Infant Acid‐Suppressant Medication, C. difficile Colonisation, and Childhood Body Mass Index in a Canadian Cohort

AIM: To determine relationships between paediatric use of acid-suppressive medications (ASMs) (proton pump inhibitors (PPI) and histamine-2 receptor antagonists (H2RA)) and preschool body mass index (BMI) and mediation by C. difficile colonisation. METHODS: ASMs were parent-reported at age 3, 6 and 12 months in 1025 infants from the CHILD Cohort Study. Targeted qPCR for C. difficile was conducted in stool collected at 3 months, and age/sex adjusted BMI-z scores were calculated at age 5 years. ASM use and BMI-z score associations were assessed by regression, and mediation analyses were conducted. RESULTS: Approximately 4% of infants received H2RAs, most before age 3 months. C. difficile colonisation was twice as likely in 3-month-old infants receiving H2RAs (OR: 2.27, 95% CI: 1.13-4.51) and was associated with higher BMI-z scores at age 5 years (β: 0.31, 95% CI: 0.16, 0.46). Mediation models showed an indirect positive effect of H2RA use on 5-year BMI-z scores, mediated through C. difficile colonisation (β: 0.065, 95% CI: 0.01, 0.13). CONCLUSIONS: We found evidence of increased preschool BMI following H2RA use in infants that was mediated through C. difficile colonisation. Further study on ASM use in infancy, the gut microbiome, and pathways to body weight health outcomes is warranted.