventions.

Objective: We aimed to collectively define contributions and distinct characteristics of respiratory phenotypes based on longitudinal wheeze and atopic sensitization patterns in the first 5 years of life.

Methods: Group-based trajectory analysis was performed in the CHILD Cohort study to identify distinct wheeze and allergic sensitization trajectories.

Secretory IgA modifies the association between early-life gut microbiota trajectories and childhood nonatopic wheeze.

Aims: Wheezing in childhood is common and evidence is accumulating for the role of the gut microbiome in the development of atopic wheeze. Changes to the early-life gut microbiota and secretory IgA (SIgA) production have been linked to childhood disease; however, their connection to nonatopic wheeze is unknown. The objectives of the present study were to evaluate the relationships between early-life gut microbiota trajectories, SIgA and childhood nonatopic wheeze.

ASXL1 deficiency causes epigenetic dysfunction, combined immunodeficiency, and EBV-associated lymphoma.

Inborn errors of immunity (IEIs) are caused by deleterious variants in immune-related genes. ASXL1 is an epigenetic modifier not previously linked to an IEI. Clonal hematopoiesis and hematologic neoplasms often feature somatic ASXL1 variants, and Bohring-Opitz syndrome, a neurodevelopmental disorder, is caused by heterozygous truncating ASXL1 variants.

Infant Acid-Suppressant Medication, C. difficile Colonisation, and Childhood Body Mass Index in a Canadian Cohort.

Aim: To determine relationships between paediatric use of acid-suppressive medications (ASMs) (proton pump inhibitors (PPI) and histamine-2 receptor antagonists (H2RA)) and preschool body mass index (BMI) and mediation by C. difficile colonisation.

Methods: ASMs were parent-reported at age 3, 6 and 12 months in 1025 infants from the CHILD Cohort Study.

Phthalates and bisphenols early-life exposure, and childhood allergic conditions: a pooled analysis of cohort studies.

Background: Exposure to plastic additives, such as phthalates and bisphenols, has been associated with a higher risk of allergic conditions, but the evidence is inconsistent for children younger than five.

Objective: To examine the association between pre- and postnatal urinary phthalates and bisphenols, and allergic conditions, and potential effect modification by sex, in pre-school children, through a pooled analysis.

Methods: We pooled data from the Barwon Infant Study (Australia), the Canadian Healthy Infant Longitudinal Development Study (Canada), the Health Outcomes and Measures of the Environment (United States) and the Environmental Influences on Child Health Outcomes-wide cohorts (United States).

Protocol: the International Milk Composition (IMiC) Consortium - a harmonized secondary analysis of human milk from four studies.

Introduction: Human milk (HM) contains a multitude of nutritive and nonnutritive bioactive compounds that support infant growth, immunity and development, yet its complex composition remains poorly understood. Integrating diverse scientific disciplines from nutrition and global health to data science, the International Milk Composition (IMiC) Consortium was established to undertake a comprehensive harmonized analysis of HM from low, middle and high-resource settings to inform novel strategies for supporting maternal-child nutrition and health.

Methods And Analysis: IMiC is a collaboration of HM experts, data scientists and four mother-infant health studies, each contributing a subset of participants: Canada (CHILD Cohort,  = 400), Tanzania (ELICIT Trial,  = 200), Pakistan (VITAL-LW Trial,  = 150), and Burkina Faso (MISAME-3 Trial,  = 290).

Associations of dietary patterns and obesity development in school-aged children: results from the CHILD Cohort Study.

Objective: We aimed to understand data-driven dietary patterns in Canadian preschoolers and their impact on obesity development among male and female individuals.

Methods: In the prospective, population-based Canadian pregnancy cohort, the CHILD Cohort Study (N = 2219), dietary intake was assessed at age 3 years using a previously developed 112-item food frequency questionnaire. At age 5 years, we measured height, weight, and waist circumference and calculated BMI and waist circumference z scores.

STAT6 gain-of-function disease: p.D519N is a new disease-causing variant that responds well to dupilumab treatment.

This case report presents a new genetic variant that causes STAT6 gain-of-function disease in 2 patients, expands the clinical phenotype of STAT6 gain-of-function disease, and describes its authors' success in using therapeutics to manage this rare disease.

Human LY9 governs CD4 T cell IFN-γ immunity to .

CD4 T cells are indispensable for optimal immunity to (), a pathogen that triggers tuberculosis (TB) in humans. -specific human CD4 T cells are known to polarize toward an interferon-γ (IFN-γ)-producing, CCR4CCR6CXCR3T-betRORγT T helper 1* cell (T1*cell) memory phenotype. We report that autosomal recessive deficiency of the human lymphocytic surface receptor LY9 (SLAMF3 and CD229), which is found in less than 10 individuals in the general population, underlies TB in three unrelated patients due to selective impairment in IFN-γ production by T1* cells.

A multimorphic variant in ThPOK causes an inborn error of immunity with T cell defects and fibrosis.

ThPOK is a transcription factor that acts as a master regulator of CD4+ T cell lineage commitment. We report the first human disease caused by a genetic alteration in ThPOK, specifically, a damaging heterozygous de novo variant in ThPOK (NM_001256455.2:c.

Early life predictors of child development at kindergarten: a structural equation model using a longitudinal cohort.

Introduction: Early child development sets the stage for lifelong health. Identifying early life factors related to child development can help guide programs and policies to bolster child health and wellbeing. The objective of this research was to examine how a broad range of predictors, measured prenatally to the third year of life, are related to child development at kindergarten.

Determining the interplay of prenatal parental BMI in shaping child BMI trajectories: the CHILD Cohort Study.

