To compare and contrast national asthma guidelines with the Global Initiative for Asthma (GINA) strategy for asthma management and prevention.
The common goal of GINA and national asthma guidelines ...is to improve asthma care using the best evidence available from published data. This evidence-based approach has evolved from an initial perspective of expert opinion but with that evolution has not always considered the breadth of asthma phenotypes. GINA and national guidelines differ in a number of ways. GINA reviews available data and updates the core document and recommendations based on the latest data on a yearly basis to offer local, regional and national guidelines materials needed for knowledge mobilization. It remains the purview of those organizations to structure and implement those locally appropriate guidelines.
Both GINA and national guidelines have furthered asthma care to narrow the care gap from what is known to how asthma care is delivered, hopefully in a more directed, personalized manner. As well, both GINA and national guidelines have helped to shape the direction of research for the future benefit of children and their families.
Pre-school children spend an average of two-hours daily using screens. We examined associations between screen-time on pre-school behavior using data from the Canadian Healthy Infant Longitudinal ...Development (CHILD) study.
CHILD participant parents completed the Child Behavior Checklist (CBCL) at five-years of age. Parents reported their child's total screen-time including gaming and mobile devices. Screen-time was categorized using the recommended threshold of two-hours/day for five-years or one-hour/day for three-years. Multiple linear regression examined associations between screen-time and externalizing behavior (e.g. inattention and aggression). Multiple logistic regression identified characteristics of children at risk for clinically significant externalizing problems (CBCL T-score≥65).
Screen-time was available for over 95% of children (2,322/2,427) with CBCL data. Mean screen-time was 1·4 hours/day (95%CI 1·4, 1·5) at five-years and 1·5 hours/day (95%CI: 1·5, 1·6) at three-years. Compared to children with less than 30-minutes/day screen-time, those watching more than two-hours/day (13·7%) had a 2·2-point increase in externalizing T-score (95%CI: 0·9, 3·5, p≤0·001); a five-fold increased odd for reporting clinically significant externalizing problems (95%CI: 1·0, 25·0, p = 0·05); and were 5·9 times more likely to report clinically significant inattention problems (95%CI: 1·6, 21·5, p = 0·01). Children with a DSM-5 ADHD T-score above the 65 clinical cut-off were considered to have significant ADHD type symptoms (n = 24). Children with more than 2-hours of screen-time/day had a 7·7-fold increased risk of meeting criteria for ADHD (95%CI: 1·6, 38·1, p = 0·01). There was no significant association between screen-time and aggressive behaviors (p>0.05).
Increased screen-time in pre-school is associated with worse inattention problems.
Breastmilk contains a complex community of bacteria that may help seed the infant gut microbiota. The composition and determinants of milk microbiota are poorly understood. Among 393 mother-infant ...dyads from the CHILD cohort, we found that milk microbiota at 3–4 months postpartum was dominated by inversely correlated Proteobacteria and Firmicutes, and exhibited discrete compositional patterns. Milk microbiota composition and diversity were associated with maternal factors (BMI, parity, and mode of delivery), breastfeeding practices, and other milk components in a sex-specific manner. Causal modeling identified mode of breastfeeding as a key determinant of milk microbiota composition. Specifically, providing pumped breastmilk was consistently associated with multiple microbiota parameters including enrichment of potential pathogens and depletion of bifidobacteria. Further, these data support the retrograde inoculation hypothesis, whereby the infant oral cavity impacts the milk microbiota. Collectively, these results identify features and determinants of human milk microbiota composition, with potential implications for infant health and development.
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•Milk microbiota variability is affected by maternal factors and other milk components•Some factors have phylum-specific effects•Some variations in milk microbiota are sex-specific•Feeding method (at the breast versus pumped) was strongly associated with milk microbiota
Moossavi et al. examine human milk microbiota in the CHILD birth cohort and use causal modeling to describe sex-specific associations with maternal, infant, and early-life factors. A strong association with feeding method (i.e., pumped versus directly at the breast) suggests some milk bacteria originate from the infant oral cavity.
