Canadian Healthy Infant Longitudinal Development Research Articles

Pre-labor and post-labor cesarean delivery and early childhood adiposity in the Canadian Healthy Infant Longitudinal Development (CHILD) Cohort Study.

Delivery by cesarean section (CS) compared to vaginal delivery has been associated with increased risk of overweight in childhood. Our study examined if the presence or absence of labor events in CS delivery altered risk of overweight in early childhood (1-5 years) compared to vaginal delivery and if this association differed according to infant sex. The study included 3073 mother-infant pairs from the CHILD Cohort Study in Canada. Data from birth records were used to categorize infants as having been vaginally delivered, or delivered by CS, with or without labor events. Age and sex adjusted weight-for-length (WFL) and body mass index (BMI) z scores were calculated from height and weight data from clinic visits at 1, 3 and 5 years and used to classify children as overweight. Associations between delivery mode and child overweight at each timepoint were assessed using regression models, adjusting for relevant confounding factors including maternal pre-pregnancy BMI. Effect modification by infant sex was tested. One in four infants (24.6%) were born by CS delivery; 13.0% involved labor events and 11.6% did not. Infants born by CS without labor had an increased odds of being overweight at age 1 year compared to vaginally delivered infants after adjustment for maternal pre-pregnancy BMI, maternal diabetes, smoking, infant sex and birthweight-for-gestational age (aOR 1.68 [95% CI 1.05-2.67]). These effects did not persist to 3 or 5 years of age and, after stratification by sex, were only seen in boys (aOR at 1 year 2.21 [95% CI 1.26-3.88]). Our findings add to the body of evidence that CS, in particular CS without labor events, may be a risk factor for overweight in early life, and that this association may be sex-specific. These findings could help to identify children at higher risk for developing obesity.

Early prediction of pediatric asthma in the Canadian Healthy Infant Longitudinal Development (CHILD) birth cohort using machine learning.

Early identification of children at risk of asthma can have significant clinical implications for effective intervention and treatment. This study aims to disentangle the relative timing and importance of early markers of asthma. Using the CHILD Cohort Study, 132 variables measured in 1754 multi-ethnic children were included in the analysis for asthma prediction. Data up to 4 years of age was used in multiple machine learning models to predict physician-diagnosed asthma at age 5 years. Both predictive performance and variable importance was assessed in these models. Early-life data (≤1 year) has limited predictive ability for physician-diagnosed asthma at age 5 years (area under the precision-recall curve (AUPRC) < 0.35). The earliest reliable prediction of asthma is achieved at age 3 years, (area under the receiver-operator curve (AUROC) > 0.90) and (AUPRC > 0.80). Maternal asthma, antibiotic exposure, and lower respiratory tract infections remained highly predictive throughout childhood. Wheezing status and atopy are the most important predictors of early childhood asthma from among the factors included in this study. Childhood asthma is predictable from non-biological measurements from the age of 3 years, primarily using parental asthma and patient history of wheezing, atopy, antibiotic exposure, and lower respiratory tract infections. Machine learning models can predict physician-diagnosed asthma in early childhood (AUROC > 0.90 and AUPRC > 0.80) using ≥3 years of non-biological and non-genetic information, whereas prediction with the same patient information available before 1 year of age is challenging. Wheezing, atopy, antibiotic exposure, lower respiratory tract infections, and the child's mother having asthma were the strongest early markers of 5-year asthma diagnosis, suggesting an opportunity for earlier diagnosis and intervention and focused assessment of patients at risk for asthma, with an evolving risk stratification over time.

