Explore the vast range of titles available.

We recently published two independent randomized controlled trials of vitamin D supplementation during pregnancy, both indicating a >20% reduced risk of asthma/recurrent wheeze in the offspring by 3 years of age. However, neither reached statistical significance. To perform a combined analysis of the two trials and investigate whether maternal 25-hydroxy-vitamin D (25(OH)D) level at trial entry modified the intervention effect. VDAART (N = 806) and COPSAC2010. (N = 581) randomized pregnant women to daily high-dose vitamin D3 (4,000 IU/d and 2,400 IU/d, respectively) or placebo. All women also received a prenatal vitamin containing 400 IU/d vitamin D3. The primary outcome was asthma/recurrent wheeze from 0-3yrs. Secondary end-points were specific IgE, total IgE, eczema and lower respiratory tract infections (LRTI). We conducted random effects combined analyses of the treatment effect, individual patient data (IPD) meta-analyses, and analyses stratified by 25(OH)D level at study entry. The analysis showed a 25% reduced risk of asthma/recurrent wheeze at 0-3yrs: adjusted odds ratio (aOR) = 0.74 (95% CI, 0.57-0.96), p = 0.02. The effect was strongest among women with 25(OH)D level ≥30ng/ml at study entry: aOR = 0.54 (0.33-0.88), p = 0.01, whereas no significant effect was observed among women with 25(OH)D level <30ng/ml at study entry: aOR = 0.84 (0.62-1.15), p = 0.25. The IPD meta-analyses showed similar results. There was no effect on the secondary end-points. This combined analysis shows that vitamin D supplementation during pregnancy results in a significant reduced risk of asthma/recurrent wheeze in the offspring, especially among women with 25(OH)D level ≥ 30 ng/ml at randomization, where the risk was almost halved. Future studies should examine the possibility of raising 25(OH)D levels to at least 30 ng/ml early in pregnancy or using higher doses than used in our studies. COPSAC2010: ClinicalTrials.gov NCT00856947; VDAART: ClinicalTrials.gov NCT00920621.

BackgroundAntibiotics are widely prescribed during pregnancy, yet their impact on offspring infection risk remains unclear. This study synthesises all available data and evaluates the association between maternal antibiotic use during pregnancy and the risk of infections in offspring during childhood.MethodsWe conducted a systematic review and meta-analysis following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, registered with PROSPERO. We searched PubMed, Embase, Ovid, ISRCTN registry, ClinicalTrials.gov and Cochrane Library for English language studies without publication date restrictions. Studies reporting quantitative data on prenatal antibiotic exposure and childhood infections after the neonatal period were included. Two authors screened and extracted data from published reports. Risk of bias was evaluated using the Newcastle-Ottawa Scale. The primary outcome was any childhood infection risk, analysed using random-effects meta-analyses with sensitivity analyses by infection type and study quality. Certainty of evidence was assessed using Grading of Recommendations Assessment, Development and Evaluation (GRADE).ResultsFrom 7317 records, 14 cohort studies (n=5 011 183 children) were included, of which 12 (n=4 995 449) provided data for meta-analysis. Prenatal antibiotic exposure was associated with an increased risk of any offspring infection (OR 1.33, 95% CI 1.01 to 1.76, p=0.04). A sensitivity analysis (n=3 647 296) of six high-quality studies showed a stronger association (OR 1.48, 95% CI 1.13 to 1.95, p<0.01). Specifically, ear, nose and throat infections were significantly increased (n=2 841 644 children) (OR 1.40, 95% CI 1.18 to 1.65, p<0.0001). The risk of bias was low in the majority of the included studies and the certainty of evidence was high for any offspring infection from the GRADE assessment.ConclusionsPrenatal antibiotic exposure was associated with increased offspring infection risk and in particular upper airway infections. These findings indicate a need for cautious antibiotic prescribing during pregnancy, although potential confounding cannot be excluded.PROSPERO registration numberCRD42024599699.

The composition of the human gut microbiome matures within the first years of life. It has been hypothesized that microbial compositions in this period can cause immune dysregulations and potentially cause asthma. Here we show, by associating gut microbial composition from 16S rRNA gene amplicon sequencing during the first year of life with subsequent risk of asthma in 690 participants, that 1-year-old children with an immature microbial composition have an increased risk of asthma at age 5 years. This association is only apparent among children born to asthmatic mothers, suggesting that lacking microbial stimulation during the first year of life can trigger their inherited asthma risk. Conversely, adequate maturation of the gut microbiome in this period may protect these pre-disposed children. Colonization of commensal bacteria is thought to impact immune development, especially in the earliest years of life. Here, the authors show, by analyzing the development of the gut microbiome of 690 children, that microbial composition at the age of 1 year is associated with asthma diagnosed in the first 5 years of life.

