ORCID Profile
0000-0003-0394-1933
Current Organisations
McMaster University
,
Hospital for Sick Children
,
University of Toronto
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Publisher: European Respiratory Society (ERS)
Date: 05-2017
DOI: 10.1183/13993003.02019-2016
Abstract: The impact of breastfeeding on respiratory health is uncertain, particularly when the mother has asthma. We examined the association of breastfeeding and wheezing in the first year of life. We studied 2773 infants from the Canadian Healthy Infant Longitudinal Development (CHILD) birth cohort. Caregivers reported on infant feeding and wheezing episodes at 3, 6 and 12 months. Breastfeeding was classified as exclusive, partial (supplemented with formula or complementary foods) or none. Overall, 21% of mothers had asthma, 46% breastfed for at least 12 months and 21% of infants experienced wheezing. Among mothers with asthma, breastfeeding was inversely associated with infant wheezing, independent of maternal smoking, education and other risk factors (adjusted rate ratio (aRR) 0.52 95% CI 0.35–0.77 for ≥12 versus months breastfeeding). Compared with no breastfeeding at 6 months, wheezing was reduced by 62% with exclusive breastfeeding (aRR 0.38 95% CI 0.20–0.71) and by 37% with partial breastfeeding supplemented with complementary foods (aRR 0.63 95% CI 0.43–0.93) however, breastfeeding was not significantly protective when supplemented with formula (aRR 0.89 95% CI 0.61–1.30). Associations were not significant in the absence of maternal asthma (p-value for interaction .01). Breastfeeding appears to confer protection against wheezing in a dose-dependent manner among infants born to mothers with asthma.
Publisher: American Medical Association (AMA)
Date: 02-07-2018
Publisher: MDPI AG
Date: 31-08-2021
DOI: 10.3390/MICROORGANISMS9091847
Abstract: Background and Aims: Few studies consider the joint effect of multiple factors related to birth, delivery mode, intrapartum antibiotic prophylaxis and the onset of labour, on the abundance of Bifidobacterium and the quantity of this genus and its species Bifidobacterium longum subsp. infantis in the infant gut microbiota. We implemented such a study. Methods: Among 1654 Canadian full-term infants, the gut microbiota of faecal s les collected at 3 months were profiled by 16S rRNA sequencing the genus Bifidobacterium and Bifidobacterium longum subsp. infantis were quantified by qPCR. Associations between Bifidobacterium and other gut microbiota were examined by Spearman’s rank correlation. Results: Following vaginal birth, maternal IAP exposure was associated with reduced absolute quantities of bifidobacteria among vaginally delivered infants (6.80 vs. 7.14 log10 (gene-copies/g faeces), p 0.05), as well as their lowered abundance relative to other gut microbiota. IAP differences in infant gut bifidobacterial quantity were independent of maternal pre-pregnancy body-mass-index (BMI), and remarkably, they were limited to breastfed infants. Pre-pregnancy BMI adjustment revealed negative associations between absolute quantities of bifidobacteria and CS with or without labour in non-breastfed infants, and CS with labour in exclusively breastfed infants. Significant correlations between Bifidobacterium abundance and other microbial taxa were observed. Conclusions: This study documented the impact of the birth mode and feeding status on the abundance of gut Bifidobacterium, and pointed to the important ecological role of the genus Bifidobacterium in gut microbiota due to its strong interaction with other gut microbiota in early infancy.
Publisher: Elsevier BV
Date: 07-2019
DOI: 10.1016/J.SLEEP.2019.01.015
Abstract: 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. To investigate the mechanistic pathways linking maternal education and infant sleep. 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. 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). Prenatal depression and birth mode sequentially mediate the effect of maternal education on infant sleep duration.
Publisher: Wiley
Date: 11-2018
DOI: 10.1111/PPE.12525
Abstract: 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. 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. 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. 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).
Publisher: Springer Science and Business Media LLC
Date: 04-05-2020
Publisher: Springer Science and Business Media LLC
Date: 14-08-2017
DOI: 10.1038/IJO.2017.189
Abstract: Breastfeeding may protect against excessive weight gain during infancy. However, the breast milk components responsible for this effect are unknown. We examined the variation of three breast milk hormones (adiponectin, leptin and insulin) according to maternal characteristics and determined their association with infant body composition. We studied a representative subset of 430 breastfed infants in the CHILD birth cohort. Breast milk was collected at 4 months postpartum and hormone concentrations were measured using the MesoScale Discovery System. Weight-for-length (WFL) and body mass index (BMI) z-scores were calculated according to the World Health Organization reference standard from infant anthropometrics measured at 4 months and 1 year. Maternal BMI and demographics were self-reported. Breast milk hormone concentrations varied widely between mothers. The geometric mean (range) was 19.4 (3.7-74.4) ngml Breast milk hormone concentrations were associated with several fixed and modifiable maternal characteristics. Higher concentrations of leptin and intermediate concentrations of insulin were associated with lower infant WFL in the first year of life.
Publisher: Wiley
Date: 12-02-2020
DOI: 10.1111/ALL.14190
Publisher: Elsevier BV
Date: 2020
DOI: 10.2139/SSRN.3716875
Publisher: Cambridge University Press (CUP)
Date: 21-12-2015
DOI: 10.1017/S2040174415007862
Abstract: Secretory immunoglobulin A (IgA) plays a critical role in gut mucosal immune defense. Initially provided by breastmilk, IgA production by the infant gut is gradually stimulated by developing gut microbiota. This study reports associations between infant fecal IgA concentrations 4 months after birth, breastfeeding status and other pre ostnatal exposures in 47 infants in the Canadian Healthy Infant Longitudinal Development cohort. Breastfed infants and first-born infants had higher median fecal IgA concentrations (23.11 v . 9.34 µg/g protein, P .01 and 22.19 v. 8.23 µg/g protein, P =0.04). IgA levels increased successively with exclusivity of breastfeeding (β-coefficient, 0.37, P .05). This statistical association was independent of maternal parity and household pets. In the absence of breastfeeding, female sex and pet exposure elevated fecal IgA to levels found in breastfed infants. In addition to breastfeeding, infant fecal IgA associations with pre ostnatal exposures may affect gut immunity and risk of allergic disease.
Publisher: American Thoracic Society
Date: 15-08-2009
Publisher: American Public Health Association
Date: 06-2019
Abstract: 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.
Publisher: Elsevier BV
Date: 2021
Publisher: Elsevier BV
Date: 11-2017
DOI: 10.1016/J.JPEDS.2017.07.012
Abstract: To determine whether different modes of infant feeding are associated with childhood asthma, including differentiating between direct breastfeeding and expressed breast milk. We studied 3296 children in the Canadian Healthy Infant Longitudinal Development birth cohort. The primary exposure was infant feeding mode at 3 months, reported by mothers and categorized as direct breastfeeding only, breastfeeding with some expressed breast milk, breast milk and formula, or formula only. The primary outcome was asthma at 3 years of age, diagnosed by trained healthcare professionals. At 3 months of age, the distribution of feeding modes was 27% direct breastfeeding, 32% breastfeeding with some expressed breast milk, 26% breast milk and formula, and 15% formula only. At 3 years of age, 12% of children were diagnosed with possible or probable asthma. Compared with direct breastfeeding, any other mode of infant feeding was associated with an increased risk of asthma. These associations persisted after adjusting for maternal asthma, ethnicity, method of birth, infant sex, gestational age, and daycare attendance (some expressed breast milk: aOR, 1.64, 95% CI, 1.12-2.39 breast milk and formula, aOR, 1.73, 95% CI, 1.17-2.57 formula only: aOR, 2.14, 95% CI, 1.37-3.35). Results were similar after further adjustment for total breastfeeding duration and respiratory infections. Modes of infant feeding are associated with asthma development. Direct breastfeeding is most protective compared with formula feeding indirect breast milk confers intermediate protection. Policies that facilitate and promote direct breastfeeding could have impact on the primary prevention of asthma.
Publisher: Informa UK Limited
Date: 2009
Publisher: Elsevier BV
Date: 05-2021
Publisher: MDPI AG
Date: 21-07-2022
DOI: 10.3390/ANTIBIOTICS11070981
Abstract: 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.
Publisher: Oxford University Press (OUP)
Date: 18-07-2020
DOI: 10.1093/PCH/PXAA053
Abstract: 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. 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. 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& .88 identified children with increased risk of overweight/obesity (BMIz & ) at age 3 years (20.3% versus 3.0%, P& .001). 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.
Publisher: BMJ
Date: 11-2021
DOI: 10.1136/BMJRESP-2021-000881
Abstract: There is no definitive cure for asthma, as prevention remains a major goal. Decision analytic models are routinely used to evaluate the value-for-money proposition of interventions. Following best practice standards in decision-analytic modelling, the objective of this study was to solicit expert opinion to develop a concept map for a policy model for primary prevention of asthma. We reviewed currently available decision analytic models for asthma prevention. A steering committee of economic modellers, allergists and respirologists was then convened to draft a conceptual model of paediatric asthma. A modified Delphi method was followed to define the context of the problem at hand (evaluation of asthma prevention strategies) and develop the concept map of the model. Consensus was achieved after three rounds of discussions, followed by concealed voting. In the final conceptual model, asthma diagnosis was based on three domains of lung function, atopy and their symptoms. The panel recommended several markers for each domain. These domains were in turn affected by several risk factors. The panel clustered all risk factors under three groups of ‘patient characteristic’, ‘family history’ and ‘environmental factors’. To be capable of modelling the interplay among risk factors, the panel recommended the use of microsimulation, with an open-population approach that would enable modelling phased implementation and gradual and incomplete uptake of the intervention. Economic evaluation of childhood interventions for preventing asthma will require modelling of several codependent risk factors and multiple domains that affect the diagnosis. The conceptual model can inform the development and validation of a policy model for childhood asthma prevention.
Publisher: American Association for the Advancement of Science (AAAS)
Date: 30-09-2015
DOI: 10.1126/SCITRANSLMED.AAB2271
Abstract: Supplementing bacterial genera reduced in infants at high risk for asthma ameliorates lung inflammation in mice.
Publisher: Springer Science and Business Media LLC
Date: 25-03-2015
DOI: 10.1038/JES.2015.7
Publisher: American Thoracic Society
Date: 15-03-2021
Publisher: Portland Press Ltd.
