Maternal antibiotic exposure during pregnancy and hospitalization with infection in offspring:a population-based cohort study

Background: The early life microbiome contributes to immune development. Antibiotics during pregnancy alter the microbiome and may influence disease risks in the offspring. We investigated the relationship between maternal antibiotic exposure before and during pregnancy, and risk of childhood hospitalization with infection.Methods: We used population-based Danish national databases for pregnancies between 1995 and 2009. Infants were followed from birth until their first infection-related hospitalization, death, 14th birthday, emigration or end-2009. Exposure was maternal antibiotics prescribed before and during pregnancy. Outcome was infection-related hospitalization.Results: 141 359 (18%) mothers had at least one antibiotic prescription during pregnancy, 230 886 (29.4% of those with complete data) in the 18 months before pregnancy. Of 776 657 live-born singletons, 443 546 infection-related hospitalizations occurred in 222 524 (28.6%) children. Pregnancy antibiotic exposure was associated with increased risk of childhood infection-related hospitalization [hazard ratio (HR) 1.18, 95% confidence interval (CI) 1.17-1.19]. In mothers prescribed antibiotics only during pregnancy whose child did not receive pre-hospitalization antibiotics, this association was present only in those born vaginally. Higher risks of infection-related hospitalization occurred when pregnancy antibiotic prescriptions were closer to birth and in mothers receiving more pregnancy antibiotics. Children born to mothers exposed to antibiotics before (but not during) pregnancy also had increased risk of infection-related hospitalization (HR 1.10, 95% CI 1.07-1.12).Conclusions: Antibiotic exposure before or during pregnancy was associated with increased risk of childhood hospitalized infections. Alteration of the maternally derived microbiome and shared heritable and environmental determinants are possible contributory mechanisms.