Asthma is believed to arise through early life aberrant immune development in response to environmental exposures that may influence the airway microbiota. Here, we examine the airway microbiota during the first three months of life by 16S rRNA gene amplicon sequencing in the population-based Copenhagen Prospective Studies on Asthma in Childhood 2010 (COPSAC 2010 ) cohort consisting of 700 children monitored for the development of asthma since birth. Microbial diversity and the relative abundances of Veillonella and Prevotella in the airways at age one month are associated with asthma by age 6 years, both individually and with additional taxa in a multivariable model. Higher relative abundance of these bacteria is furthermore associated with an airway immune profile dominated by reduced TNF-α and IL-1β and increased CCL2 and CCL17, which itself is an independent predictor for asthma. These findings suggest a mechanism of microbiota-immune interactions in early infancy that predisposes to childhood asthma. Here, Thorsen et al. examine the microbiota during the first three months of life in a cohort of 700 children and find that microbial diversity and the relative abundances of Veillonella and Prevotella in the airways at one month of age are associated with topical immune mediators and asthma by age 6 years.

Abstract Rationale The frequency of pneumonia and bronchiolitis exhibits considerable variation in otherwise healthy children, and suspected risk factors explain only a minor proportion of the variation. We hypothesized that alterations in the airway microbiome in early life may be associated with susceptibility to pneumonia and bronchiolitis in young children. Objectives To investigate the relation between neonatal airway colonization and pneumonia and bronchiolitis during the first 3 years of life. Methods Participants comprised children of the Copenhagen Prospective Studies on Asthma in Childhood2000 (COPSAC2000) cohort, a prospective birth cohort study of 411 children born to mothers with asthma. Aspirates from the hypopharynx at age 4 weeks were cultured for Streptococcus pneumoniae, Haemophilus influenzae, Moraxella catarrhalis, and Staphylococcus aureus. Clinical information on pneumonia and bronchiolitis within the first 3 years of life was prospectively collected by the research physicians at the center. Analyses were adjusted for covariates associated with pneumonia and bronchiolitis and bacterial airway colonization. Measurements and Main Results Hypopharyngeal aspirates and full clinical follow-up until 3 years of age were available for 265 children. Of these, 56 (21%) neonates were colonized with S. pneumoniae, H. influenzae, and/or M. catarrhalis at 4 weeks of age. Colonization with at least one of these microorganisms (but not S. aureus) was significantly associated with increased incidence of pneumonia and bronchiolitis (adjusted incidence rate ratio, 1.79 [1.29–2.48]; P < 0.005) independently of concurrent or later asthma. Conclusions Neonatal airway colonization with S. pneumoniae, H. influenzae, or M. catarrhalis is associated with increased risk of pneumonia and bronchiolitis in early life independently of asthma. This suggests a role of pathogenic bacterial colonization of the airways in neonates for subsequent susceptibly to pneumonia and bronchiolitis.

Epidemiological studies have suggested an association between maternal vitamin D dietary intake during pregnancy and risk of asthma and allergy in the offspring. However, prospective clinical studies on vitamin D measured in cord blood and development of clinical end-points are sparse. To investigate the interdependence of cord blood 25-hydroxyvitamin D (25(OH)-Vitamin D) level and investigator-diagnosed asthma- and allergy-related conditions during preschool-age. Cord blood 25(OH)-Vitamin D level was measured in 257 children from the Copenhagen Prospective Studies on Asthma in Childhood (COPSAC2000) at-risk mother-child cohort. Troublesome lung symptoms (TROLS), asthma, respiratory infections, allergic rhinitis, and eczema, at age 0-7 yrs were diagnosed exclusively by the COPSAC pediatricians strictly adhering to predefined algorithms. Objective assessments of lung function and sensitization were performed repeatedly from birth. After adjusting for season of birth, deficient cord blood 25(OH)-Vitamin D level (<50 nmol/L) was associated with a 2.7-fold increased risk of recurrent TROLS (HR = 2.65; 95% CI = 1.02-6.86), but showed no association with respiratory infections or asthma. We saw no association between cord blood 25(OH)-Vitamin D level and lung function, sensitization, rhinitis or eczema. The effects were unaffected from adjusting for multiple lifestyle factors. Cord blood 25(OH)-Vitamin D deficiency associated with increased risk of recurrent TROLS till age 7 years. Randomized controlled trials of vitamin D supplementation during pregnancy are needed to prove causality.