Date: 26-10-2016
DOI: 10.1042/CS20160349
Abstract: Asthma is a chronic disease of the airways affecting one in ten children in Westernized countries. Recently, our group showed that specific bacterial genera in early life are associated with atopy and wheezing in 1-year-old children. However, little is known about the link between the early life gut microbiome and the diagnosis of asthma in preschool age children. To determine the role of the gut microbiota in preschool age asthma, children up to 4 years of age enrolled in the Canadian Healthy Infant Longitudinal Development (CHILD) study were classified as asthmatic (n=39) or matched healthy controls (n=37). 16S rRNA sequencing and quantitative PCR (qPCR) were used to analyse the composition of the 3-month and 1-year gut microbiome of these children. At 3 months the abundance of the genus, Lachnospira (L), was decreased (P=0.008), whereas the abundance of the species, Clostridium neonatale (C), was increased (P=0.07) in asthmatics. Quartile analysis of stool composition at 3-months revealed a negative association between the ratio of these two bacteria (L/C) and asthma risk by 4 years of age [quartile 1: odds ratio (OR)=15, P=0.02, CI (confidence interval)= 1.8–124.7 quartile 2: OR=1.0, ns quartile 3: OR=0.37, ns]. We conclude that opposing shifts in the relative abundances of Lachnospira and C. neonatale in the first 3 months of life are associated with preschool age asthma, and that the L/C ratio may serve as a potential early life biomarker to predict asthma development.
Publisher: BMJ
Date: 11-06-2015
DOI: 10.1136/THORAXJNL-2015-207246
Abstract: 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 s ling, 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, erse biological s les and rigorous phenotyping, will inform early developmental pathways to allergy, asthma and other chronic inflammatory diseases.
Publisher: Informa UK Limited
Date: 11-08-2020
Publisher: American Society for Microbiology
Date: 29-06-2021
Abstract: Recent evidence suggests an immunomodulatory role for commensal fungi (mycobiota) in the gut, yet little is known about the composition and dynamics of early-life gut fungal communities. In this work, we show for the first time that the composition of the gut mycobiota of Canadian infants changes dramatically over the course of the first year of life, is associated with environmental factors such as geographical location, diet, and season of birth, and can be used in conjunction with knowledge of a small number of key early-life factors to predict inhalant atopy status at age 5 years.
Publisher: European Respiratory Society (ERS)
Date: 08-11-2013
DOI: 10.1183/09031936.00005512
Abstract: The lung clearance index (LCI) is more sensitive than spirometry in detecting abnormal lung function in children with cystic fibrosis. LCI is thought to be independent of age, but recent evidence suggests that the upper limit of normal is higher in infants and preschool children than in older subjects. This study examines whether LCI remains independent of body size throughout childhood. Multiple-breath washout data from healthy children and adolescents were collated from three centres using the mass spectrometer system and the inert gas sulfur hexafluoride. Reference equations for LCI and functional residual capacity (FRC) were constructed using the LMS (lambda-mu-sigma) method. Data were available from 497 subjects (2 weeks to 19 years of age) tested on 659 occasions. LCI was dependent on body size, decreasing in a nonlinear pattern as height increased. Changes were particularly marked in the first 5 years of life. Height, age and sex were all independent predictors of FRC. Minimal between-centre differences allowed unified reference equations to be developed. LCI is not independent of body size. Although a constant upper normal limit would suffice for cross-sectional clinical assessments from 6 years of age, appropriate reference equations are essential for accurate interpretation of results during early childhood.
Publisher: Wiley
Date: 15-01-2020
DOI: 10.1111/CEA.13551
Abstract: 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. We determined the association between maternal depression and stress symptom trajectories and infant fecal sIgA concentrations. 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. 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 s ling, 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. 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.
Publisher: Elsevier BV
Date: 08-2020
Publisher: Wiley
Date: 28-09-2015
Abstract: Dysbiosis of the infant gut microbiota may have long-term health consequences. This study aimed to determine the impact of maternal intrapartum antibiotic prophylaxis (IAP) on infant gut microbiota, and to explore whether breastfeeding modifies these effects. Prospective pregnancy cohort of Canadian infants born in 2010-2012: the Canadian Healthy Infant Longitudinal Development (CHILD) Study. General community. Representative sub-s le of 198 healthy term infants from the CHILD Study. Maternal IAP exposures and birth method were documented from hospital records and breastfeeding was reported by mothers. Infant gut microbiota was characterised by Illumina 16S rRNA sequencing of faecal s les at 3 and 12 months. Infant gut microbiota profiles. In this cohort, 21% of mothers received IAP for Group B Streptococcus prophylaxis or pre-labour rupture of membranes another 23% received IAP for elective or emergency caesarean section (CS). Infant gut microbiota community structures at 3 months differed significantly with all IAP exposures, and differences persisted to 12 months for infants delivered by emergency CS. Taxon-specific composition also differed, with the genera Bacteroides and Parabacteroides under-represented, and Enterococcus and Clostridium over-represented at 3 months following maternal IAP. Microbiota differences were especially evident following IAP with emergency CS, with some changes (increased Clostridiales and decreased Bacteroidaceae) persisting to 12 months, particularly among non-breastfed infants. Intrapartum antibiotics in caesarean and vaginal delivery are associated with infant gut microbiota dysbiosis, and breastfeeding modifies some of these effects. Further research is warranted to explore the health consequences of these associations. Maternal #antibiotics during childbirth alter the infant gut #microbiome.
Publisher: Elsevier BV
Date: 06-2022
DOI: 10.1016/J.JACI.2021.10.039
Abstract: Wheezing in early life is associated with asthma in adulthood however, the determinants of wheezing trajectories and their associations with asthma and lung function in childhood remain poorly understood. In the CHILD Cohort Study, we aimed to identify wheezing trajectories and examine the associations between these trajectories, risk factors, and clinical outcomes at age 5 years. Wheeze data were collected at 8 time points from 3 months to 5 years of age. We used group-based trajectory models to derive wheeze trajectories among 3154 children. Associations with risk factors and clinical outcomes were analyzed by weighted regression models. We identified 4 trajectories: a never/infrequent trajectory, transient wheeze, intermediate-onset (preschool) wheeze, and persistent wheeze. Higher body mass index was a common risk factor for all wheeze trajectories compared with that in the never/infrequent group. The unique predictors for specific wheeze trajectories included male sex, lower respiratory tract infections, and day care attendance for transient wheeze paternal history of asthma, atopic sensitization, and child genetic risk score of asthma for intermediate wheeze and maternal asthma for persistent wheeze. Blood eosinophil counts were higher in children with the intermediate wheeze trajectory than in those children with the other trajectories at the ages of 1 and 5 years. All wheeze trajectories were associated with decreased lung function and increased risk of asthma at age 5 years. We identified 4 distinct trajectories in children from 3 months to 5 years of age, reflecting different phenotypes of early childhood wheeze. These trajectories were characterized by different biologic and physiologic traits and risk factors.
Publisher: Wiley
Date: 16-09-2021
DOI: 10.1111/PAI.13658
Abstract: 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. 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. Early CMV infection was associated with increased beta and decreased alpha ersity of the gut microbiota. Both changes in ersity 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. 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.
Publisher: Cold Spring Harbor Laboratory
Date: 02-03-2023
DOI: 10.1101/2023.03.02.530668
Abstract: Accumulating evidence suggests prenatal air pollution exposure alters DNA methylation (DNAm), which could go on to affect long-term health. However, it remains unclear whether prenatal DNAm alterations persist through early life. Identifying DNAm changes that persist from birth into childhood would provide greater insight into the molecular mechanisms that most likely contribute to the association of prenatal air pollution exposure with health outcomes such as atopic disease. This study investigated the persistence of DNAm changes associated with prenatal NO 2 exposure (a surrogate measure of traffic-related air pollution) at age one to begin characterizing which DNAm changes most likely to contribute to atopic disease. We used an atopy-enriched subset of CHILD study participants (N=145) to identify in idual and regional cord blood DNAm differences associated with prenatal NO 2 , followed by an investigation of persistence in age one peripheral blood. As we had repeated DNAm measures, we also isolated postnatal-specific DNAm changes and examined their association with NO 2 exposure in the first year of life. MANOVA tests were used to examine the association between DNAm changes associated with NO 2 and child wheeze and atopy. We identified 24 regions of altered cord blood DNAm, with several annotated to HOX genes. Two regions annotated to MPDU1 and C5orf63 were significantly associated with age one wheeze. Further, we found the effect of prenatal NO 2 exposure across CpGs within all altered regions remained similar at age one. A single region of postnatal-specific DNAm annotated to HOXB6 was associated with year one NO 2 and age one atopy. Regional cord blood DNAm changes associated with prenatal NO 2 exposure persist through at least the first year of life, and some of these changes are associated with age one wheeze. The early-postnatal period remains a sensitive window to DNAm perturbations that may also influence child health.
Publisher: Wiley
Date: 25-05-2018
DOI: 10.1111/IJPO.12291
Abstract: Maternal overweight or obesity (OWOB) is linked to gestational diabetes, fetal macrosomia and higher rates of caesarean delivery. The study aims to assess whether maternal pre-pregnancy OWOB is associated with infant overweight in a sex-dependent manner, independent of microbiota-altering variables. Weight and length measurements of 955 mother-infant pairs were obtained from the Canadian Healthy Infant Longitudinal Development cohort. Maternal pre-pregnancy weight was defined as follows: normal, overweight (25 ≤ body mass index 97th percentile were classified as infant overweight at age 1 year. Associations between pre-pregnancy and infant overweight were determined by linear and logistic regression, adjusting for covariates. Maternal pre-pregnancy OWOB were associated with infant weight-for-length and overweight risk at 1 year. Except for pre-pregnancy obesity, these associations were not attenuated appreciably after adjustment for birth mode, exclusivity of breastfeeding, exposure to antibiotics and infant sex. Yet only boys born to mothers with obesity were three times more likely to become overweight at age 1 independent of microbiota-altering variables. Pre-pregnancy obesity was associated with weight-for-length in male and female infants. Maternal pre-pregnancy OWOB increases the risk of infant overweight, and this association is more evident in male infants.