Maturational patterns of the infant gut mycobiome are associated with early-life body mass index

Unlike the bacterial microbiome, the role of early-life gut fungi in host metabolism and childhood obesity development remains poorly characterized. To address this, we investigate the relationship between the gut mycobiome of 100 infants from the Canadian Healthy Infant Longitudinal Development (CHILD) Cohort Study and body mass index Z scores (BMIz) in the first 5 years of life. An increase in fungal richness during the first year of life is linked to parental and infant BMI. The relationship between richness pattern and early-life BMIz is modified by maternal BMI, maternal diet, infant antibiotic exposure, and bacterial beta diversity. Further, the abundances of Saccharomyces, Rhodotorula, and Malassezia are differentially associated with early-life BMIz. Using structural equation modeling, we determine that the mycobiome's contribution to BMIz is likely mediated by the bacterial microbiome. This demonstrates that mycobiome maturation and infant growth trajectories are distinctly linked, advocating for inclusion of fungi in larger pediatric microbiome studies.

Early Life Antimicrobial Exposure: Impact on Clostridioides difficile Colonization in Infants.

The relationship between antibiotic use and Clostridioides difficile (C. difficile) has been well established in adults and older children but remains unclear and is yet to be fully examined in infant populations. This study aimed to determine the separate and cumulative impact from antibiotics and household cleaning products on C. difficile colonization in infants. This study included 1429 infants at 3–4 months of age and 1728 infants at 12 months of age from the Canadian Healthy Infant Longitudinal Development (CHILD) birth cohort. The levels of infant antimicrobial exposure were obtained from hospital birth charts and standardized questionnaires. Infant gut microbiota was characterized by Illumina 16S ribosomal ribonucleic acid (rRNA) gene sequencing. Analysis of C. difficile was performed using a quantitative polymerase chain reaction (qPCR). Overall, C. difficile colonized 31% and 46% of infants at 3–4 months and 12 months, respectively. At 3–4 months, C. difficile colonization was significantly higher in infants exposed to both antibiotics and higher (above average) usage of household cleaning products (adjusted odds ratio (aOR) 1.50, 95% CI 1.03–2.17; p = 0.032) than in infants who had the least antimicrobial exposure. This higher colonization persisted up to 12 months of age. Our study suggests that cumulative exposure to systemic antibiotics and higher usage of household cleaning products facilitates C. difficile colonization in infants. Further research is needed to understand the future health impacts.

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

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

DNA methylation changes in cord blood and the developmental origins of health and disease \u2013 a systematic review and replication study

BackgroundEnvironmental 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.MethodsWe 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.ResultsWe 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.ConclusionsMaternal 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.

Factors associated with breast-feeding initiation and continuation in Canadian-born and non-Canadian-born women: a multi-centre study.

To identify factors associated with breast-feeding initiation and continuation in Canadian-born and non-Canadian-born women. Prospective cohort of mothers and infants born from 2008 to 2012: the Canadian Healthy Infant Longitudinal Development (CHILD) Cohort Study. General community setting in four Canadian provinces. In total, 3455 pregnant women from Vancouver, Edmonton, Winnipeg and Toronto between 2008 and 2012. 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. 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.

Breastfeeding in the First Days of Life Is Associated With Lower Blood Pressure at 3 Years of Age.

BackgroundBreastfeeding in infancy is associated with lower cardiovascular disease risk in adulthood; however, the amount of breastfeeding required to achieve this benefit is unknown.Methods and ResultsIn the CHILD (Canadian Healthy Infant Longitudinal Development) Cohort Study, we analyzed 2382 children with complete data on early life feeding and blood pressure. Infant feeding was documented from hospital records in the first few days of life and reported by mothers throughout infancy. Blood pressure was measured at 3 years of age. Analyses controlled for birth weight, gestational age, socioeconomic status, maternal body mass index, and other potential confounders. We found that nearly all children (2333/2382; 97.9%) were ever breastfed, of whom 98 (4.2%) only briefly received breast milk during their birth hospitalization (“early limited breastfeeding”). At 3 years of age, blood pressure was higher in children who were never breastfed (mean systolic/diastolic 103/60 mm Hg) compared with those who were ever breastfed (99/58 mm Hg), including those who received only early limited breastfeeding (99/57 mm Hg). These differences in systolic blood pressure persisted in adjusted models (ever breastfed: −3.47 mm Hg, 95% CI, −6.14 to −0.80; early limited breastfeeding: −4.24 mm Hg, 95% CI, −7.45 to −1.04). Among breastfed children, there was no significant dose‐response association according to the duration or exclusivity of breastfeeding. Associations were not mediated by child body mass index.ConclusionsAlthough the benefits of sustained and exclusive breastfeeding are indisputable, this study indicates any breastfeeding, regardless of duration or exclusivity, is associated with lower blood pressure at 3 years of age. Further research examining the bioactive components of early breast milk, underlying mechanisms, and long‐term associations is warranted.

