Burden of Infections in Early Life and Risk of Infections and Systemic Antibiotics Use in Childhood.

Importance: A high infection burden in early childhood is common and a risk factor for later disease development. However, longitudinal birth cohort studies investigating early-life infection burden and later risk of infection and antibiotic episodes are lacking.

Objective: To investigate whether early-life infection burden is associated with a later risk of infection and systemic antibiotic treatment episodes in childhood.

Levels of total IgE versus specific IgE during childhood for defining and predicting T2-high asthma.

Background: T2-high asthma is characterized by elevated blood eosinophils (b-eos), and/or fractional exhaled nitric oxide (FeNO), and/or being "allergy-driven", which is not well-defined.

Objective: To investigate the role of total and specific immunoglobulin E (tIgE/sIgE) for defining and predicting T2-high asthma in childhood as biomarkers of "allergy-driven".

Methods: We utilized data from the COPSAC2000 (n = 411) and COPSAC2010 (n = 700) mother-child cohorts with repeated measurements of tIgE, sIgE, b-eos and FeNO through childhood.

Machine Learning for the Identification of Key Predictors to Bayley Outcomes: A Preterm Cohort Study.

Background: The aim of this study was to understand how neurological development of preterm infants can be predicted at earlier stages and explore the possibility of applying personalized approaches.

Methods: Our study included a cohort of 64 preterm infants, between 24 and 34 weeks of gestation. Linear and nonlinear models were used to evaluate feature predictability to Bayley outcomes at the corrected age of 2 years.

Children hospitalised with gastroenteritis before and during the COVID-19 pandemic.

Aims: The COVID-19 pandemic altered the pattern of many paediatric infections. We aimed to assess the incidence and characteristics of children hospitalised with gastroenteritis during the early and the late pandemic, relative to previous years.

Methods: In a retrospective study, we collected data from patient files of children aged 1 month to 5 years, admitted with gastroenteritis to a paediatric department in Denmark during January-June, of 2017 to 2021, comparing incidence rates and clinical features in the early pandemic (March to June 2020), and late pandemic period (January to June 2021), to similar pre-pandemic months.

Asthma development is associated with low mucosal IL-10 during viral infections in early life.

Background: Viral infection is a common trigger of severe respiratory illnesses in early life and a risk factor for later asthma development. The mechanism leading to asthma could involve an aberrant airway immune response to viral infections, but this has rarely been studied in a human setting.

Objectives: To investigate in situ virus-specific differences in upper airway immune mediator levels during viral episodes of respiratory illnesses and the association with later asthma.

Design of the 18-year follow-up of the Danish COPSAC birth cohort.

Background: Atopic diseases, obesity and neuropsychiatric disorders are lifestyle-related and environmental-related chronic inflammatory disorders, and the incidences have increased in the last years.

Objective: To outline the design of the 18-year follow-up of the Copenhagen Prospective Study on Asthma in Childhood (COPSAC) birth cohort, where risk factors of atopic diseases, obesity and neuropsychiatric disorders are identified through extensive characterisation of the environment, along with deep clinical phenotyping and biosampling for omics profiling.

Methods: COPSAC is a Danish prospective clinical birth cohort study of 411 children born to mothers with asthma who were enrolled at 1 month of age and closely followed at the COPSAC clinical research unit through childhood for the development of atopic diseases.

Infantile colic is associated with development of later constipation and atopic disorders.

Background: Infantile colic is a common condition with limited knowledge about later clinical manifestations. We evaluated the role of the early life gut microbiome in infantile colic and later development of atopic and gastrointestinal disorders.

Methods: Copenhagen Prospective Studies on Asthma in Childhood cohort was followed with 6 years of extensive clinical phenotyping.

Atopic diseases-Diagnostics, mechanisms, and exposures.

Epidemiological data suggest that atopic diseases begin in early life and that most cases present clinically during early childhood. The diseases are highly prevalent and increase as communities adopt western lifestyles. Disentangling the pathophysiological mechanisms leading to disease debut is necessary to identify beneficial/harmful exposures so that successful prevention and treatment can be generated.