Publisher: Elsevier BV
Date: 08-2018
DOI: 10.1016/J.SLEEP.2018.04.005
Abstract: Both short sleep duration and sleep-disordered breathing (SDB) are associated with poor neurocognitive development. However, the co-contributions of short sleep duration and SDB on neurodevelopment in pre-school children are relatively unknown. We assessed both sleep duration and SDB by quarterly questionnaire from three months to two years of age among Canadian Healthy Infant Longitudinal Development (CHILD) birth cohort participants. Group-based modeling determined trajectories of total, daytime, and nighttime sleep duration and SDB. Linear regression was used to assess the impact of sleep duration and SDB trajectories on cognitive (primary outcome) and language (secondary) development at two years of age as assessed by the Bayley Scale of Infant Development (BSID-III) (mean 100 standard deviation of 15). Of the 822 CHILD Edmonton participants, 703 (86%) were still enrolled at two years of age with 593 having BSID-III data at two years of age. Trajectory analysis identified four total sleep durations phenotypes [short sleepers (17.9%), decline to short sleepers (21.1%), intermediate sleepers (36.9%) and long sleepers (24.1%)]. Compared to children with intermediate sleep durations, short sleepers had a 5.2-point lower cognitive development score at two years of age [standard error (SE) 1.7 p = 0.002]. Nocturnal sleep duration, compared to daytime sleep duration had the greatest effect on cognitive development. We also identified three SDB symptom trajectories [early-onset SDB (15.7%), late-onset SDB (14.2%), and persistent SDB (5.3%)] and 79.5% of children had no SDB symptoms. Children with persistent SDB also had a 5.3-point lower language score (SE 2.7 p = 0.05) compared to children with no SDB. SDB trajectories were not associated with cognitive development. In a population-representative birth cohort study, both short sleep duration and SDB were associated with adverse neurodevelopment at two years of age. Children with short nighttime sleep duration had lowered cognitive and language scores and children with persistent SDB also had lower language scores.
Publisher: American Medical Association (AMA)
Date: 04-2018
Publisher: Frontiers Media SA
Date: 13-10-2022
DOI: 10.3389/FIMMU.2022.977470
Abstract: The human milk proteome comprises a vast number of proteins with immunomodulatory functions, but it is not clear how this relates to allergy of the mother or allergy development in the breastfed infant. This study aimed to explore the relation between the human milk proteome and allergy of both mother and child. Proteins were analyzed in milk s les from a subset of 300 mother-child dyads from the Canadian CHILD Cohort Study, selected based on maternal and child allergy phenotypes. For this selection, the definition of “allergy” included food allergy, eczema, allergic rhinitis, and asthma. Proteins were analyzed with non-targeted shotgun proteomics using filter-aided s le preparation (FASP) and nanoLC-Orbitrap-MS/MS. Protein abundances, based on label-free quantification, were compared using multiple statistical approaches, including univariate, multivariate, and network analyses. Using univariate analysis, we observed a trend that milk for infants who develop an allergy by 3 years of age contains higher abundances of immunoglobulin chains, irrespective of the allergy status of the mother. This observation suggests a difference in the milk’s immunological potential, which might be related to the development of the infant’s immune system. Furthermore, network analysis showed overall increased connectivity of proteins in the milk of allergic mothers and milk for infants who ultimately develop an allergy. This difference in connectivity was especially noted for proteins involved in the protein translation machinery and may be due to the physiological status of the mother, which is reflected in the interconnectedness of proteins in her milk. In addition, it was shown that network analysis complements the other methods for data analysis by revealing complex associations between the milk proteome and mother-child allergy status. Together, these findings give new insights into how the human milk proteome, through differences in the abundance of in idual proteins and protein-protein associations, relates to the allergy status of mother and child. In addition, these results inspire new research directions into the complex interplay of the mother-milk-infant triad and allergy.
Publisher: European Respiratory Society (ERS)
Date: 08-02-2013
DOI: 10.1183/09031936.00069712
Abstract: Inert gas washout tests, performed using the single- or multiple-breath washout technique, were first described over 60 years ago. As measures of ventilation distribution inhomogeneity, they offer complementary information to standard lung function tests, such as spirometry, as well as improved feasibility across wider age ranges and improved sensitivity in the detection of early lung damage. These benefits have led to a resurgence of interest in these techniques from manufacturers, clinicians and researchers, yet detailed guidelines for washout equipment specifications, test performance and analysis are lacking. This manuscript provides recommendations about these aspects, applicable to both the paediatric and adult testing environment, whilst outlining the important principles that are essential for the reader to understand. These recommendations are evidence based, where possible, but in many places represent expert opinion from a working group with a large collective experience in the techniques discussed. Finally, the important issues that remain unanswered are highlighted. By addressing these important issues and directing future research, the hope is to facilitate the incorporation of these promising tests into routine clinical practice.
Publisher: Frontiers Media SA
Date: 10-04-2017
Publisher: European Respiratory Society (ERS)
Date: 11-2017
DOI: 10.1183/13993003.00280-2017
Abstract: Asthma during pregnancy is associated with retardation of fetal growth in a sex-specific manner. Lactobacilli microbes influence infant growth. This study aimed to determine whether lactobacilli and other microbes are reduced in the gut of infants born to an asthmatic mother, and whether this differs by the sex of the infant. Mother-infant pairs (N=1021) from the Canadian Healthy Infant Longitudinal Development full-term cohort were studied. The abundance of infant faecal microbiota at 3–4 months, profiled by gene sequencing, was compared between both women with and without asthma treatment during pregnancy. Infant sex, maternal ethnicity, pre-pregnancy overweight and atopy status, birth mode, breastfeeding status and intrapartum antibiotic treatment were tested as covariates. Independent of birth mode and other covariates, male, Caucasian infants born to women with prenatal asthma harboured fewer lactobacilli in the gut at 3–4 months of age. If asthmatic mothers had pre-pregnancy overweight, the abundance of Lactobacillus in males was further reduced in the infant gut, whereas the microbiota of female infants was enriched with Bacteroidaceae . Similar differences in infant gut microbial composition according to maternal prenatal asthma status were also more evident among women with food or environmental allergies. Gut lactobacilli were less abundant in male infants, but Bacteroidaceae were more abundant in female infants at 3–4 months of age, following maternal asthma during pregnancy.
Publisher: Frontiers Media SA
Date: 06-09-2022
Abstract: Food sensitization is a first and strong indicator of immune deviation in the progression to other allergic conditions. Sensitization to food or other allergens and related inflammation during critical windows of infant development may adversely affect neurodevelopmental milestones. However, additional research is needed to test this association further. Associations between atopic (any food or aeroallergen) or food sensitization (specific to egg, soybean, peanut, and milk) at age 1 year and neurodevelopment up to 2 years of age were evaluated in the national CHILD Cohort Study, with a secondary aim examining whether these associations were sex-specific. Food and atopic sensitization were assessed by skin prick tests (SPT) in 1-year-old infants, with neurodevelopment assessed using the cognitive, language, motor, and social-emotional subscales of the Bayley Scales of Infant Development (BSID-III) administered at 1 and 2 years of age. Atopic sensitization was present among 16.4% of infants, while 13.4% had food sensitizations. Only socioemotional scores reached statistical significance among the four BSID-III domains. Both atopic and food sensitization at 1 year of age was associated with lower social-emotional scores, independent of the infant's ethnicity. These findings were sex-specific and only observed among boys, among whom social-emotional scores were lowered by 5 points if atopic sensitization was present (−5.22 [95% CI: −9.96, −0.47], p = 0.03) or if food sensitization was present (−4.85 [95% CI: −9.82,0.11], p = 0.06). Similar results were observed using the standard SPT cut-off of ≥3 mm — for atopic sensitization (−5.17 [95% CI: −11.14, −0.80], p = 0.09) and for food sensitization (−4.61 [95% CI: −10.96, 1.74], p = 0.15). In our study of term infants, we found an inverse, cross-sectional association between atopic and food sensitization status and social-emotional development scores in male children but not female children.
Publisher: Springer Science and Business Media LLC
Date: 26-06-2021
DOI: 10.1038/S41370-021-00350-4
Abstract: As smoking prevalence has decreased in Canada, particularly during pregnancy and around children, and technological improvements have lowered detection limits, the use of traditional tobacco smoke biomarkers in infant populations requires re-evaluation. We evaluated concentrations of urinary nicotine biomarkers, cotinine and trans -3’-hydroxycotinine (3HC), and questionnaire responses. We used machine learning and prediction modeling to understand sources of tobacco smoke exposure for infants from the CHILD Cohort Study. Multivariable linear regression models, chosen through a combination of conceptual and data-driven strategies including random forest regression, assessed the ability of questionnaires to predict variation in urinary cotinine and 3HC concentrations of 2017 3-month-old infants. Although only 2% of mothers reported smoking prior to and throughout their pregnancy, cotinine and 3HC were detected in 76 and 89% of the infants’ urine ( n = 2017). Questionnaire-based models explained 31 and 41% of the variance in cotinine and 3HC levels, respectively. Observed concentrations suggest 0.25 and 0.50 ng/mL as cut-points in cotinine and 3HC to characterize SHS exposure. This cut-point suggests that 23.5% of infants had moderate or regular smoke exposure. Though most people make efforts to reduce exposure to their infants, parents do not appear to consider the pervasiveness and persistence of secondhand and thirdhand smoke. More than half of the variation in urinary cotinine and 3HC in infants could not be predicted with modeling. The pervasiveness of thirdhand smoke, the potential for dermal and oral routes of nicotine exposure, along with changes in public perceptions of smoking exposure and risk warrant further exploration.
Publisher: BMJ
Date: 15-06-2018
DOI: 10.1136/THORAXJNL-2017-211351
Abstract: The care of infants with recurrent wheezing relies largely on clinical assessment. The lung clearance index (LCI), a measure of ventilation inhomogeneity, is a sensitive marker of early airway disease in children with cystic fibrosis, but its utility has not been explored in infants with recurrent wheezing. To assess ventilation inhomogeneity using LCI among infants with a history of recurrent wheezing compared with healthy controls. This is a case–control study, including 37 infants with recurrent wheezing recruited from outpatient clinics, and 113 healthy infants from a longitudinal birth cohort, the Canadian Healthy Infant Longitudinal Development study. All infants, at a time of clinical stability, underwent functional assessment including multiple breath washout, forced expiratory flows and body plethysmography. LCI z-score values among infants with recurrent wheeze were 0.84 units (95% CI 0.41 to 1.26) higher than healthy infants (mean (95% CI): 0.26 (−0.11 to 0.63) vs −0.58 (−0.79 to 0.36), p .001)). Nineteen percent of recurrently wheezing infants had LCI values that were above the upper limit of normal ( .64 z-scores). Elevated exhaled nitric oxide, but not symptoms, was associated with abnormal LCI values in infants with recurrent wheeze (p=0.05). Ventilation inhomogeneity is present in clinically stable infants with recurrent wheezing.
