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Background and aims Sensitive outcome measures to assess the efficacy of therapeutic interventions in patients with cystic fibrosis (CF) with mild lung disease are currently lacking. Our objective was to study the ability of the lung clearance index (LCI), a measure of ventilation inhomogeneity, to detect a treatment response to hypertonic saline inhalation in paediatric patients with CF with normal spirometry. Methods In a crossover trial, 20 patients with CF received 4 weeks of hypertonic saline (HS) and isotonic saline (IS) in a randomised sequence separated by a 4 week washout period. The primary end point was the change in the LCI due to HS versus IS. Results Baseline characteristics including the LCI were not significantly different between both study periods. Four weeks of twice-daily HS inhalation significantly improved the LCI compared with IS (1.16, 95% CI 0.26 to 2.05; p=0.016), whereas other outcome measures such as spirometry and quality of life failed to reach statistical significance. Randomisation order had no significant impact on the treatment effect. Conclusions The LCI, but not spirometry was able to detect a treatment effect from HS inhalation in patients with CF with mild disease and may be a suitable tool to assess early intervention strategies in this patient population. [ABSTRACT FROM AUTHOR]

The article discusses the etiology, epidemiology and risk factors of asthma during conception, childhood and adulthood. It notes that smoking, stress and use of antibiotics during pregnancy are causes of asthma for pregnant women. Lung function, use of antibiotics and exposure to tobacco smoke are associated with asthma in childhood. Recurrence of asthma in childhood, exposure to substances that may cause asthma in workplace and smoking of tobacco and marijuana cause asthma during adulthood.

The Canadian Healthy Infant Longitudinal Development (CHILD) birth cohort study recruited 3624 pregnant women, most partners and 3542 eligible offspring. We hypothesise that early life physical and psychosocial environments, immunological, physiological, nutritional, hormonal and metabolic influences interact with genetics influencing allergic diseases, including asthma. Environmental and biological sampling, innate and adaptive immune responses, gene expression, DNA methylation, gut microbiome and nutrition studies complement repeated environmental and clinical assessments to age 5. This rich data set, linking prenatal and postnatal environments, diverse biological samples and rigorous phenotyping, will inform early developmental pathways to allergy, asthma and other chronic inflammatory diseases. [ABSTRACT FROM AUTHOR]

The article presents a study which evaluates the response of eosinophilic airway inflammation and exercise-induced bronchoconstriction (EIB) to inhaled costicosteroid (ICS) therapy. Twenty-six steroid-naive asthmatic patients with EIB were included in the study. The result indicates that only high-dose ICS therapy attenuated the sputum eosinophil percentage. In addition, it reveals that sputum eosinophil percentage is correlated with EIB severity.

Objectives Asthma is a chronic lung condition that can be exacerbated when triggered by viruses. Pandemic public health restrictions aimed to reduce COVID-19 transmission indirectly effected other circulating viruses. This study assessed the impact of the pandemic and associated public health measures on acute paediatric asthma across four tertiary sites in three Canadian provinces. We queried whether pandemic-related changes would impair preventive care and delay presentation to care, increasing asthma exacerbation severity. Methods This retrospective study compared the frequency of acute care access and severity of presentation to emergency departments (ED) for acute asthma to four tertiary care children's hospitals during the COVID-19 pandemic (from March 17, 2020 to June 30, 2021) to a pre-lockdown control period (July 1, 2018 to March 16, 2020). Data was subjected to interrupted time series and Chi-square analysis. Results Our study included 26,316 acute asthma visits to ED. Sites experienced a 63% to 89% reduction in acute asthma visits during the pandemic, compared with pre-lockdown controls, and a 17% to 85% reduction in asthma, that is out of proportion as a fraction of all-cause ED visits. For asthma, there was no difference in severity measured by rate of ward admission or rate of Paediatric Intensive Care Unit (PICU) admission. Conclusions Public health measures appear to have resulted in a specific protective association on acute asthma with reduced acute care utilization over and above the reduction in all-cause presentations, without an increase in severity upon presentation. Our study indicates an importance to antiviral public health and engineering strategies to reduce viral transmission and thereby asthma morbidity. [ABSTRACT FROM AUTHOR]

Background: A lack of safety data on postpartum medication use presents a potential barrier to breastfeeding and may result in infant exposure to medications in breastmilk. The type and extent of medication use by lactating women requires investigation. Methods: Data were collected from the CHILD Cohort Study which enrolled pregnant women across Canada between 2008 and 2012. Participants completed questionnaires regarding medications and non-prescription medications used and breastfeeding status at 3, 6 and 12 months postpartum. Medications, along with self-reported reasons for medication use, were categorized by ontologies [hierarchical controlled vocabulary] as part of a large-scale curation effort to enable more robust investigations of reasons for medication use. Results: A total of 3542 mother-infant dyads were recruited to the CHILD study. Breastfeeding rates were 87.4%, 75.3%, 45.5% at 3, 6 and 12 months respectively. About 40% of women who were breastfeeding at 3 months used at least one prescription medication during the first three months postpartum; this proportion decreased over time to 29.5% % at 6 months and 32.8% at 12 months. The most commonly used prescription medication by breastfeeding women was domperidone at 3 months (9.0%, n = 229/2540) and 6 months (5.6%, n = 109/1948), and norethisterone at 12 months (4.1%, n = 48/1180). The vast majority of domperidone use by breastfeeding women (97.3%) was for lactation purposes which is off-label (signifying unapproved use of an approved medication). Non-prescription medications were more often used among breastfeeding than non-breastfeeding women (67.6% versus 48.9% at 3 months, p < 0.0001), The most commonly used non-prescription medications were multivitamins and Vitamin D at 3, 6 and 12 months postpartum. Conclusions: In Canada, medication use is common postpartum; 40% of breastfeeding women use prescription medications in the first 3 months postpartum. A diverse range of medications were used, with many women taking more than one prescription and non-prescription medicines. The most commonly used prescription medication by breastfeeding women were domperidone for off-label lactation support, signalling a need for more data on the efficacy of domperidone for this indication. This data should inform research priorities and communication strategies developed to optimize care during lactation. [ABSTRACT FROM AUTHOR]

BACKGROUND: Evidence suggests that prenatal air pollution exposure alters DNA methylation (DNAm), which could go on to affect long-term health. It remains unclear whether DNAm alterations present at birth persist through early life. Identifying persistent DNAm changes would provide greater insight into the molecular mechanisms contributing to the association of prenatal air pollution exposure with atopic diseases. OBJECTIVES: This study investigated DNAm differences associated with prenatal nitrogen dioxide (NO2) exposure (a surrogate measure of trafficrelated air pollution) at birth and 1 y of age and examined their role in atopic disease. We focused on regions showing persistent DNAm differences from birth to 1 y of age and regions uniquely associated with postnatal NO2 exposure. METHODS: Microarrays measured DNAm at birth and at 1 y of age for an atopy-enriched subset of Canadian Health Infant Longitudinal Development (CHILD) study participants. Individual and regional DNAm differences associated with prenatal NO2 (푛= 128) were identified, and their persistence at age 1 y were investigated using linear mixed effects models (푛= 124). Postnatal-specific DNAm differences (푛= 125) were isolated, and their association with NO2 in the first year of life was examined. Causal mediation investigated whether DNAm differences mediated associations between NO2 and age 1 y atopy or wheeze. Analyses were repeated using biological sex-stratified data. RESULTS: At birth (푛= 128), 18 regions of DNAm were associated with NO2, with several annotated to HOX genes. Some of these regions were specifically identified in males (푛= 73), but not females (푛= 55). The effect of prenatal NO2 across CpGs within altered regions persisted at 1 y of age. No significant mediation effects were identified. Sex-stratified analyses identified postnatal-specific DNAm alterations. DISCUSSION: Regional cord blood DNAm differences associated with prenatal NO2 persisted through at least the first year of life in CHILD participants. Some differences may represent sex-specific alterations, but replication in larger cohorts is needed. The early postnatal period remained a sensitive window to DNAm perturbations. [ABSTRACT FROM AUTHOR]

