Higher
risk of allergies at 4-6 years of age after systemic antibiotics in the
first week of life
To the editor,
In humans, the first 100 days appear to be a ”critical window” of
colonization during which microbial communities shape immune maturation.1,2. The use of antibiotics early in life may disrupt
the normal maturation process leading to adverse health outcomes such as
atopic disorders 1,3-5. The effects of antibiotic
exposure immediately in the first week of life have rarely been
investigated, nor the differences between treatment of 2-3 days and a
prolonged treatment of 5-7 days. In the INCA study, a prospective birth
cohort study of 151 infants receiving broad-spectrum antibiotics in
their first week of life (AB+), and 285 healthy controls (AB-), we
previously showed that antibiotic treatment in the first week of life
was associated with an increased risk of wheezing, infantile colic and a
trend towards more allergic sensitization in the first year of life6. The aim of this follow-up study in 418 eligible
children was to determine if antibiotic treatment in the first week of
life in term-born children was associated with an increase in atopic
disorders at 4-6 years of age, using ISAAC questionnaires filled out by
parents, ICPC codes derived from general physicians, and pharmaceutical
records from local pharmacies. Detailed information regarding the
subjects and methods is described in the online Appendix.
In total, 341 of 418 (82%) questionnaires were filled out (114 AB+ and
227 AB-), Parental reported allergy was significantly higher in AB+ vs
AB- children (23% vs 11% respectively, p=0.003) as was
doctor-diagnosed allergy (12% vs 4% respectively, p=0.008). Confirmed
food allergies were more common in AB+ children compared with AB-
children (10 vs. 4% respectively, p=0.03). After correcting for sex,
age, daycare attendance, family atopy, and parental level of education,
parental-reported allergy was clearly associated with antibiotics use in
the first week of life (aOR 2.40 [95%CI 1.22-4.72, p=0.01]).
Additional adjustment for treatment duration showed that only 5-7 and
not 2-3 days AB treatment was associated with a higher risk of parental
reported allergy (aOR 2.85 [95%CI 1.37-5.91, p=0.005]). More
importantly, this effect was independent of exposure to acid-suppressive
drugs or additional antibiotics in the first two years of life (36% and
35% in AB- and AB+ group, respectively). The prevalence of eczema,
wheezing/asthma, or allergic rhinitis was not different between AB+ and
AB- children (Table 2).
These results suggest that very early exposure to AB in the first week
of life has a higher impact on microbiota and immune development than
when administered later in childhood. It also emphasizes the need for
judicious use of AB in neonates, especially prolonged treatment of 5-7
days. Moreover, our findings accentuate the need for finding strategies
to modify microbiome development after AB exposure to minimize aberrant
immune development.
Strengths of this study are the prospective design, the high response
rate (82%), and the combined information collected from doctors and
pharmacists, contributing to the reliability of the reported results,
which allowed us to distinguish between the effect of antibiotics within
and after the first week of life. A limitation of the study is the
4-6-year follow-up, which may have been too short for diagnosing asthma
and allergic rhinitis.
In conclusion, the risk of having
an allergy at 4-6 years of age increased nearly 3-fold in children after
antibiotic treatment for 5-7 days in their first week of life,
independent of later AB treatment. These long-term adverse health
effects of neonatal antibiotic use emphasize the need to implement AB
stewardship programs to avoid AB overuse and reduce the duration of AB
treatment where possible in the first week of life.