Publisher: European Respiratory Society (ERS)
Date: 31-10-2013
Publisher: Springer Science and Business Media LLC
Date: 03-2014
Publisher: American Medical Association (AMA)
Date: 06-10-2022
DOI: 10.1001/JAMANETWORKOPEN.2022.34714
Abstract: Despite advances in asthma therapeutics, the burden remains highest in preschool children therefore, it is critical to identify primary care tools that distinguish preschool children at high risk for burdensome disease for further evaluation. Current asthma prediction tools, such as the modified Asthma Predictive Index (mAPI), require invasive tests, limiting their applicability in primary care and low-resource settings. To develop and evaluate the use of a symptom-based screening tool to detect children at high risk of asthma, persistent wheeze symptoms, and health care burden. The cohort for this diagnostic study included participants from the CHILD Study (n = 2511) from January 1, 2008, to December 31, 2012, the Raine Study from January 1, 1989, to December 31, 2012 (n = 2185), and the Canadian Asthma Primary Prevention Study (CAPPS) from January 1, 1989, to December 31, 1995 (n = 349), with active follow-up to date. Data analysis was performed from November 1, 2019, to May 31, 2022. The CHILDhood Asthma Risk Tool (CHART) identified factors associated with asthma in patients at 3 years of age (timing and number of wheeze or cough episodes, use of asthma medications, and emergency department visits or hospitalizations for asthma or wheeze) to identify children with asthma or persistent symptoms at 5 years of age. Within the CHILD Study cohort, CHART was evaluated against specialist clinician diagnosis and the mAPI. External validation was performed in both a general population cohort (Raine Study [Australia]) and a high-risk cohort (CAPPS [Canada]). Predictive accuracy was measured by sensitivity, specificity, area under the receiver operating characteristic curve (AUROC), and positive and negative predicted values. Among 2511 children (mean [SD] age at 3-year clinic visit, 3.08 [0.17] years 1324 [52.7%] male 1608 of 2476 [64.9%] White) with sufficient questionnaire data to apply CHART at 3 years of age, 2354 (93.7%) had available outcome data at 5 years of age. CHART applied in the CHILD Study at 3 years of age outperformed physician assessments and the mAPI in predicting persistent wheeze (AUROC, 0.94 95% CI, 0.90-0.97), asthma diagnosis (AUROC, 0.73 95% CI, 0.69-0.77), and health care use (emergency department visits or hospitalization for wheeze or asthma) (AUROC, 0.70 95% CI, 0.61-0.78). CHART had a similar predictive performance for persistent wheeze in the Raine Study (N = 2185) in children at 5 years of age (AUROC, 0.82 95% CI, 0.79-0.86) and CAPPS (N = 349) at 7 years of age (AUROC, 0.87 95% CI, 0.80-0.94). In this diagnostic study, CHART was able to identify children at high risk of asthma at as early as 3 years of age. CHART could be easily incorporated as a routine screening tool in primary care to identify children who need monitoring, timely symptom control, and introduction of preventive therapies.
Publisher: Cambridge University Press (CUP)
Date: 09-12-2020
DOI: 10.1017/S2040174420001129
Abstract: New guidelines for peanut allergy prevention in high-risk infants recommend introducing peanut during infancy but do not address breastfeeding or maternal peanut consumption. We assessed the independent and combined association of these factors with peanut sensitization in the general population CHILD birth cohort ( N = 2759 mother–child dyads). Mothers reported peanut consumption during pregnancy, timing of first infant peanut consumption, and length of breastfeeding duration. Child peanut sensitization was determined by skin prick testing at 1, 3, and 5 years. Overall, 69% of mothers regularly consumed peanuts and 36% of infants were fed peanut in the first year (20% while breastfeeding and 16% after breastfeeding cessation). Infants who were introduced to peanut early (before 1 year) after breastfeeding cessation had a 66% reduced risk of sensitization at 5 years compared to those who were not (1.9% vs. 5.8% sensitization aOR 0.34, 95% CI 0.14–0.68). This risk was further reduced if mothers introduced peanut early while breastfeeding and regularly consumed peanut themselves (0.3% sensitization aOR 0.07, 0.01–0.25). In longitudinal analyses, these associations were driven by a higher odds of outgrowing early sensitization and a lower odds of late-onset sensitization. There was no apparent benefit (or harm) from maternal peanut consumption without breastfeeding. Taken together, these results suggest the combination of maternal peanut consumption and breastfeeding at the time of peanut introduction during infancy may help to decrease the risk of peanut sensitization. Mechanistic and clinical intervention studies are needed to confirm and understand this “triple exposure” hypothesis.
Publisher: Wiley
Date: 02-07-2018
DOI: 10.1111/ALL.13476
Publisher: Wiley
Date: 08-2017
DOI: 10.1111/PAI.12739
Abstract: The effect of infant feeding practices on the development of food allergy remains controversial. We examined the relationship between timing and patterns of food introduction and sensitization to foods at age 1 year in the Canadian Healthy Infant Longitudinal Development (CHILD) birth cohort study. Nutrition questionnaire data prospectively collected at age 3, 6, 12, 18, and 24 months were used to determine timing of introduction of cow's milk products, egg, and peanut. At age 1 year, infants underwent skin prick testing to cow's milk, egg white, and peanut. Logistic regression models were fitted to assess the impact of timing of food exposures on sensitization outcomes, and latent class analysis was used to study patterns of food introduction within the cohort. Among 2124 children with sufficient data, delaying introduction of cow's milk products, egg, and peanut beyond the first year of life significantly increased the odds of sensitization to that food (cow's milk adjOR 3.69, 95% CI 1.37-9.08 egg adjOR 1.89, 95% CI 1.25-2.80 peanut adjOR 1.76, 95% CI 1.07-3.01). Latent class analysis produced a three-class model: early, usual, and delayed introduction. A pattern of delayed introduction, characterized by avoidance of egg and peanut during the first year of life, increased the odds of sensitization to any of the three tested foods (adjOR 1.78, 95% CI 1.26-2.49). Avoidance of potentially allergenic foods during the first year of life significantly increased the odds of sensitization to the corresponding foods.
Publisher: Elsevier BV
Date: 05-2021
Publisher: Elsevier BV
Date: 07-2019
DOI: 10.1016/J.JSAMS.2019.01.003
Abstract: Primary: examine associations between meeting the 24-Hour Movement Guidelines for the Early Years and behavioral and emotional problems in a large s le of 3-year-old children. Secondary: determine the proportion of children meeting the Canadian 24-Hour Movement Guidelines. Cross-sectional. Participants were 3-year olds (n=539) from the Edmonton site of the Canadian Healthy Infant Longitudinal Development (CHILD) birth cohort. Physical activity and sleep duration were accelerometer-derived while screen time was parent-reported. Meeting the overall guidelines was defined as: (1) ≥180min/day of total physical activity, including 60min/day of moderate- to vigorous-intensity physical activity, (2) ≤1h/day of screen time, and (3) 10-13h of sleep per 24-hour period. Externalizing, internalizing, and total problem scores (lower scores representing fewer problems) were calculated from the parent-reported Child Behavior Checklist (CBCL). Descriptive statistics and linear regression models were completed. Only 5% of children met the overall guidelines (all three recommendations), with 19.3%, 50.5%, and 83.1% meeting the physical activity, screen time, and sleep recommendations, respectively. Meeting more recommendations was associated with lower scores for total (B=-1.78, 95%CI: -3.03, -0.54), externalizing (B=-1.51, 95%CI: -2.80, -0.22) and internalizing (B=-1.35, 95%CI: -2.60, -0.01) problems. Similar findings were also observed for the specific combinations of: (1) physical activity and screen time and (2) sleep duration and screen time. Meeting more recommendations within the 24-hour Movement Guidelines was associated with fewer behavioral and emotional problems at 3-years. Few 3-year-olds met the overall guidelines. Findings support an integrated approach for healthy growth and development.
Publisher: CMA Joule Inc.
Date: 17-02-2020
DOI: 10.1503/CMAJ.190819
Publisher: American Thoracic Society
Date: 10-2020
Publisher: Scientific and Practical Reviewed Journal Pulmonology
Date: 10-06-2021
DOI: 10.18093/0869-0189-2021-31-3-272-295
Abstract: This document provides clinical recommendations for the management of severe asthma. Comprehensive evidence syntheses, including metaanalyses, were performed to summarise all available evidence relevant to the European Respiratory Society/American Thoracic Society Task Force’s questions. The evidence was appraised using the GRADE (Grading of Recommendations, Assessment, Development and Evaluation) approach and the results were summarised in evidence profiles. The evidence syntheses were discussed and recommendations formulated by a multidisciplinary Task Force of asthma experts, who made specific recommendations on six specific questions. After considering the balance of desirable and undesirable consequences, quality of evidence, feasibility, and acceptability of various interventions, the Task Force made the following recommendations: • suggest using anti-interleukin (IL)-5 and anti-IL-5 receptor α for severe uncontrolled adult eosinophilic asthma phenotypes • suggest using a blood eosinophil cut-point ≥150 μL −1 to guide anti-IL-5 initiation in adult patients with severe asthma • suggest considering specific eosinophil (≥260 μL −1 ) and exhaled nitric oxide fraction (≥19.5 ppb) cut-offs to identify adolescents or adults with the greatest likelihood of response to anti-IgE therapy • suggest using inhaled tiotropium for adolescents and adults with severe uncontrolled asthma despite Global Initiative for Asthma (GINA) step 4 – 5 or National Asthma Education and Prevention Program (NAEPP) step 5 therapies • suggest a trial of chronic macrolide therapy to reduce asthma exacerbations in persistently symptomatic or uncontrolled patients on GINA step 5 or NAEPP step 5 therapies, irrespective of asthma phenotype • suggest using anti-IL-4/13 for adult patients with severe eosinophilic asthma and for those with severe corticosteroid-dependent asthma regardless of blood eosinophil levels. These recommendations should be reconsidered as new evidence becomes available.
Publisher: MDPI AG
Date: 27-09-2022
Abstract: Limited data exist on pharmaceutical product use by infants, although available data suggests higher prevalence of use among children under 12 months of age. We conducted a descriptive study of 3050 infants recruited in the CHILD Cohort Study, a prospective, multicenter, longitudinal cohort following children from pregnancy through childhood. Parents were surveyed for use of prescription and over-the-counter drugs, and natural health products (NHPs, including homeopathic products and vitamins) at 3, 6, and 12 months after delivery. By one year of age, 96.0% of children had taken at least one pharmaceutical product. Among 307 reported products, 32 were given to at least 1% of cohort infants. Vitamin D, acetaminophen, ibuprofen, topical hydrocortisone, amoxicillin, and nystatin were the most common medications and natural health products (NHPs) received, with 8/32 of the most frequently used products being NHPs. Overall, 14.7% of pharmaceutical products administered to children were off-label and 35.8% were NHPs or products without a Drug Identification Number (DIN). The use of over-the-counter medications and NHPs is common and off-label use of drugs is frequent, even in the first year of life. This study highlights the importance of conducting studies on medication use in infants, and of infant medication use monitoring by healthcare providers.