Burden and Subtypes of Early Life Infections Increase the Risk of Asthma.

Background: Early life respiratory tract infections have been linked to the development of asthma, but studies on the burden and subtypes of common infections in asthma development are sparse.

Objective: To examine the association between burden of early life infections, including subtypes, with the risk of asthma from age 3 to 10 years and lung function at age 10 years.

Methods: We included 662 children from the Copenhagen Prospective Studies on Asthma in Childhood 2010 birth cohort, for whom infections such as colds, acute tonsillitis, acute otitis media, pneumonia, gastroenteritis, and fever were registered prospectively in daily diaries at age 0 to 3 years and asthma was diagnosed longitudinally from age 3 to 10 years.

Vertical Metabolome Transfer from Mother to Child: An Explainable Machine Learning Method for Detecting Metabolomic Heritability.

Vertical transmission of metabolic constituents from mother to child contributes to the manifestation of disease phenotypes in early life. This study probes the vertical transmission of metabolites from mothers to offspring by utilizing machine learning techniques to differentiate between true mother-child dyads and randomly paired non-dyads. Employing random forests (RF), light gradient boosting machine (LGBM), and logistic regression (Elasticnet) models, we analyzed metabolite concentration discrepancies in mother-child pairs, with maternal plasma sampled at 24 weeks of gestation and children's plasma at 6 months.

Core Outcome Set for IgE-mediated food allergy clinical trials and observational studies of interventions: International Delphi consensus study 'COMFA'.

Background: IgE-mediated food allergy (FA) is a global health concern with substantial individual and societal implications. While diverse intervention strategies have been researched, inconsistencies in reported outcomes limit evaluations of FA treatments. To streamline evaluations and promote consistent reporting, the Core Outcome Measures for Food Allergy (COMFA) initiative aimed to establish a Core Outcome Set (COS) for FA clinical trials and observational studies of interventions.

Normal saline for children with bronchiolitis: study protocol for a randomised controlled non-inferiority trial.

Introduction: Bronchiolitis is one of the most common reasons for hospital admissions in early childhood. As supportive treatment, some treatment guidelines suggest using nasal irrigation with normal saline (NS) to facilitate clearance of mucus from the airways. In addition, most paediatric departments in Denmark use nebulised NS for the same purpose, which can mainly be administered as inpatient care.

Bacterial colonisation of the airway in neonates and risk of asthma and allergy until age 18 years.

Background: We previously showed an association between neonatal bacterial airway colonisation and increased risk of persistent wheeze/asthma until age 5 years. Here, we study the association with persistent wheeze/asthma and allergy-related traits until age 18 years.

Methods: We investigated the association between airway colonisation with , and/or in 1-month-old neonates from the COPSAC mother-child cohort and the development of persistent wheeze/asthma and allergy-related traits longitudinally until age 18 years using generalised estimating equations.

Exhaled nitric oxide is only an asthma-relevant biomarker among children with allergic sensitization.

Background: Fraction of exhaled nitric oxide (FeNO) is used for diagnosing and monitoring asthma in children, but the influence of allergic sensitization is still poorly understood. Here, we investigate how asthma and allergic sensitization influence FeNO levels during childhood.

Methods: We investigated the associations between asthma, aeroallergen sensitization, and FeNO measured from age 5-18 years in the COPSAC birth cohort of 411 children using repeated measurement mixed models adjusted for gestational age, sex, concurrent airway infection, inhaled corticosteroids, and tobacco exposure.

Key risk factors of asthma-like symptoms are mediated through infection burden in early childhood.

Background: Risk factors of asthma-like symptoms in childhood may act through an increased infection burden because infections often trigger these symptoms.

Objective: We sought to investigate whether the effect of established risk factors of asthma-like episodes in early childhood is mediated through burden and subtypes of common infections.

Methods: The study included 662 children from the Copenhagen Prospective Studies on Asthma in Childhood 2010 mother-child cohort, in which infections were registered prospectively in daily diaries from age 0 to 3 years.

Asthma medication and risk of dental diseases in children - A prospective cohort study.

