Objectives This study aimed to assess the association between postpartum hospital length-of-stay and the composition of gut microbiota at 3 and 12 months of age in different birth modes. Design Prospective cohort of Canadian infants from the Canadian Healthy Infant Longitudinal Development (CHILD) Study born between 2008 and 2012. Setting General community. Sample 1313 infants from three study sites (Edmonton, Vancouver, and Winnipeg) of the CHILD cohort Methods Duration of hospital stay was documented in hospital records. Infants’ gut microbiota was characterized by Illumina 16S rRNA sequencing of fecal samples at 3 and 12 months. Main outcome measures Infant gut microbiota profiles. Results: In the absence of maternal intrapartum antibiotic (IAP) exposure, vaginally delivered infants (VD) with a longer hospital length-of-stay (LOS) had a higher abundance of bacteria in their gut known to cause hospital-acquired Infections (HAI), including Enterococcus at 3 months and 12 months and Citrobacter at 3 months of age. Moreover, HAI-causing bacteria Enterobacteriaceae were more abundant in later infancy in postnatal prolonged hospital stayed IAP-exposed caesarean section (CS) infants. Enterococcus or Citrobacter abundance at 3 months significantly mediated the association of LOS with low relative abundance of Bacteroidaceae and a high relative abundance of Enterococcaeae/Bacteriodaceae or Enterobacteriaceae/Bacteroidaceae ratio at 12 months of age in VD infants without IAP exposure. Conclusions LOS after birth is associated with infant gut dysbiosis. Further research is needed to explore the health outcomes of these associations.

Background: Quantifying age trends in healthcare costs of pediatric asthma leads to better understanding of the natural history of the disease and informed decision-making on the allocation of healthcare resources. Methods: We identified children with incident asthma from the health administrative data of British Columbia, Canada (Jan 1998 to Dec 2015), and followed them from their first diagnosis of asthma or wheezing until age 18. We estimated direct medical costs (in 2016 Canadian dollars [$]), including inpatient and outpatient encounters and pharmacy costs, attributed to asthma (primary outcome) and other respiratory diseases (secondary outcome). We assessed the impact of sex and socioeconomic status on age trends, adjusting for calendar effect. Results: The final analysis included 44,552 children with asthma (62% boys). From age 0 to 18, costs of asthma/wheezing and other respiratory conditions decreased from $1,036 to $29/child-year, and from $1,145 to $31/child-year, respectively. Children under 3 years of age incurred 4–fold higher costs for asthma/wheezing and other respiratory conditions. In particular, costs of asthma hospitalizations were 10 times higher in this age group compared to older children. Age trends were generally similar between sex groups and across socioeconomic status. However, medication costs for asthma/wheezing decreased in boys, whereas those in girls declined during childhood but increased during adolescence. Conclusions: The highest costs of pediatric asthma are concentrated in children younger than 3. Age trends were generally consistent between sex and across socioeconomic status.

Background: Quantifying age trends in healthcare costs of pediatric asthma leads to better understanding of the natural history of the disease and informed decision-making on the allocation of healthcare resources. Methods: We identified children with incident asthma from the health administrative data of British Columbia, Canada (Jan 1998 to Dec 2015), and followed them from their first diagnosis of asthma or wheezing until age 18. We estimated direct medical costs (in 2016 Canadian dollars [$]), including inpatient and outpatient encounters and pharmacy costs, attributed to asthma (primary outcome) and other respiratory diseases (secondary outcome). We assessed the impact of sex and socioeconomic status on age trends, adjusting for calendar effect. Results: The final analysis included 44,552 children with asthma (62% boys). From age 0 to 18, costs of asthma/wheezing and other respiratory conditions decreased from $1,036 to $29/child-year, and from $1,145 to $31/child-year, respectively. Children under 3 years of age incurred 4–fold higher costs for asthma/wheezing and other respiratory conditions. In particular, costs of asthma hospitalizations were 10 times higher in this age group compared to older children. Age trends were generally similar between sex groups and across socioeconomic status. However, medication costs for asthma/wheezing decreased in boys, whereas those in girls declined during childhood but increased during adolescence. Conclusions: The highest costs of pediatric asthma are concentrated in children younger than 3. Age trends were generally consistent between sex and across socioeconomic status.

Background: Asthma is a multifactorial disease with numerous associated genetic and environmental risk factors, however, gene-environment interactions are poorly understood in modulating disease risk. This study determines the polygenic effects of multiple genetic loci and interactions with environmental exposures during early infancy on risk of recurrent wheeze and asthma in pre-school aged children. Methods: We conducted genome-wide association studies (GWAS) and applied a thresholding method to calculate genetic risk scores (GRS) of recurrent wheeze and asthma in 2835 children of the CHILD Cohort Study. Recurrent wheeze was defined as two or more episodes in one year between ages 2-5 years and asthma was diagnosed at age 5 years. In addition, we tested for interaction effects between the GRS and environmental exposures on these respiratory outcomes. Results: GWAS identified associations with known asthma loci on chromosome 17q12 - 17q21 (p < 5e-8). GRS analysis determined that the weighted addition of alleles at four childhood-asthma loci correlated with more than 2-fold higher prevalence of recurrent wheeze (p =1.5e-08) and asthma (p = 9.4e-08) between high vs. low GRS groups. In addition, the GRS interacts with breastfeeding (p = 0.02) and traffic air pollution (NO2; p < 0.01) during the first year of life to modulate risk of recurrent wheeze and childhood-onset asthma. Conclusions: This study reports polygenic effects of multiple genetic loci, which interact with early-life exposures, to determine risk of respiratory outcomes during early childhood. Thus, asthma risk may be determined early in infancy when exposures may modulate genetic risk.