Search

[Display omitted] 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. This study aimed to elucidate the timing and specific factors mediating the relationship between systemic (oral or intravenous) antibiotic usage and AD. 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. 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 (β indirect = 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. 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. [ABSTRACT FROM AUTHOR]

Ultra short echo time (UTE) magnetic resonance imaging (MRI) pulse sequences have shown promise for airway assessment, but the feasibility and repeatability in the pediatric lung are unknown. The purpose of this work was to develop a semiautomated UTE MRI airway segmentation pipeline from the trachea-to-tertiary airways in pediatric participants and assess repeatability and lumen diameter correlations to lung function. A total of 29 participants (n = 7 healthy, n = 11 cystic fibrosis, n = 6 asthma, and n = 5 ex-preterm), aged 7-18 years, were imaged using a 3D stack-of-spirals UTE examination at 3 T. Two independent observers performed airway segmentations using a pipeline developed in-house; observer 1 repeated segmentations 1 month later. Segmentations were extracted using region-growing with leak detection, then manually edited if required. The airway trees were skeletonized, pruned, and labeled. Airway lumen diameter measurements were extracted using ray casting. Intra- and interobserver variability was assessed using the Sørensen-Dice coefficient (DSC) and intra-class correlation coefficient (ICC). Correlations between lumen diameter and pulmonary function were assessed using Spearman's correlation coefficient. For airway segmentations and lumen diameter, intra- and interobserver DSCs were 0.88 and 0.80, while ICCs were 0.95 and 0.89, respectively. The variability increased from the trachea-to-tertiary airways for intra- (DSC: 0.91-0.64; ICC: 0.91-0.49) and interobserver (DSC: 0.84-0.51; ICC: 0.89-0.21) measurements. Lumen diameter was significantly correlated with forced expiratory volume in 1 second and forced vital capacity (P <.05). UTE MRI airway segmentation from the trachea-to-tertiary airways in pediatric participants across a range of diseases is feasible. The UTE MRI-derived lumen measurements were repeatable and correlated with lung function. [ABSTRACT FROM AUTHOR]

Wheezing in early life is associated with asthma in adulthood; however, the determinants of wheezing trajectories and their associations with asthma and lung function in childhood remain poorly understood. In the CHILD Cohort Study, we aimed to identify wheezing trajectories and examine the associations between these trajectories, risk factors, and clinical outcomes at age 5 years. Wheeze data were collected at 8 time points from 3 months to 5 years of age. We used group-based trajectory models to derive wheeze trajectories among 3154 children. Associations with risk factors and clinical outcomes were analyzed by weighted regression models. We identified 4 trajectories: a never/infrequent trajectory, transient wheeze, intermediate-onset (preschool) wheeze, and persistent wheeze. Higher body mass index was a common risk factor for all wheeze trajectories compared with that in the never/infrequent group. The unique predictors for specific wheeze trajectories included male sex, lower respiratory tract infections, and day care attendance for transient wheeze; paternal history of asthma, atopic sensitization, and child genetic risk score of asthma for intermediate wheeze; and maternal asthma for persistent wheeze. Blood eosinophil counts were higher in children with the intermediate wheeze trajectory than in those children with the other trajectories at the ages of 1 and 5 years. All wheeze trajectories were associated with decreased lung function and increased risk of asthma at age 5 years. We identified 4 distinct trajectories in children from 3 months to 5 years of age, reflecting different phenotypes of early childhood wheeze. These trajectories were characterized by different biologic and physiologic traits and risk factors. [Display omitted] [ABSTRACT FROM AUTHOR]

Increasing evidence supports the role of early-life gut microbiota in developing atopic diseases, but ecological changes to gut microbiota during infancy in relation to food sensitization remain unclear. We aimed to characterize and associate these changes with the development of food sensitization in children. In this observational study, using 16S rRNA amplicon sequencing, we characterized the composition of 2844 fecal microbiota in 1422 Canadian full-term infants. Atopic sensitization outcomes were measured by skin prick tests at age 1 year and 3 years. The association between gut microbiota trajectories, based on longitudinal shifts in community clusters, and atopic sensitization outcomes at age 1 and 3 years were determined. Ethnicity and early-life exposures influencing microbiota trajectories were initially examined, and post-hoc analyses were conducted. Four identified developmental trajectories of gut microbiota were shaped by birth mode and varied by ethnicity. The trajectory with persistently low Bacteroides abundance and high Enterobacteriaceae/Bacteroidaceae ratio throughout infancy increased the risk of sensitization to food allergens, particularly to peanuts at age 3 years by 3-fold (adjusted odds ratio [OR] 2.82, 95% confidence interval [CI] 1.13–7.01). A much higher likelihood for peanut sensitization was found if infants with this trajectory were born to Asian mothers (adjusted OR 7.87, 95% CI 2.75–22.55). It was characterized by a deficiency in sphingolipid metabolism and persistent Clostridioides difficile colonization. Importantly, this trajectory of depleted Bacteroides abundance mediated the association between Asian ethnicity and food sensitization. This study documented an association between persistently low gut Bacteroides abundance throughout infancy and sensitization to peanuts in childhood. It is the first to show a mediation role for infant gut microbiota in ethnicity-associated development of food sensitization. [Display omitted] [ABSTRACT FROM AUTHOR]