The gut microbiota is essential to human health throughout life, yet the acquisition and development of this microbial community during infancy remains poorly understood. Meanwhile, there is ...increasing concern over rising rates of cesarean delivery and insufficient exclusive breastfeeding of infants in developed countries. In this article, we characterize the gut microbiota of healthy Canadian infants and describe the influence of cesarean delivery and formula feeding.
We included a subset of 24 term infants from the Canadian Healthy Infant Longitudinal Development (CHILD) birth cohort. Mode of delivery was obtained from medical records, and mothers were asked to report on infant diet and medication use. Fecal samples were collected at 4 months of age, and we characterized the microbiota composition using high-throughput DNA sequencing.
We observed high variability in the profiles of fecal microbiota among the infants. The profiles were generally dominated by Actinobacteria (mainly the genus Bifidobacterium) and Firmicutes (with diverse representation from numerous genera). Compared with breastfed infants, formula-fed infants had increased richness of species, with overrepresentation of Clostridium difficile. Escherichia-Shigella and Bacteroides species were underrepresented in infants born by cesarean delivery. Infants born by elective cesarean delivery had particularly low bacterial richness and diversity.
These findings advance our understanding of the gut microbiota in healthy infants. They also provide new evidence for the effects of delivery mode and infant diet as determinants of this essential microbial community in early life.
Human milk oligosaccharides (HMOs) shape the developing gut microbiome and influence immune function. Aside from genetic Secretor status, the factors influencing HMO synthesis and secretion are ...largely unknown.
We aimed to identify modifiable and nonmodifiable factors associated with HMO concentrations.
This prospective observational study included a representative subset of 427 mothers participating in the CHILD birth cohort (mean age: 33 y, 73% Caucasian). Breast milk was collected at 3–4 mo postpartum. Concentrations of 19 predominant HMOs were measured by rapid high-throughput HPLC. Secretor status was defined by the presence of 2’-fucosylactose. Associations with maternal, infant, and environmental factors were explored using multivariable regression. Breastfeeding duration was explored as a secondary outcome.
Overall, 72% of mothers were Secretors and the mean ± SD duration of any breastfeeding was 12.8 ± 5.7 mo. HMO profiles were highly variable; total HMO concentrations varied 3.7-fold and individual HMOs varied 20- to >100-fold. Secretor mothers had higher total HMO concentrations than did non-Secretors (mean: 15.91 ± 2.80 compared with 8.94 ± 1.51 μmol/mL, P < 0.001) and all individual HMOs differed by Secretor status, except for disialyllacto-N-tetraose (DSLNT). Most HMO concentrations were lower in milk collected later in lactation, although some were higher including DSLNT and 3’-sialyllactose. Independent of Secretor status and lactation stage, seasonal and geographic variation was observed for several HMOs. Parity, ethnicity, and breastfeeding exclusivity also emerged as independent factors associated with some HMOs, whereas diet quality and mode of delivery did not. Together, these factors explained between 14% (for 6’-sialyllactose) and 92% (for 2’-fucosyllactose) of the observed variation in HMO concentrations. Lower concentrations of lacto-N-hexaose or fucodisialyllacto-N-hexaose were associated with earlier breastfeeding cessation.
HMO concentrations vary widely between mothers and are associated with multiple characteristics beyond genetic Secretor status, as well as feeding practices and environmental factors. Further research is warranted to determine how these associations affect infant health. This study was registered at clinicaltrials.gov as NCT03225534.
Gut microbiota play a critical role in infant health. It is now accepted that breastmilk contains live bacteria from endogenous and exogenous sources, but it remains unclear whether these bacteria ...transfer to the infant gut and whether this process is influenced by breastmilk feeding practices. Here, we show that certain bacteria, including Streptococcus spp. and Veillonella dispar, co-occur in mothers’ milk and their infants’ stool, and co-occurrence is reduced when infants receive pumped breastmilk. The relative abundances of commonly shared species are positively correlated between breastmilk and stool. Overall, gut microbiota composition is strongly associated with breastfeeding exclusivity and duration but not breastmilk feeding mode (nursing versus pumping). Moreover, breastmilk bacteria contributed to overall gut microbiota variation to a similar extent as other modifiers of the infant microbiome, such as birth mode. These results provide evidence that breastmilk may transfer bacteria to the infant gut and influence microbiota development.
