The impact of hospital length-of-stay after birth on infant gut microbiota

Introduction: Infants delivered by cesarean section normally stay longer in hospital after birth and are treated with antibiotics, both of which promote hospital-acquired infection with Enterococcus spp., and enterobacterial species of the Proteobacteria. How prolonged exposure to a hospital environment affects infant gut microbial development and ultimately, health is still unknown. Objective: The study aimed to assess the association between prolonged hospitalization following any delivery type and infant gut microbial composition at 3 and 12 months of age. Methods: This was a study of 1313 infants in the Canadian Healthy Infant Longitudinal Development (CHILD) Cohort Study, excluding home births. Infant gut microbiota was characterized by Illumina 16S rRNA sequencing of fecal samples collected at 3 months and 12 months of age. The gut microbial profile of infants hospitalized for >1 day in vaginal birth (VB) and ≥3 days in cesarean delivery (CD) were compared to profiles of infants with shorter-length hospitalization. Vaginally delivered infants were further stratified based on a maternal intrapartum antibiotic (IAP). Relative abundances of dominant taxa were compared by Mann-Whitney U-test and LEfSe analysis. Associations between prolonged hospitalization and gut microbiota composition were determined by logistic regression, adjusting for gestational age and breastfeeding status. Results: Prolonged hospitalization after VB was associated with persistent enrichment of family Clostridiaceae, namely Clostridium; Veillonella; and species of Proteobacteria: Citrobacter (p=<0.01, 3 months) and Sutterella (p=<0.01, 12 months). There was an over-representation of Veillonella, and several Enterobacteriaceae after CD but at 12 months only. At 3 months, beneficial bacteria Bacteroides (p=0.03) were depleted in VB infants and Bifidobacterium (p=0.025) in CD infants. Already depleted in CD [median abundance=0.0008, IQR (0.0003 - 0.0056)] versus VB [median abundance=0.301, IQR (0.001-0.597)] at 3 months (p=<0.01), prolonged hospitalization following CD further lowered the abundance of Bacteroides (0.47 [95% CI:0.28-0.80], p=<0.01) at 12 months. In the absence of IAP exposure, VB term infants with a longer hospital stay and non-exclusively breastfed were more likely to have a higher abundance of Enterococcus in their gut both at 3 months (aOR=1.35 [95%CI:0.99-1.85], p=0.059) and 12 months (aOR=1.42 [95%CI:1.02-1.97], p=0.036) of age. The same group of infants with longer hospital stays also had higher abundances of Citrobacter (aOR=1.39 [95%CI: 1.02-1.898], p=0.037) and lower abundances of Bacteroides (aOR=0.73 [95%CI: 0.54-1.00], p=0.05) at 3 months. Conclusion: Prolonged infant exposure to the hospital microbial environment after birth can lead to over-representation of gut microbiota associated with hospital-acquired infections, as well as the depletion of several beneficial microbiota.