Background Advances in metabolomics are anticipated to decipher associations between dietary exposures and health. Replication biomarker studies in different populations are critical to demonstrate generalizability. Objectives To identify and validate robust serum metabolites associated with diet quality and specific foods in a multiethnic cohort of pregnant women. Design In this cross-sectional analysis of 3 multiethnic Canadian birth cohorts, we collected semiquantitative FFQ and serum data from 900 women at the second trimester of pregnancy. We calculated a diet quality score (DQS), defined as daily servings of "healthy" minus "unhealthy" foods. Serum metabolomics was performed by multisegment injection-capillary electrophoresis-mass spectrometry, and specific serum metabolites associated with maternal DQSs were identified. We combined the results across all 3 cohorts using meta-analysis to classify robust dietary biomarkers (r > ± 0.1; P < 0.05). Results Diet quality was higher in the South Asian birth cohort (mean DQS = 7.1) than the 2 white Caucasian birth cohorts (mean DQS <3.2). Sixty-six metabolites were detected with high frequency (>75%) and adequate precision (CV <30%), and 47 were common to all cohorts. Hippuric acid was positively associated with healthy diet score in all cohorts, and with the overall DQS only in the primarily white Caucasian cohorts. We observed robust correlations between: 1) proline betaine—citrus foods; 2) 3-methylhistidine—red meat, chicken, and eggs; 3) hippuric acid—fruits and vegetables; 4) trimethylamine N -oxide (TMAO)—seafood, meat, and eggs; and 5) tryptophan betaine—nuts/legumes. Conclusions Specific serum metabolites reflect intake of citrus fruit/juice, vegetables, animal foods, and nuts/legumes in pregnant women independent of ethnicity, fasting status, and delays to storage across multiple collection centers. Robust biomarkers of overall diet quality varied by cohort. Proline betaine, 3-methylhistidine, hippuric acid, TMAO, and tryptophan betaine were robust dietary biomarkers for investigations of maternal nutrition in diverse populations. [ABSTRACT FROM AUTHOR]

Background Fatty acids are a vital component of human milk. They influence infant neurodevelopment and immune function, and they provide ∼50% of milk's energy content. Objectives The objectives of this study were to characterize the composition of human milk fatty acids in a large Canadian birth cohort and identify factors influencing their variability. Methods In a subset of the CHILD cohort (n  = 1094), we analyzed milk fatty acids at 3–4 mo postpartum using GLC. Individual and total SFAs, MUFAs, and n–3 and n–6 PUFAs were analyzed using SD scores and principal component analysis (PCA). Maternal diet, sociodemographic, health, and environmental factors were self-reported. Single-nucleotide polymorphisms were assessed in the fatty acid desaturase 1 (FADS1-rs174556) and 2 (FADS2-rs174575) genes. Results Fatty acid profiles were variable, with individual fatty acid proportions varying from 2- to >30-fold between women. Using PCA, we identified 4 milk fatty acid patterns: "MUFA and low SFA," "high n–6 PUFA," "high n–3 PUFA," and "high medium-chain fatty acids." In multivariable-adjusted analyses, fish oil supplementation and fatty cold water fish intake were positively associated with DHA and the "high n–3 PUFA" pattern. Mothers carrying the minor allele of FADS1-rs174556 had lower proportions of arachidonic acid (ARA; 20:4n–6). Independent of selected dietary variables and genetic variants, Asian ethnicity was associated with higher linoleic acid (18:2n–6) and total n–3 PUFAs. Ethnic differences in ARA were explained by FADS1 genotype. Maternal obesity was independently associated with higher total SFAs, the "high medium-chain fatty acid" pattern, and lower total MUFAs. Lactation stage, season, study site, and maternal education were also independently associated with some milk fatty acids. No associations were observed for maternal age, parity, delivery mode, or infant sex. Conclusions This study provides unique insights about the "normal" variation in the composition of human milk fatty acids and the contributing dietary, genetic, sociodemographic, health, and environmental factors. Further research is required to assess implications for infant health. [ABSTRACT FROM AUTHOR]

