Antibiotics taken within the first year of life are linked to infant gut microbiome disruption and elevated atopic dermatitis risk.

BACKGROUND: Atopic dermatitis (AD) is the most common chronic inflammatory skin disease in both pediatric and adult populations. The development of AD has been linked to antibiotic usage, which causes perturbation of the microbiome and has been associated with abnormal immune system function. However, imbalances in the gut microbiome itself associated with antibiotic usage have been inconsistently linked to AD. OBJECTIVES: This study aimed to elucidate the timing and specific factors mediating the relationship between systemic (oral or intravenous) antibiotic usage and AD. METHODS: We used statistical modeling and differential analysis to link CHILD Cohort Study participants' history of antibiotic usage and early-life gut microbiome alterations to AD. RESULTS: Here we report that systemic antibiotics during the first year of life, as compared to later, are associated with AD risk (adjusted odds ratio [aOR] = 1.81; 95% CI: 1.28-2.57; P < .001), with an increased number of antibiotic courses corresponding to a dose response-like increased risk of AD risk (1 course: aOR: 1.67; 95% CI: 1.17-2.38; 2 or more courses: aOR: 2.16; 95% CI: 1.30-3.59). Further, we demonstrate that microbiome alterations associated with both AD and systemic antibiotic usage fully mediate the effect of antibiotic usage on the development of AD (ßindirect = 0.072; P < .001). Alterations in the 1-year infant gut microbiome of participants who would later develop AD included increased Tyzzerella nexilis, increased monosaccharide utilization, and parallel decreased Bifidobacterium and Eubacterium spp, and fermentative pathways. CONCLUSIONS: These findings indicate that early-life antibiotic usage, especially in the first year of life, modulates key gut microbiome components that may be used as markers to predict and possibly prevent the development of AD.

Early-immune development in asthma: A review of the literature.

This review presents a comprehensive examination of the various factors contributing to the immunopathogenesis of asthma from the prenatal to preschool period. We focus on the contributions of genetic and environmental components as well as the role of the nasal and gut microbiome on immune development. Predisposing genetic factors, including inherited genes associated with increased susceptibility to asthma, are discussed alongside environmental factors such as respiratory viruses and pollutant exposure, which can trigger or exacerbate asthma symptoms. Furthermore, the intricate interplay between the nasal and gut microbiome and the immune system is explored, emphasizing their influence on allergic immune development and response to environmental stimuli. This body of literature underscores the necessity of a comprehensive approach to comprehend and manage asthma, as it emphasizes the interactions of multiple factors in immune development and disease progression.

Cohort profile: investigating SARS-CoV-2 infection and the health and psychosocial impact of the COVID-19 pandemic in the Canadian CHILD Cohort.

The coronavirus disease 2019 (COVID-19) pandemic has affected all Canadian families, with some impacted differently than others. Our study aims to: (1) determine the prevalence and transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection among Canadian families, (2) identify predictors of infection susceptibility and severity of SARS-CoV-2, and (3) identify health and psychosocial impacts of the COVID-19 pandemic. This study builds upon the CHILD Cohort Study, an ongoing multi-ethnic general population prospective cohort consisting of 3,454 Canadian families with children born in Vancouver, Edmonton, Manitoba, and Toronto between 2009 and 2012. During the pandemic, CHILD households were invited to participate in the CHILD COVID-19 Add-On Study involving: (1) brief biweekly surveys about COVID-19 symptoms and testing; (2) quarterly questionnaires assessing COVID-19 exposure and testing, vaccination status, physical and mental health, and pandemic-driven life changes; and (3) in-home biological sampling kits to collect blood and stool. In total, 1,462 households (5,378 participants) consented to the CHILD COVID-19 Add-On Study: 2,803 children (mean±standard deviation [SD], 9.0±2.7 years; range, 0-17 years) and 2,576 adults (mean±SD, 43.0±6.5 years; range, 18-85 years). We will leverage the wealth of pre-pandemic CHILD data to identify risk and resilience factors for susceptibility and severity to the direct and indirect pandemic effects. Our short-term findings will inform key stakeholders and knowledge users to shape current and future pandemic responses. Additionally, this study provides a unique resource to study the long-term impacts of the pandemic as the CHILD Cohort Study continues.

Development of a Symptom-Based Tool for Screening of Children at High Risk of Preschool Asthma.

