The effect of neonatal and infant feeding practices on childhood obesity is unclear. The gut microbiome is strongly influenced by feeding practices and has been linked to obesity.To characterize the association between breastfeeding, microbiota, and risk of overweight during infancy, accounting for the type and timing of supplementary feeding.In this study of a subset of 1087 infants from the prospective CHILD pregnancy cohort, mothers were recruited between January 1, 2009, and December 31, 2012. Statistical analysis was performed from February 1 to December 20, 2017.Feeding was reported by mothers and documented from hospital records. Fecal microbiota at 3 to 4 months (from 996 infants) and/or 12 months (from 821 infants) were characterized by 16S ribosomal RNA sequencing. Infants with a weight for length exceeding the 85th percentile were considered to be at risk for overweight.There were 1087 infants in the study (507 girls and 580 boys); at 3 months, 579 of 1077 (53.8%) were exclusively breastfed according to maternal report. Infants who were exclusively formula fed at 3 months had an increased risk of overweight in covariate-adjusted models (53 of 159 [33.3%] vs 74 of 386 [19.2%]; adjusted odds ratio, 2.04; 95% CI, 1.25-3.32). This association was attenuated (adjusted odds ratio, 1.33; 95% CI, 0.79-2.24) after further adjustment for microbiota features characteristic of formula feeding at 3 to 4 months, including higher overall richness and enrichment of Lachnospiraceae. A total of 179 of 579 infants who were exclusively breastfed (30.9%) received formula as neonates; this brief supplementation was associated with lower relative abundance of Bifidobacteriaceae and higher relative abundance of Enterobacteriaceae at 3 to 4 months but did not influence the risk of overweight. At 12 months, microbiota profiles differed significantly according to feeding practices at 6 months; among partially breastfed infants, formula supplementation was associated with a profile similar to that of nonbreastfed infants (higher diversity and enrichment of Bacteroidaceae), whereas the introduction of complementary foods without formula was associated with a profile more similar to that of exclusively breastfed infants (lower diversity and enrichment of Bifidobacteriaceae and Veillonellaceae). Microbiota profiles at 3 months were more strongly associated with risk of overweight than were microbiota profiles at 12 months.Breastfeeding may be protective against overweight, and gut microbiota may contribute to this effect. Formula feeding appears to stimulate changes in microbiota that are associated with overweight, whereas other complementary foods do not. Subtle microbiota differences emerge after brief exposure to formula in the hospital. These results identify important areas for future research and distinguish early infancy as a critical period when transient gut dysbiosis may lead to increased risk of overweight.
BACKGROUND. Antibiotic exposure in early childhood is a possible contributor to the increasing asthma prevalence in industrialized countries. Although a number of published studies have tested this hypothesis, the results have been conflicting. OBJECTIVE. To explore the association between antibiotic exposure before 1 year of age and development of childhood asthma. METHODS. Using administrative data, birth cohorts from 1997 to 2003 were evaluated (N = 251817). Antibiotic exposure was determined for the first year of life. After the first 24 months of life, the incidence of asthma was determined in both those exposed and not exposed to antibiotics in the first 12 months of life. Cox proportional hazards models were used to adjust for potential confounders and determine the hazard ratios associated with antibiotic exposure for the development of asthma. RESULTS. Antibiotic exposure in the first year of life was associated with a small risk of developing asthma in early childhood after adjusting for gender, socioeconomic status at birth, urban or rural address at birth, birth weight, gestational age, delivery method, frequency of physician visits, hospital visit involving surgery, visits to an allergist, respirologist, or immunologist, congenital anomalies, and presence of otitis media, acute, or chronic bronchitis, and upper and lower respiratory tract infections during the first year of life. As the number of courses of antibiotics increased, this was associated with increased asthma risk, with the highest risk being in children who received >4 courses. All antibiotics were associated with an increased risk of developing asthma, with the exception of sulfonamides. CONCLUSIONS. This study provides evidence that the use of antibiotics in the first year of life is associated with a small risk of developing asthma, and this risk increases with the number of courses of antibiotics prescribed.