Objectives: Primary: examine associations between meeting the 24-Hour Movement Guidelines for the Early Years and behavioral and emotional problems in a large sample of 3-year-old children. Secondary: determine the proportion of children meeting the Canadian 24-Hour Movement Guidelines.Design: Cross-sectional.Methods: Participants were 3-year olds (n=539) from the Edmonton site of the Canadian Healthy Infant Longitudinal Development (CHILD) birth cohort. Physical activity and sleep duration were accelerometer-derived while screen time was parent-reported. Meeting the overall guidelines was defined as: (1) ≥180min/day of total physical activity, including 60min/day of moderate- to vigorous-intensity physical activity, (2) ≤1h/day of screen time, and (3) 10-13h of sleep per 24-hour period. Externalizing, internalizing, and total problem scores (lower scores representing fewer problems) were calculated from the parent-reported Child Behavior Checklist (CBCL). Descriptive statistics and linear regression models were completed.Results: Only 5% of children met the overall guidelines (all three recommendations), with 19.3%, 50.5%, and 83.1% meeting the physical activity, screen time, and sleep recommendations, respectively. Meeting more recommendations was associated with lower scores for total (B=-1.78, 95%CI: -3.03, -0.54), externalizing (B=-1.51, 95%CI: -2.80, -0.22) and internalizing (B=-1.35, 95%CI: -2.60, -0.01) problems. Similar findings were also observed for the specific combinations of: (1) physical activity and screen time and (2) sleep duration and screen time.Conclusions: Meeting more recommendations within the 24-hour Movement Guidelines was associated with fewer behavioral and emotional problems at 3-years. Few 3-year-olds met the overall guidelines. Findings support an integrated approach for healthy growth and development. [ABSTRACT FROM AUTHOR]

Perfluoroalkyl substances (PFASs) are known to be toxic, bioaccumulative, and persistent. However, exposure routes and toxic effects to humans are still widely unknown. Our objectives were to evaluate potential correlations between concentrations of PFASs in maternal plasma and infant cord blood with home characteristics and developmental effects, including wheezing. The concentrations of 17 PFASs were measured in plasma from prenatal women (n = 414), postnatal women (n = 247), and cord blood (n = 50) from a subset of participants in a population-based birth cohort in Winnipeg, Manitoba, Canada, using online solid phase extraction (SPE) with liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS). Multiple linear regression and principal component analysis (PCA) were used to evaluate possible associations with PFAS concentrations. Surveys were used to collect information regarding maternal characteristics (e.g. age, parity, duration of breastfeeding), infant characteristics (e.g. birth weight, birth length, head circumference, gestational age, and incidence of recurrent wheezing), and home characteristics (e.g. home age,carpet coverage in the most used room, presence of new furniture, or recent home renovations). PFASs in plasma were associated with maternal characteristics but not home characteristics or early childhood wheezing. PFASs were not associated with developmental effects, with the exception that perfluoroundecanoic acid (PFUA) was negatively associated with birth weight. Further studies investigating the potential influences of PFUA on birth weight are warranted. Image 1 • PFASs in pre- and postnatal blood were associated with maternal characteristics. • PFASs in pre- and postnatal blood were not associated with home characteristics. • Perfluoroundecanoic acid (PFUA) was negatively associated with birth weight. • No correlations between PFASs in blood and incidence of recurrent wheeze in infants. • Perfluoropentanoic acid (PFPA) was among the higher measuring analytes in blood. Principal component analysis showed that PFASs in maternal blood were related to maternal characteristics and, for the most part, not home characteristics or developmental effects. [ABSTRACT FROM AUTHOR]