We hypothesize that children characterized by deprived factors have poorer health outcomes. We aim to identify clustering of determinants and estimate risk of early childhood diseases. This 1993–2019 longitudinal cohort study combines three Canadian pediatric cohorts and their families. Mothers and children are clustered using latent class analysis (LCA) by 16 indicators in three domains (maternal and newborn; socioeconomic status [SES] and neighbourhood; environmental exposures). Hazard ratios (HR) of childhood asthma, allergic rhinitis (AR), and eczema are quantified with Cox proportional hazard (PH) regression. Rate ratios (RR) of children's health services use (HSU) are estimated with Poisson regression. Here we report the inclusion of 15,724 mother–child pairs; our LCA identifies four mother-clusters. Classes 1 and 2 mothers are older (30–40 s), non-immigrants with university education, living in high SES neighbourhoods; Class 2 mothers have poorer air quality and less greenspace. Classes 3 and 4 mothers are younger (20–30 s), likely an immigrant/refugee, with high school-to-college education, living in lower SES neighborhoods with poorer air quality and less greenspace. Children's outcomes differ by Class, in comparison to Class 1. Classes 3 and 4 children have higher risks of asthma (HR 1.24, 95% CI 1.11–1.37 and HR 1.39, 95% CI 1.22–1.59, respectively), and similar higher risks of AR and eczema. Children with AR in Class 3 have 20% higher all-cause physician visits (RR = 1.20, 95% CI 1.10–1.30) and those with eczema have 18% higher all-cause emergency department visits (RR = 1.18, 95% CI 1.09–1.28) and 14% higher all-cause physician visits (RR = 1.14, 95% CI 1.09–1.19). Multifactorial-LCA mother-clusters may characterize associations of children's health outcomes and care, adjusting for interrelationships. [ABSTRACT FROM AUTHOR]

Background. Di-(2-ethylhexyl) phthalate (DEHP), which is ubiquitous in indoor environments, was the predominant phthalate measured in house dust in the Canadian CHILD Cohort and was found to be associated with a large increased risk of childhood asthma. Objective. To inform interventions by identifying sources of DEHP in dust and assessing behaviors related to DEHP concentrations in house dust. Methods. DEHP levels were measured in 726 dust samples collected at ~3 months of age in CHILD as well as in ~50 homes at two time points (June and November) in the CHILD pilot study. DEHP metabolites were measured in urine for a subset of the ~3-month-old infants. Housing characteristics were assessed at the time of dust and urine collection. Numerous factors from these surveys were investigated as potential sources of DEHP using univariate analyses and multivariable regressions. Correlations between DEHP in dust and urinary metabolites and between repeat dust samples were examined to study the relationship between dust measurement and DEHP exposure. Results. Overall, DEHP dust concentrations were higher for lower-income families. Homes with vinyl flooring in the kitchen and bathroom showed higher levels of DEHP than those without vinyl flooring. The quantity of vinyl furniture and the presence of mold were associated with higher DEHP concentrations, while the use of mattress covers reduced concentration. No other significant associations were found. DEHP concentrations in dust were consistent over 6 months, although the correlation between dust and DEHP metabolites in urine was low. Conclusion. DEHP in house dust persisted over multiple months, contributed to infant internal exposure, and was associated with specific housing characteristics. These findings may inform the public on their choice of building materials and products, as well as future policies, aimed at reducing the health risk associated with exposures in the indoor environment especially for children. [ABSTRACT FROM AUTHOR]

The article highlights L. Orfei and colleagues as they discuss the effect of fetal environment on the adult outcomes. Two historical birth cohorts in the Great Britain that correlate birth-weight and lung function measurements at middle age were analyzed by Orfei and colleagues. They examined the effects of air pollution, social class, postnatal growth and birth weight on the function of adult lung and report an important effect of birth weight in adult lung-function parameters. It discusses that the study conducted by Orfei and colleagues strengthens the hypothesis that adult pathology have roots in fetal programming.

Background: Childhood obesity is a global health concern and can lead to lifetime cardiometabolic disease. New advances in metabolomics can provide biochemical insights into the early development of obesity, so we aimed to characterize serum metabolites associated with overweight and adiposity in early childhood and to stratify associations by sex. Methods: Nontargeted metabolite profiling was conducted in the Canadian CHILD birth cohort (discovery cohort) at age 5 years (n = 900) by multisegment injection-capillary electrophoresis-mass spectrometry. Clinical outcome was defined using novel combined measures of overweight (WHO-standardized body mass index ≥ 85th percentile) and/or adiposity (waist circumference ≥ 90th percentile). Associations between circulating metabolites and child overweight/adiposity (binary and continuous outcomes) were determined by multivariable linear and logistic regression, adjusting for covariates and false discovery rate, and by subsequent sex-stratified analysis. Replication was assessed in an independent replication cohort called FAMILY at age 5 years (n = 456). Results: In the discovery cohort, each standard deviation (SD) increment of branched-chain and aromatic amino acids, glutamic acid, threonine, and oxoproline was associated with 20–28% increased odds of overweight/adiposity, whereas each SD increment of the glutamine/glutamic acid ratio was associated with 20% decreased odds. All associations were significant in females but not in males in sex-stratified analyses, except for oxoproline that was not significant in either subgroup. Similar outcomes were confirmed in the replication cohort, where associations of aromatic amino acids, leucine, glutamic acid, and the glutamine/glutamic acid ratio with childhood overweight/adiposity were independently replicated. Conclusions: Our findings show the utility of combining measures of both overweight and adiposity in young children. Childhood overweight/adiposity at age 5 years has a specific serum metabolic phenotype, with the profile being more prominent in females compared to males. [ABSTRACT FROM AUTHOR]

Background: Childhood obesity is a global health concern and can lead to lifetime cardiometabolic disease. New advances in metabolomics can provide biochemical insights into the early development of obesity, so we aimed to characterize serum metabolites associated with overweight and adiposity in early childhood and to stratify associations by sex. Methods: Nontargeted metabolite profiling was conducted in the Canadian CHILD birth cohort (discovery cohort) at age 5 years (n = 900) by multisegment injection-capillary electrophoresis-mass spectrometry. Clinical outcome was defined using novel combined measures of overweight (WHO-standardized body mass index ≥ 85th percentile) and/or adiposity (waist circumference ≥ 90th percentile). Associations between circulating metabolites and child overweight/adiposity (binary and continuous outcomes) were determined by multivariable linear and logistic regression, adjusting for covariates and false discovery rate, and by subsequent sex-stratified analysis. Replication was assessed in an independent replication cohort called FAMILY at age 5 years (n = 456). Results: In the discovery cohort, each standard deviation (SD) increment of branched-chain and aromatic amino acids, glutamic acid, threonine, and oxoproline was associated with 20–28% increased odds of overweight/adiposity, whereas each SD increment of the glutamine/glutamic acid ratio was associated with 20% decreased odds. All associations were significant in females but not in males in sex-stratified analyses, except for oxoproline that was not significant in either subgroup. Similar outcomes were confirmed in the replication cohort, where associations of aromatic amino acids, leucine, glutamic acid, and the glutamine/glutamic acid ratio with childhood overweight/adiposity were independently replicated. Conclusions: Our findings show the utility of combining measures of both overweight and adiposity in young children. Childhood overweight/adiposity at age 5 years has a specific serum metabolic phenotype, with the profile being more prominent in females compared to males. [ABSTRACT FROM AUTHOR]

