Early antibiotic exposure tied to immune-mediated diseases in children, young adults

A registry-based cohort study presented at ERS 2024 demonstrates a relationship between antibiotic exposure in early life and the development of immune-mediated diseases (IMDs) in childhood and young adulthood.

“Our nationwide Danish registry study revealed significant associations between antibiotic use in the first year of life and the subsequent development of asthma and other diseases,” said Sarah Brandt, PhD student from the Copenhagen Prospective Studies on Asthma in Childhood at Copenhagen University Hospital, Herlev-Gentofte, Denmark.

To explore the link between early-life antibiotic use and diseases in childhood, Brandt and her team leveraged data from comprehensive national Danish health registries. The final study population comprised over half a million children born between 1998 and 2006. [ERS 2024, abstract OA5570]

The investigators evaluated several outcomes, including asthma, allergy, eczema, coeliac disease, juvenile arthritis, overweight, and type 1 diabetes (T1D) from childhood up to 18 years of age, and adjusted for familial factors by sibling analysis. The participants were followed for an average of 13 years. About 40 percent (n=209,013) of the overall cohort were exposed to systemic antibiotics before the age of 1 year.

A significant association was observed between early antibiotic exposure and increased risk of all hospitalization- and prescription-based outcomes except for T1D, with adjusted hazard ratios (HRs) ranging between 1.25 and 1.52.

When the sibling design was taken into context, the estimates were attenuated except for asthma and eczema (adjusted HRs ranging between 1.07 and 1.35). The outcome for asthma remained significant after adjusting for familial factors. According to Brandt, this implies that some of the associations may be explained by familial context.

A marker for underlying familial predispositions

Early-life antibiotic use is associated with the disruption of the microbiome, which can lead to dysregulation of the immune system and subsequent disease. [Gut Microbes 2012;3:4-14; Cell Res 2020;30:492-506]

Evidence has shown a correlation between antibiotics and several diseases, but these may have been limited by small sample sizes and confounding by indication. Also, most of the studies have not taken into account the familial setting. [J Infect 2022;85:213-300; Lancet Respir Med 2014;2:621-630; BMC Pediatr 2019;19:225; Antibiot Basel Switz 2023;12:314]

“[Our findings have shown that] early-life antibiotic exposure is linked to IMDs in childhood and young adulthood, but familial and unmeasured factors within the family context may provide partial explanations,” Brandt said.

“[Hence,] early antibiotic exposure may be a marker for underlying familial predispositions rather than a direct cause of disease, which might trigger some immune responses for later disease development,” she added.

Furthermore, the persistent associations with asthma highlight potential specific risks, Brandt pointed out. “The study emphasizes the need to better understand the interplay between antibiotics, familial proneness, and immune-mediated pathogenesis to identify potential strategies [for asthma prevention].”

Although the sibling analysis controlled for unmeasured confounders, it may have also introduced potential bias. [Epidemiol Camb Mass 2012;23:713-720] Moreover, detailed environmental data was lacking despite the large dataset. Despite the limitations, Brandt noted that there was little to no bias in recording exposure and outcomes.