Background: Obesity is a major public health concern affecting millions of people globally. Early identification of individuals susceptible to obesity is crucial for reducing the burden of obesity. Obesity is often defined based on body-mass-index (BMI), and tracking BMI trajectories from early childhood offers a valuable tool for risk stratification.

A Germline Heterozygous Dominant Negative IKZF2 Variant Causing Syndromic Primary Immune Regulatory Disorder and ICHAD.

Monogenic defects that impair the control of inflammation and tolerance lead to profound immune dysregulation, including autoimmunity and atopy. Studying these disorders reveals important molecular and cellular factors that regulate human immune homeostasis and identifies potential precision medicine targets. Here, we provide a detailed immunological assessment of a pediatric patient with a recently discovered syndrome causing Immunodysregulation, Craniofacial anomalies, Hearing impairment, Athelia, and Developmental delay (or ICHAD syndrome).

Gene-by-environment interactions modulate the infant gut microbiota in asthma and atopy.

Background: Gut microbiota has been associated with health and susceptibility to childhood diseases, including asthma and allergies. However, the genomic factors contributing to interindividual variations in gut microbiota remain poorly understood.

Objective: We sought to integrate host genomics with early-life exposures to investigate main and interaction effects on gut microbiota during the first year of life.

Primary atopic disorders: inborn errors of immunity causing severe allergic disease.

Allergic diseases, including asthma, allergic rhinitis, atopic dermatitis, and food allergies, are driven by dysregulated immune responses, often involving IgE-mediated mast cell and basophil activation, Th2 inflammation, and epithelial dysfunction. While environmental factors are well-known contributors, the genetic components underpinning these conditions are increasingly understood. Traditionally viewed as polygenic multifactorial disorders, allergic diseases can also be caused by single-gene defects affecting the immune system and skin epithelial barrier, leading to profoundly dysregulated allergic responses.

Long-Term Outcomes of Children Born to Anti-Ro Antibody-Positive Mothers With and Without Rheumatic Disease.

Objective: The objective of this study was to estimate the prevalence of allergy, and/or neurodevelopmental and autoimmune diagnoses in children born to anti-Ro antibody-positive mothers.

Methods: We conducted a cohort study of children born to anti-Ro antibody-positive mothers observed in the neonatal lupus erythematosus (NLE) clinic at The Hospital for Sick Children. Participants one year of age or older were invited to complete a health status questionnaire.

Gut microbiota metabolites, secretory immunoglobulin A and Bayley-III cognitive scores in children from the CHILD Cohort Study.

Background: Dysbiosis of the gut microbiota has been demonstrated in neurodevelopmental disorders but the underlying mechanisms that may explain these associations are poorly understood. Gut secretory immunoglobulin A (SIgA) binds pathogenic microbes, preventing mucosal penetration. Gut microbes also influence SIgA production and its binding characteristics through short-chain fatty acid (SCFA) metabolites, allowing them to regulate the immune response.

Exploring the potential mediating role of systemic antibiotics in the association between early-life lower respiratory tract infections and asthma at age 5 in the CHILD study.

Objective: Lower respiratory tract infections (LRTIs) in early life are one of the strongest risk factors for childhood asthma and are often treated with systemic antibiotics (IV or oral). We aimed to explore the association between early-life LRTIs and systemic antibiotics on asthma development and the potential mediating role of antibiotics in this relationship.

Methods: Data were collected as part of the longitudinal, general Canadian population CHILD Study.

Ultraprocessed Food Consumption and Obesity Development in Canadian Children.

Importance: Ultraprocessed foods (UPF), characterized as shelf-stable but nutritionally imbalanced foods, pose a public health crisis worldwide. In adults, UPF consumption is associated with increased obesity risk, but findings among children are inconsistent.

Objectives: To examine the associations among UPF intake, anthropometric adiposity indicators, and obesity status in Canadian children.

Impact analysis of infant antibiotic exposure on the burden of asthma: a simulation modeling study.

Background: Infant antibiotic use is associated with increased risk of asthma. We examined the population impact of antibiotic exposure in the first year of life on the burden of pediatric asthma in British Columbia, Canada, using simulation modeling.

Methods: We performed a Bayesian meta-analysis of empirical studies to construct dose-response equations between antibiotic exposure in the first year of life and pediatric (<19 years of age) asthma.

Pets and related allergens modify the association between early life DEHP exposure and respiratory outcomes in children.

Introduction: Throughout the perinatal period children are exposed to complex mixtures, including indoor chemicals such as phthalates, and biological agents. However, few studies focus on interactions between early-life co-exposures to shed light on how co-exposures modify their individual effects. Therefore, our study aims to assess whether early-life exposure to pets and related biological agents, namely pet allergens and endotoxin, modifies the association between di-(2-ethylhexyl) phthalate (DEHP) and asthma and wheeze in preschoolers to gain insight into interactions.

How the early life microbiome shapes immune programming in childhood asthma and allergies.

Despite advances in our understanding of their diagnosis and treatment, pediatric allergies impose substantial burdens on affected children, families, and healthcare systems. Further, the prevalence of allergic diseases has dramatically increased over the past half-century, leading to additional concerns and concerted efforts to identify the origins, potential predictors and preventions, and therapies of allergic diseases. Together with the increase in allergic diseases, changes in lifestyle and early-life environmental influences have corresponded with changes in colonization patterns of the infant gut microbiome.

Reduce, reinforce, and replenish: safeguarding the early-life microbiota to reduce intergenerational health disparities.

Socioeconomic (SE) disparity and health inequity are closely intertwined and associated with cross-generational increases in the rates of multiple chronic non-communicable diseases (NCDs) in North America and beyond. Coinciding with this social trend is an observed loss of biodiversity within the community of colonizing microbes that live in and on our bodies. Researchers have rightfully pointed to the microbiota as a key modifiable factor with the potential to ease existing health inequities.