Early Antibiotics Could Influence Pediatric Asthma Risk

A Vancouver-based cohort shows association between increased infancy antibiotic use, gut microbiome manipulation, and asthma development by age 5.

David M. Patrick, MD

The careful use of antibiotics during infancy in past years may have overall benefitted the rate of pediatric asthma cases, according to new study findings.

In a new Vancouver-based study assessing the prevalence of pediatric asthma at the population level since 2000, a team of investigators observed that preservation of the gut microbial community due to pragmatic antibiotic use was associated with gradual decreases in individual asthma risk through age 5.

Investigators, led by David M. Patrick, MD, of the School of Population and Public Health at the University of British Columbia, sought to understand the reason for recently reported decreases of pediatric asthma incidence in regions across North America and Europe.

As antibiotic use in infancy has been clinically associated to a child’s increased risk of developing asthma, the team investigated the hypothesis that asthma incidence decrease is linked to reduced antibiotic prescribing.

Patrick and colleagues conducted a series of population-based and prospective cohort analyses with data from the British Columbia administration and the Canadian Healthy Infant Longitudinal Development (CHILD) birth cohort, respectively.

The administrative data provided investigators with information on the 4.7 million-person population of the province, including annual rates of antibiotic prescriptions and asthma diagnosis.

The 2644-patient CHILD cohort provided data to examine for the association between systemic antibiotic use at age <1 year with the diagnosis of asthma at 5 years. Investigators also conducted a mechanistic investigation of 917 children from the cohort with available 16S rRNA gene sequencing data from fecal samples at age ≤1 year to analyze the composition of gut microbiota, relative to antibiotic exposure and asthma incidence.

The team observed an asthma incidence decrease of 7.1 per 1000 children aged 1-4 years at the population level, between 2000-2014 (27.3 vs 20.2)—a relative decrease of 26%. The incidence reduction over the observed period was associated with decreased use of antibiotics in infancy (age <1 year): prescriptions decreased from 1253.8 (95% CI, 1219.3-1288.9) per 1000 infants, to 489.1 (95% CI, 467.6-511.2) per 1000 (P <.0001).

For each 10% increase in antibiotic prescribing, pediatric asthma incidence increased by 24% (adjusted rate ratio [RR], 1.24; 95% CI, 1.20-1.28; P <.0001).

In the CHILD cohort, after excluding children who received antibiotics for respiratory symptoms, infants who received antibiotics were at a two-fold greater risk of asthma diagnosis (adjusted odds ratio [aOR], 2.15; 95% CI, 1.37-3.39; P = .0009).

A significant dose-response adjusted asthma risk increase was observed in association with antibiotics. Just 5.2% of children not exposed to antibiotics had asthma by age 5; 8.1% of those exposed once developed asthma; 10.2% of those exposed twice developed asthma, and 17.6% of those exposed ≥3 times developed asthma (aOR, 1.44; 95% CI, 1.16-1.79; P = .0008).

In observation of fecal sample, investigators observed an adjusted 32% reduced risk of asthma at age 5 years in patients in the 25th percentile versus 75th percentile in increased alpha-diversity of the microbiota.

In an interview with HCPLive® while at the American College of Allergy, Asthma, and Immunology (ACAAI) 2019 Annual Meeting in Houston, Carina Venter, PhD, RD, an associate professor of Pediatric Allergy & Immunology at the University of Colorado School of Medicine, explained how the gut microbiome has been identified as a key factor in allergic condition prevention and management.

That said, there is little understanding as to how it could be manipulated to reduce pediatric allergic development.

“We do know that the gut microbiome is central in modulating whatever is going on in the immune system, and that the gut microbiome produced short chain fatty acids such as butyrate, which regulates or up-regulates T regulatory cells, which sort of just calm down the immune system,” Venter explained.

Patrick and colleagues believe that the gut microbiota at age 1—as characterized by alpha- and beta-diversity, as well as amplicon sequence variants modified by antibiotic exposure—could be a significant mediator between outpatient antibiotic exposure in infancy and pediatric asthma diagnosis.

The study, “Decreasing antibiotic use, the gut microbiota, and asthma incidence in children: evidence from population-based and prospective cohort studies,” was published online in The Lancet Respiratory Medicine.