Background: Childhood obesity is a global health concern and can lead to lifetime cardiometabolic disease. New advances in metabolomics can provide biochemical insights into the early development of obesity, so we aimed to characterize serum metabolites associated with overweight and adiposity in early childhood and to stratify associations by sex. Methods: Nontargeted metabolite profiling was conducted in the Canadian CHILD birth cohort (discovery cohort) at age 5 years (n = 900) by multisegment injection-capillary electrophoresis-mass spectrometry. Clinical outcome was defined using novel combined measures of overweight (WHO-standardized body mass index ≥ 85th percentile) and/or adiposity (waist circumference ≥ 90th percentile). Associations between circulating metabolites and child overweight/adiposity (binary and continuous outcomes) were determined by multivariable linear and logistic regression, adjusting for covariates and false discovery rate, and by subsequent sex-stratified analysis. Replication was assessed in an independent replication cohort called FAMILY at age 5 years (n = 456). Results: In the discovery cohort, each standard deviation (SD) increment of branched-chain and aromatic amino acids, glutamic acid, threonine, and oxoproline was associated with 20–28% increased odds of overweight/adiposity, whereas each SD increment of the glutamine/glutamic acid ratio was associated with 20% decreased odds. All associations were significant in females but not in males in sex-stratified analyses, except for oxoproline that was not significant in either subgroup. Similar outcomes were confirmed in the replication cohort, where associations of aromatic amino acids, leucine, glutamic acid, and the glutamine/glutamic acid ratio with childhood overweight/adiposity were independently replicated. Conclusions: Our findings show the utility of combining measures of both overweight and adiposity in young children. Childhood overweight/adiposity at age 5 years has a specific serum metabolic phenotype, with the profile being more prominent in females compared to males. [ABSTRACT FROM AUTHOR]

Asthma is a heterogeneous disorder with a complex etiology. Prevalence rates for asthma have been increasing in many countries over the past few decades. While it is unclear why this increase is occurring, the variation reported in asthma prevalence and severity associated with ethnicity offers some insight into the determinants of asthma. In this chapter, we discuss the data linking asthma to ethnicity and some of the factors that may explain this association. These include socioeconomic status, environmental exposures, the host microbiome, and genetics. A better understanding of these processes may inform future mechanistic studies and identify modifiable risk factors for targeted health care interventions. [ABSTRACT FROM AUTHOR]

Infant vitamin D liquid formulations often contain non-medicinal excipients such as glycerin (ie. glycerol) and 1,2-propanediol (1,2-PD). We examined whether infant vitamin D supplementation is associated with fecal glycerol and 1,2-PD concentrations at 3 months of age and characterized associations between these two molecules, and gut microbiota and their metabolites. Fecal metabolites and microbiota were quantified using Nuclear Magnetic Resonance Spectroscopy and 16S rRNA sequencing, respectively, in 575 infants from the CHILD Study at 3 months of age. Vitamin D supplement use was determined using questionnaires. Vitamin D supplementation was associated with greater odds of high 1,2-PD (adjusted OR 1.65 95% CI: 1.06, 2.53) and with decreased odds of high fecal glycerol (adjusted OR: 0.62 95% CI: 0.42, 0.90) after adjustment for breastfeeding and other covariates. Our findings were confirmed in linear regression models; vitamin D supplementation was positively associated with fecal 1,2-PD and inversely associated with glycerol (aβ: 0.37, 95% CI 0.03, 0.71 & aβ: −0.23 95% CI −0.44, −0.03, respectively). Fecal 1,2-PD and glycerol concentrations were negatively correlated with each other. Positive correlations between fecal 1,2-PD, Bifidobacteriaceae, Lactobacillaceae, Enterobacteriaceae and acetate levels were observed. Our research demonstrates that infant vitamin D supplement administration may differentially and independently influence infant gut microbiota metabolites. [ABSTRACT FROM AUTHOR]

Background: The infant fecal microbiome is known to impact subsequent asthma risk, but the environmental exposures impacting this association, the role of the maternal microbiome, and how the microbiome impacts different childhood asthma phenotypes are unknown. Methods: Our objective was to identify associations between features of the prenatal and early‐life fecal microbiomes and child asthma phenotypes. We analyzed fecal 16 s rRNA microbiome profiling and fecal metabolomic profiling from stool samples collected from mothers during the third trimester of pregnancy (n = 120) and offspring at ages 3–6 months (n = 265), 1 (n = 436) and 3 years (n = 506) in a total of 657 mother–child pairs participating in the Vitamin D Antenatal Asthma Reduction Trial. We used clinical data from birth to age 6 years to characterize subjects with asthma as having early, transient or active asthma phenotypes. In addition to identifying specific genera that were robustly associated with asthma phenotypes in multiple covariate‐adjusted models, we clustered subjects by their longitudinal microbiome composition and sought associations between fecal metabolites and relevant microbiome and clinical features. Results: Seven maternal and two infant fecal microbial taxa were robustly associated with at least one asthma phenotype, and a longitudinal gut microenvironment profile was associated with early asthma (Fisher exact test p =.03). Though mode of delivery was not directly associated with asthma, we found substantial evidence for a pathway whereby cesarean section reduces fecal Bacteroides and microbial sphingolipids, increasing susceptibility to early asthma. Conclusion: Overall, our results suggest that the early‐life, including prenatal, fecal microbiome modifies risk of asthma, especially asthma with onset by age 3 years. [ABSTRACT FROM AUTHOR]

Study Objectives: Children with late-onset (2-5 years) or persistent (3 months-5 years) sleep-related breathing disorder (SRBD) have an increased risk of behavior problems compared to children with no or early-onset SRBD. We sought to determine whether a combination of urine metabolites and sleep questionnaires could identify children at risk for SRBD-associated behavior problems.Methods: Urine and data were analyzed from the Edmonton site of the CHILD birth cohort study. We measured urine metabolites (random, mid-stream) at age three-years among a sub-cohort of participants (n = 165). Random Forest with a Boruta wrapper was used to identify important metabolites (creatinine-corrected, z-scores) for late/persistent SRBD versus no/early SRBD (reference). An algorithm was subsequently generated to predict late/persistent SRBD in children with a history of snoring using a metabolite composite score (z-scores < or ≥ 0) plus the SDBeasy score defined as [age (yrs.) of most recent positive SRBD]2 - [age (yrs.) first reported ever snoring]2.Results: Of the 165 children with SRBD data, 40 participants had late/persistent SRBD. Seven urinary metabolites in addition to the SDBeasy score were confirmed as important for late/persistent SRBD (AUC = 0.87). Among children with an ever-snoring history and a metabolite composite score ≥0, those with SDBeasy score ≥3 were over 13-fold more likely to have late/persistent SRBD (OR 13.7; 95%CI: 3.0, 62.1; p = 0.001). This algorithm has a Sensitivity of 69.6%, Specificity of 85.7% and a positive likelihood ratio (+LR) of 4.9.Conclusions: We developed a predictive algorithm using a combination of questionnaires and urine metabolites at age three-years to identify children with late/persistent SRBD by five-years of age. [ABSTRACT FROM AUTHOR]

Introduction: Previously developed cesarean section (CS) and emergency CS prediction tools use antenatal and intrapartum risk factors. We aimed to develop a predictive model for the risk of emergency CS before the onset of labour utilizing antenatal obstetric and non-obstetric factors. Methods: We completed a secondary analysis of data collected from the CHILD Cohort Study. The analysis was limited to term (≥37 weeks), singleton pregnant women with cephalic presentation. The sample was divided into a training and validation dataset. The emergency CS prediction model was developed in the training dataset and the performance accuracy was assessed by the area under the receiver operating characteristic curve(AUC) of the receiver operating characteristic analysis (ROC). Our final model was subsequently evaluated in the validation dataset. Results: The participant sample consisted of 2,836 pregnant women. Mean age of participants was 32 years, mean BMI of 25.4 kg/m2 and 39% were nulliparous. 14% had emergency CS delivery. Each year of increasing maternal age increased the odds of emergency CS by 6% (adjusted Odds Ratio (aOR 1.06,1.02–1.08). Likewise, there was a 4% increase odds of emergency CS for each unit increase in BMI (aOR 1.04,1.02–1.06). In contrast, increase in maternal height has a negative association with emergency CS. The final emergency CS delivery predictive model included six variables (hypertensive disorders of pregnancy, antenatal depression, previous vaginal delivery, age, height, BMI). The AUC for our final prediction model was 0.74 (0.72–0.77) in the training set with a similar AUC in the validation dataset (0.77; 0.71–0.82). Conclusion: The developed and validated emergency CS delivery prediction model can be used in counselling prospective parents around their CS risk and healthcare resource planning. Further validation of the tool is suggested. [ABSTRACT FROM AUTHOR]