Overweight in childhood has been characterized by a distinct profile of fecal short chain fatty acids (SCFA), derived from the gut microbial fermentation of dietary substrates. Overweight children are also less likely to be breastfed as infants. The study objective was to explore associations between fecal SCFA and infant diet at 3–4 months of age, as well as associations between fecal metabolites at 3–4 months of age and overweight status at age 3 years. Metabolic profiling (using nuclear magnetic resonance (NMR)) of fecal samples taken at 3–4 months from a subset of 118 infants enrolled in the Canadian Healthy Infant Longitudinal Study (CHILD) general population cohort was conducted. Infant and maternal characteristics, including breastfeeding status at 3 months of age (none, partial breastfeeding, exclusive breastfeeding), were collected using standardized questionnaires. Anthropometric measurements taken at 3 years of age were used to classify children as normal weight (<85 th centile), at‐risk of overweight (≥85 th centile) or overweight/obese (≥97 th centile) according to BMI‐for‐age z‐scores. Seventy seven (65.3%) infants were classified as normal weight, 31 (26.3%) as at‐risk of overweight and 10 (8.5%) as overweight or obese at 3 years of age. 28.2% were exclusively breastfed, 45.3% were partially breastfed and 26.5% were not breastfed at 3–4 months of age. Exclusively breastfed infants had significantly lower fecal concentrations of total SCFA, acetate, butyrate, propionate, isobutyrate, isovalerate, and valerate compared to non‐breastfed infants and partially breastfed infants (p≤0.002; Mann Whitney U test adjusted for multiple comparisons). Exclusively breastfed infants had significantly higher acetate compared to non‐breastfed and partially breastfed infants when measured as a proportion of total SCFA concentration (p<0.001; Mann Whitney U test). There was a weak positive correlation between total SCFA concentration at 3–4 months of age and BMIz score at age 3 years (Spearman's rho 0.24, p=0.01). No correlation between SCFA and BMIz score was seen following stratification by breastfeeding status. Total SCFA concentrations were significantly higher in children classified as at risk of overweight, overweight or obese at 3 years compared to normal weight children. No significant differences in relative proportions of SCFA according to overweight status were observed. Odds of being at risk, overweight or obese at 3 years were over 3 times higher in infants with total SCFA or acetate concentrations in the 4 th quartile compared to 1 st quartile (OR 3.58 95% CI 1.13 to 11.37 and 3.23 95% CI 1.08 to 9.66 respectively). After adjustment for breastfeeding the effect was still evident but diminished (aOR 3.08 95% CI 0.85 to 11.12 and 2.83 95% CI 0.83 to 9.63 respectively). In preliminary analysis, significant differences in fecal SCFA concentrations were observed according to breastfeeding status at 3–4 months; concentrations of all SCFA were lower in exclusively breastfed infants compared to partially or non‐breastfed infants. Fecal SCFA in early life were predictive of overweight status at 3 years of age, but may be explained to an extent by breastfeeding. Nonetheless, fecal SCFA concentrations during infancy may provide a novel biomarker for childhood overweight risk. Support or Funding Information Canadian Institutes of Health Research (Grant #227312); Women and Children's Health Research Institute
Objective: 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. Methods: 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. Results: 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. Conclusions: 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.
Introduction: Greater prescribing of antibiotics to infants has coincided with an epidemic of allergic disease. Through meta-analytic synthesis, accumulating evidence from prospective or database cohorts suggests a link between infant antibiotic treatment and the development of atopy. Stronger associations seen with multiple course and broad-spectrum antibiotic treatment add to biological plausibility. A major bias, confounding by indication, has been addressed in studies on antibiotic treatment of conditions which do not precede allergic disease.Areas covered: Our review provides an up-to-date synthesis of the current literature on associations between infant antibiotic exposure and future allergic disease. We discuss methods that assist in reducing study bias and look at new insights from studies of the infant gut microbiome.Expert commentary: Large-scale profiling of the gut microbiome provides a new tool for disentangling biases found in observational studies of infant antibiotic use. To date, microbial dysbiosis of the infant gut has been reported to predict allergic disease independent of antibiotic exposure up to 3 months after birth. However, these studies have not accounted for antibiotic treatment in later infancy. Continued study of the infant gut microbiome, mycobiome, or resistome will provide a closer link to antibiotic treatment or refute it as a cause of allergic disease.
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