Reduced infant antibiotic use tied to lower childhood asthma incidence

Last Updated: 2020-04-09

By Lisa Rapaport

(Reuters Health) - Reduced incidence of pediatric asthma in recent years might be an unexpected benefit of prudent antibiotic use during infancy, a population-based prospective cohort analysis in Canada suggests.

Researchers used administrative data from British Columbia on annual rates of antibiotic prescriptions and asthma diagnoses, to assess the association between antibiotic prescribing before age 1 and asthma incidence from ages 1 to 4.

At the population level, between 2000 and 2014, asthma incidence in children aged 1 to 4 showed an absolute decrease of 7.1 new diagnoses per 1,000 children, from 27.3 to 20.2 per 1,000 children (a relative decrease of 26%).

Over the same period, antibiotic use before age 1 declined from 1,254 to 489 prescriptions per 1,000 infants.

"Antibiotics very likely cause a predisposition to asthma and do so by perturbing the normal interaction between gut microflora and the developing immune system," said lead author Dr. David Patrick, a researcher at the University of British Columbia School of Population and Public Health and director of research at the British Columbia Centre for Disease Control.

"Big reductions in antibiotic use in infancy would appear to reduce the risk of asthma in an entire birth cohort of kids," Patrick said by email. "This means that we may have identified a new way to reverse the asthma epidemic in countries and regions where antibiotic use in babies can be safely reduced."

Asthma incidence increased by 24% with each 10% increase in antibiotic prescribing, the study found.

Separately, the researchers examined data on 2,644 children from the Canadian Healthy Infant Longitudinal Development (CHILD) prospective birth cohort, analyzing the association between systemic antibiotic use before age 1 and an asthma diagnosis by age 5.

After exclusion of children who received antibiotics for respiratory symptoms, infant antibiotic use was associated with more than doubled the odds of an asthma diagnosis by age 5 (adjusted odds ratio 2.15).

Heavier antibiotic use was associated with a higher asthma risk, the researchers report in the Lancet Respiratory Medicine.

Overall, by age 5, asthma rates were 5.2% in children who didn't receive antibiotics by age 1, 8.1% in kids who received one course of antibiotics, 10.2% in children who received 2 courses, and 17.6% of kids who had 3 or more courses of antibiotics by age 1.

In 917 children with 16S rRNA gene sequencing data from fecal samples taken by age 1, increasing diversity of the gut microbiota was associated with a 32% reduced risk of asthma at age 5 years. Gut microbiota diversity appeared to be a significant mediator between outpatient antibiotic exposure in the first year of life and asthma diagnosis at age 5.

In addition, the 6 bacterial taxa that differed in their relative abundance between antibiotic-exposed, asthmatic children and non-exposed, non-asthmatic children have established links with immunomodulatory functions, the study team notes.

The researchers say that while they deliberately focused on the effect of antibiotics on the composition of the gut microbiota, the gut also contains fungal communities that might be modulated by antibiotics and potentially involved in the pathogenesis of asthma.

Another limitation is that other bacterial communities in the body were not sampled, such as the airway microbiota, the authors note.

"In a study like the present one, we can never be all certain that other factors both influencing susceptibility to receiving antibiotics and also to asthma are not the true cause for the findings," said Dr. Jakob Stokholm, author of an editorial accompanying the study and a senior researcher at the Copenhagen Prospective Studies on Asthma in Childhood at Herlev and Gentofte Hospital and the University of Copenhagen.

Still, the results offer yet another reason to promote good antibiotic stewardship in treating infants, Stokholm said by email.

"Antibiotics shall of course be administered to children suffering from acute bacterial infections," Stokholm said. "However, many children may be treated unnecessarily for a self-limiting, mainly viral infection, which may show exactly the same symptoms as a bacterial infection."

SOURCE: https://bit.ly/3aXrr6Z Lancet Respiratory Medicine, online March 24, 2020.