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.

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.

Limited clinical role of blood eosinophil levels in early life atopic disease: A mother-child cohort study.

Background: Blood eosinophil count is a well-established biomarker of atopic diseases in older children and adults. However, its predictive role for atopic diseases in preschool children is not well established.

Objective: To investigate the association between blood eosinophil count in children and development of atopic diseases up to age 6 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.

Hepatic Glucose Production, Ureagenesis, and Lipolysis Quantified using the Perfused Mouse Liver Model.

The liver has numerous functions, including nutrient metabolism. In contrast to other in vitro and in vivo models of liver research, the isolated perfused liver allows the study of liver biology and metabolism in the whole liver with an intact hepatic architecture, separated from the influence of extra-hepatic factors. Liver perfusions were originally developed for rats, but the method has been adapted to mice as well.

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.

European and multi-ancestry genome-wide association meta-analysis of atopic dermatitis highlights importance of systemic immune regulation.

Atopic dermatitis (AD) is a common inflammatory skin condition and prior genome-wide association studies (GWAS) have identified 71 associated loci. In the current study we conducted the largest AD GWAS to date (discovery N = 1,086,394, replication N = 3,604,027), combining previously reported cohorts with additional available data. We identified 81 loci (29 novel) in the European-only analysis (which all replicated in a separate European analysis) and 10 additional loci in the multi-ancestry analysis (3 novel).

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.

Handgrip strength associates with effort-dependent lung function measures among adolescents with and without asthma.

Studies have shown association between handgrip strength (HGS) and FEV1, but the importance of this in relation to asthma pathophysiology and diagnostics remains unclear. We investigated the relationship between HGS and lung function metrics and its role in diagnosing asthma. We included 330 participants (mean age: 17.

Maternal vitamin D-related metabolome and offspring risk of asthma outcomes.

Background: Gestational vitamin D deficiency is implicated in development of respiratory diseases in offspring, but the mechanism underlying this relationship is unknown.

Objective: We sought to study the link between gestational vitamin D exposure and childhood asthma phenotypes using maternal blood metabolomics profiling.

Methods: Untargeted blood metabolic profiles were acquired using liquid chromatography-mass spectrometry at 1 week postpartum from 672 women in the Copenhagen Prospective Studies on Asthma in Childhood (COPSAC) mother-child cohort and at pregnancy weeks 32 to 38 from 779 women in the Vitamin D Antenatal Asthma Reduction Trial (VDAART) mother-child cohort.

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.

Bone mineral density loci specific to the skull portray potential pleiotropic effects on craniosynostosis.

Skull bone mineral density (SK-BMD) provides a suitable trait for the discovery of key genes in bone biology, particularly to intramembranous ossification, not captured at other skeletal sites. We perform a genome-wide association meta-analysis (n ~ 43,800) of SK-BMD, identifying 59 loci, collectively explaining 12.5% of the trait variance.

Elevated third trimester corticosteroid levels are associated with fewer offspring infections.

Respiratory infections are a leading cause of morbidity and mortality in early life, and recurrent infections increase the risk of developing chronic diseases. The maternal environment during pregnancy can impact offspring health, but the factors leading to increased infection proneness have not been well characterized during this period. Steroids have been implicated in respiratory health outcomes and may similarly influence infection susceptibility.

Omega-3 Fatty Acids Interact with Region Genotype in Association with Childhood Atopy.

Associations of omega-3 fatty acids (-3) with allergic diseases are inconsistent, perhaps in part due to genetic variation. We sought to identify and validate genetic variants that modify associations of -3 with childhood asthma or atopy in participants in the Vitamin D Antenatal Asthma Reduction Trial (VDAART) and the Copenhagen Prospective Studies on Asthma in Childhood 2010 (COPSAC). Dietary -3 was derived from food frequency questionnaires and plasma -3 was measured via untargeted mass spectrometry in early childhood and children aged 6 years old.

Novel Connections of Common Childhood Illnesses Based on More Than 5 Million Diary Registrations From Birth Until Age 3 Years.

Background: All children experience numerous episodes of illness during the first 3 years of life. Most episodes are mild and handled without medical attention but nevertheless burden the families and society. There is a large, and still unexplained, variation in the burden of illness between children.

The Impact of Baseline 25-Hydroxyvitamin D Level and Gestational Age on Prenatal Vitamin D Supplementation to Prevent Offspring Asthma or Recurrent Wheezing.

Background: Prenatal vitamin D deficiency is associated with asthma or recurrent wheezing in offspring. However, evidence from randomized trials on the efficacy of vitamin D supplementation is inconclusive.

Objectives: We aimed to examine the differential efficacy of prenatal vitamin D supplementation based on the maternal baseline vitamin D status and the starting time of supplementation to prevent early life asthma or recurrent wheezing.

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.

Associations of pre- and postnatal exposures with optic nerve status in young adults.

Purpose: We aimed to explore the effect of multiple pre- and postnatal exposures on optic nerve status in young adults due to this critical period for development.

Methods: We analysed peripapillary retinal nerve fibre layer (RNFL) status and macular thickness at age 18 years in the Copenhagen Prospective Studies on Asthma in Childhood 2000 (COPSAC ) cohort in relation to several exposures.

Results: Of the 269 participants (median (IQR) age, 17.

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.

Environmental and genetic associations with aberrant early-life gut microbial maturation in childhood asthma.

Background: Environmental, genetic, and microbial factors are independently associated with childhood asthma.

Objective: We sought to determine the roles of environmental exposures and 17q12-21 locus genotype in the maturation of the early-life microbiome in childhood asthma.

Methods: We analyzed fecal 16s rRNA sequencing at age 3 to 6 months and age 1 year to characterize microbial maturation of offspring of participants in the Vitamin D Antenatal Reduction Trial.

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.