Burden of Infections in Early Life and Risk of Infections and Systemic Antibiotics Use in Childhood
Authors: Brustad Nicklas , Buchvald Frederik , Jensen Signe Kjeldgaard , Kyvsgaard Julie Nyholm , Vahman Nilo , Thorsen Jonathan , Schoos Ann-Marie Malby , Nygaard Ulrikka , Vissing Nadja , Stokholm Jakob , Bønnelykke Klaus , Chawes Bo 
Published: January 2025

Importance

A high infection burden in early childhood is common and a risk factor for later disease development. However, longitudinal birth cohort studies investigating early-life infection burden and later risk of infection and antibiotic episodes are lacking.

Objective

To investigate whether early-life infection burden is associated with a later risk of infection and systemic antibiotic treatment episodes in childhood.

Design, Setting, and Participants

This longitudinal cohort study of children from birth to age 10 or 13 years included data from the Danish population-based Copenhagen Prospective Studies on Asthma in Childhood (COPSAC) birth cohort between November 2008 to November 2010. Children were monitored for infection diagnoses and systemic antibiotic prescriptions from national databases until February 1, 2024, by which time they had completed the age 10- or 13-year visit. Children with immune deficiencies or congenital diseases were excluded.

Exposures

Daily diary-registered common infection episodes of cold, acute otitis media, tonsillitis, pneumonia, gastroenteritis, and fever episodes from birth to 3 years.

Main Outcome and Measures

After age 3 years, the incidence of moderate to severe infection diagnoses and systemic antibiotic prescriptions were estimated using adjusted incidence rate ratios (AIRRs) calculated from quasi-Poisson regression models. All analyses were adjusted for social and environmental confounders.

Results

A total of 614 children (317 male [51.6%]) with diary data from birth to 3 years had completed follow-up until age 10 or 13 years. No differences in baseline characteristics between the children having vs not having available diary data were noted. Children with a high vs low burden of diary-registered infections between birth and 3 years (ie, equal to and above vs below the median of 16) had an increased risk of later moderate to severe infections (181 vs 87 episodes; AIRR, 2.39; 95% CI, 1.52-3.89) and systemic antibiotic treatments (799 vs 623 episodes; AIRR, 1.34; 95% CI, 1.07-1.68) until age 10 or 13 years. Each diary infection episode also increased the later risk of moderate to severe infections (AIRR, 1.05; 95% CI, 1.02-1.08) and systemic antibiotic treatments (AIRR, 1.02; 95% CI, 1.01-1.04). Subtype analyses showed significant associations between each cold, acute otitis media, pneumonia, gastroenteritis, and fever episode between birth and 3 years and risk of later moderate to severe infections or systemic antibiotic treatments.

Conclusions and relevance

This longitudinal cohort study suggests that early-life infection burden may continue throughout childhood and is associated with later antibiotic treatments independent of social and environmental risk factors. These findings are important for prognosis and follow-up of children experiencing a high burden of common infections in early life.