OBJECTIVES: To examine the associations among UPF intake, anthropometric adiposity indicators, and obesity status in Canadian children.
DESIGN, SETTING, AND PARTICIPANTS: In the CHILD Cohort Study, one of the largest prospective, multicenter, population-based pregnancy cohorts in Canada, diet was assessed during the 3-year visit (September 2011 to June 2016), and anthropometric measurements were assessed at the 5-year visit (December 2013 to April 2018). Data analysis was performed between July 1, 2023, and June 30, 2024.
EXPOSURE: Diet intake was assessed using a semiquantitative food frequency questionnaire at 3 years of age. UPFs were identified using the NOVA classification system.
MAIN OUTCOMES AND MEASURES: Anthropometric adiposity indicators were measured at 5 years of age and used to calculate age- and sex-standardized z scores for body mass index (BMI), waist to height ratio, and subscapular and triceps skinfold thicknesses, and obesity, which was defined using BMI z score cutoffs. Multivariable-adjusted regression analyses were used to examine the associations of UPF with adiposity and obesity development, accounting for parental, birth, and early-childhood factors.
RESULTS: Among 2217 participants included in this study, median age at the outcome assessment was 5.0 (IQR, 5.0-5.1) years, and 1175 (53.0%) were males. At 3 years of age, UPF contributed 45.0% of total daily energy intake. UPF energy contribution was higher in males vs females (46.0% vs 43.9%; P
OBJECTIVES: This study investigated DNAm differences associated with prenatal nitrogen dioxide (NO2) exposure (a surrogate measure of traffic-related 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 (n=128) were identified, and their persistence at age 1 y were investigated using linear mixed effects models (n=124). Postnatal-specific DNAm differences (n=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 (n=128), 18 regions of DNAm were associated with NO2, with several annotated to HOX genes. Some of these regions were specifically identified in males (n=73), but not females (n=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. https://doi.org/10.1289/EHP13034.
METHODS: Data were collected as part of the longitudinal, general Canadian population CHILD Study. LRTIs during the first 18 months of life were identified through parental symptom report at regular study visits. Systemic antibiotic use was defined as at least one dose of oral/intravenous antibiotics between birth and the 18-month visit and were further categorized by indication as either given for a respiratory indication (upper or lower respiratory symptoms) or non-respiratory indication. Asthma was diagnosed by in-study pediatricians at the 5-year study visit. Adjusted logistic regression models and mediation analyses via systemic antibiotics use were performed.
RESULTS: Among 2,073 participants included in our analysis, 72 (4.9%) had asthma age 5, and 609 (29.3%) used systemic antibiotics before the 18-month visit. Among children who had taken antibiotics, 61.6% also had an LRTI in that period compared to 49.7% among children without exposure to systemic antibiotics (p
METHODS: For a subsample of 178 children from the Canadian CHILD Cohort Study, gut microbiota of fecal samples collected at 3-4 months and 12 months was profiled using 16S rRNA sequencing. Gut bacterial metabolites levels and SIgA level were measured by nuclear magnetic resonance (NMR) based metabolomics and SIgA enzyme-linked immunosorbent assay at 3-4 months, respectively. Bayley-III Scale of Infant Development was assessed at 12 and 24 months. We evaluated direct relationships in multiple linear regression models and putative causal relationships in statistical mediation models.
RESULTS: Propionate and butyrate levels at 3-4 months were associated with decreased Bayley cognitive score at 24 months (p-values: 0.01 and 0.02, respectively) in adjusted multiple linear regression models, but when we investigated an indirect relationship mediated by decreased SIgA level at 3-4 months, it did not reach statistical significance (p-values: 0.18 and 0.20, respectively). Lactate level at 3-4 months was associated with increased Bayley cognitive score at 24 months in adjusted multiple linear regression models (p-value: 0.01), but the statistical model mediated by increased SIgA level at 3-4 months did not reach statistical significance neither (p-value: 0.20).
CONCLUSIONS: Our study contributes to growing evidence that neurodevelopment is influenced by the infant gut microbiota and that it might involve SIgA level, but larger studies are required.
