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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: 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]

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: 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 infant gut is rapidly colonized by microorganisms soon after birth, and the composition of the microbiota is dynamic in the first year of life. Although a stable microbiome may not be established until 1 to 3 years after birth, the infant gut microbiota appears to be an important predictor of health outcomes in later life. Methods: We obtained stool at one year of age from 173 white Caucasian and 182 South Asian infants from two Canadian birth cohorts to gain insight into how maternal and early infancy exposures influence the development of the gut microbiota. We investigated whether the infant gut microbiota differed by ethnicity (referring to groups of people who have certain racial, cultural, religious, or other traits in common) and by breastfeeding status, while accounting for variations in maternal and infant exposures (such as maternal antibiotic use, gestational diabetes, vegetarianism, infant milk diet, time of introduction of solid food, infant birth weight, and weight gain in the first year). Results: We demonstrate that ethnicity and infant feeding practices independently influence the infant gut microbiome at 1 year, and that ethnic differences can be mapped to alpha diversity as well as a higher abundance of lactic acid bacteria in South Asians and a higher abundance of genera within the order Clostridiales in white Caucasians. Conclusions: The infant gut microbiome is influenced by ethnicity and breastfeeding in the first year of life. Ethnic differences in the gut microbiome may reflect maternal/infant dietary differences and whether these differences are associated with future cardiometabolic outcomes can only be determined after prospective follow-up. [ABSTRACT FROM AUTHOR]

Background: Exposure to traffic-related air pollution (TRAP) can adversely impact health but epidemiologic studies are limited in their abilities to assess long-term exposures and incorporate variability in indoor pollutant infiltration. Methods: In order to examine settled house dust levels of hopanes, engine lubricating oil byproducts found in vehicle exhaust, as a novel TRAP exposure measure, dust samples were collected from 171 homes in five Canadian cities and analyzed by gas chromatography-mass spectrometry. To evaluate source contributions, the relative abundance of the highest concentration hopane monomer in house dust was compared to that in outdoor air. Geographic variables related to TRAP emissions and outdoor NO2 concentrations from city-specific TRAP land use regression (LUR) models were calculated at each georeferenced residence location and assessed as predictors of variability in dust hopanes. Results: Hopanes relative abundance in house dust and ambient air were significantly correlated (Pearson's r=0.48, p<0.05), suggesting that dust hopanes likely result from traffic emissions. The proportion of variance in dust hopanes concentrations explained by LUR NO2 was less than 10% in Vancouver, Winnipeg and Toronto while the correlations in Edmonton and Windsor explained 20 to 40% of the variance. Modeling with household factors such as air conditioning and shoe removal along with geographic predictors related to TRAP generally increased the proportion of explained variability (10-80%) in measured indoor hopanes dust levels. Conclusions: Hopanes can consistently be detected in house dust and may be a useful tracer of TRAP exposure if determinants of their spatiotemporal variability are well-characterized, and when home-specific factors are considered. [ABSTRACT FROM AUTHOR]

Background: A growing number of studies observe associations between the amount of green space around a mother's home and positive birth outcomes; however, the robustness of this association and potential pathways of action remain unclear. Objectives: To examine associations between mother's residential green space and term birth weight within the Canadian Healthy Infant Longitudinal Development (CHILD) study and examine specific hypothesized pathways. Methods: We examined 2510 births located in Vancouver, Edmonton, Winnipeg, and Toronto Canada. Green space was estimated around mother's residences during pregnancy using Landsat 30 m normalized difference vegetation index (NDVI). We examined hypothesized pathways of: (1) reduction of environmental exposure; (2) built environment features promoting physical activity; (3) psychosocial conditions; and (4) psychological influences. Linear regression was used to assess associations between green space and term birth weight adjusting first for a comprehensive set of confounding factors and then incrementally for pathway variables. Results: Fully adjusted models showed non-statistically significant increases in term birth weight with increasing green space. For example, a 0.1 increase in NDVI within 500 m was associated with a 21.5 g (95% CI − 4.6, 47.7) increase in term birth weight. Associations varied by city and were most robust for high-density locations. For the two largest cities (Vancouver and Toronto), we observed an increase in birth weight of 41.2 g (95% CI 7.8, 74.6) for a 0.1 increase in NDVI within 500 m. We did not observe substantial reductions in the green space effect on birth weight when adjusting for pathway variables. Conclusion: Our results highlight the need to further characterize the interactions between green space, urban density and climate related factors as well as the pathways linking residential green space to birth outcomes. [ABSTRACT FROM AUTHOR]

Background: Exposure to traffic-related air pollution (TRAP) can adversely impact health but epidemiologic studies are limited in their abilities to assess long-term exposures and incorporate variability in indoor pollutant infiltration.Methods: In order to examine settled house dust levels of hopanes, engine lubricating oil byproducts found in vehicle exhaust, as a novel TRAP exposure measure, dust samples were collected from 171 homes in five Canadian cities and analyzed by gas chromatography-mass spectrometry. To evaluate source contributions, the relative abundance of the highest concentration hopane monomer in house dust was compared to that in outdoor air. Geographic variables related to TRAP emissions and outdoor NO2 concentrations from city-specific TRAP land use regression (LUR) models were calculated at each georeferenced residence location and assessed as predictors of variability in dust hopanes.Results: Hopanes relative abundance in house dust and ambient air were significantly correlated (Pearson's r=0.48, p<0.05), suggesting that dust hopanes likely result from traffic emissions. The proportion of variance in dust hopanes concentrations explained by LUR NO2 was less than 10% in Vancouver, Winnipeg and Toronto while the correlations in Edmonton and Windsor explained 20 to 40% of the variance. Modeling with household factors such as air conditioning and shoe removal along with geographic predictors related to TRAP generally increased the proportion of explained variability (10-80%) in measured indoor hopanes dust levels.Conclusions: Hopanes can consistently be detected in house dust and may be a useful tracer of TRAP exposure if determinants of their spatiotemporal variability are well-characterized, and when home-specific factors are considered. [ABSTRACT FROM AUTHOR]