Publisher: American Chemical Society (ACS)
Date: 28-05-2021
Publisher: Cold Spring Harbor Laboratory
Date: 27-07-2019
DOI: 10.1101/713974
Abstract: Overweight and obesity affect over 20% of children worldwide. Emerging evidence shows that nonnutritive sweeteners (NNS) could adversely influence weight gain and metabolic health, particularly during critical periods of development. Thus, we aimed to investigate the impact of prenatal NNS exposure on postnatal growth and adiposity. Among 2298 families participating in the CHILD cohort study, children born to mothers who regularly consumed NNS during pregnancy had elevated body mass index and adiposity at 3 years of age. In a complementary study designed to eliminate confounding by human lifestyle factors and investigate causal mechanisms, we exposed pregnant mice and cultured adipocytes to NNS (aspartame or sucralose) at doses relevant to human consumption. In mice, maternal NNS exposure caused elevated body weight, adiposity and insulin resistance in offspring, especially in males. Further, in 3T3-L1 pre-adipocyte cells, sucralose exposure during early stages of differentiation caused increased lipid accumulation and expression of adipocyte differentiation genes (e.g. C/EBP-α, FABP4, FAS). The same genes were upregulated in the adipose tissue of male mouse offspring born to sucralose-fed dams. Together, these clinical and experimental findings provide evidence suggesting that maternal NNS consumption induces obesity risk in the offspring through effects on adiposity and adipocyte differentiation. Maternal consumption of non-nutritive sweeteners during pregnancy stimulates adipocyte differentiation, insulin resistance, weight gain, and adiposity in mouse and human offspring.
Publisher: Elsevier BV
Date: 12-2019
DOI: 10.1093/AJCN/NQZ229
Publisher: European Respiratory Society (ERS)
Date: 06-11-2020
Publisher: Springer Science and Business Media LLC
Date: 15-04-2022
DOI: 10.1038/S41366-022-01117-Z
Abstract: The steep rise in childhood obesity has emerged as a worldwide public health problem. The first 4 years of life are a critical window where long-term developmental patterns of body mass index (BMI) are established and a critical period for microbiota maturation. Understanding how the early-life microbiota relate to preschool growth may be useful for identifying preventive interventions for childhood obesity. We aim to investigate whether longitudinal shifts within the bacterial community between 3 months and 1 year of life are associated with preschool BMI z -score trajectories. BMI trajectories from birth to 5 years of age were identified using group-based trajectory modeling in 3059 children. Their association with familial and environmental factors were analyzed. Infant gut microbiota at 3 months and 1 year was defined by 16S RNA sequencing and changes in ersity and composition within each BMIz trajectory were analyzed. Four BMIz trajectories were identified: low stable, normative, high stable, and rapid growth. Infants in the rapid growth trajectory were less likely to have been breastfed, and gained less microbiota ersity in the first year of life. Relative abundance of Akkermansia increased with age in children with stable growth, but decreased in those with rapid growth, abundance of Ruminococcus and Clostridium at 1 year were elevated in children with rapid growth. Children who were breastfed at 6 months had increased levels of Sutterella , and decreased levels of Ruminococcus and Clostridium . This study provides new insights into the relationship between the gut microbiota in infancy and patterns of growth in a cohort of preschool Canadian children. We highlight that rapid growth since birth is associated with bacteria shown in animal models to have a causative role in weight gain. Our findings support a novel avenue of research targeted on tangible interventions to reduce childhood obesity.
Publisher: Elsevier BV
Date: 02-2018
DOI: 10.1016/J.BBI.2017.10.007
Abstract: Secretory Immunoglobulin A (sIgA) plays a critical role to infant gut mucosal immunity. Delayed IgA production is associated with greater risk of allergic disease. Murine models of stressful events during pregnancy and infancy show alterations in gut immunity and microbial composition in offspring, but little is known about the stress-microbiome-immunity pathways in humans. We investigated differences in infant fecal sIgA concentrations according to the presence of maternal depressive symptoms during and after pregnancy. A subs le of 403 term infants from the Canadian Healthy Infant Longitudinal Development (CHILD) cohort were studied. Their mothers completed the Center of Epidemiologic Studies Depression Scale when enrolled prenatally and again postpartum. Quantified by Immundiagnostik sIgA ELISA kit, sIgA from infant stool was compared across maternal depressive symptom categories using Mann-Whitney U-tests and logistic regression models that controlled for various covariates. Twelve percent of women reported clinically significant depressive symptoms only prenatally, 8.7% had only postpartum symptoms and 9.2% had symptoms both pre and postnatally. Infants born to mothers with pre and postnatal symptoms had significantly lower median sIgA concentrations than those in the reference group (4.4 mg/g feces vs. 6.3 mg/g feces p = 0.033). The odds for sIgA concentrations in the lowest quartile was threefold higher (95% CI: 1.25-7.55) when mothers had pre and postnatal symptoms, after controlling for breastfeeding status, infant age, antibiotics exposure and other covariates. Postnatal symptoms were not associated with fecal sIgA, independently of breastfeeding status. Infants born to mothers with depressive symptoms appear to have lower fecal sIgA concentrations, predisposing them to higher risk for allergic disease.
Publisher: International Scientific Research Publications MY SDN. BHD.
Date: 20-05-2016
Publisher: Elsevier BV
Date: 12-2022
DOI: 10.1016/J.SLEEP.2022.09.015
Abstract: 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. 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 ersistent SRBD versus no/early SRBD (reference). An algorithm was subsequently generated to predict late ersistent 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] Of the 165 children with SRBD data, 40 participants had late ersistent SRBD. Seven urinary metabolites in addition to the SDBeasy score were confirmed as important for late ersistent 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 ersistent 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. We developed a predictive algorithm using a combination of questionnaires and urine metabolites at age three-years to identify children with late ersistent SRBD by five-years of age.
Publisher: Wiley
Date: 23-05-2018
DOI: 10.1002/PPUL.24063
Abstract: Pulmonary function testing is commonly performed for diagnosis and clinical management of respiratory diseases. It is important to use appropriate reference equations from healthy subjects for interpretation of data from infants with lung disease. This study aimed to determine if published reference equations were similar to forced flow measures and plethysmographic infant pulmonary function testing data collected in the Canadian Healthy Infant Longitudinal Development (CHILD) Study. Reference equations for five pulmonary function variables (FEV The current analysis included 131 infants (on 181 test occasions) with forced flow measures and 161 infants (on 246 test occasions) with plethysmography measures, aged 3-24 months. Age and length were major determinants of both forced flow and plethysmography measures. In addition, ethnicity (Caucasian vs non-Caucasian) was significantly associated with FEV Our current data support the need for population and device specific reference data for infant pulmonary function studies. By deriving new equipment-specific reference equations for our healthy population, we provide normative data to other centers utilizing this equipment.
Publisher: American Thoracic Society
Date: 04-2013
Publisher: European Respiratory Society (ERS)
Date: 26-09-2019
DOI: 10.1183/13993003.00588-2019
Abstract: This document provides clinical recommendations for the management of severe asthma. Comprehensive evidence syntheses, including meta-analyses, were performed to summarise all available evidence relevant to the European Respiratory Society/American Thoracic Society Task Force's questions. The evidence was appraised using the GRADE (Grading of Recommendations, Assessment, Development and Evaluation) approach and the results were summarised in evidence profiles. The evidence syntheses were discussed and recommendations formulated by a multidisciplinary Task Force of asthma experts, who made specific recommendations on six specific questions. After considering the balance of desirable and undesirable consequences, quality of evidence, feasibility, and acceptability of various interventions, the Task Force made the following recommendations: 1) suggest using anti-interleukin (IL)-5 and anti-IL-5 receptor α for severe uncontrolled adult eosinophilic asthma phenotypes 2) suggest using a blood eosinophil cut-point ≥150 μL −1 to guide anti-IL-5 initiation in adult patients with severe asthma 3) suggest considering specific eosinophil (≥260 μL −1 ) and exhaled nitric oxide fraction (≥19.5 ppb) cut-offs to identify adolescents or adults with the greatest likelihood of response to anti-IgE therapy 4) suggest using inhaled tiotropium for adolescents and adults with severe uncontrolled asthma despite Global Initiative for Asthma (GINA) step 4–5 or National Asthma Education and Prevention Program (NAEPP) step 5 therapies 5) suggest a trial of chronic macrolide therapy to reduce asthma exacerbations in persistently symptomatic or uncontrolled patients on GINA step 5 or NAEPP step 5 therapies, irrespective of asthma phenotype and 6) suggest using anti-IL-4/13 for adult patients with severe eosinophilic asthma and for those with severe corticosteroid-dependent asthma regardless of blood eosinophil levels. These recommendations should be reconsidered as new evidence becomes available.
Publisher: Elsevier BV
Date: 02-2018
DOI: 10.1016/J.JACI.2017.08.024
Abstract: The atopic march describes the progression from atopic dermatitis during infancy to asthma and allergic rhinitis in later childhood. In a Canadian birth cohort we investigated whether concomitant allergic sensitization enhances subsequent development of these allergic diseases at age 3 years. Children completed skin prick testing at age 1 year. Children were considered sensitized if they produced a wheal 2 mm or larger than that elicited by the negative control to any of 10 inhalant or food allergens. Children were also assessed for atopic dermatitis by using the diagnostic criteria of the UK Working Party. At age 3 years, children were assessed for asthma, allergic rhinitis, food allergy, and atopic dermatitis. Data from 2311 children were available. Atopic dermatitis without allergic sensitization was not associated with an increased risk of asthma at age 3 years after adjusting for common confounders (relative risk [RR], 0.46 95% CI, 0.11-1.93). Conversely, atopic dermatitis with allergic sensitization increased the risk of asthma more than 7-fold (RR, 7.04 95% CI, 4.13-11.99). Atopic dermatitis and allergic sensitization had significant interactions on both the additive (relative excess risk due to interaction, 5.06 95% CI, 1.33-11.04) and multiplicative (ratio of RRs, 5.80 95% CI, 1.20-27.83) scales in association with asthma risk. There was also a positive additive interaction between atopic dermatitis and allergic sensitization in their effects on food allergy risk (relative excess risk due to interaction, 15.11 95% CI, 4.19-35.36). Atopic dermatitis without concomitant allergic sensitization was not associated with an increased risk of asthma. In combination, atopic dermatitis and allergic sensitization had strong interactive effects on both asthma and food allergy risk at age 3 years.