Background: Human milk oligosaccharides (HMOs) shape the developing gut microbiome and influence immune function. Aside from genetic Secretor status, the factors influencing HMO synthesis and secretion are largely unknown.Objective: We aimed to identify modifiable and nonmodifiable factors associated with HMO concentrations.Methods: This prospective observational study included a representative subset of 427 mothers participating in the CHILD birth cohort (mean age: 33 y, 73% Caucasian). Breast milk was collected at 3-4 mo postpartum. Concentrations of 19 predominant HMOs were measured by rapid high-throughput HPLC. Secretor status was defined by the presence of 2'-fucosylactose. Associations with maternal, infant, and environmental factors were explored using multivariable regression. Breastfeeding duration was explored as a secondary outcome.Results: Overall, 72% of mothers were Secretors and the mean ± SD duration of any breastfeeding was 12.8 ± 5.7 mo. HMO profiles were highly variable; total HMO concentrations varied 3.7-fold and individual HMOs varied 20- to >100-fold. Secretor mothers had higher total HMO concentrations than did non-Secretors (mean: 15.91 ± 2.80 compared with 8.94 ± 1.51 μmol/mL, P < 0.001) and all individual HMOs differed by Secretor status, except for disialyllacto-N-tetraose (DSLNT). Most HMO concentrations were lower in milk collected later in lactation, although some were higher including DSLNT and 3'-sialyllactose. Independent of Secretor status and lactation stage, seasonal and geographic variation was observed for several HMOs. Parity, ethnicity, and breastfeeding exclusivity also emerged as independent factors associated with some HMOs, whereas diet quality and mode of delivery did not. Together, these factors explained between 14% (for 6'-sialyllactose) and 92% (for 2'-fucosyllactose) of the observed variation in HMO concentrations. Lower concentrations of lacto-N-hexaose or fucodisialyllacto-N-hexaose were associated with earlier breastfeeding cessation.Conclusions: HMO concentrations vary widely between mothers and are associated with multiple characteristics beyond genetic Secretor status, as well as feeding practices and environmental factors. Further research is warranted to determine how these associations affect infant health. This study was registered at clinicaltrials.gov as NCT03225534. [ABSTRACT FROM AUTHOR]

Background: Canada is an ethnically diverse nation, which introduces challenges for health care providers tasked with providing evidence-based dietary advice.Objectives: We aimed to harmonize food-frequency questionnaires (FFQs) across 4 birth cohorts of ethnically diverse pregnant women to derive robust dietary patterns to investigate maternal and newborn outcomes.Methods: The NutriGen Alliance comprises 4 prospective birth cohorts and includes 4880 Canadian mother-infant pairs of predominantly white European [CHILD (Canadian Healthy Infant Longitudinal Development) and FAMILY (Family Atherosclerosis Monitoring In earLY life)], South Asian [START (SouTh Asian birth cohoRT)-Canada], or Aboriginal [ABC (Aboriginal Birth Cohort)] origins. CHILD used a multiethnic FFQ based on a previously validated instrument designed by the Fred Hutchinson Cancer Research Center, whereas FAMILY, START, and ABC used questionnaires specifically designed for use in white European, South Asian, and Aboriginal people, respectively. The serving sizes and consumption frequencies of individual food items within the 4 FFQs were harmonized and aggregated into 36 common food groups. Principal components analysis was used to identify dietary patterns that were internally validated against self-reported vegetarian status and externally validated against a modified Alternative Healthy Eating Index (mAHEI).Results: Three maternal dietary patterns were identified-"plant-based," "Western," and "health-conscious"-which collectively explained 29% of the total variability in eating habits observed in the NutriGen Alliance. These patterns were strongly associated with self-reported vegetarian status (OR: 3.85; 95% CI: 3.47, 4.29; r2 = 0.30, P < 0.001; for a plant-based diet), and average adherence to the plant-based diet was higher in participants in the fourth quartile of the mAHEI than in the first quartile (mean difference: 46.1%; r2 = 0.81, P < 0.001).Conclusion: Dietary data collected by using FFQs from ethnically diverse pregnant women can be harmonized to identify common dietary patterns to investigate associations between maternal dietary intake and health outcomes. [ABSTRACT FROM AUTHOR]

