The fact that early losses due to infections weigh heavily on individuals in terms of health-associated costs and increase the incidence of morbidity and mortality worldwide does not suggest that this number of infections experienced in childhood is at risk for future development of atopic diseases, cardiometabolic risks, and mental disorders. Hence, identifying and monitoring children closely for the future occurrence of any other conditions becomes a necessity.
Furthermore, the patient’s environmental and social context should also be taken into consideration, particularly since many factors seem to be associated with recurring respiratory injurious conditions in early childhood infections.
A study published in the JAMA Network aimed to determine whether the infection burden during early life attenuates with age. To answer this, longitudinal studies recorded relevant exposure information in detail. We pursued this kind of follow-up with the Copenhagen Prospective Studies on Asthma in Childhood 2010 (COPSAC2010) cohort in which children were followed from birth up to the ages of 10 or 13 years.
According to this longitudinal cohort study focuses on children from birth to the age of 10 or 13 years, it gathers the data from a Danish population-based cohort-National COPSAC birth cohort, which longitudinally records children from Nov 2008 to Nov 2010. The children thus followed up in terms of infection diagnoses and prescriptions of systemic antibiotics from national data sources until Feb 1, 2024, when they completed the 10- or 13-year visit. Those with immune deficiencies or diseases are excluded from consideration. As per the diary kept by each family, information about episodes of common cold, gastroenteritis, tonsillitis, acute otitis media, pneumonia, and fever was recorded daily from birth until the age of 3 years.
Incidence of the moderate to severe infection diagnoses & systemic antibiotics use after the age of 3 was evaluated using adjusted incidence rate ratios (AIRRs) and calculated by quasi-Poisson regression models. All analyses were controlled for social & environmental confounders.
Follow-up data were collected for 614 children, including 317 males (51.6%), tracking their health from birth to over 10 years of age or from ages 3 years to 13 years. No significant baseline differences were observed in children with or without available diary data. Children with a higher burden of infections recorded in their diaries between birth and age 3 (≥16 infections) were more likely to experience moderate to severe infections later (181 vs. 87 matched episodes; AIRR, 2.39; 95% CI, 1.52-3.89) and require systemic antibiotics between ages 10 and 13 (799 vs. 623 episodes; AIRR, 1.34; 95% CI, 1.07-1.68). Each infection recorded in the diary was associated with an increased risk of later moderate to severe infections (AIRR, 1.05; 95% CI, 1.02-1.08) and the need for systemic antibiotics (AIRR, 1.02; 95% CI, 1.01-1.04).
The foremost merit of this study is following the longitudinal clinical chart of the children from birth until late childhood for at least ten years, as well as the detailed documentation of each child’s diagnosis and medication prescriptions- the most important carrying feature revealed in this analysis. The children recruited were cited in multiple scheduled and emergency visits to the COPSAC clinic, thus ensuring consistency in the diagnosis of acute respiratory illness episodes between the children.
We also had unique day-to-day diary registrations of the most common infection types from birth to 3 years that thoroughly described early infection burden. The cohort is population-based; hence, the findings should be generalizable. Many possible external risk factors, such as social and environmental exposures, were also considered across the follow-up period per child in order to reduce the risk of confounding. Thus, data were also collected regarding virus types from as many acute respiratory illness episodes as possible during the first 3 years of life, allowing for a detailed investigation of specific airway pathogens.
Although we attained a high follow-up rate of 92% over 10 years until age 10 years, this study may be affected by attrition bias. First, our cohort is confined to the Danish population, and therefore, our findings might not be applicable to populations around the world. Lastly, only a small subgroup of children met the criterion for testing by an acute airway virus sample in early childhood, based on troublesome lung symptoms.
Thus, regarding qualitative studies, this study was based on a cohort of 614 children with follow-ups after a duration of 10 to 13 years, collecting unique data from diaries maintained for them while in early childhood. We show how the burden of common infection episodes during the early years could sensitize later risk for moderate to severe infections as well as systemic antibiotic treatments, causally related rather than due to social and environmental risk factors. The implications might include prognostic insights and follow-up strategies for children who experience an early burden of infections that are understood as common.
Reference: Brustad N, Buchvald F, Jensen SK, et al. Burden of Infections in Early Life and Risk of Infections and Systemic Antibiotics Use in Childhood. JAMA Netw Open. 2025;8(1):e2453284. doi:10.1001/jamanetworkopen.2024.53284