Objective: To identify factors associated with breast-feeding initiation and continuation in Canadian-born and non-Canadian-born women. Design: Prospective cohort of mothers and infants born from 2008 to 2012: the Canadian Healthy Infant Longitudinal Development (CHILD) Cohort Study. Setting: General community setting in four Canadian provinces. Participants: In total, 3455 pregnant women from Vancouver, Edmonton, Winnipeg and Toronto between 2008 and 2012. Results: Of 3010 participants included in the current study, the majority were Canadian-born (75·5 %). Breast-feeding initiation rates were high in both non-Canadian-born (95·5 %) and Canadian-born participants (92·7 %). The median breast-feeding duration was 10 months in Canadian-born participants and 11 months in non-Canadian-born participants. Among Canadian-born participants, factors associated with breast-feeding initiation and continuation were older maternal age, higher maternal education, living with their partner and recruitment site. Rooming-in during the hospital stay was also associated with higher rates of breast-feeding initiation, but not continuation at 6-month postpartum. Factors associated with non-initiation of breast-feeding and cessation at 6-month postpartum were maternal smoking, living with a current smoker, caesarean birth and early-term birth. Among non-Canadian-born participants, maternal smoking during pregnancy was associated with lower odds of breast-feeding initiation and lower odds of breast-feeding continuation at 6 months, and older maternal age and recruitment site were associated with breast-feeding continuation at 6 months. Conclusions: Although Canadian-born and non-Canadian-born women in the CHILD cohort have similar breast-feeding initiation rates, breast-feeding initiation and continuation are more strongly associated with socio-demographic characteristics in Canadian-born participants. Recruitment site was strongly associated with breast-feeding continuation in both groups and may indicate geographic disparities in breast-feeding rates nationally. [ABSTRACT FROM AUTHOR]

Background: Environmental exposures in utero which modify DNA methylation may have a long-lasting impact on health and disease in offspring. We aimed to identify and replicate previously published genomic loci where DNA methylation changes are attributable to in utero exposures in the NutriGen birth cohort studies Alliance. Methods: We reviewed the literature to identify differentially methylated sites of newborn DNA which are associated with the following five traits of interest maternal diabetes, pre-pregnancy body mass index (BMI), diet during pregnancy, smoking, and gestational age. We then attempted to replicate these published associations in the Canadian Healthy Infant Longitudinal Development (CHILD) and the South Asian birth cohort (START) cord blood epigenome-wide data. Results: We screened 68 full-text articles and identified a total of 17 cord blood epigenome-wide association studies (EWAS) of the traits of interest. Out of the 290 CpG sites reported, 19 were identified in more than one study; all of them associated with maternal smoking. In CHILD and START EWAS, thousands of sites associated with gestational age were identified and maintained significance after correction for multiple testing. In CHILD, there was differential methylation observed for 8 of the published maternal smoking sites. No other traits tested (i.e., folate levels, gestational diabetes, birthweight) replicated in the CHILD or START cohorts. Conclusions: Maternal smoking during pregnancy and gestational age are strongly associated with differential methylation in offspring cord blood, as assessed in the EWAS literature and our birth cohorts. There are a limited number of reported methylation sites associated in more than two independent studies related to pregnancy. Additional large studies of diverse populations with fine phenotyping are needed to produce robust epigenome-wide data in order to further elucidate the effect of intrauterine exposures on the infants' methylome. [ABSTRACT FROM AUTHOR]

Background: The lung clearance index (LCI) is a measure of pulmonary function. Variable feasibility (50‐>80%) in preschool children has been reported. There are limited studies exploring its relationship to respiratory symptoms and how it predicts persistent wheeze. We aimed to assess the association with respiratory symptoms in preschool‐aged children with LCI and determine its utility in predicting persistent wheeze. Methods: LCI was measured in a subcohort of the CHILD Cohort Study at age 3 years using SF6 multiple breath washout test mass spectrometry. Respiratory symptom phenotypes at age 3 were derived from children's respiratory symptoms reported by their parents. Responses were used to categorize children into 4 symptom groups: recurrent wheeze (3RW), recurrent cough (3RC), infrequent symptoms (IS), and no current symptoms (NCS). At age 5 years, these children were seen by a specialist clinician and assessed for persistent wheeze (PW). Results: At age 3 years, 69% (234/340) had feasible LCI. Excluding two children with missing data, 232 participants were categorized as follows: 33 (14%) 3RW; 28 (12%) 3RC; 17 (7%) IS; and 154 (66%) NCS. LCI z‐score at age 3 years was highest in children with 3RW compared to 3RC (mean (SD): 1.14 (1.56) vs. 0.09 (0.95), p <.01), IS (mean (SD): −0.14 (0.59), p <.01), and NCS (mean (SD): −0.08 (1.06), p <.01). LCI z‐score at age 3 was predictive of persistent wheeze at age 5 (PW) (AUROC: 0.87). Conclusions: LCI at age 3 was strongly associated with recurrent wheeze at age 3, and predictive of its persistence to age 5. [ABSTRACT FROM AUTHOR]

Background: The "old friends" hypothesis posits that reduced exposure to previously ubiquitous microorganisms is one factor involved in the increased rates of allergic diseases. Cytomegalovirus (CMV) may be one of the "old friends" hypothesized to help prevent allergic diseases. We sought to elucidate whether early‐life CMV infection is associated with childhood atopy via perturbations of the gut microbiota. Methods: Participants were recruited from a population‐based birth cohort (CHILD study) and followed prospectively until age 5 years in four Canadian cities. A total of 928 participants provided stool microbiome data, urine for CMV testing, skin prick tests, and questionnaire‐based detailed environmental exposures. Cytomegalovirus infection was assessed in the first year of life while the main outcome was defined by persistent sensitization to any allergen at ages 1, 3, and 5 years. Results: Early CMV infection was associated with increased beta and decreased alpha diversity of the gut microbiota. Both changes in diversity measures and early CMV infection were associated with persistent allergic sensitization at age 5 years (aOR = 2.08; 95% CI: 1, 4.33). Mediation analysis demonstrated that perturbation of gut microbial composition explains 30% of the association. Conclusions: Early‐life CMV infection is associated with an alteration in the intestinal microbiota, which mediates the effect of the infection on childhood atopy. This work indicates that preventing CMV infection would not put children at increased risk of developing atopy. Rather, a CMV vaccine, in addition to preventing CMV‐associated morbidity and mortality, might reduce the risk of childhood allergic diseases. [ABSTRACT FROM AUTHOR]

Purpose: This is a pilot study that describes the feasibility and clinical course of a cohort of preschool children with severe asthma undergoing a combined adenotonillectomy (TA), bronchoscopy (B), and bronchoalveolar lavage (BAL) procedure. Methods: A retrospective cohort study of preschool patients with severe asthma who underwent a combined TA-B-BAL procedure between 2012 and 2019. Subjects were treated at a tertiary care asthma clinic and had a diagnosis of preschool asthma according to the Canadian Thoracic Society Guidelines. Data on demographics, clinical characteristics, medication use, virology and microbiology from bronchoalveolar lavage, and asthma control questionnaires were collected. Variables were analyzed using paired t test. Results: Eighteen preschool subjects (mean age 3.19 ± 1.13 years) with severe asthma were identified through the asthma clinic. Patients treated with standard asthma care and a combined TA-B-BAL procedure experienced a decrease in the number of oral steroid courses (p = 0.017), emergency department visits (p = 0.03) and wheezing exacerbations (p = 0.026) following the procedure. Ten patients experienced clinically meaningful improvements in TRACK scores after the procedure (p < 0.001). Conclusion: This pilot study provides early evidence that a combined TA-B-BAL procedure is feasible in preschool children with severe asthma and that the procedure may reduce asthma medication use and hospital visits. [ABSTRACT FROM AUTHOR]