Background: Inhaled corticosteroid therapy improves exercise symptoms in asthmatic subjects. Objective: We sought to evaluate exercise-induced bronchoconstriction (EIB) as a method of determining the dose and time responses of inhaled corticosteroid therapy. Methods: In this double-blind, randomized, cross-over study with 2 parallel arms, 4 doses of inhaled ciclesonide (40 μg and 160 μg or 80 μg and 320 μg) were compared over 3 weeks of treatment. Twenty-six asthmatic subjects (age range, 14-27 years) with baseline FEV1 values of greater than 70% of predicted value were enrolled. The primary outcome was the maximum percentage decrease in FEV1 after standardized exercise challenge. Results: After 1 week of therapy, the mean ± SEM reduction in maximum decrease in FEV1 in the ciclesonide 40-μg/80-μg dose group was 9% ± 2.6% (95% CI, 3.9% to 14%), with no additional reduction thereafter. In the ciclesonide 160-μg/320-μg dose group, there was an 8.7% ± 2.5% (95% CI, 3.7% to 13.7%) reduction in maximum decrease in FEV1 after week 1, which continued in a linear fashion during subsequent weeks of treatment. No difference was found between the 2 treatment arms in the temporal response of EIB to ciclesonide treatment. The maximum percentage attenuation in EIB achieved was 51.1% ± 7.9%, which was achieved by using the 320-μg dose after 3 weeks of treatment. Conclusions: A significant improvement in EIB was demonstrated for all doses of ciclesonide. Use of 160 μg/320 μg of ciclesonide resulted in a continuing improvement in FEV1 with time, and no plateau was seen in protective effect during 3 weeks of treatment. Clinical implications: Attenuation in exercise-induced decrease can be seen as early as after 1 week of therapy with inhaled ciclesonide at doses greater than 40 μg. However, maximal attenuation in exercise response continues to increase at doses greater than or equal to 200 μg, even after 3 weeks of therapy. [Copyright &y& Elsevier]

Background: Treatment with inhaled steroids is an effective method of reducing bronchoconstriction and airway inflammation after allergen challenge. However, the durationof the protective effects of inhaled steroids after discontinuation of therapy has not been established. Objective: We sought to evaluate the protective effect of 1 week of inhaled steroid therapy against inhaled allergen challenge 12 hours after discontinuation of therapy. Methods: In this randomized, double-blind, placebo-controlled crossover trial, 26 asthmatic subjects (>18 years old) not using inhaled steroids were administered 200 μg of budesonide twice daily, 200 μg of fluticasone twice daily, or placebo twice daily for 1 week. Twelve hours after discontinuation of therapy, subjects were administered an inhaled allergen challenge. Each treatment period was separated by a 3-week washout period. Results: When compared with placebo (26% ± 14%), there was a slight but significant protection against the allergen-induced early response after fluticasone treatment (19% ± 10%, P =.001) but not after budesonide treatment (23% ± 13%, P =.08). However, when the area under the curve for the early airway response was examined, there was no difference between the 2 drugs in the amount of protection (P =.62). Partial protection was demonstrated against the late-response allergen-induced sputum eosinophilia with both treatments (P =.001). By contrast, no protection was observed against allergen-induced airway hyperresponsiveness for either treatment. Conclusions: The protective effects of inhaled steroids against allergen-induced early responses, airway eosinophilia, and allergen-induced airway hyperresponsiveness are partially or completely lost as early as 12 hours after discontinuation of therapy. [ABSTRACT FROM AUTHOR]

Few studies, even those with cohort designs, test the mediating effects of infant gut microbes and metabolites on the onset of disease. We undertook such a study. Methods: Using structural equation modeling path analysis, we tested directional relationships between first pregnancy, birth mode, prolonged labor and breastfeeding; infant gut microbiota, metabolites, and IgA; and childhood body mass index and atopy in 1667 infants. After both cesarean birth and prolonged labor with a first pregnancy, a higher Enterobacteriaceae/Bacteroidaceae ratio at 3 months was the dominant path to overweight; higher Enterobacteriaceae/Bacteroidaceae ratios and Clostridioides difficile colonization at 12 months were the main pathway to atopic sensitization. Depletion of Bifidobacterium after prolonged labor was a secondary pathway to overweight. Influenced by C difficile colonization at 3 months, metabolites propionate and formate were secondary pathways to child outcomes, with a key finding that formate was at the intersection of several paths. Pathways from cesarean section and first pregnancy to child overweight and atopy share many common mediators of the infant gut microbiome, notably C difficile colonization. [ABSTRACT FROM AUTHOR]

Allergic disease is the most frequent chronic health issue in children and has been linked to early-life gut microbiome dysbiosis. Many lines of evidence suggest that microbially derived short-chain fatty acids, and particularly butyrate, can promote immune tolerance. We sought to determine whether bacterial butyrate production in the gut during early infancy is protective against the development of atopic disease in children. We used shotgun metagenomic analysis to determine whether dysbiosis in butyrate fermentation could be identified in human infants, before their developing allergic disease. We found that the microbiome of infants who went on to develop allergic sensitization later in childhood lacked genes encoding key enzymes for carbohydrate breakdown and butyrate production. Our findings support the importance of microbial carbohydrate metabolism during early infancy in protecting against the development of allergies. [ABSTRACT FROM AUTHOR]