Influence of Neighborhood Characteristics and Weather on Movement Behaviors at Age 3 and 5 Years in a Longitudinal Birth Cohort.

Movement behaviors (physical activity, sedentary time, and sleep) established in early childhood track into adulthood and interact to influence health outcomes. This study examined the associations between neighborhood characteristics and weather with movement behaviors in preschoolers. A subset of Canadian Healthy Infant Longitudinal Development birth cohort (n = 385, 50.6% boys) with valid movement behaviors data were enrolled at age 3years and followed through to age 5years. Objective measures of neighborhood characteristics were derived by ArcGIS software, and weather variables were derived from the Government of Canada weather website. Random forest and linear mixed models were used to examine predictors of movement behaviors. Cross-sectional analyses were stratified by age and season (winter and nonwinter). Neighborhood safety, temperature, green space, and roads were important neighborhood characteristics for movement behaviors in 3- and 5-year-olds. An increase in temperature was associated with greater light physical activity longitudinally from age 3 to 5years and also in the winter at age 5years in stratified analysis. A higher percentage of expressways was associated with less nonwinter moderate to vigorous physical activity at age 3years. Future initiatives to promote healthy movement behaviors in the early years should consider age differences, neighborhood characteristics, and season.

Bacteroides-dominant gut microbiome of late infancy is associated with enhanced neurodevelopment

ABSTRACT Dysbiosis of gut microbiota has been retrospectively linked to autism spectrum disorders but the temporal association between gut microbiota and early neurodevelopment in healthy infants is largely unknown. We undertook this study to determine associations between gut microbiota at two critical periods during infancy and neurodevelopment in a general population birth cohort. Here, we analyzed data from 405 infants (199 females) from the CHILD (Canadian Healthy Infant Longitudinal Development) Cohort Study. Neurodevelopmental outcomes were objectively assessed using the Bayley Scale of Infant Development (BSID-III) at 1 and 2 years of age. Microbiota profiling with 16S rRNA gene sequencing was conducted on fecal samples obtained at a mean age of 4 and 12 months. Using clustering methods, we identified three groups of infants based on relative abundance of gut microbiota at 12 months: Proteobacteria-dominant cluster (22.4% higher abundance at 12 months), Firmicutes-dominant cluster (46.0% higher abundance at 12 months) and Bacteroidetes-dominant cluster (31.6% higher abundance at 12 months). Relative to the Proteobacteria-dominant cluster, the Bacteroidetes-dominant cluster was associated with higher scores for cognitive (4.8 points; FDRp = .02), language (4.2 points; FDRp≤0.001), and motor (3.1 points; FDRp = .03) development at age 2 in models adjusted for covariates. When stratified by sex, only male infants with a Bacteroidetes-dominant microbiota had more favorable cognitive (5.9 points, FDRp = .06) and language (7.9 points; FDRp≤0.001) development. Genus Bacteroides abundance in gut microbiota was positively correlated with cognitive and language scores at age 2. Fully adjusted linear mixed model analysis revealed a positive association between Bacteroidetes-dominant cluster and change in cognitive and language performance from 1 to 2 years, predominantly among males. No associations were evident between 4-month microbiota clusters and BSID-II scores. Noteworthy is that enhanced sphingolipid synthesis and metabolism, and antagonism or competition between Bacteroides and Streptococcus were characteristic of a Bacteroidetes-dominant gut microbiota. This study found strong evidence of positive associations between Bacteroidetes gut microbiota in late infancy and subsequent neurodevelopment, most prominently among males but not females.