Organophosphate ester flame retardants and plasticizers (OPEs) are common exposures in modern built environments. Toxicological models report that some OPEs reduce dopamine and serotonin in the brain. Deficiencies in these neurotransmitters are associated with anxiety and depression. We hypothesized that exposure to higher concentrations of OPEs in house dust would be associated with a greater risk of depression and stress in mothers across the prenatal and postpartum periods. We conducted a nested prospective cohort study using data collected on mothers (n = 718) in the CHILD Cohort Study, a longitudinal multi-city Canadian birth cohort (2008–2012). OPEs were measured in house dust sampled at 3–4 months postpartum. Maternal depression and stress were measured at 18 and 36 weeks gestation and 6 months and 1 year postpartum using the Centre for Epidemiologic Studies for Depression Scale (CES-D) and Perceived Stress Scale (PSS). We used linear mixed models to examine the association between a summed Z-Score OPE index and continuous depression and stress scores. In adjusted models, one standard deviation increase in the OPE Z-score index was associated with a 0.07-point (95% CI: 0.01, 0.13) increase in PSS score. OPEs were not associated with log-transformed CES-D (β: 0.63%, 95% CI: −0.18%, 1.46%). The effect of OPEs on PSS score was strongest at 36 weeks gestation and weakest at 1 year postpartum. We observed small increases in maternal perceived stress levels, but not depression, with increasing OPEs measured in house dust during the prenatal and early postpartum period in this cohort of Canadian women. Given the prevalence of prenatal and postpartum anxiety and the ubiquity of OPE exposures, additional research is warranted to understand if these chemicals affect maternal mental health. • Flame retardant exposures from house dust may impact maternal mental health. • Pregnancy may be a period of vulnerability to flame retardants. • Some flame retardant compounds may affect stress and depression more than others. [ABSTRACT FROM AUTHOR]

Background World Health Organization (WHO) growth standards for children aged 0 to 5 years describe growth under optimal conditions and were adopted for use in Canada in 2012. We are seeking to validate these charts in a well-characterized, longitudinal cohort of healthy, Canadian youngsters, assess tracking over time, and evaluate the prognostic implications of early growth. Methods Data from 2,795 mother–infant dyads from the CHILD birth cohort were classified by feeding modality at 6 months as exclusively breastfed, partially breastfed, or formula-fed. WHO z-scores (z) were calculated at birth, 3 months, 1 year, and 3 years. Receiver operator characteristics (ROC) assessed the predictive performance of early weight (WT), weight-for-length (WfL), or body mass index (BMI) z-scores for overweight/obesity at 3 years. Results Compared to WHO standards, Canadian children at birth had lower median WfLz (−0.73) and BMIz (−0.29), with more positive scores by 3 years (WfLz=BMIz=0.58). At both 1 and 3 years, formula feeding was associated with higher scores than breastfeeding, even after regression adjustment for covariates. Head circumference z-score was typically positive at all times and regardless of feeding modality. At 1 year, ROC area under the curve was 0.79 for WTz, WfLz, and BMIz, and BMIz>0.88 identified children with increased risk of overweight/obesity (BMIz >2) at age 3 years (20.3% versus 3.0%, P<0.001). Conclusions Compared to WHO growth charts, Canadian children at 3 years show an upward shift in BMIz and WfLz, particularly when formula-fed. Infant growth parameters may identify infants with increased risk of overweight/obesity at age 3 years; early recognition may allow targeting infants at higher risk. [ABSTRACT FROM AUTHOR]

Overall, children below 3 years of age incurred 3.6 times higher asthma costs and in particular 9.3 times higher asthma-related hospitalization costs than those aged 4 and older. The substantially higher costs in the first 3 years of life reflect the challenge of managing asthma in young children because, despite the early diagnosis, they were frequently hospitalized for asthma and other respiratory conditions. Right panel, direct medical costs related to other respiratory conditions, total and by components gl Figures S3 and S4 respectively present the sex- and SES-stratified age trends of costs related to asthma and other respiratory conditions. Between 4 and 18 years of age, per child-year asthma-related costs steadily declined, but at a slower rate of -14.1%, while hospitalization costs declined by -30.0% every year. [Extracted from the article]

Background: Polyunsaturated fatty acids (PUFAs) may influence immune development. We examined the association of PUFAs in human milk with food sensitization and atopic dermatitis among breastfed infants. Methods: In a selected subgroup of 1109 mother‐infant dyads from the CHILD Cohort Study, human milk was analyzed by gas‐liquid chromatography to quantify PUFAs including arachidonic acid (ARA) and docosahexaenoic acid (DHA). At 1 year of age, food sensitization was determined by skin‐prick testing for egg, peanut, cow's milk, and soybean, and atopic dermatitis was diagnosed by pediatricians. Logistic regression analyses controlled for breastfeeding exclusivity, family history of atopy, and other potential confounders. Results: Overall, 184 infants (17%) were sensitized to one or more food allergens and 160 (14%) had atopic dermatitis. Sex‐specific associations were observed between these conditions and milk PUFAs. Girls receiving human milk with lower proportions of DHA had lower odds of food sensitization (aOR 0.35; 95% CI 0.12, 0.99 for lowest vs highest quintile), and a clear dose‐dependent association was observed for the ARA/DHA ratio (aOR 2.98; 95% CI 1.10, 8.06 for lowest vs highest quintile). These associations were not seen in boys. Similar sex‐specific tendencies were observed for atopic dermatitis. Conclusions: Human milk PUFA proportions and their ratios are associated with infant atopic conditions in a sex‐specific manner. In female infants, a higher ratio of ARA/DHA may reduce the risk of food sensitization and atopic dermatitis. Further research is needed to determine the underlying mechanisms and clinical relevance of this sex‐specific association. [ABSTRACT FROM AUTHOR]

Bacterial members of the infant gut microbiota and bacterial-derived short-chain fatty acids (SCFAs) have been shown to be protective against childhood asthma, but a role for the fungal microbiota in asthma etiology remains poorly defined. We recently reported an association between overgrowth of the yeast Pichia kudriavzevii in the gut microbiota of Ecuadorian infants and increased asthma risk. In the present study, we replicated these findings in Canadian infants and investigated a causal association between early life gut fungal dysbiosis and later allergic airway disease (AAD). In a mouse model, we demonstrate that overgrowth of P. kudriavzevii within the neonatal gut exacerbates features of type-2 and -17 inflammation during AAD later in life. We further show that P. kudriavzevii growth and adherence to gut epithelial cells are altered by SCFAs. Collectively, our results underscore the potential for leveraging inter-kingdom interactions when designing putative microbiota-based asthma therapeutics. [ABSTRACT FROM AUTHOR]

Background: Multiplex tests allow for measurement of allergen‐specific IgE responses to multiple extracts and molecular allergens and have several advantages for large cohort studies. Due to significant methodological differences, test systems are difficult to integrate in meta‐analyses/systematic reviews since there is a lack of datasets with direct comparison. We aimed to create models for statistical integration of allergen‐specific IgE to peanut/tree nut allergens from three IgE test platforms. Methods: Plasma from Canadian and Austrian children/adolescents with peanut/tree nut sensitization and a cohort of sensitized, high‐risk, pre‐school asthmatics (total n = 166) were measured with three R&D multiplex IgE test platforms: Allergy Explorer version 1 (ALEX) (Macro Array Dx), MeDALL‐chip (Mechanisms of Development of Allergy) (Thermo Fisher), and EUROLINE (EUROIMMUN). Skin prick test (n = 51) and ImmunoCAP (Thermo Fisher) (n = 62) results for extracts were available in a subset. Regression models (Multivariate Adaptive Regression Splines, local polynomial regression) were applied if >30% of samples were positive to the allergen. Intra‐test correlations between PR‐10 and nsLTP allergens were assessed. Results: Using two regression methods, we demonstrated the ability to model allergen‐specific relationships with acceptable measures of fit (r2 = 94%‐56%) for peanut and tree nut sIgE testing at the extract and molecular‐level, in order from highest to lowest: Ara h 2, Ara h 6, Jug r 1, Ana o 3, Ara h 1, Jug r 2, and Cor a 9. Conclusion: Our models support the notion that quantitative conversion is possible between sIgE multiplex platforms for extracts and molecular allergens and may provide options to aggregate data for future meta‐analysis. [ABSTRACT FROM AUTHOR]