Objective: To determine the lifetime prevalence of allergies in childhood nephrotic syndrome, the seasonality of presentation and relapses, and the impact of allergies on subsequent relapses.Study Design: In a longitudinal cohort of children with nephrotic syndrome (ages 1-18 years), assessment for allergic diseases was conducted using the validated and modified version of the International Study of Asthma and Allergies in Childhood questionnaire at enrollment. Outcomes included frequently relapsing nephrotic syndrome, relapse rates, and the relapse-free duration after initial steroid therapy.Results: Among 277 participants, the majority were male (65%) with a median age of 3.7 years (IQR 2.8-5.8) at presentation. A total of 64% reported lifetime allergies with 20% having asthma, 33% wheezing, 27% eczema, and 24% rhinitis. Over 3.3 years of follow-up, presence of asthma and allergies was not associated with frequently relapsing nephrotic syndrome (OR 1.20; 95% CI 0.60, 2.40), higher relapse rates (relative risk 0.95; 95% CI 0.71, 1.27), or risk of first relapse (hazard ratio 1.10; 95% CI 0.83, 1.47) compared with those with no history of allergic diseases. There was also no seasonal variation evident at initial presentation or frequency of relapses.Conclusions: Two-thirds of children with nephrotic syndrome at presentation have allergic symptoms and asthma; however, neither are associated with an increased frequency of relapses. [ABSTRACT FROM AUTHOR]

Background The atopic march describes the progression from atopic dermatitis during infancy to asthma and allergic rhinitis in later childhood. In a Canadian birth cohort we investigated whether concomitant allergic sensitization enhances subsequent development of these allergic diseases at age 3 years. Methods Children completed skin prick testing at age 1 year. Children were considered sensitized if they produced a wheal 2 mm or larger than that elicited by the negative control to any of 10 inhalant or food allergens. Children were also assessed for atopic dermatitis by using the diagnostic criteria of the UK Working Party. At age 3 years, children were assessed for asthma, allergic rhinitis, food allergy, and atopic dermatitis. Data from 2311 children were available. Results Atopic dermatitis without allergic sensitization was not associated with an increased risk of asthma at age 3 years after adjusting for common confounders (relative risk [RR], 0.46; 95% CI, 0.11-1.93). Conversely, atopic dermatitis with allergic sensitization increased the risk of asthma more than 7-fold (RR, 7.04; 95% CI, 4.13-11.99). Atopic dermatitis and allergic sensitization had significant interactions on both the additive (relative excess risk due to interaction, 5.06; 95% CI, 1.33-11.04) and multiplicative (ratio of RRs, 5.80; 95% CI, 1.20-27.83) scales in association with asthma risk. There was also a positive additive interaction between atopic dermatitis and allergic sensitization in their effects on food allergy risk (relative excess risk due to interaction, 15.11; 95% CI, 4.19-35.36). Conclusions Atopic dermatitis without concomitant allergic sensitization was not associated with an increased risk of asthma. In combination, atopic dermatitis and allergic sensitization had strong interactive effects on both asthma and food allergy risk at age 3 years. [ABSTRACT FROM AUTHOR]

Objective: To determine whether different modes of infant feeding are associated with childhood asthma, including differentiating between direct breastfeeding and expressed breast milk.Study Design: We studied 3296 children in the Canadian Healthy Infant Longitudinal Development birth cohort. The primary exposure was infant feeding mode at 3 months, reported by mothers and categorized as direct breastfeeding only, breastfeeding with some expressed breast milk, breast milk and formula, or formula only. The primary outcome was asthma at 3 years of age, diagnosed by trained healthcare professionals.Results: At 3 months of age, the distribution of feeding modes was 27% direct breastfeeding, 32% breastfeeding with some expressed breast milk, 26% breast milk and formula, and 15% formula only. At 3 years of age, 12% of children were diagnosed with possible or probable asthma. Compared with direct breastfeeding, any other mode of infant feeding was associated with an increased risk of asthma. These associations persisted after adjusting for maternal asthma, ethnicity, method of birth, infant sex, gestational age, and daycare attendance (some expressed breast milk: aOR, 1.64, 95% CI, 1.12-2.39; breast milk and formula, aOR, 1.73, 95% CI, 1.17-2.57; formula only: aOR, 2.14, 95% CI, 1.37-3.35). Results were similar after further adjustment for total breastfeeding duration and respiratory infections.Conclusions: Modes of infant feeding are associated with asthma development. Direct breastfeeding is most protective compared with formula feeding; indirect breast milk confers intermediate protection. Policies that facilitate and promote direct breastfeeding could have impact on the primary prevention of asthma. [ABSTRACT FROM AUTHOR]