Publisher: Wiley
Date: 14-12-2021
DOI: 10.1111/PAI.13713
Abstract: The lung clearance index (LCI) is a measure of pulmonary function. Variable feasibility (50‐ %) 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. LCI was measured in a subcohort of the CHILD Cohort Study at age 3 years using SF 6 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). 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). LCI at age 3 was strongly associated with recurrent wheeze at age 3, and predictive of its persistence to age 5.
Publisher: Elsevier BV
Date: 11-2020
Publisher: Public Library of Science (PLoS)
Date: 26-01-2023
DOI: 10.1371/JOURNAL.PMED.1004036
Abstract: Preterm birth is the leading cause of perinatal morbidity and mortality and is associated with adverse developmental and long-term health outcomes, including several cardiometabolic risk factors and outcomes. However, evidence about the association of preterm birth with later body size derives mainly from studies using birth weight as a proxy of prematurity rather than an actual length of gestation. We investigated the association of gestational age (GA) at birth with body size from infancy through adolescence. We conducted a two-stage in idual participant data (IPD) meta-analysis using data from 253,810 mother–child dyads from 16 general population-based cohort studies in Europe (Denmark, Finland, France, Italy, Norway, Portugal, Spain, the Netherlands, United Kingdom), North America (Canada), and Australasia (Australia) to estimate the association of GA with body mass index (BMI) and overweight (including obesity) adjusted for the following maternal characteristics as potential confounders: education, height, prepregnancy BMI, ethnic background, parity, smoking during pregnancy, age at child’s birth, gestational diabetes and hypertension, and preecl sia. Pregnancy and birth cohort studies from the LifeCycle and the EUCAN-Connect projects were invited and were eligible for inclusion if they had information on GA and minimum one measurement of BMI between infancy and adolescence. Using a federated analytical tool (DataSHIELD), we fitted linear and logistic regression models in each cohort separately with a complete-case approach and combined the regression estimates and standard errors through random-effects study-level meta-analysis providing an overall effect estimate at early infancy ( .0 to 0.5 years), late infancy ( .5 to 2.0 years), early childhood ( .0 to 5.0 years), mid-childhood ( .0 to 9.0 years), late childhood ( .0 to 14.0 years), and adolescence ( .0 to 19.0 years). GA was positively associated with BMI in the first decade of life, with the greatest increase in mean BMI z-score during early infancy (0.02, 95% confidence interval (CI): 0.00 0.05, p 0.05) per week of increase in GA, while in adolescence, preterm in iduals reached similar levels of BMI (0.00, 95% CI: −0.01 0.01, p 0.9) as term counterparts. The association between GA and overweight revealed a similar pattern of association with an increase in odds ratio (OR) of overweight from late infancy through mid-childhood (OR 1.01 to 1.02) per week increase in GA. By adolescence, however, GA was slightly negatively associated with the risk of overweight (OR 0.98 [95% CI: 0.97 1.00], p 0.1) per week of increase in GA. Although based on only four cohorts ( n = 32,089) that reached the age of adolescence, data suggest that in iduals born very preterm may be at increased odds of overweight (OR 1.46 [95% CI: 1.03 2.08], p 0.05) compared with term counterparts. Findings were consistent across cohorts and sensitivity analyses despite considerable heterogeneity in cohort characteristics. However, residual confounding may be a limitation in this study, while findings may be less generalisable to settings in low- and middle-income countries. This study based on data from infancy through adolescence from 16 cohort studies found that GA may be important for body size in infancy, but the strength of association attenuates consistently with age. By adolescence, preterm in iduals have on average a similar mean BMI to peers born at term.
Publisher: Elsevier BV
Date: 02-2023
Publisher: Springer Science and Business Media LLC
Date: 19-06-2013
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 03-08-2021
Abstract: Breastfeeding in infancy is associated with lower cardiovascular disease risk in adulthood however, the amount of breastfeeding required to achieve this benefit is unknown. In 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. Although 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.
Publisher: Frontiers Media SA
Date: 16-05-2019
Publisher: Oxford University Press (OUP)
Date: 12-06-2020
Abstract: Machine learning (ML) may provide insights into the underlying sleep stages of accelerometer-assessed sleep duration. We examined associations between ML-sleep patterns and behavior problems among preschool children. Children from the CHILD Cohort Edmonton site with actigraphy and behavior data at 3-years (n = 330) and 5-years (n = 304) were included. Parent-reported behavior problems were assessed by the Child Behavior Checklist. The Hidden Markov Model (HMM) classification method was used for ML analysis of the accelerometer sleep period. The average time each participant spent in each HMM-derived sleep state was expressed in hours per day. We analyzed associations between sleep and behavior problems stratified by children with and without sleep-disordered breathing (SDB). Four hidden sleep states were identified at 3 years and six hidden sleep states at 5 years using HMM. The first sleep state identified for both ages (HMM-0) had zero counts (no movement). The remaining hidden states were merged together (HMM-mov). Children spent an average of 8.2 ± 1.2 h/day in HMM-0 and 2.6 ± 0.8 h/day in HMM-mov at 3 years. At age 5, children spent an average of 8.2 ± 0.9 h/day in HMM-0 and 1.9 ± 0.7 h/day in HMM-mov. Among SDB children, each hour in HMM-0 was associated with 0.79-point reduced externalizing behavior problems (95% CI −1.4, −0.12 p & 0.05), and a 1.27-point lower internalizing behavior problems (95% CI −2.02, −0.53 p & 0.01). ML-sleep states were not associated with behavior problems in the general population of children. Children with SDB who had greater sleep duration without movement had lower behavioral problems. The ML-sleep states require validation with polysomnography.
Publisher: Public Library of Science (PLoS)
Date: 06-10-2022
DOI: 10.1371/JOURNAL.PONE.0268229
Abstract: 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. 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 s le was ided 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. The participant s le 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). 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.
Publisher: eLife Sciences Publications, Ltd
Date: 20-04-2021
DOI: 10.7554/ELIFE.67740
Abstract: 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.
Publisher: Springer Science and Business Media LLC
Date: 22-10-2019
DOI: 10.1038/S41370-019-0182-X
Abstract: 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 s les 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.
Publisher: Frontiers Media SA
Date: 26-09-2017
Publisher: Springer Science and Business Media LLC
Date: 02-01-2019
DOI: 10.1007/S10995-018-2691-Y
Abstract: 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 r
Publisher: Elsevier BV
Date: 09-2016
DOI: 10.1016/J.MICINF.2016.05.001
Abstract: Colonization of infants with Clostridium difficile is on the rise. Although better tolerated by infants than adults, it is a risk factor for future allergic disease. The present study describes associations between infant fecal immunoglobulin A (IgA) and colonization with C. difficile in 47 infants enrolled in the Canadian Healthy Infant Longitudinal Development (CHILD) study. C. difficile colonization was observed in over half (53%) of the infants. Median IgA was lower in infants colonized with C. difficile (10.9 μg versus 25.5 μg per g protein p = 0.18). A smaller proportion of infants with IgA in the highest tertile were colonized with C. difficile compared to the other tertiles (31.3% versus 64.5%, p = 0.03). In unadjusted analysis, odds of colonization with C. difficile was reduced by 75% (OR 0.25 95% CI 0.07, 0.91 p = 0.04) among infants with IgA in the highest tertile compared to those in the other tertiles. Following adjustment for parity, birth mode and breastfeeding, this association was even stronger (aOR 0.17, 95% CI 0.03, 0.94, p = 0.04). Our study provides evidence that high fecal IgA, independent of breastfeeding, is associated with reduced likelihood of C. difficile colonization in infancy.
Publisher: Oxford University Press (OUP)
Date: 11-2017
DOI: 10.1093/SLEEP/ZSX177
Publisher: American Academy of Pediatrics (AAP)
Date: 10-2018
Abstract: 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. 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. 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. 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.
Publisher: MDPI AG
Date: 19-01-2023
DOI: 10.3390/BIOM13020200
Abstract: 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.
Publisher: Informa UK Limited
Date: 31-12-2020
Publisher: Public Library of Science (PLoS)
Date: 17-04-2019
Publisher: Wiley
Date: 24-09-2022
DOI: 10.1111/ALL.15516
Abstract: 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. 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 s les 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. 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. Overall, our results suggest that the early‐life, including prenatal, fecal microbiome modifies risk of asthma, especially asthma with onset by age 3 years.
Publisher: Elsevier BV
Date: 07-2021
Publisher: Elsevier BV
Date: 2020
DOI: 10.1016/J.JAIP.2019.09.039
Abstract: 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.
Publisher: Elsevier BV
Date: 06-2014
Publisher: Cold Spring Harbor Laboratory
Date: 03-06-2022
DOI: 10.1101/2022.06.01.22275859
Abstract: Preterm birth is the leading cause of perinatal morbidity and mortality, and is associated with adverse developmental and long-term health outcomes, including several cardio-metabolic risk factors. However, evidence about the association of preterm birth with later body size derives mainly from studies using birth weight as proxy of prematurity rather than actual length of gestation. We investigated the association of gestational age at birth (GA) with body size from infancy through adolescence. We conducted a two-stage In idual Participant Data (IPD) meta-analysis using data from 253,810 mother-children dyads from 16 general population-based cohort studies in Europe, North America and Australasia to estimate the association of GA with standardized Body Mass Index (BMI) and overweight (including obesity) adjusted for confounders. Using a federated analytical tool (DataSHIELD), we fitted linear and logistic regression models in each cohort separately, and combined the regression estimates and standard errors through random-effects study-level meta-analysis providing an overall effect estimate at early infancy ( .0-0.5 years), late infancy ( .5-2.0 years), early childhood ( .0-5.0 years), mid-childhood ( .0-9.0 years), late childhood ( .0-14.0 years) and adolescence ( .0-19.0 years). GA was positively associated with BMI in the first decade of life with mean differences in BMI z-score (0.01-0.02) per week of increase in GA, however preterm infants reached similar levels of BMI as term infants by adolescence. The association of GA with risk of overweight revealed a similar pattern of results from late infancy through mid-childhood with an increased odds of overweight (OR 1.01-1.02) per week increase in GA. By adolescence, however, GA was slightly negatively associated with risk of overweight (OR 0.98 [95% CI: 0.97:1.00]) per week of increase in GA, and children born very preterm had increased odds of overweight (OR 1.46 [95% CI: 1.03 2.08]) compared with term. The findings were consistent across cohorts and sensitivity analyses, despite considerable heterogeneity in cohort characteristics. Higher GA is potentially clinically important for higher BMI in infancy, while the association attenuates consistently with age. By adolescence, preterm children have on average a similar mean BMI to those born term.