OBJECTIVE: We investigated associations between OPE exposures as measured in house dust and emotional and behavioral problems in young children.
METHODS: We used data from the CHILD Cohort Study (n = 601), a prospective birth cohort recruited in 5 cities across Canada (2008-2012). OPEs were measured in house dust at 3-4 months postpartum, and parents completed the Child Behavior Checklist (CBCL), which measures emotional and behavioral problems when their child was 5 years. We used logistic regression to examine associations between OPE Z-scores (individual and summed chlorinated [ΣOPECl] and non-chlorinated [ΣOPENCl]) and CBCL problem scale scores (borderline and clinical T-scores ≥60 and normal <60).
RESULTS: Tris(2-chloroethyl) phosphate (TCEP) showed strong, positive associations with CBCL Total and Externalizing scores at or above the clinical cutoff, meaning children with higher levels of TCEP in house dust postpartum had higher odds of developing clinically relevant behavioral problems in early childhood compared to children with lower levels (Total ORadj: 1.37, 95% CI: 1.01, 1.87; Externalizing ORadj: 1.36, 95% CI: 1.00, 1.85). Similarly, 4-isopropylphenyl diphenyl phosphate, a Firemaster 550 component, had a strong, positive association with Internalizing scores (ORadj: 1.24, 95% CI: 1.02, 1.51). We observed a weak association between ΣOPECl and Total scores (Odds Ratio [OR] adjusted: 1.14, 95% Confidence Intervals [CI]: 0.97, 1.33) and null associations for ΣOPENCl. Associations were generally stronger among boys (ΣOPECl Total ORadj: 1.31, 95% CI: 1.02, 1.68). Visual summary of this manuscript, created with Microsoft PowerPoint.
IMPACT: Organophosphate esters (OPEs) are common aspects of our built environment and increasingly recognized as developmental neurotoxicants. Using data from a large Canadian birth cohort, we investigated associations between OPE exposures as measured in house dust postpartum and emotional and behavioral problems in children. We found that levels of two OPE compounds (tris(2-chloroethyl) phosphate and a component of Firemaster 550) were associated with increased odds of clinically relevant behavioral problems in early childhood. This important work underscores the urgent need for public health policies to limit the use of certain OPEs in consumer products to reduce children's exposure to harmful chemicals.
OBJECTIVE: We aimed to collectively define contributions and distinct characteristics of respiratory phenotypes based on longitudinal wheeze and atopic sensitization patterns in the first 5 years of life.
METHODS: Group-based trajectory analysis was performed in the CHILD Cohort Study to identify distinct wheeze and allergic sensitization trajectories. Trajectories were evaluated for associated risk factors, health care utilization, biologic determinants, and clinical outcomes. Stool samples for shotgun metagenomic sequencing profiles of infant microbiomes collected at ages 3 months and 1 year were assessed for phenotype-specific biomarkers.
RESULTS: A total of 6 distinct respiratory phenotypes were identified on the basis of samples from 2902 children; the phenotypes differed by temporal wheeze and allergic sensitization patterns. Although allergic wheeze phenotypes (found in 11.6% of participants) carried the highest risk of asthma diagnosis, the more common nonallergic phenotypes (in 88.3% of participants) contributed to the majority of 5-year asthma diagnoses (61.4% of diagnoses). Most importantly, nonallergic phenotypes accounted for more than two-thirds of health care utilization in this age group. Phenotypes differed by lung function, blood eosinophil counts, allergic comorbidities, and weight-for-age z score. Moreover, microbiome profiles developed from 1439 infants revealed that largely nonoverlapping microbial signatures at age 1 year are associated with each phenotype.
CONCLUSION: We identified novel early-childhood respiratory phenotypes to disentangle nonoverlapping paths to preschool wheezing. Our findings highlight the continued clinical relevance of nonatopic wheeze phenotypes, which remain undertreated despite accounting for a substantial proportion of health care utilization and asthma diagnoses.