Associations of prenatal antibiotic exposure and delivery mode on childhood asthma inception.

BACKGROUND: Prenatal antibiotic exposure and delivery mode may affect the gut microbiome in early life and influence the development of childhood asthma, but the combined effect of these two factors is unknown.

OBJECTIVE: To identify the individual and combined effects of prenatal antibiotic exposure and delivery mode on the development of asthma in children and the potential mechanisms underlying these associations.

METHODS: A total of 789 children were enrolled from the Cohort for Childhood Origin of Asthma and Allergic Diseases (COCOA) birth cohort study. Asthma was defined as physician-confirmed diagnosis with asthma symptoms in the previous 12 months at age 7. Information on the prenatal antibiotic exposure was obtained by mothers using questionnaire. Logistic regression analysis was used. Gut microbiota analysis using 16S rRNA gene sequencing of fecal specimens obtained at 6 months was undertaken for 207 infants.

RESULTS: Prenatal antibiotic exposure and cesarean section delivery (adjusted odds ratio [aOR], 95% confidence interval [CI], 5.70 [1.25-22.81] and 1.57 [1.36-6.14], respectively) were associated with childhood asthma, especially synergistically when compared to the vaginal delivery-prenatal antibiotic exposure reference group (aOR, 7.35; 95% CI, 3.46-39.61; Interaction P=.033). Prenatal antibiotic exposure was associated with childhood asthma with aORs 21.79 and 27.03 for one and two or more exposures, respectively. Significant small-airway dysfunction (R5-R20 in impulse oscillometry) was observed with prenatal antibiotic exposure and cesarean-section delivery, compared to those with spontaneous delivery without prenatal antibiotic exposure. There was no significant difference in the diversity of gut microbiota among the four groups. However, the relative abundance of Clostridium was significantly increased in infants with prenatal antibiotic exposure and delivered via cesarean section.

CONCLUSION: Prenatal antibiotic exposure and delivery mode might modulate asthma development in children and small-airway dysfunction, potentially through early-life gut microbiota alterations.