Publisher: Springer Science and Business Media LLC
Date: 05-06-2020
DOI: 10.1186/S12866-020-01829-0
Abstract: 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 erse and viable bacteria, but few studies have assessed the ersity of fungi in human milk. Here we profiled mycobiota in milk from 271 mothers in the CHILD birth cohort and detected fungi in 58 (21.4%). S les 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. 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.
Publisher: Elsevier BV
Date: 12-2019
Publisher: American Medical Association (AMA)
Date: 07-2016
DOI: 10.1001/JAMAPEDIATRICS.2016.0301
Abstract: The consumption of artificial sweeteners has increased substantially in recent decades, including among pregnant women. Animal studies suggest that exposure to artificial sweeteners in utero may predispose offspring to develop obesity however, to our knowledge, this has never been studied in humans. To determine whether maternal consumption of artificially sweetened beverages during pregnancy is associated with infant body mass index (BMI [calculated as weight in kilograms ided by height in meters squared]). This cohort study included 3033 mother-infant dyads from the Canadian Healthy Infant Longitudinal Development (CHILD) Study, a population-based birth cohort that recruited healthy pregnant women from 2009 to 2012. Women completed dietary assessments during pregnancy, and their infants' BMI was measured at 1 year of age (n = 2686 89% follow-up). Statistical analysis for this study used data collected after the first year of follow-up, which was completed in October 2013. The data analysis was conducted in August 2015. Maternal consumption of artificially sweetened beverages and sugar-sweetened beverages during pregnancy, determined by a food frequency questionnaire. Infant BMI z score and risk of overweight at 1 year of age, determined from objective anthropometric measurements and defined according to World Health Organization reference standards. The mean (SD) age of the 3033 pregnant women was 32.4 (4.7) years, and their mean (SD) BMI was 24.8 (5.4). The mean (SD) infant BMI z score at 1 year of age was 0.19 (1.05), and 5.1% of infants were overweight. More than a quarter of women (29.5%) consumed artificially sweetened beverages during pregnancy, including 5.1% who reported daily consumption. Compared with no consumption, daily consumption of artificially sweetened beverages was associated with a 0.20-unit increase in infant BMI z score (adjusted 95% CI, 0.02-0.38) and a 2-fold higher risk of infant overweight at 1 year of age (adjusted odds ratio, 2.19 95% CI, 1.23-3.88). These effects were not explained by maternal BMI, diet quality, total energy intake, or other obesity risk factors. There were no comparable associations for sugar-sweetened beverages. To our knowledge, we provide the first human evidence that maternal consumption of artificial sweeteners during pregnancy may influence infant BMI. Given the current epidemic of childhood obesity and widespread use of artificial sweeteners, further research is warranted to confirm our findings and investigate the underlying biological mechanisms, with the ultimate goal of informing evidence-based dietary recommendations for pregnant women.
Publisher: MDPI AG
Date: 18-01-2023
Abstract: How gut immunity in early life is shaped by birth in relation to delivery mode, intrapartum antibiotic prophylaxis (IAP) and labor remains undetermined. We aimed to address this gap with a study of secretory Immunoglobulin A (SIgA) in the infant gut that also tested SIgA-stimulating pathways mediated by gut microbiota and metabolites. Among 1017 Canadian full-term infants, gut microbiota of fecal s les collected at 3 and 12 months were profiled using 16S rRNA sequencing C. difficile was quantified by qPCR fecal metabolites and SIgA levels were measured by NMR and SIgA enzyme-linked immunosorbent assay, respectively. We assessed the putative causal relationships from birth events to gut microbiota and metabolites, and ultimately to SIgA, in statistical sequential mediation models, adjusted for maternal gravida status in 551 infants. As birth mode influences the ability to breastfeed, the statistical mediating role of breastfeeding status and milk metabolites was also evaluated. Relative to vaginal birth without maternal IAP, cesarean section (CS) after labor was associated with reduced infant gut SIgA levels at 3 months (6.27 vs. 4.85 mg/g feces, p 0.05) this association was sequentially mediated through gut microbiota and metabolites of microbial or milk origin. Mediating gut microbiota included Enterobacteriaceae, C. difficile, and Streptococcus. The milk or microbial metabolites in CS-SIgA mediating pathways were galactose, fucose, GABA, choline, lactate, pyruvate and 1,2-propanediol. This cohort study documented the impact of birth on infant gut mucosal SIgA. It is the first to characterize gut microbe-metabolite mediated pathways for early-life SIgA maturation, pathways that require experimental verification.
Publisher: Wiley
Date: 02-03-2020
DOI: 10.1111/PAI.13219
Publisher: American Thoracic Society
Date: 15-11-2008
Publisher: Elsevier BV
Date: 09-2020
Publisher: Informa UK Limited
Date: 2021
Publisher: Springer Science and Business Media LLC
Date: 06-04-2017
Publisher: Elsevier BV
Date: 08-2018
DOI: 10.1016/J.SLEEP.2018.04.008
Abstract: 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. 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. 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). Childhood SDB symptoms, rather than being a homogenous disorder, may comprise multiple overlapping phenotypes each with unique risk factors.
Publisher: Cambridge University Press (CUP)
Date: 03-12-2021
DOI: 10.1017/S1368980021004699
Abstract: 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.
Publisher: Human Kinetics
Date: 05-2021
Abstract: Background : 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. Methods : A subset of Canadian Healthy Infant Longitudinal Development birth cohort (n = 385, 50.6% boys) with valid movement behaviors data were enrolled at age 3 years and followed through to age 5 years. 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). Results : 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 5 years and also in the winter at age 5 years in stratified analysis. A higher percentage of expressways was associated with less nonwinter moderate to vigorous physical activity at age 3 years. Conclusions : Future initiatives to promote healthy movement behaviors in the early years should consider age differences, neighborhood characteristics, and season.
Publisher: Elsevier BV
Date: 06-2019
DOI: 10.1016/J.ENVPOL.2019.03.054
Abstract: Perfluoroalkyl substances (PFASs) are known to be toxic, bioaccumulative, and persistent. However, exposure routes and toxic effects to humans are still widely unknown. Our objectives were to evaluate potential correlations between concentrations of PFASs in maternal plasma and infant cord blood with home characteristics and developmental effects, including wheezing. The concentrations of 17 PFASs were measured in plasma from prenatal women (n = 414), postnatal women (n = 247), and cord blood (n = 50) from a subset of participants in a population-based birth cohort in Winnipeg, Manitoba, Canada, using online solid phase extraction (SPE) with liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS). Multiple linear regression and principal component analysis (PCA) were used to evaluate possible associations with PFAS concentrations. Surveys were used to collect information regarding maternal characteristics (e.g. age, parity, duration of breastfeeding), infant characteristics (e.g. birth weight, birth length, head circumference, gestational age, and incidence of recurrent wheezing), and home characteristics (e.g. home age,carpet coverage in the most used room, presence of new furniture, or recent home renovations). PFASs in plasma were associated with maternal characteristics but not home characteristics or early childhood wheezing. PFASs were not associated with developmental effects, with the exception that perfluoroundecanoic acid (PFUA) was negatively associated with birth weight. Further studies investigating the potential influences of PFUA on birth weight are warranted.
Publisher: Public Library of Science (PLoS)
Date: 14-05-2020
Publisher: Cold Spring Harbor Laboratory
Date: 18-12-2020
DOI: 10.1101/2020.12.15.20248275
Abstract: There is no definitive cure for asthma as such, prevention remains a major goal. Decision-analytic models are routinely used to evaluate the value-for-money proposition of interventions. Following best practice standards in decision-analytic modeling, the objective of this study was to solicit expert opinion to develop a concept map for a policy model for primary prevention of asthma. We reviewed currently available decision-analytic models for asthma prevention. A steering committee of economic modelers, allergists, and respirologists was then convened to draft a conceptual model of pediatric asthma. A modified Delphi method was followed to define the context of the problem at hand (evaluation of asthma prevention strategies) and develop the concept map of the model. Consensus was achieved after three rounds of discussions, followed by concealed voting. In the final conceptual model, asthma diagnosis was based on three domains of lung function, atopy, and their symptoms. The panel recommended several markers for each domain. These domains were in turn affected by several risk factors. The panel clustered all risk factors under three groups of ‘patient characteristic’, ‘family history’, and ‘environmental factors’. To be capable of modeling the interplay among risk factors, the panel recommended the use of microsimulation, with an open-population approach that would enable modeling phased implementation and gradual and incomplete uptake of the intervention. Economic evaluation of childhood interventions for preventing asthma will require modeling of several co-dependent risk factors and multiple domains that affect the diagnosis. The conceptual model can inform the development and validation of a policy model for childhood asthma prevention. Genome Canada Large-Scale Applied Research Project
Publisher: American Thoracic Society
Date: 03-2018
Publisher: Wiley
Date: 02-03-2018
DOI: 10.1111/BIRT.12345
Abstract: 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. 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. 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). 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.
Publisher: Environmental Health Perspectives
Date: 09-2015
DOI: 10.1289/EHP.1408700
Publisher: Wiley
Date: 10-03-2020
DOI: 10.1111/ALL.14244
Publisher: Wiley
Date: 04-2000
DOI: 10.1002/(SICI)1099-0496(200004)29:4<291::AID-PPUL9>3.0.CO;2-A
Abstract: Inhaled mannitol has been developed for bronchial challenge testing in adults. This study determined if mannitol could identify children with active asthma and responsive to methacholine, and whether mannitol challenge was faster to complete than methacholine challenge. Twenty-five children (aged 6-13 years) responsive to methacholine and 10 nonasthmatic children unresponsive to methacholine were studied. The methacholine challenge (Cockcroft protocol) was followed by a mannitol challenge on separate days. Twenty-one asthmatic children were positive to mannitol. Three taking inhaled corticosteroids with borderline methacholine responsiveness did not respond to mannitol, and one could not complete the mannitol challenge due to cough. The geometric mean (GM) and 95% confidence interval (CI) for PD(15) for mannitol was 39 mg (19, 78), and PC(20) for methacholine was 0.6 mg/mL (0.35-1.02) (r(p) = 0.75, p < 0.001, n = 21). Responses to mannitol were repeatable: GM PD(15) for the first challenge was 29 mg (CI: 17,50), and for the second challenge, 33 mg (CI: 20, 55) (P = 0.44, n = 9). Mannitol was faster to administer than methacholine (median (range)) 14 min (5-32) vs. 29 min (19-49), respectively (P < 0.001). Time to recover to baseline FEV(1) spontaneously and after bronchodilator administration was similar for both challenges. There were no significant falls in arterial oxygen saturations. During mannitol challenge, the mean (SD) fall in FEV(1) in nonasthmatic children was 3.1% (2.9). We conclude that mannitol identifies children with airway hyperresponsiveness and is faster to perform than the methacholine challenge.