Antibiotic treatment during pregnancy and birth is very common. In this study, we describe the estimated prevalence of antibiotic administration during pregnancy and birth in the COPSAC2010 pregnancy cohort, and analyze dependence on social and lifestyle-related factors. 706 pregnant women from the novel unselected Copenhagen Prospective Study on Asthma in Childhood (COPSAC2010) pregnancy cohort participated in this analysis. Detailed information on oral antibiotic prescriptions during pregnancy filled at the pharmacy was obtained and verified longitudinally. Information on intrapartum antibiotics, social, and lifestyle-factors was obtained by personal interviews. The prevalence of antibiotic use was 37% during pregnancy and 33% intrapartum. Lower maternal age at birth; adjusted odds ratio (aOR) 0.94, 95% CI, [0.90-0.98], p = 0.003 and maternal smoking; aOR 1.97, 95% CI, [1.07-3.63], p = 0.030 were associated with use of antibiotics for urinary tract infection during pregnancy. Maternal educational level (low vs. high), aOR 2.32, 95% CI, [1.24-4.35], p = 0.011, maternal asthma; aOR 1.99, 95% CI, [1.33-2.98], p < 0.001 and previous childbirth; aOR 1.80, 95% CI, [1.21-2.66], p = 0.004 were associated with use of antibiotics for respiratory tract infection during pregnancy. Lower gestational age; aOR 0.72, 95% CI, [0.61-0.85], p < 0.001, maternal smoking; aOR 2.84, 95% CI, [1.33-6.06], p = 0.007, and nulliparity; aOR 1.79, 95% CI, [1.06-3.02], p = 0.030 were associated with administration of intrapartum antibiotics in women giving birth vaginally. Antibiotic administration during pregnancy and birth may be influenced by social and lifestyle-factors. Understanding such risk factors may guide preventive strategies in order to avoid unnecessary use of antibiotics.

Supplementation with fish oil–derived fatty acids during pregnancy reduced the incidence of cases of persistent wheeze or asthma in offspring. The incidence of asthma and wheezing disorders has more than doubled in westernized countries in recent decades. 1 These conditions often originate in early childhood 2 and currently affect one in five young children. 3 Concomitantly, the increased use of vegetable oils in cooking and of grain in the feeding of livestock has resulted in an increase in the intake of n−6 polyunsaturated fatty acids and a decrease in the intake of n−3 polyunsaturated fatty acids, especially the long-chain polyunsaturated fatty acids (LCPUFAs) — eicosapentaenoic acid (20:5n–3, EPA) and docosahexaenoic acid (22:6n–3, DHA) — found in cold-water fish. 4 Observational studies have suggested an . . .

BackgroundInhaled short-acting β2-agonists (SABA) is recognised as an effective treatment in adults and older children with asthma, but the effect in young children and infants is still up for debate. We examine the efficacy of inhaled SABA for preschool-aged children presenting with acute wheeze/asthma in this systematic review and meta-analysis.MethodsPubMed and Embase were searched through August 2024. Clinical trials investigating the effect of inhaled SABA on acute wheeze/asthma symptoms in children below age 6 years were included. The study followed Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Summary standardised mean differences, 95% CIs and p values were derived from random effects meta-analyses to analyse the effect on clinical composite respiratory score, respiratory rate, oxygen saturation, respiratory work and degree of wheezing.ResultsA total of 19 studies including 1022 children were included. Treatment with inhaled SABA showed decreased respiratory score within 60 min (10 studies, N=523): standardised mean difference −2.05 points (95% CI −2.50; −1.59), I2=86%, p<0.001, decreased respiratory rate (8 studies, N=319): −0.86 (95% CI −1.30; −0.41), I2=87%, p<0.001, increased oxygen saturation (7 studies, N=190): 0.56 (95% CI 0.16; 0.95), I2=71%, p<0.01, decreased respiratory work (3 studies, N=68): −0.80 (95% CI −1.60; −0.00), I2=74%, p=0.05 and decreased wheezing score (3 studies, N=68): −1.07 (95% CI −1.80; −0.33), I2=72%, p<0.01. Subgroup analyses of children below age 2 years showed similar significant effects for all outcomes.ConclusionsInhaled SABA treatment for acute wheeze/asthma symptoms showed beneficial effects in young children and infants. Findings from this study may provide evidence to support inhaled SABA in future treatment guidelines for acute wheeze/asthma among young children and infants; however, an overall high heterogeneity and small sample size of the studies were a limitation.PROSPERO registration numberCRD42023429381.

BackgroundInfants and young children might be particularly susceptible to the potential side effects from inhaled corticosteroid (ICS) on height and bone mineral content (BMC), but this has rarely been studied in long-term prospective studies.MethodsChildren from two Copenhagen Prospective Studies on Asthma in Childhood cohorts were included. ICS use was registered prospectively from birth to age 6 and the cumulative dose was calculated. Primary outcomes were height and BMC from dual-energy X-ray absorptiometry (DXA) scans at age 6.ResultsAt age 6, a total of 930 children (84%) from the cohorts had a valid height measurement and 792 (71%) had a DXA scan. 291 children (31%) received a cumulated ICS dose equivalent to or above 10 weeks of standard treatment before age 6. We found an inverse association between ICS use and height, −0.26 cm (95% CI: −0.45 to −0.07) per 1 year standard treatment from 0 to 6 years of age, p=0.006. This effect was mainly driven by children with ongoing treatment between age 5 and 6 years (−0.31 cm (95% CI: −0.52 to −0.1), p=0.004), while there was no significant association in children who stopped treatment at least 1 year before age 6 (−0.09 cm (95% CI: −0.46 to 0.28), p=0.64). There was no association between ICS use and BMC at age 6.ConclusionsICS use in early childhood was associated with reduced height at age 6 years but only in children with continued treatment in the sixth year of life.