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