Cardiorespiratory Monitoring Data during Sleep in Healthy Canadian Infants

Rationale: Sleep study interpretation in children needs to be based on age-specific normal values. Although several studies have reported normal cardiorespiratory parameters during sleep in children and adolescents, few have included younger children.Objectives: To describe cardiopulmonary indices, specifically oxygen saturation and heart rate, as well as frequency of obstructive and central apneas in healthy 1-year-old Canadian infants during sleep.Methods: Home sleep cardiorespiratory monitoring was performed among infants participating in the Edmonton subcohort of the CHILD (Canadian Healthy Infant Longitudinal Development) study at their 1-year follow-up visit. A portable sleep monitoring device, which included a nasal pressure cannula, an oronasal thermal airflow sensor, a pulse oximeter, and respiratory inductance plethysmography belts, was used to collect sleep architecture and cardiorespiratory data during one night of monitoring in the home. Sleep scoring was done in blocks of 5 minutes using a novel pilot sleep scoring algorithm.Results: Among the 562 subjects (mean ± standard deviation age 1.1 ± 0.2 yr) who attempted home sleep cardiorespiratory monitoring, 91% provided technically acceptable data with no loss of signal preventing analysis of any parameter. Obstructive and central apneas were rare, with a median obstructive apnea index of 0.0 events/h (10th percentile, 0.0; 90th percentile, 0.5) and a median central apnea index of 2.5 events/h (10th percentile, 0.6; 90th percentile, 7.1). Median oxygen saturation was 97.0% (10th percentile, 95.4; 90th percentile, 97.9). The oxygen desaturation index was 6.7 events/h (10th percentile, 1.4; 90th percentile, 15.8), with infants spending only 0.1% (10th percentile, 0.0; 90th percentile, 0.6) of the time with an oxygen saturation below 92%.Conclusions: These results provide important reference data for healthy infants undergoing cardiorespiratory monitoring during sleep.

Polygenic risk score for atopic dermatitis in the Canadian population

Atopic dermatitis (AD) is characterized by a damaged skin barrier that allows allergens to penetrate the body, leading to sensitization and a higher risk of developing food allergies (relative risk [RR], 33.79), asthma (RR, 7.04), and/or rhinitis (RR, 11.75), all features of the atopic march.1 Recent evidence has shown that the atopic march can be modified in high-risk infants with early interventions directed at reestablishing and/or maintaining skin barrier function with intense use of simple emollients, and introducing food allergens early into the diet.2, 3, 4, 5 Although these constitute examples of low-intensity, high-impact interventions for health care systems, their successful and indiscriminate implementation in the whole population is neither feasible nor realistic. In this context, building a predictive tool to identify children at high risk of developing moderate to severe AD (MSAD) would allow targeted interventions with maximized impact. In this study, a polygenic risk score (PRS) with an area under the curve (AUC) of 88% and explaining 37% of MSAD variance was established for the Canadian population.

Decreasing antibiotic use, the gut microbiota, and asthma incidence in children: evidence from population-based and prospective cohort studies

