3.4 Cumulative prenatal antibiotic courses and AD risk
We observed a significant dose-response association between number of prenatal antibiotic courses and AD. With a mean of 2.1 courses of antibiotic use during pregnancy, the adjusted HRs were 1.05 (95% CI 1.04-1.06) for 1-2 courses of antibiotic use, 1.08 (95% CI 1.06-1.1) for 3-4 courses of antibiotic use, and 1.11 (95% CI 1.09-1.14) for ≥5 courses of antibiotic use (Table S1).
Discussion
In this population-based study, we found a positive association between prenatal antibiotic exposure in all trimesters and development of AD in childhood. This association remained significant after adjusting for several established AD risk factors in the hazards model analysis. The positive association remained significant in the subgroup analysis regardless of postnatal antibiotic use after excluding AD diagnosed before 1 year of age, but the association did not persist in children who were not exposed to postnatal acetaminophen. We also found an apparent dose-response relationship with an 11% increased risk when exposed to ≥5 courses prenatally. To our knowledge, this is the largest study to date to investigate the relationship between maternal antibiotic use during pregnancy and offspring AD.
The gut microbiome and the intestinal immune system develop in parallel in the first trimester, which is also when enrichment of innate immune cells in skin takes place.13,14 Studies have reported that intrauterine samples/placenta harbor bacterial DNA or biomass and its colonization may begin in utero.7,14-16 However, whether the bacterial DNA are present in the placenta is still a matter of debate, as some studies have suggested the presence of DNA may be caused by contamination during the DNA purification process.16 Nevertheless, the maternal microbiome can potentially influence fetal immune maturation through agonists of toll-like receptors (TLRs), short-chain fatty acids (SCFAs) or lipopolysaccharides (LPS) via the placenta.16,17Proper differentiation, specification and complete development of adaptive immunity rely on the interactions between gastrointestinal-associated lymphoid tissue (GALT) and the gut microbiome.14 Dysbiosis, which refers to imbalances in gut microflora and changes in their functional composition, local distribution, and metabolic activities,18 may potentially lead to allergy and atopic diseases.14,19Dysbiosis that occurs during the critical time window of immune development, even within a short-term period, may have a long-term impact on immune health.14