Publisher: European Respiratory Society (ERS)
Date: 31-10-2013
Publisher: Springer Science and Business Media LLC
Date: 29-03-2017
Publisher: Frontiers Media SA
Date: 11-12-2019
Publisher: Springer Science and Business Media LLC
Date: 12-2014
Publisher: CMA Impact Inc.
Date: 16-09-2018
DOI: 10.1503/CMAJ.170809
Publisher: Elsevier BV
Date: 12-2019
DOI: 10.1016/J.JACI.2019.06.029
Abstract: Allergic disease is the most frequent chronic health issue in children and has been linked to early-life gut microbiome dysbiosis. Many lines of evidence suggest that microbially derived short-chain fatty acids, and particularly butyrate, can promote immune tolerance. We sought to determine whether bacterial butyrate production in the gut during early infancy is protective against the development of atopic disease in children. We used shotgun metagenomic analysis to determine whether dysbiosis in butyrate fermentation could be identified in human infants, before their developing allergic disease. We found that the microbiome of infants who went on to develop allergic sensitization later in childhood lacked genes encoding key enzymes for carbohydrate breakdown and butyrate production. Our findings support the importance of microbial carbohydrate metabolism during early infancy in protecting against the development of allergies.
Publisher: Cold Spring Harbor Laboratory
Date: 21-10-2022
DOI: 10.1101/2022.10.19.22281242
Abstract: The COVID-19 pandemic is affecting all Canadian families, with some impacted differently than others. Our study aims to: 1) determine the prevalence and transmission of SARS-CoV-2 infection among Canadian families, 2) identify predictors of infection susceptibility and severity of SARS-CoV-2 and 3) identify health and psychosocial impacts of the COVID-19 pandemic. This study builds upon the CHILD Cohort Study, an ongoing multi-ethnic general population prospective cohort consisting of 3454 Canadian families with children born in Vancouver, Edmonton, Manitoba, and Toronto between 2009-12. During the pandemic, 1462 CHILD households (5378 in iduals) consented to participate in the CHILD COVID-19 Add-On Study involving: (1) brief biweekly surveys about COVID-19 symptoms and testing (2) quarterly questionnaires assessing COVID-19 exposure, testing and vaccination status, physical and mental health, and pandemic-driven life changes (3) in-home biological s ling kits to collect blood and stool. Mean ages were 9 years (range 0-17) for children and 43 years (range 18-85) for adults. Prevalence of SARS-CoV-2 infection will be estimated from survey data and confirmed through serology testing. We will combine these new data with a wealth of pre-pandemic CHILD data and use multivariate modelling and machine learning methods to identify risk and resilience factors for susceptibility and severity to the direct and indirect effects of the pandemic. Our short-term findings will inform key stakeholders and knowledge users to shape current and future pandemic responses. Additionally, this study provides a unique resource to study the long-term impacts of the pandemic as the CHILD Cohort Study continues.
Publisher: Elsevier BV
Date: 06-2016
Publisher: Springer Science and Business Media LLC
Date: 19-03-2022
DOI: 10.1186/S12864-022-08451-6
Abstract: 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. 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. 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. 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 erse 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.
Publisher: Elsevier BV
Date: 2020
DOI: 10.2139/SSRN.3728570
Publisher: Elsevier BV
Date: 06-2021
Publisher: Wiley
Date: 06-06-2019
DOI: 10.1002/PPUL.24381
Abstract: 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.
Publisher: Wiley
Date: 25-02-2015
DOI: 10.1111/CEA.12487
Abstract: The gut microbiota is established during infancy and plays a fundamental role in shaping host immunity. Colonization patterns may influence the development of atopic disease, but existing evidence is limited and conflicting. To explore associations of infant gut microbiota and food sensitization. Food sensitization at 1 year was determined by skin prick testing in 166 infants from the population-based Canadian Healthy Infant Longitudinal Development (CHILD) study. Faecal s les were collected at 3 and 12 months, and microbiota was characterized by Illumina 16S rRNA sequencing. Twelve infants (7.2%) were sensitized to ≥ 1 common food allergen at 1 year. Enterobacteriaceae were overrepresented and Bacteroidaceae were underrepresented in the gut microbiota of food-sensitized infants at 3 months and 1 year, whereas lower microbiota richness was evident only at 3 months. Each quartile increase in richness at 3 months was associated with a 55% reduction in risk for food sensitization by 1 year (adjusted odds ratio 0.45, 95% confidence interval 0.23-0.87). Independently, each quartile increase in Enterobacteriaceae/Bacteroidaceae ratio was associated with a twofold increase in risk (2.02, 1.07-3.80). These associations were upheld in a sensitivity analysis among infants who were vaginally delivered, exclusively breastfed and unexposed to antibiotics. At 1 year, the Enterobacteriaceae/Bacteroidaceae ratio remained elevated among sensitized infants, who also tended to have decreased abundance of Ruminococcaceae. Low gut microbiota richness and an elevated Enterobacteriaceae/Bacteroidaceae ratio in early infancy are associated with subsequent food sensitization, suggesting that early gut colonization may contribute to the development of atopic disease, including food allergy.
Publisher: Wiley
Date: 15-12-2017
DOI: 10.1111/CEA.13063
Abstract: While allergic sensitization and atopic dermatitis (AD) are known to increase the risk for allergic diseases, the impact of different temporal and clinical patterns of sensitization and AD is less well defined. We investigated patterns of sensitization and AD from early infancy to age 3, and the differential risk of developing allergic diseases within each pattern in a general cohort. Children (n = 2629) from the Canadian Healthy Infant Longitudinal Development (CHILD) Study underwent skin prick tests and were assessed clinically for AD at ages 1 and 3 years. We applied an unsupervised latent class analysis (LCA) to the following 5 factors at these ages: AD, food sensitization, inhalant sensitization, poly-sensitization to foods and poly-sensitization to inhalants. The risks for developing asthma, allergic rhinitis and food allergy at 3 years were evaluated for each identified group. Five distinct classes were revealed by LCA: healthy (81.8%), atopic dermatitis (7.6%), inhalant sensitization (3.5%), transient sensitization (4.1%) and persistent sensitization (3.2%). Using healthy children as the baseline, children in the "atopic dermatitis" group had the next lowest risk for all allergic outcomes at 3 years those in the "inhalant sensitization" group had the highest risk for allergic rhinitis children in the "transient sensitization" group were at an increased risk for food allergy while children in the "persistent sensitization" group had the highest risk for all allergic diseases. There is substantial heterogeneity among allergen-sensitized children. Researchers and clinicians need to be aware of the non-specificity associated with labelling children simply as "atopic" and "non-atopic" without considering the timing of their atopic history, type of sensitization and AD status. Children with AD who were poly-sensitized to foods at an early age appear to be at greatest risk of developing other allergic diseases.
Publisher: Elsevier BV
Date: 02-2023
Publisher: Wiley
Date: 18-04-2021
DOI: 10.1111/PAI.13515
Publisher: SAGE Publications
Date: 08-2018
Abstract: 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. 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. 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. 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.
Publisher: Springer Science and Business Media LLC
Date: 15-07-2022
DOI: 10.1038/S41366-022-01183-3
Abstract: Differences in gut microbiota, metabolites and immune markers have been observed between in iduals with and without obesity. Our study determined the temporal association between infant fecal gut metabolites, sIgA and body mass index (BMI) z score of preschool children, independent of pre ostnatal factors. The study includes a subset of 647 infants from the CHILD Cohort Study (recruited between January 1, 2009, and December 31, 2012). Fecal metabolites and sIgA were measured at 3-4 months of age, and age and sex adjusted BMI z scores at 1 and 3 years of age. Associations between the metabolites, IgA, and child BMI z scores at age 1 and 3 years were tested using linear regression adjusted for pre ostnatal factors (breastfeeding, birthweight-for-gestational age, birthmode and IAP, solid food introduction). Mean BMI z score for all infants was 0.34 (SD 1.16) at 1 year (N = 647) and 0.71 (SD 1.06) at 3 years (N = 573). High fecal formate in infancy was associated with a significantly lower BMI z score (adjusted mean difference -0.23 (95% CI -0.42, -0.04)) and high butyrate was associated with a higher BMI z score (adjusted mean difference 0.21 (95% CI 0.01, 0.41)) at age 3 years only. The influence of formate and butyrate on BMI z score at age 3 were seen only in those that were not exclusively breastfed at stool s le collection (adjusted mean difference for high formate/EBF- group: -0.33 (95%CI -0.55, -0.10) and 0.25 (95% CI 0.02, 0.47) for high butyrate/EBF- group). No associations were seen between sIgA and BMI z score at age 1 or 3 years in adjusted regression models. Differences in fecal metabolite levels in early infancy were associated with childhood BMI. This study identifies an important area of future research in understanding the pathogenesis of obesity.
Publisher: Springer Science and Business Media LLC
Date: 12-2018
Publisher: Informa UK Limited
Date: 07-2022
DOI: 10.2147/NSS.S363211
Publisher: Elsevier BV
Date: 10-2020
DOI: 10.1093/CDN/NZAA144
Publisher: Cold Spring Harbor Laboratory
Date: 21-04-2020
DOI: 10.1101/2020.04.20.050195
Abstract: Artificial sweetener consumption by pregnant women has been associated with an increased risk of infant obesity, but the underlying mechanisms are unknown. We aimed to determine if maternal consumption of artificially sweetened beverages (ASB) during pregnancy is associated with modifications of infant gut bacterial community composition during the first year of life, and whether these alterations are linked with infant body mass index (BMI) at one year of age. This research included 100 infants from the prospective Canadian CHILD Cohort Study, selected based on maternal ASB consumption during pregnancy (50 non-consumers and 50 daily consumers). We identified four microbiome clusters, of which two recapitulated the maturation trajectory of the infant gut bacterial communities from immature to mature and two deviated from this trajectory. Maternal ASB consumption was associated with the depletion of several Bacteroides sp. and higher infant BMI. As we face an unprecedented rise in childhood obesity, future studies should evaluate the causal role of gut microbiota in the association between maternal ASB consumption, infant development and metabolism, and body composition.
Start Date: 2021
End Date: 2025
Funder: Canadian Institutes of Health Research
View Funded ActivityStart Date: 2020
End Date: 2020
Funder: Canadian Institutes of Health Research
View Funded ActivityStart Date: 2021
End Date: 2022
Funder: Canadian Institutes of Health Research
View Funded Activity