Rationale: Sleep duration is critical to growth, learning, and immune function development in infancy. Strategies to ensure that national recommendations for sleep duration in infants are met require knowledge of perinatal factors that affect infant sleep.Objectives: To investigate the mechanistic pathways linking maternal education and infant sleep.Methods: An observational study was conducted on 619 infants whose mothers were enrolled at the Edmonton site of the CHILD birth cohort. Infant sleep duration at three months was assessed using the Brief Infant Sleep Questionnaire. Maternal education was collected via maternal report. Prenatal and postnatal depression scores were obtained from the 20-item Center for Epidemiologic Studies Depression Scale (CES-D). Birth records and maternal report were the source of covariate measures. Mediation analysis (PROCESS v3.0) was used to examine the indirect effects of maternal education on infant sleep duration mediated through prenatal depression and birth mode.Measurements and Main Results: At three months of age, infants slept on average 14.1 h. Lower maternal education and prenatal depression were associated with significantly shorter infant sleep duration. Emergency cesarean section birth was associated with 1-hour shorter sleep duration at three months compared to vaginal birth [without intrapartum antibiotic prophylaxis] (β: -0.99 h; 95% CI: -1.51, -0.48). Thirty percent of the effect of lower maternal education on infant total sleep duration was mediated sequentially through prenatal depression and birth mode (Total Indirect Effects: -0.12, 95% CI: -0.22, -0.03, p < 0.05).Conclusions: Prenatal depression and birth mode sequentially mediate the effect of maternal education on infant sleep duration. [ABSTRACT FROM AUTHOR]

Objective: Childhood sleep-disordered breathing (SDB) symptoms may comprise multiple phenotypes depending on craniofacial anatomy, tonsil and adenoid growth, body habitus, and rhinitis symptoms. The primary objective of this study is to identify and characterize the different SDB phenotypes to two years of age.Methods: Data from 770 infants in the Edmonton sub-cohort of the Canadian Healthy Infant Longitudinal Study (CHILD) were analyzed to identify SDB phenotypes based on age of onset and duration of symptoms. Parents completed the 22-item sleep-related breathing disorder (SRBD) scale. Children with a SRBD ratio greater than 0.33 were considered positive for SDB at each quarterly assessment between three months and two years. The STATA Proc trajectory extension identified SDB phenotypes based on their age of onset and duration of symptoms and attributed the percentage chance of a participant being assigned to each phenotype. Multivariate linear regression identified factors associated with increased risk of being assigned to each SDB phenotype.Results: Trajectory analysis identified four phenotypes: no SDB (65.7%), early-onset SDB (15.7%) with peak symptoms at nine months, late-onset SDB (14.2%) with peak symptoms at 18 months, and persistent SDB (5.3%) with symptoms from 3 to 24 months. Rhinitis was associated with all three SDB symptom trajectories (p < 0.05). Children with gastroesophageal reflux disease presented with early (p = 0.03) and late SDB (p < 0.001). Maternal obstructive sleep apnea syndrome (OSAS) was associated with persistent (p = 0.01) and late SDB (p < 0.001). Atopy (positive skin prick test at one year) was associated with persistent SDB (p = 0.04). Infants born prior to 36.5 weeks gestational age were more likely to present with late SDB (p = 0.03).Conclusion: Childhood SDB symptoms, rather than being a homogenous disorder, may comprise multiple overlapping phenotypes each with unique risk factors. [ABSTRACT FROM AUTHOR]