• Immune dysfunction in asthma is the result of genetic predisposition and exposures that lead to chronic inflammatory processes in the airways. • Cross-talk between the maternal microbiome and fetal immune development may occur during initial seeding or through regulation of Th2 skew leading to asthma. • Given the "missing heritability" of asthma, interactions with environmental factors likely play a larger role than previously thought. • Future work will need to integrate cellular dynamics, lung physiology, immunology and microbiome interactions to further our understanding of asthma. 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. [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: Preschool children with recurrent wheezing suffer high morbidity. It is unclear whether objective measures of asthma control, such as pulmonary function tests (PFTs), provide additional information to the clinical assessment. Methods: We recruited children between 3 and 6 years old, with a history of recurrent wheezing in the preceding year and treated for acute wheezing exacerbation in the emergency department (ED) into an observational cohort study. Children attended two outpatient visits: the first study visit within five days of discharge from the ED and the second study visit 12 weeks after the ED visit. We performed standardized symptom score (test for respiratory and asthma control in kids (TRACK)), multiple breath washout (MBW), spirometry, and clinical assessment at both visits. Results: Seventy‐four children, mean (standard deviation (SD)) age of 4.32 years (0.84), attended both visits. Paired FEV0.75 and lung clearance index (LCI) measurements at both time points were obtained in 37 and 34 subjects, respectively. Feasibility for all tests improved at visit 2 and was not age‐dependent. At the second study visit, a third had controlled asthma based on the TRACK score, and the mean lung clearance index (LCI) improved from 9.86 to 8.31 (P =.003); however, 46% had an LCI in the abnormal range. FEV0.75z‐score improved from −1.66 to −1.17 (P =.05) but remained in the abnormal range in 24%. LCI was abnormal in more than half of the children with "well‐controlled" asthma based on the TRACK score. There was no correlation between PFT measures and TRACK scores at either visit. Conclusions: Lung clearance index demonstrates a persistent deficit post‐exacerbation in a large proportion of preschoolers with recurrent wheezing, highlighting that symptom scores alone may not suffice for monitoring these children. [ABSTRACT FROM AUTHOR]

Keywords: atopic dermatitis; atopy; food sensitization; live biotherapeutic product; microbiota EN atopic dermatitis atopy food sensitization live biotherapeutic product microbiota 1 4 4 07/29/20 20200801 NES 200801 Abbreviations LBP live biotherapeutic product rDNA ribosomal deoxyribonucleic acid SCFA short-chain fatty acid Forty percent of the world's population is sensitized to at least one environmental allergen, and atopic diseases such as asthma, atopic dermatitis, and food allergy are among the most frequent health challenges faced by children today. Specifically, increased bacterial diversity (as quantified by the Shannon -diversity index) was associated with protection against allergic sensitization (atopy), wheeze, AW, FS, and AD (Figure 1A and Figure E4). [Extracted from the article]

Here, using data from the Canadian CHILD Cohort Study, we performed a sex-stratified analysis of human milk adiponectin, leptin, and insulin concentrations and their association with possible or probable asthma development by 3 years of age. For this analysis, asthma was classified as "possible or probable asthma" or "no asthma." Milk hormone concentrations did not differ in milk produced for sons vs. daughters (Table, Figure A); however, sex-specific associations were observed between milk hormone concentrations and child asthma (Table, Figure B). It is known that circulating leptin can stimulate the production of pro-inflammatory cytokines, potentially mediating the asthma-obesity axis; however, it is not known whether leptin in human milk can trigger similar responses. [Extracted from the article]

Keywords: allergic disease; atopy; CHILD Study; cord blood; dendritic cell; hemopoietic progenitor cell EN allergic disease atopy CHILD Study cord blood dendritic cell hemopoietic progenitor cell 1762 1765 4 07/14/20 20200701 NES 200701 To the Editor, The lineage commitment of cord blood (CB) hemopoietic progenitor cells (HPCs) and mobilization of differentiated pro-allergic effector cells is orchestrated by genetic and environmental factors. We used 60 children participating in the Canadian Healthy Infant Longitudinal Development (CHILD) Study and examined HPC and DC receptor expression at birth in relation to the development of atopy and allergic disease, and to lung function (as measured by lung clearance index (LCI)) at ages 1 and 3. [Extracted from the article]

Background: Fungi constitute an important yet frequently neglected component of the human microbiota with a possible role in health and disease. Fungi and bacteria colonise the infant gastrointestinal tract in parallel, yet most infant microbiome studies have ignored fungi. Milk is a source of diverse and viable bacteria, but few studies have assessed the diversity of fungi in human milk. Results: Here we profiled mycobiota in milk from 271 mothers in the CHILD birth cohort and detected fungi in 58 (21.4%). Samples containing detectable fungi were dominated by Candida, Alternaria, and Rhodotorula, and had lower concentrations of two human milk oligosaccharides (disialyllacto-N-tetraose and lacto-N-hexaose). The presence of milk fungi was associated with multiple outdoor environmental features (city, population density, and season), maternal atopy, and early-life antibiotic exposure. In addition, despite a strong positive correlation between bacterial and fungal richness, there was a co-exclusion pattern between the most abundant fungus (Candida) and most of the core bacterial genera. Conclusion: We profiled human milk mycobiota in a well-characterised cohort of mother-infant dyads and provide evidence of possible host-environment interactions in fungal inoculation. Further research is required to establish the role of breastfeeding in delivering fungi to the developing infant, and to assess the health impact of the milk microbiota in its entirety, including both bacterial and fungal components. [ABSTRACT FROM AUTHOR]

Background: The global prevalence of childhood eczema has increased over the last few decades, with a marked increase in high-income countries. Differences in prevalence of childhood eczema between countries and ethnicities suggest that genetic and early modifiable environmental factors, such as dietary intake, may underlie this observation. To investigate the association between pregnancy diet and infant eczema in a consortium of prospective Canadian birth cohorts predominantly comprised of white Europeans and South Asians. Methods: We evaluated the association of maternal dietary patterns reported during pregnancy (assessed at 24–28 weeks gestation using a semi-quantitiative food-frequency questionnaire) with parent-reported physician-diagnosed infant eczema at 1-year from 2,160 mother-infant pairs. Using three dietary patterns ("Western", "plant-based", and "Balanced") previously derived in this cohort using principal component analysis, we used multivariable logistic regression to determine the association of these dietary patterns with infant eczema, adjusted for potential confounders. Results: We observed a lower odds of eczema in the full sample combining white Europeans and South Asians with greater adherence to a plant-based (OR = 0.65; 95% CI: 0.55, 0.76; <0.001) and Western dietary pattern (OR = 0.73; 95% CI: 0.60, 0.89; P<0.01), after adjusting for other known predictors of eczema, including ethnicity, which was not significant. No associations were observed for the balanced diet. An interaction between the Western diet and ethnicity was observed (P<0.001). Following stratification by ethnicity, a protective association between the plant-based diet and infant eczema was confirmed in both white Europeans (OR = 0.59; 95% CI: 0.47, 0.74; P<0.001) and South Asians (OR = 0.77; 95% CI: 0.61, 0.97; P = 0.025). In white Europeans only, a Western diet was associated with a lower odds of infant eczema (OR = 0.69; 95% CI: 0.56, 0.87; P = 0.001) while a balanced diet increased the odds of infant eczema (OR = 1.23; 95% CI: 1.02, 1.49; P = 0.03). Beyond a plant-based diet, no significant associations with other dietary patterns were observed in South Asians. Conclusion: A plant-based diet during pregnancy is associated with a lowered odds of infant eczema at 1 year in all participants. Future studies of the components of plant-based diet which underlie the lower risk of eczema are needed. [ABSTRACT FROM AUTHOR]