Importance: Despite advances in asthma therapeutics, the burden remains highest in preschool children; therefore, it is critical to identify primary care tools that distinguish preschool children at high risk for burdensome disease for further evaluation. Current asthma prediction tools, such as the modified Asthma Predictive Index (mAPI), require invasive tests, limiting their applicability in primary care and low-resource settings. Objective: To develop and evaluate the use of a symptom-based screening tool to detect children at high risk of asthma, persistent wheeze symptoms, and health care burden. Design, Setting, and Participants: The cohort for this diagnostic study included participants from the CHILD Study (n = 2511) from January 1, 2008, to December 31, 2012, the Raine Study from January 1, 1989, to December 31, 2012 (n = 2185), and the Canadian Asthma Primary Prevention Study (CAPPS) from January 1, 1989, to December 31, 1995 (n = 349), with active follow-up to date. Data analysis was performed from November 1, 2019, to May 31, 2022. Exposures: The CHILDhood Asthma Risk Tool (CHART) identified factors associated with asthma in patients at 3 years of age (timing and number of wheeze or cough episodes, use of asthma medications, and emergency department visits or hospitalizations for asthma or wheeze) to identify children with asthma or persistent symptoms at 5 years of age. Main Outcomes and Measures: Within the CHILD Study cohort, CHART was evaluated against specialist clinician diagnosis and the mAPI. External validation was performed in both a general population cohort (Raine Study [Australia]) and a high-risk cohort (CAPPS [Canada]). Predictive accuracy was measured by sensitivity, specificity, area under the receiver operating characteristic curve (AUROC), and positive and negative predicted values. Results: Among 2511 children (mean [SD] age at 3-year clinic visit, 3.08 [0.17] years; 1324 [52.7%] male; 1608 of 2476 [64.9%] White) with sufficient questionnaire data to apply CHART at 3 years of age, 2354 (93.7%) had available outcome data at 5 years of age. CHART applied in the CHILD Study at 3 years of age outperformed physician assessments and the mAPI in predicting persistent wheeze (AUROC, 0.94; 95% CI, 0.90-0.97), asthma diagnosis (AUROC, 0.73; 95% CI, 0.69-0.77), and health care use (emergency department visits or hospitalization for wheeze or asthma) (AUROC, 0.70; 95% CI, 0.61-0.78). CHART had a similar predictive performance for persistent wheeze in the Raine Study (N = 2185) in children at 5 years of age (AUROC, 0.82; 95% CI, 0.79-0.86) and CAPPS (N = 349) at 7 years of age (AUROC, 0.87; 95% CI, 0.80-0.94). Conclusions and Relevance: In this diagnostic study, CHART was able to identify children at high risk of asthma at as early as 3 years of age. CHART could be easily incorporated as a routine screening tool in primary care to identify children who need monitoring, timely symptom control, and introduction of preventive therapies.

Moderate-to-severe lower respiratory tract infection in early life is associated with increased risk of polysensitization and atopic dermatitis: Findings from the CHILD Study.

Background: Respiratory infections in infancy are associated with the development of allergic asthma and atopy. Delineating whether symptomatic infections are a marker of atopic predisposition or contribute to atopic development is important for preventive strategies. We hypothesized that early, severe lower respiratory tract infections (LRTIs) may be a risk factor for the development of atopic disease. Objective: Our aim was to determine whether clinically defined, moderate-to-severe LRTIs in infancy are associated with the development of atopic dermatitis and allergic sensitization at preschool age. Methods: LRTI timing and severity in the first 18 months of life was defined by using the Canadian Healthy Infant Longitudinal Development study questionnaires. Polysensitization and atopic dermatitis were determined by standardized skin prick testing and structured clinical assessments. Longitudinal associations between LRTI severity and clinical outcomes at ages 3 years and 5 years were determined by adjusted repeated measures generalized estimation equations. Results: Moderate-to-severe LRTIs were associated with increased odds of polysensitization (odds ratio = 1.91 [95% CI = 1.16-3.15]; P = .014) and atopic dermatitis (odds ratio = 2.19 [95% CI 1.41-3.39]; P < .001) as compared with the odds in children with no history of LRTI in the first 18 months of life. The association between moderate-to-severe LRTI and polysensitization or atopic dermatitis remained robust after adjusting for sex; study site; breast-feeding duration; and mother, father, or both-parent atopy or asthma. Conclusions: These results highlight severe infant LRTI as an important risk factor for allergic and atopic disease (ie, polysensitization and atopic dermatitis), and they suggest that this risk is independent of maternal in utero environment, both-parent history of asthma, and both-parent genetic predisposition.

A systematic review and meta-analysis of pediatric normative peripheral quantitative computed tomography data.

BACKGROUND: Peripheral-quantitative computed tomography (pQCT) provides an intriguing diagnostic alternative to dual-energy X-ray absorptiometry (DXA) since it can measure 3D bone geometry and differentiate between the cortical and trabecular bone compartments. OBJECTIVE: To investigate and summarize the methods of pQCT image acquisition of in children, adolescents and/or young adults (up to age 20) and to aggregate the published normative pQCT data. EVIDENCE ACQUISITION: A literature search was conducted in MEDLINE and EMBASE from 1947 to December 2020. Quality of the included articles was assessed using Standards for Reporting of Diagnostic Accuracy (STARD) scoring system and United States Preventative Services Task Force (USPSTF) Study Design Categorization. Seven articles, encompassing a total of 2134 participants, were aggregated in the meta-analysis. Due to dissimilar age groups and scan sites, only seven pQCT parameters of the 4% radius, 4% tibia and 38% tibia were analyzed in this meta-analysis. EVIDENCE SYNTHESIS: The overall fixed-effect estimates of trabecular vBMD of the 4% radius were: 207.16 (201.46, 212.86), mg/cm3 in 8 to 9 year-old girls, 210.42 (201.91, 218.93)in 10 to 12 year-old girls, 226.99 (222.45, 231.54) in 12 to 13 year-old girls, 259.97 (254.85, 265.10) in 12 to 13 year-old boys and 171.55 (163.41,179.69) in 16 to 18 year-old girls. 21 of 54 (38.9%) primary papers received a 'good' STARD quality of reporting score (<90 and 70 ≥ %) (mean STARD score of all articles = 69.4%). The primary articles of this review had a 'good' level USPSTF study design categorization. However, most of the normative data in these articles were non-comparable and non-aggregable due to a lack of standardization of reference lines, acquisition parameters and/or age at acquisition. CONCLUSION: There is not sufficient evidence to suggest that pQCT is appropriately suited for use in the pediatric clinical setting. Normative pediatric data must be systematically derived for pQCT should it ever be a modality that is used outside of research. CLINICAL IMPACT: We demonstrate the need for normative pQCT reference data and for clinical guidelines that standardize pediatric acquisition parameters and delineate its use in pediatric settings.