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•Breastfeeding exclusivity and duration strongly influence infant gut microbiota•A few bacterial species co-occur in mothers’ milk and their infants’ stool•This co-occurrence is reduced when breastmilk is pumped and fed from a bottle•Bacteria in breastmilk contribute to overall infant gut microbiota composition
Fehr et al. analyze infant gut microbiota in the CHILD cohort and identify associations with breastmilk feeding practices (exclusivity, duration, and pumping) and breastmilk microbiota. Within mother-infant dyads, co-occurrence of bacteria in breastmilk and stool suggests bacteria in breastmilk may transfer to the infant and influence the developing gut microbiota.
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.
ABSTRACT BACKGROUND Emerging links between household cleaning products and childhood overweight may involve the gut microbiome. We determined mediating effects of infant gut microbiota on ...associations between home use of cleaning products and future overweight. METHODS From the Canadian Healthy Infant Longitudinal Development (CHILD) birth cohort, we tested associations between maternal report of cleaning product use and overweight at age 3, and whether associations were mediated by microbial profiles of fecal samples in 3- to 4-month-old infants. RESULTS Among 757 infants, the abundance of specific gut microbiota was associated with household cleaning with disinfectants and eco-friendly products in a dose-dependent manner. With more frequent use of disinfectants, Lachnospiraceae increasingly became more abundant (highest v. lowest quintile of use: adjusted odds ratio AOR 1.93, 95% confidence interval CI 1.08 to 3.45) while genus Haemophilus declined in abundance (highest v. lowest quintile of use: AOR 0.36, 95% CI 0.20 to 0.65). Enterobacteriaceae were successively depleted with greater use of eco-friendly products (AOR 0.45, 95% CI 0.27 to 0.74). Lachnospiraceae abundance significantly mediated associations of the top 30th centile of household disinfectant use with higher body mass index (BMI) z score ( p = 0.02) and with increased odds of overweight or obesity ( p = 0.04) at age 3. Use of eco-friendly products was associated with decreased odds of overweight or obesity independently of Enterobacteriaceae abundance (AOR 0.44, 95% CI 0.22 to 0.86), with no significant mediation ( p = 0.2). INTERPRETATION Exposure to household disinfectants was associated with higher BMI at age 3, mediated by gut microbial composition at age 3–4 months. Although child overweight was less common in households that cleaned with eco-friendly products, the lack of mediation by infant gut microbiota suggests another pathway for this association.
Changes in maternal innate immunity during healthy human pregnancy are not well understood. Whether basal immune status in vivo is largely unaffected by pregnancy, is constitutively biased towards an ...inflammatory phenotype (transiently enhancing host defense) or exhibits anti-inflammatory bias (reducing potential responsiveness to the fetus) is unclear. Here, in a longitudinal study of healthy women who gave birth to healthy infants following uncomplicated pregnancies within the Canadian Healthy Infant Longitudinal Development (CHILD) cohort, we test the hypothesis that a progressively altered bias in resting innate immune status develops. Women were examined during pregnancy and again, one and/or three years postpartum. Most pro-inflammatory cytokine expression, including CCL2, CXCL10, IL-18 and TNFα, was reduced in vivo during pregnancy (20-57%, p<0.0001). Anti-inflammatory biomarkers (sTNF-RI, sTNF-RII, and IL-1Ra) were elevated by ~50-100% (p<0.0001). Systemic IL-10 levels were unaltered during vs. post-pregnancy. Kinetic studies demonstrate that while decreased pro-inflammatory biomarker expression (CCL2, CXCL10, IL-18, and TNFα) was constant, anti-inflammatory expression increased progressively with increasing gestational age (p<0.0001). We conclude that healthy resting maternal immune status is characterized by an increasingly pronounced bias towards a systemic anti-inflammatory innate phenotype during the last two trimesters of pregnancy. This is resolved by one year postpartum in the absence of repeat pregnancy. The findings provide enhanced understanding of immunological changes that occur in vivo during healthy human pregnancy.
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