Background: Comprehensive longitudinal studies are important for understanding the complex risk factors, pathways, exposures and interactions that lead to the development and persistence of asthma. We aimed to examine associations between use of household cleaning products in early life and childhood respiratory and allergic disease using data from the Canadian Healthy Infant Longitudinal Development (CHILD) Cohort Study.Methods: We summed responses from parental questionnaires that indicated the frequency of use of 26 household cleaning products in the homes of 2022 children from this birth cohort when they were 3-4 months of age to create a cumulative Frequency of Use Score (FUS). We used multivariable logistic regression models to assess whether frequent compared with less frequent use was associated with recurrent wheeze, atopy or asthma diagnosis, as defined by the questionnaire and clinical assessments at age 3 years. Data were collected between 2008 and 2015.Results: Children in homes with a higher frequency of use of cleaning products in infancy, as determined by an interquartile range increase, had higher odds of recurrent wheeze (adjusted odds ratio [OR] 1.35, 95% confidence interval [CI] 1.11-1.64), recurrent wheeze with atopy (adjusted OR 1.49, 95% CI 1.02-2.16) and asthma diagnosis (adjusted OR 1.37, 95% CI 1.09-1.70), but no increase in the odds of atopy at age 3 years (adjusted OR 1.14, 95% CI 0.96-1.35). Compared with the lowest tertile of FUS exposure, infants in the highest tertile had higher odds of acquiring asthma. Stratification of the results showed that females had higher ORs than males for all outcomes, although the p values for this sex difference did not reach statistical significance.Interpretation: Frequent use of household cleaning products in early life was associated with an increased risk for childhood wheeze and asthma but not atopy at age 3 years. Our findings add to the understanding of how early life exposures to cleaning products may be associated with the development of allergic airway disease and help to identify household behaviours as a potential area for intervention. [ABSTRACT FROM AUTHOR]

Background: Maternal pre‐postnatal psychosocial distress increases the risk for childhood allergic disease. This may occur through a host immunity pathway that involves intestinal secretory immunoglobulin A (sIgA). Experimental animal models show changes in the gut microbiome and immunity of offspring when exposed to direct or prenatal maternal stress, but little is known in humans. Objective: We determined the association between maternal depression and stress symptom trajectories and infant fecal sIgA concentrations. Methods: 1043 term infants from the Canadian Healthy Infant Longitudinal Development (CHILD) birth cohort were studied. Trajectories of maternal perceived stress and depression were based on scored scales administered in pregnancy and postpartum. sIgA was quantified in infant stool (mean age 3.7 months) with Immundiagnostik ELISA. Linear regression and logistic regression were employed to test associations. Results: Very low fecal sIgA concentrations were more common in infants of mothers in the antepartum and persistent depression trajectories (6% and 2% of women, respectively). Independent of breastfeeding status at fecal sampling, infant antibiotic exposure or other covariates, the antepartum depressive symptom trajectory was associated with reduced mean infant sIgA concentrations (β=−0.07, P <.01) and a two fold risk for lowest quartile concentrations (OR, 1.86; 95% CI: 1.02, 3.40). This lowering of sIgA yielded a large effect size in older infants (4‐8 months)—breastfed and not. No associations were seen with postpartum depressive symptoms (7% of women) or with any of the perceived stress trajectories. Conclusion and clinical relevance: Despite improved mood postpartum and independent of breastfeeding status, mothers experiencing antepartum depressive symptoms delivered offspring who exhibited lower fecal sIgA concentrations especially in later infancy. The implications of lowered sIgA concentrations in infant stool are altered microbe‐sIgA interactions, greater risk for C difficile colonization and atopic disease in later years. [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]

Objectives Prenatal maternal metabolic problems such as pre-pregnancy adiposity, excess gestational weight gain, and gestational diabetes mellitus (GDM) are associated with an increased risk of psychopathology in offspring. We examined whether these exposures were linked to symptoms of emotional and behavioral problems in offspring at 2 years of age, or if associations were due to confounding variables. Methods Data from 815 mother–child pairs enrolled at the Edmonton site of the Canadian Healthy Infant Longitudinal Development cohort were used to examine associations between gestational metabolic complications and scores on the externalizing and internalizing scales of the Child Behavior Checklist (CBCL-1½ to 5) at age two. Associations between maternal metabolic complications and offspring psychopathology were assessed before and after adjustment for gestational diet, socioeconomic status (SES), postpartum depression (PPD), prenatal smoking and breastfeeding. Results Pre-pregnancy body mass index and GDM, but not gestational weight gain, predicted more offspring externalizing and internalizing problems. However, after adjustment for confounding variables, these associations were no longer statistically significant. Post-hoc analyses revealed that gestational diet accounted for unique variance in both externalizing (semi-partial rdiet = − 0.20, p < 0.001) and internalizing (semi-partial rdiet = − 0.16, p = 0.01) problems. PPD and SES also accounted for a similar amount of variance for both externalizing (semi-partial rPPD = 0.17, p < 0.001; rses = − 0.11, p = 0.03) and internalizing problems (semi-partial rPPD = 0.21, p < 0.001; rses = − 0.14, p = 0.004). Conclusions for Practice Since the confounding effect of gestational diet persisted after adjustment for, and was similar in magnitude to, SES and PPD, future research should consider the impact of unhealthy prenatal diets on offspring neurodevelopment. [ABSTRACT FROM AUTHOR]

Background: Pre-school children spend an average of two-hours daily using screens. We examined associations between screen-time on pre-school behavior using data from the Canadian Healthy Infant Longitudinal Development (CHILD) study. Methods: CHILD participant parents completed the Child Behavior Checklist (CBCL) at five-years of age. Parents reported their child’s total screen-time including gaming and mobile devices. Screen-time was categorized using the recommended threshold of two-hours/day for five-years or one-hour/day for three-years. Multiple linear regression examined associations between screen-time and externalizing behavior (e.g. inattention and aggression). Multiple logistic regression identified characteristics of children at risk for clinically significant externalizing problems (CBCL T-score≥65). Results: Screen-time was available for over 95% of children (2,322/2,427) with CBCL data. Mean screen-time was 1·4 hours/day (95%CI 1·4, 1·5) at five-years and 1·5 hours/day (95%CI: 1·5, 1·6) at three-years. Compared to children with less than 30-minutes/day screen-time, those watching more than two-hours/day (13·7%) had a 2·2-point increase in externalizing T-score (95%CI: 0·9, 3·5, p≤0·001); a five-fold increased odd for reporting clinically significant externalizing problems (95%CI: 1·0, 25·0, p = 0·05); and were 5·9 times more likely to report clinically significant inattention problems (95%CI: 1·6, 21·5, p = 0·01). Children with a DSM-5 ADHD T-score above the 65 clinical cut-off were considered to have significant ADHD type symptoms (n = 24). Children with more than 2-hours of screen-time/day had a 7·7-fold increased risk of meeting criteria for ADHD (95%CI: 1·6, 38·1, p = 0·01). There was no significant association between screen-time and aggressive behaviors (p>0.05). Conclusion: Increased screen-time in pre-school is associated with worse inattention problems. [ABSTRACT FROM AUTHOR]