Childhood asthma incidence is decreasing in some parts of Europe and North America. Antibiotic use in infancy has been associated with increased asthma risk. In the present study, we tested the hypothesis that decreases in asthma incidence are linked to reduced antibiotic prescribing and mediated by changes in the gut bacterial community. This study comprised population-based and prospective cohort analyses. At the population level, we used administrative data from British Columbia, Canada (population 4·7 million), on annual rates of antibiotic prescriptions and asthma diagnoses, to assess the association between antibiotic prescribing (at age <1 year) and asthma incidence (at age 1-4 years). At the individual level, 2644 children from the Canadian Healthy Infant Longitudinal Development (CHILD) prospective birth cohort were examined for the association of systemic antibiotic use (at age <1 year) with the diagnosis of asthma (at age 5 years). In the same cohort, we did a mechanistic investigation of 917 children with available 16S rRNA gene sequencing data from faecal samples (at age ≤1 year), to assess how composition of the gut microbiota relates to antibiotic exposure and asthma incidence. At the population level between 2000 and 2014, asthma incidence in children (aged 1-4 years) showed an absolute decrease of 7·1 new diagnoses per 1000 children, from 27·3 (26·8-28·3) per 1000 children to 20·2 (19·5-20·8) per 1000 children (a relative decrease of 26·0%). Reduction in incidence over the study period was associated with decreasing antibiotic use in infancy (age <1 year), from 1253·8 prescriptions (95% CI 1219·3-1288·9) per 1000 infants to 489·1 (467·6-511·2) per 1000 infants (Spearman's r=0·81; p<0·0001). Asthma incidence increased by 24% with each 10% increase in antibiotic prescribing (adjusted incidence rate ratio 1·24 [95% CI 1·20-1·28]; p<0·0001). In the CHILD cohort, after excluding children who received antibiotics for respiratory symptoms, asthma diagnosis in childhood was associated with infant antibiotic use (adjusted odds ratio [aOR] 2·15 [95% CI 1·37-3·39]; p=0·0009), with a significant dose-response; 114 (5·2%) of 2182 children unexposed to antibiotics had asthma by age 5 years, compared with 23 (8·1%) of 284 exposed to one course, five (10·2%) of 49 exposed to two courses, and six (17·6%) of 34 exposed to three or more courses (aOR 1·44 [1·16-1·79]; p=0·0008). Increasing α-diversity of the gut microbiota, defined as an IQR increase (25th to 75th percentile) in the Chao1 index, at age 1 year was associated with a 32% reduced risk of asthma at age 5 years (aOR for IQR increase 0·68 [0·46-0·99]; p=0·046). In a structural equation model, we found the gut microbiota at age 1 year, characterised by α-diversity, β-diversity, and amplicon sequence variants modified by antibiotic exposure, to be a significant mediator between outpatient antibiotic exposure in the first year of life and asthma diagnosis at age 5 years (β=0·08; p=0·027). Our findings suggest that the reduction in the incidence of paediatric asthma observed in recent years might be an unexpected benefit of prudent antibiotic use during infancy, acting via preservation of the gut microbial community. British Columbia Ministry of Health, Pharmaceutical Services Branch; Canadian Institutes of Health Research; Allergy, Genes and Environment (AllerGen) Network of Centres of Excellence; Genome Canada; and Genome British Columbia.

Association of use of cleaning products with respiratory health in a Canadian birth cohort.

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. 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. 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. 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.

Increased behavioral problems at 5 years of age are associated with sleep disordered breathing phenotypes, based on parent-reported symptoms: the Canadian healthy infant longitudinal development birth cohort study

Increased behavioral problems at 5 years of age are associated with sleep disordered breathing phenotypes, based on parent-reported symptoms: the Canadian healthy infant longitudinal development birth cohort study

Timing of Introduction, Sensitization, and Allergy to Highly Allergenic Foods at Age 3 Years in a General-Population Canadian Cohort

Early dietary introduction of highly allergenic foods has been associated with decreased risk of food allergy in high-risk infants. Early introduction of highly allergenic foods for lower risk infants was examined using Canadian Healthy Infant Longitudinal Development (CHILD) Study data. CHILD participants were recruited from the general population before birth. Every 6 months, caregivers reported food introduction and allergic reactions. At ages 1 and 3 years, sensitization to peanut, egg, and cow's milk was measured by skin prick testing (SPT) and atopic dermatitis diagnosed at clinical visits. Multivariable logistic regression was used to examine associations between timing of introduction to peanut, egg, and cow's milk and the presence at 3 years of sensitization (positive SPT) and probable clinical IgE-mediated allergy (sensitization with no current consumption and convincing history of allergic reaction to the specific food). Among 2669 CHILD participants at age 3 years, 101 (3.80%) showed sensitization to peanut, 59 (2.21%) to egg, and 30 (1.12%) to cow's milk; 46 (1.78%) showed probable clinical IgE-mediated allergy to peanut, 4 (0.16%) to egg, and 2 (0.08%) to cow's milk. Infants introduced to peanut after 12 months had increased odds of sensitization (odds ratio [OR]: 2.38, 95% confidence interval [CI]: 1.39-4.07) and probable clinical allergy (OR: 4.04, 95% CI: 1.66-9.85) to peanut at 3 years. Associations persisted after exclusion of high-risk infants with moderate-to-severe atopic dermatitis in the first year/egg sensitization at 1 year. General-population infants introduced to peanut after age 12 months were more likely to have sensitization and probable clinical allergy to peanut at 3 years.

