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.

No association between the early-life gut microbiota and childhood body mass index and body composition.

Background: The gut microbiota has been implicated in adult obesity, but the causality is still unclear. It has been hypothesized that an obesity-prone gut microbiota can be established in infancy, but only few studies have examined the early-life gut microbiota in relation to obesity in childhood, and no consistent associations have been reported. Here, we examine the association between the early-life gut microbiota and body mass index (BMI) development and body composition throughout childhood.

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.

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.

Urban metabolic and airway immune profiles increase the risk of infections in early childhood.

Background: Infections in childhood remain a leading global cause of child mortality and environmental exposures seem crucial. We investigated whether urbanicity at birth was associated with the risk of infections and explored underlying mechanisms.

Methods: Children (n=633) from the COPSAC mother-child cohort were monitored daily with symptom diaries of infection episodes during the first 3 years and prospectively diagnosed with asthma until age 6 years.

MAGinator enables accurate profiling of de novo MAGs with strain-level phylogenies.

Metagenomic sequencing has provided great advantages in the characterisation of microbiomes, but currently available analysis tools lack the ability to combine subspecies-level taxonomic resolution and accurate abundance estimation with functional profiling of assembled genomes. To define the microbiome and its associations with human health, improved tools are needed to enable comprehensive understanding of the microbial composition and elucidation of the phylogenetic and functional relationships between the microbes. Here, we present MAGinator, a freely available tool, tailored for profiling of shotgun metagenomics datasets.

Co-localization of antibiotic resistance genes is widespread in the infant gut microbiome and associates with an immature gut microbial composition.

Background: In environmental bacteria, the selective advantage of antibiotic resistance genes (ARGs) can be increased through co-localization with genes such as other ARGs, biocide resistance genes, metal resistance genes, and virulence genes (VGs). The gut microbiome of infants has been shown to contain numerous ARGs, however, co-localization related to ARGs is unknown during early life despite frequent exposures to biocides and metals from an early age.

Results: We conducted a comprehensive analysis of genetic co-localization of resistance genes in a cohort of 662 Danish children and examined the association between such co-localization and environmental factors as well as gut microbial maturation.

Escherichia coli CRISPR arrays from early life fecal samples preferentially target prophages.

CRISPR-Cas systems are defense mechanisms against phages and other nucleic acids that invade bacteria and archaea. In Escherichia coli, it is generally accepted that CRISPR-Cas systems are inactive in laboratory conditions due to a transcriptional repressor. In natural isolates, it has been shown that CRISPR arrays remain stable over the years and that most spacer targets (protospacers) remain unknown.

Differential responses of the gut microbiome and resistome to antibiotic exposures in infants and adults.

Despite their crucial importance for human health, there is still relatively limited knowledge on how the gut resistome changes or responds to antibiotic treatment across ages, especially in the latter case. Here, we use fecal metagenomic data from 662 Danish infants and 217 young adults to fill this gap. The gut resistomes are characterized by a bimodal distribution driven by E.

The infant gut virome is associated with preschool asthma risk independently of bacteria.

Bacteriophage (also known as phage) communities that inhabit the gut have a major effect on the structure and functioning of bacterial populations, but their roles and association with health and disease in early life remain unknown. Here, we analyze the gut virome of 647 children aged 1 year from the Copenhagen Prospective Studies on Asthma in Childhood (COPSAC) mother-child cohort, all deeply phenotyped from birth and with longitudinally assessed asthma diagnoses. Specific temperate gut phage taxa were found to be associated with later development of asthma.

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.

The real-world use and efficacy of pomalidomide for relapsed and refractory multiple myeloma in the era of CD38 antibodies.

Pomalidomide-dexamethasone (Pd) has been a standard care treatment for relapsed and refractory multiple myeloma since 2013. However, the outcomes of Pd after exposure to CD38 antibodies are not known. Here we describe the real-world use and efficacy of pomalidomide in a Danish, nationwide cohort of daratumumab-exposed patients.

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.

The airway microbiota of neonates colonized with asthma-associated pathogenic bacteria.

Culture techniques have associated colonization with pathogenic bacteria in the airways of neonates with later risk of childhood asthma, whereas more recent studies utilizing sequencing techniques have shown the same phenomenon with specific anaerobic taxa. Here, we analyze nasopharyngeal swabs from 1 month neonates in the COPSAC prospective birth cohort by 16S rRNA gene sequencing of the V3-V4 region in relation to asthma risk throughout childhood. Results are compared with previous culture results from hypopharyngeal aspirates from the same cohort and with hypopharyngeal sequencing data from the later COPSAC cohort.

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.

Expanding known viral diversity in the healthy infant gut.

The gut microbiome is shaped through infancy and impacts the maturation of the immune system, thus protecting against chronic disease later in life. Phages, or viruses that infect bacteria, modulate bacterial growth by lysis and lysogeny, with the latter being especially prominent in the infant gut. Viral metagenomes (viromes) are difficult to analyse because they span uncharted viral diversity, lacking marker genes and standardized detection methods.

Risk Factors and Age-Related Patterns of Asthma-Like Symptoms in Early Childhood.

Background: Episodes of asthma-like symptoms in young children are common, but little is known about risk factors and their patterns for the daily symptom burden.

Objective: We investigated a variety of possible risk factors and their age-related impact on the number of asthma-like episodes during age 0 to 3 years.

Methods: The study population included 700 children from the Copenhagen Prospective Studies on Asthma in Childhood mother-child cohort followed prospectively from birth.

Can breastfeeding promote an antibiotic-resilient microbiome?

In this issue of Med, Dai, Petersen, and colleagues report that the antibiotic-associated risk of asthma in children may be mitigated by breastfeeding in early life. They find that breastfeeding promotes a specific microbiome composition responsible for this resilience, mainly driven by the bacterium Bifidobacterium longum subspecies infantis.

Middle ear effusion, ventilation tubes and neurological development in childhood.

Background: Otitis media with middle ear effusion (MEE) can be treated with ventilation tubes (VT) insertion, and it has been speculated that prolonged MEE in childhood can affect neurological development, which in turn may be important for later academic achievements.

Objective: To investigate the association between middle ear effusion (MEE), treatment with ventilation tubes (VT) and childhood neurological development.

Study Design: We examined 663 children from the Copenhagen Prospective Studies on Asthma in Childhood 2010 (COPSAC2010) unselected mother-child cohort study.