Background: Both short sleep duration and sleep-disordered breathing (SDB) are associated with poor neurocognitive development. However, the co-contributions of short sleep duration and SDB on neurodevelopment in pre-school children are relatively unknown.Methods: We assessed both sleep duration and SDB by quarterly questionnaire from three months to two years of age among Canadian Healthy Infant Longitudinal Development (CHILD) birth cohort participants. Group-based modeling determined trajectories of total, daytime, and nighttime sleep duration and SDB. Linear regression was used to assess the impact of sleep duration and SDB trajectories on cognitive (primary outcome) and language (secondary) development at two years of age as assessed by the Bayley Scale of Infant Development (BSID-III) (mean 100; standard deviation of 15).Results: Of the 822 CHILD Edmonton participants, 703 (86%) were still enrolled at two years of age with 593 having BSID-III data at two years of age. Trajectory analysis identified four total sleep durations phenotypes [short sleepers (17.9%), decline to short sleepers (21.1%), intermediate sleepers (36.9%) and long sleepers (24.1%)]. Compared to children with intermediate sleep durations, short sleepers had a 5.2-point lower cognitive development score at two years of age [standard error (SE) 1.7; p = 0.002]. Nocturnal sleep duration, compared to daytime sleep duration had the greatest effect on cognitive development. We also identified three SDB symptom trajectories [early-onset SDB (15.7%), late-onset SDB (14.2%), and persistent SDB (5.3%)] and 79.5% of children had no SDB symptoms. Children with persistent SDB also had a 5.3-point lower language score (SE 2.7; p = 0.05) compared to children with no SDB. SDB trajectories were not associated with cognitive development.Conclusion: In a population-representative birth cohort study, both short sleep duration and SDB were associated with adverse neurodevelopment at two years of age. Children with short nighttime sleep duration had lowered cognitive and language scores and children with persistent SDB also had lower language scores. [ABSTRACT FROM AUTHOR]

Colonization of infants with Clostridium difficile is on the rise. Although better tolerated by infants than adults, it is a risk factor for future allergic disease. The present study describes associations between infant fecal immunoglobulin A (IgA) and colonization with C. difficile in 47 infants enrolled in the Canadian Healthy Infant Longitudinal Development (CHILD) study. C. difficile colonization was observed in over half (53%) of the infants. Median IgA was lower in infants colonized with C. difficile (10.9 μg versus 25.5 μg per g protein; p = 0.18). A smaller proportion of infants with IgA in the highest tertile were colonized with C. difficile compared to the other tertiles (31.3% versus 64.5%, p = 0.03). In unadjusted analysis, odds of colonization with C. difficile was reduced by 75% (OR 0.25 95% CI 0.07, 0.91 p = 0.04) among infants with IgA in the highest tertile compared to those in the other tertiles. Following adjustment for parity, birth mode and breastfeeding, this association was even stronger (aOR 0.17, 95% CI 0.03, 0.94, p = 0.04). Our study provides evidence that high fecal IgA, independent of breastfeeding, is associated with reduced likelihood of C. difficile colonization in infancy. [ABSTRACT FROM AUTHOR]

• Proximity to natural urban environments – their vegetation, soil or water – may be beneficial for early life microbiota. • Tested influence of a natural environment within 500 m of a home residence on infant gut microbiota at age 4 months. • Proximity to a natural environment plus pet ownership reduced microbial diversity of infants not breastfed. • Notable changes in gut microbial composition included enrichment of Proteobacteria that are commonly found in vegetation. The biodiversity hypothesis that contact with natural environments (e.g. native vegetation) and biodiversity, through the influence of environmental microbes, may be beneficial for human commensal microbiota has been insufficiently tested. We aimed to study the association between living near natural environments in the urban context, and gut microbiota diversity and composition in young infants. Based on data linkage between the unique Urban Primary Land and Vegetation Inventory (uPLVI) for the city of Edmonton and 355 infants in the CHILD Cohort Study, infant exposure to natural environments (any and specific types, yes/no) was determined within 500 m and 1000 m of their home residence. Gut microbiota composition and diversity at age 4 months was assessed in infant fecal samples. Adjusted for covariates, we observed a reduced odds of high microbial alpha-diversity in the gut of infants exposed to any natural environment within 500 m [Shannon index aOR (95%CI) = 0.63 (0.40, 0.98) and Simpson index = 0.63 (0.41, 0.98)]. In stratified analyses, these associations remained only among infants not breastfed or living with household pets. When doubly stratifying by these variables, the reduced likelihood of high alpha-diversity was present only among infants who were not breastfed and lived with household pets [9% of the study population, Shannon index = 0.07 (0.01, 0.49) and Simpson index = 0.11 (0.02, 0.66)]. Differences in beta-diversity was also seen (p = 0.04) with proximity to a nature space in not breastfed and pets-exposed infants. No associations were observed among infants who were fully formula-fed but without pets at home. When families and their pets had close access to a natural environment, Verrucomicrobiales colonization was reduced in the gut microbiota of formula-fed infants, the abundance of Clostridiales was depleted, whereas the abundance of Enterobacteriales was enriched. Our double-stratified results indicate that proximity to a natural environment plus pet ownership has the capacity to alter the gut microbiota of formula-fed infants. Further research is needed to replicate and better interpret these results, as well as to understand their health consequences. [ABSTRACT FROM AUTHOR]