Early life exposure to phthalates in the Canadian Healthy Infant Longitudinal Development (CHILD) study: a multi-city birth cohort.

Few studies have examined phthalate exposure during infancy and early life, critical windows of development. The Canadian Healthy Infant Longitudinal Development (CHILD) study, a population-based birth cohort, ascertained multiple exposures during early life. To characterize exposure to phthalates during infancy and early childhood. Environmental questionnaires were administered, and urine samples collected at 3, 12, and 36 months. In the first 1578 children, urine was analyzed for eight phthalate metabolites: mono-methyl phthalate (MMP), mono-ethyl phthalate (MEP), mono-butyl phthalate (MBP), mono-benzyl phthalate (MBzP), mono-2-ethylhexyl phthalate (MEHP), mono-(2-ethyl-5-oxohexyl) phthalate (MEOHP), mono-(2-ethyl-5-hydroxyhexyl) phthalate (MEHHP), and mono-3-carboxypropyl phthalate (MCPP). Geometric mean (GM) concentrations were calculated by age, together with factors that may influence concentrations. Trends with age were examined using mixed models and differences within factors examined using ANOVA. The highest urinary concentration was for the metabolite MBP at all ages (GM: 15-32 ng/mL). Concentrations of all phthalate metabolites significantly increased with age ranging from GM: 0.5-15.1 ng/mL at 3 months and 1.9-32.1 ng/mL at 36 months. Concentrations of all metabolites were higher in the lowest income categories except for MEHP at 3 months, among children with any breastfeeding at 12 months, and in urine collected on dates with warmer outdoor temperatures (>17 °C), except for MBzP at 3 months and MEHP at 3 and 12 months. No consistent differences were found by gender, study site, or maternal age. Higher phthalate metabolite concentrations were observed among children in lower income families. Examination of factors associated with income could inform interventions aimed to reduce infant phthalate exposure.

Early-life antibiotic exposure, the gut microbiome, and the risk of childhood asthma

OPS 07: Farm animals, antibiotics, infections and the microbiome, Room 110, Floor 1, August 27, 2019, 10:30 AM - 12:00 PM Background: Many early-life features of Westernized lifestyle are risk factors for asthma. Several of these factors, in particular antibiotics, are modifiable, yet have not been addressed despite: (1) high asthma prevalence, (2) mounting evidence in support of exposure to beneficial microbes in infancy, and (3) documented decreased antibiotic prescriptions in British Columbia (BC), Canada, that parallels a decrease in pediatric asthma. Here, we harness the power of a three-tier study to explore causation and biological plausibility by defining the associations between early-life antibiotic use, the structure of the gut microbiome, and the risk of asthma. Methods: We used administrative linked health data to examine the association between antibiotic prescribing (age<1yr) and asthma incidence (ages 1-4yr) at the ecological level and examined 2,644 children from the Canadian Healthy Infant Longitudinal Development (CHILD) Study, who were clinically assessed for asthma (5yr). In an asthma-enriched subset (n=1,000), gut microbiota was defined by 16SrRNA sequencing of stool samples collected at 3 and 12 months of age Results: We report a 76% decrease in antibiotic use among children in BC and a decline in asthma incidence. Antibiotic prescribing predicted asthma incidence (IRR=1.2 for 10% increase; p<0.001). In the CHILD study, we also demonstrate a near doubling of asthma risk among participants who received systemic antibiotic use in the first year of life (aOR: 1.8, p=0.006), while this risk was reduced with increased gut microbiota α-diversity (aOR=0.68 for one IQR increase; p=0.046). The gut microbiota, represented by diversity and differentially expressed taxa, was a significant mediator between antibiotics and asthma (p=0.041). Conclusion: Antibiotic exposure in the first year of life increases the risk of being diagnosed with asthma in childhood. Our findings are consistent with a mechanism by which antibiotics disturb the balance of the microflora skewing the developing immune system toward hypersensitivity.