Objectives. To identify trajectory patterns of maternal depressive symptoms and perceived stress from midpregnancy to 2 years postpartum and determine relationships with selected sociodemographic factors including income, education, immigration, and postpartum employment. Methods. Pregnant women (n = 3307) recruited from the general population in 4 regions in Canada provided 6 waves of data from pregnancy to 2 years postpartum. The study was conducted from 2009 to 2015. Results. We determined 5 trajectory groups distinguished by time and magnitude for both depressive symptoms and perceived stress. Immigrants living in Canada for more than 5 up to 10 years, but not more recent arrivals, were at higher risk for persistent stress and depression independent of income status. Being employed at 1 year postpartum was associated with a lower likelihood of postpartum depression and perceived stress, while mothers reporting work exhaustion were substantially more likely to experience persistent depression and stress. Conclusions. The study highlighted the heterogeneous nature of depressive symptoms and perceived stress. Targeting interventions toward women 5 to 10 years after immigration and those experiencing exhaustion from postpartum work may be particularly beneficial. [ABSTRACT FROM AUTHOR]

Objective: Past cross-sectional studies have reported that mothers from ethnic minorities experience higher levels of prenatal and post-partum psychosocial distress compared with mothers from ethnic majorities. However, no studies have examined how the pattern varies longitudinally in a Canadian population of heterogeneous ethnicity.Methods: We analyzed data from 3,138 mothers participating in the Canadian Healthy Infant Longitudinal Development (CHILD) Study, a longitudinal multi-center study incorporating 10 distinct waves of psychosocial data collection from pregnancy until the index child was aged 5 y. Maternal self-identified ethnicity was grouped as White Caucasian, First Nations, Black, Southeast Asian, East Asian, South Asian, Middle Eastern, Hispanic and mixed ethnicity. We performed a multi-level regression to determine whether mothers of specific minority ethnicities were more likely to experience higher levels of distress (i.e. depressive symptoms and perceived stress) compared to white Caucasian mothers.Results: Mothers self-identifying as Black or First Nations had consistently higher distress scores than mothers from other ethnicities across all data collection times. After adjusting for relevant variables (history of depression, education, household income, marital status, and social support), First Nations mothers had a 20% increase in the mean scores of depressive symptoms compared to White Caucasian Mothers.Conclusions: Increased levels of perinatal and post-partum distress were seen in only some ethnic minority groups. Studies should avoid collapsing all categories into ethnic minority or majority and may need to consider how ethnicity interacts with other sociodemographic factors such as poverty. [ABSTRACT FROM AUTHOR]

Background: Breastfeeding has many established health benefits for women and children. We examined the association between maternal education, newborn feeding in hospital, and long‐term breastfeeding duration. Methods: We studied 3195 Canadian mother‐infant dyads in the CHILD pregnancy cohort. Newborn feeding was documented from hospital records. Caregivers reported sociodemographic factors and infant feeding at 3, 6, 12, 18, and 24 months. Results: Overall, 97% of newborns initiated breastfeeding and 74% were exclusively breastfed in hospital. Exclusively breastfed newborns were ultimately breastfed longer compared with those who received formula supplementation during their hospital stay (median 11.0 vs 7.0 months, P < .001). After controlling for maternal age, ethnicity, birth mode, and gestational age, exclusively breastfed newborns had a 21% reduced risk of breastfeeding cessation (HR = 0.79, 0.71‐0.87). This effect was strongest among women without a postsecondary education (HR = 0.65, 0.53‐0.79). Discussion: Exclusive breastfeeding in hospital is associated with longer breastfeeding duration, particularly among women of lower socioeconomic status. Initiatives that support exclusive breastfeeding of newborns in hospital could improve long‐term breastfeeding rates and help reduce health inequities arising in early life. [ABSTRACT FROM AUTHOR]

Background: Persisting atopic dermatitis (AD) is known to be associated with more serious allergic diseases at later ages; however, making an accurate diagnosis during infancy is challenging. We assessed the diagnostic performance of questionnaire-based AD measures with criteria-based in-person clinical assessments at age 1 year and evaluated the ability of these diagnostic methods to predict asthma, allergic rhinitis and food allergies at age 5 years.Methods: Data relate to 3014 children participating in the Canadian Healthy Infant Longitudinal Development (CHILD) Study who were directly observed in a clinical assessment by an experienced healthcare professional using the UK Working Party criteria. The majority (2221; 73.7%) of these children also provided multiple other methods of AD ascertainment: a parent reporting a characteristic rash on a questionnaire, a parent reporting the diagnosis provided by an external physician and a combination of these two reports.Results: Relative to the direct clinical assessment, the area under the Receiver Operating Characteristic curve for a parental report of a characteristic rash, reported physician diagnosis and a combination of both were, respectively, 0.60, 0.69 and 0.70. The strongest predictor of asthma at 5 years was AD determined by criteria-based in-person clinical assessment followed by the combination of parental and physician report.Conclusions: These findings suggest that questionnaire data cannot accurately substitute for assessment by experienced healthcare professionals using validated criteria for diagnosis of atopic dermatitis. Combining the parental report with diagnosis by a family physician might sometimes be appropriate (eg to avoid costs of a clinical assessment). [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]

OBJECTIVES: Studies addressing breastfeeding and obesity rarely document the method of breast milk feeding, type of supplementation, or feeding in hospital. We investigated these practices in the CHILD birth cohort. METHODS: Feeding was reported by mothers and documented from hospital records. Weight and BMI z scores (BMIzs) were measured at 12 months. Analyses controlled for maternal BMI and other confounders. RESULTS: Among 2553 mother-infant dyads, 97% initiated breastfeeding, and the median breastfeeding duration was 11.0 months. Most infants (74%) received solids before 6 months. Among "exclusively breastfed" infants, 55% received some expressed breast milk, and 27% briefly received formula in hospital. Compared with exclusive direct breastfeeding at 3 months, all other feeding styles were associated with higher BMIzs: adjusted β: +.12 (95% confidence interval [CI]: .01 to .23) for some expressed milk, +.28 (95% CI: .16 to .39) for partial breastfeeding, and +.45 (95% CI: .30 to .59) for exclusive formula feeding. Brief formula supplementation in hospital did not alter these associations so long as exclusive breastfeeding was established and sustained for at least 3 months. Formula supplementation by 6 months was associated with higher BMIzs (adjusted β: +.25; 95% CI: .13 to .38), whereas supplementation with solid foods was not. Results were similar for weight gain velocity. CONCLUSIONS: Breastfeeding is inversely associated with weight gain velocity and BMI. These associations are dose dependent, partially diminished when breast milk is fed from a bottle, and substantially weakened by formula supplementation after the neonatal period. [ABSTRACT FROM AUTHOR]

Background: Emerging links between household cleaning products and childhood overweight may involve the gut microbiome. We determined mediating effects of infant gut microbiota on associations between home use of cleaning products and future overweight.Methods: From the Canadian Healthy Infant Longitudinal Development (CHILD) birth cohort, we tested associations between maternal report of cleaning product use and overweight at age 3, and whether associations were mediated by microbial profiles of fecal samples in 3- to 4-month-old infants.Results: Among 757 infants, the abundance of specific gut microbiota was associated with household cleaning with disinfectants and eco-friendly products in a dose-dependent manner. With more frequent use of disinfectants, Lachnospiraceae increasingly became more abundant (highest v. lowest quintile of use: adjusted odds ratio [AOR] 1.93, 95% confidence interval [CI] 1.08 to 3.45) while genus Haemophilus declined in abundance (highest v. lowest quintile of use: AOR 0.36, 95% CI 0.20 to 0.65). Enterobacteriaceae were successively depleted with greater use of eco-friendly products (AOR 0.45, 95% CI 0.27 to 0.74). Lachnospiraceae abundance significantly mediated associations of the top 30th centile of household disinfectant use with higher body mass index (BMI) z score (p = 0.02) and with increased odds of overweight or obesity (p = 0.04) at age 3. Use of eco-friendly products was associated with decreased odds of overweight or obesity independently of Enterobacteriaceae abundance (AOR 0.44, 95% CI 0.22 to 0.86), with no significant mediation (p = 0.2).Interpretation: Exposure to household disinfectants was associated with higher BMI at age 3, mediated by gut microbial composition at age 3-4 months. Although child overweight was less common in households that cleaned with eco-friendly products, the lack of mediation by infant gut microbiota suggests another pathway for this association. [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]