Background: Dental caries and enamel defects are the main causes of poor dental health in children, with a substantial impact on their well-being. Use of inhaled asthma medication is a suspected risk factor, but there is a lack of prospective studies investigating this and other prenatal and early life risk factors.

Methods: Copenhagen Prospective Studies on Asthma in Childhood 2010 mother-child cohort (COPSAC ) consists of 700 women who were recruited at 24 weeks of pregnancy.

Atopic and non-atopic effects of fish oil supplementation during pregnancy.

Background: We recently conducted a double-blinded randomised controlled trial showing that fish-oil supplementation during pregnancy reduced the risk of persistent wheeze or asthma in the child by 30%. Here, we explore the mechanisms of the intervention.

Methods: 736 pregnant women were given either placebo or n-3 long-chain polyunsaturated fatty acids (LCPUFAs) in the third trimester in a randomised controlled trial.

Exposures to perfluoroalkyl substances and asthma phenotypes in childhood: an investigation of the COPSAC2010 cohort.

Background: Exposure to perfluoroalkyl substances may affect offspring immune development and thereby increase risk of childhood asthma, but the underlying mechanisms and asthma phenotype affected by such exposure is unknown.

Methods: In the Danish COPSAC2010 cohort of 738 unselected pregnant women and their children plasma PFOS and PFOA concentrations were semi-quantified by untargeted metabolomics analyses and calibrated using a targeted pipeline in mothers (gestation week 24 and 1 week postpartum) and children (age ½, 1½ and 6 years). We examined associations between pregnancy and childhood PFOS and PFOA exposure and childhood infections, asthma, allergic sensitization, atopic dermatitis, and lung function measures, and studied potential mechanisms by integrating data on systemic low-grade inflammation (hs-CRP), functional immune responses, and epigenetics.

25 Years of translational research in the Copenhagen Prospective Studies on Asthma in Childhood (COPSAC).

The Copenhagen Prospective Studies on Asthma in Childhood (COPSAC) mother-child cohorts have provided a foundation of 25 years of research on the origins, prevention, and natural history of childhood asthma and related disorders. COPSAC's approach is characterized by clinical translational research with longitudinal deep phenotyping and exposure assessments from pregnancy, in combination with multi-omic data layers and embedded randomized controlled trials. One trial showed that fish oil supplementation during pregnancy prevented childhood asthma and identified pregnant women with the highest benefits from supplementation, thereby creating the potential for personalized prevention.

[Spontaneous pneumomediastinum initially interpreted as anaphylaxis in a boy].

Spontaneous pneumomediastinum is a rare but maybe also underdiagnosed condition in the paediatric population. Symptoms are often mild, and the disease course is often benign, but more serious differential diagnosis must be excluded. This case report is about a four-year-old boy admitted to the children's department with a suspected allergic reaction because off swelling of his chin after taking NSAID.

Persistent Asthma in Childhood.

Asthma is the most common chronic disease in children and a cause of great distress for both the children and their families [...

Supplementation With Fish Oil in Pregnancy Reduces Gastroenteritis in Early Childhood.

Background: We hypothesized that insufficient intake of fish oil-derived omega-3 long-chain polyunsaturated fatty acids (n-3 LCPUFAs) during pregnancy is a contributing factor to gastroenteritis in early childhood. We examined the effect of n-3 LCPUFA supplementation on gastroenteritis symptoms in the offspring's first 3 years of life.

Methods: This was a double-blinded, randomized controlled trial whereby 736 mothers were administered n-3 LCPUFA or control from pregnancy week 24 until 1 week after birth.

Increasing severity of early-onset atopic dermatitis, but not late-onset, associates with development of aeroallergen sensitization and allergic rhinitis in childhood.

Background: Early exposure to allergens through a defect skin barrier has been proposed as a mechanism for inducing sensitization and development of allergic diseases. We hypothesized that early-onset, severe atopic dermatitis (AD) is associated with development of aeroallergen sensitization and allergic rhinitis.

Methods: We included 368 children from the Copenhagen Prospective Studies on Asthma in Childhood (COPSAC ) at-risk mother-child cohort.