Patterns of health care use related to respiratory conditions in early life: A birth cohort study with linked administrative data.

To identify distinctive patterns of respiratory-related health services use (HSU) between birth and 3 years of age, and to examine associated symptom and risk profiles. This study included 729 mother and child pairs enrolled in the Toronto site of the Canadian Healthy Infant Longitudinal Development study in 2009-2012; they were linked to Ontario health administrative databases (2009-2016). A model-based cluster analysis was performed to identify distinct groups of children who followed a similar pattern of respiratory-related HSU between birth and 3 years of age, regarding hospitalization, emergency department (ED) and physician office visits for respiratory conditions and total health care costs (2016 Canadian dollars). The majority (estimated cluster weight = 0.905) showed a pattern of low and stable respiratory care use (low HSU) while the remainder (weight = 0.095) showed a pattern of high use (high HSU). From 0 to 3 years of age, the low- and high-HSU groups differed in mean trajectories of total health care costs ($783 per 6 months decreased to $114, vs $1796 to $177, respectively). Compared to low-HSU, the high-HSU group was associated with a constant risk of hospitalizations, early high ED utilization and physician visits for respiratory problems. The two groups differed significantly in the timing of wheezing (late onset in low-HSU vs early in high-HSU) and future total costs (stable vs increased). One in ten children had high respiratory care use in early life. Such information can help identify high-risk young children in a large population, monitor their long-term health, and inform resource allocation.

Clostridioides Difficile Colonization Is Differentially Associated with Gut Microbiota Composition in Breastfed versus Formula Fed Infants (OR01-02-19)

ObjectivesColonization with Clostridioides difficile occurs in up to half of infants and is predicted by formula feeding. Although this microbe does not appear to pose any immediate risks for infants, its presence has been associated with susceptibility to chronic disease later in childhood, perhaps by promoting changes in the gut microbiome that may increase opportunity for colonization of pathogenic bacteria. We explored these compositional changes in exclusively breastfed, partially breastfed and exclusively formula fed infants to describe the microbial community and C. difficile colonization in infants with distinct diets. MethodsThis study includes 1562 infants enrolled in the Canadian Healthy Infant Longitudinal Development (CHILD) Study. Infants provided a fecal sample at 3–4 months of age (Mean: 3.56, SD: 1.00) which was analyzed using 16S rRNA sequencing and targeted qPCR for C. difficile. Mode of feeding was recorded in a questionnaire at a 3 month follow-up visit. C. difficile colonization was defined as positive detection (CD+) in the fecal sample (reference: not present, CD-). Multivariate association with linear models (MaAslin) was used to determine changes in microbiota composition following arsine-square root transformation of relative abundances and FDR correction. ResultsThe prevalence of C. difficile colonization among all infants was 30.9%. Colonization rates differed among feeding groups: 22.63% of exclusively breastfed infants, 35.96% of partially breastfed infants and 49.63% of exclusively formula fed infants (P < 0.001). Microbes of the genus Bifidobacterium were decreased in CD + exclusively breastfed infants compared to non-carriers of the same diet (q = 0.02). Additionally, Blautia, Coprococcus and Clostridium, of the Lachnospiraceae family, and microbes of the Bacteroidetes phylum were of higher relative abundance (all q < 0.01) in breastfed CD + infants (both partial and exclusive). In exclusively formula fed infants, C. difficile colonization was not significantly associated with microbiota composition. ConclusionsC. difficile colonization may have a dysbiotic effect on the gut microbiota composition of breastfed infants, changes which have previously been associated with childhood atopy and obesity. Funding SourcesCanadian Institutes of Health Research (CIHR).AllerGen Network of Centres of Excellence (NCE)