A study of more than 4 million children in South Korea found no association between antibiotic exposure during pregnancy or early infancy and increased incidence of autoimmune diseases, researchers reported yesterday in PLOS Medicine.
The study, conducted by researchers with Sungkyunkwan University in South Korea, is the latest to examine whether early exposure to antibiotics is associated with increased risk of childhood-onset diseases and neurodevelopmental conditions. Antibiotics are the most commonly prescribed medication in young children and are frequently overused, and animal research suggests antibiotic exposure at an early age may increase the risk of these conditions by disrupting the gut microbiome while it’s still developing.
To date, studies exploring potential links between early antibiotic exposure and development of autoimmune diseases have produced conflicting results. But the authors of the new study say previous research has been limited by potential confounding variables, such as infection and genetic factors.
Analyzing antibiotic exposure during pregnancy, early infancy
For the retrospective cohort study, the researchers used data from the South Korea National Health Insurance Service–National Health Insurance Database to identify children born from April 2009 through December 2020 and their mothers. They then analyzed autoimmune-related outcomes in two distinct groups—children who were exposed to antibiotics during pregnancy and those who were exposed during infancy or early childhood—and compared them with children who had no antibiotic exposure.
The outcomes of interest included six autoimmune conditions: type 1 diabetes, juvenile idiopathic arthritis, ulcerative colitis, Crohn’s disease, systemic lupus erythematosus, and Hashimoto’s thyroiditis. Children were followed for an average of more than 7 years.
To mitigate confounding, the researchers used inverse probability of treatment weighting (IPTW) to adjust for known risk factors and conducted sibling-matched analyses. They also restricted the analysis to patients with infections, explaining that infections are a well-established contributor to the development of autoimmune disease. “This design allowed for a more precise assessment of the independent association between antibiotic exposure and autoimmune disease risk in children,” they wrote.
The pregnancy cohort included more than 2.7 million children, of whom 56.1% were exposed to antibiotics in utero. The infection-restricted IPTW analysis found no association between antibiotic exposure and increased incidence of any of the six autoimmune conditions: type 1 diabetes (hazard ratio [HR], 1.14; 95% confidence interval [CI], 0.96 to 1.35), juvenile idiopathic arthritis (HR, 1.02; 95% CI, 0.85 to 1.22), ulcerative colitis (HR, 1.02; 95% CI, 0.76 to 1.37), Crohn’s disease (HR, 1.16; 95% CI, 0.98 to 1.36), systemic lupus erythematosus (HR, 0.70; 95% CI, 0.49 to 1.01), and Hashimoto’s thyroiditis (HR, 1.06; 95% CI, 0.91 to 1.23).
In the infancy cohort, which included more than 3.3 million (57.5% of whom received antibiotics), the findings were similar. There was no difference between the exposed and non-exposed groups for incidence of type 1 diabetes (HR, 1.05; 95% CI, 0.88 to 1.26), juvenile idiopathic arthritis (HR 1.11; 95% CI, 0.93 to 1.33), ulcerative colitis (HR, 0.95; 95% CI, 0.67 to 1.36), Crohn’s disease (HR 1.07; 95% CI, 0.91 to 1.25), systemic lupus erythematosus (HR, 1.46; 95% CI, 0.95 to 2.26), or Hashimoto’s thyroiditis (HR, 1.14; 95% CI, 0.97 to 1.33).
In both cohorts, the results of infection-restricted sibling-matched analyses also showed no association between antibiotic exposure and incidence of autoimmune conditions.
“Our findings suggest no association between antibiotic exposure during the prenatal period or early infancy and the development of autoimmune diseases in children,” the authors wrote. “This observation contrasts with several previous studies reporting increased risks and underscores the importance of carefully accounting for the underlying indications for antibiotic use and familial genetic susceptibility when interpreting such associations.”
Some elevated risk in specific populations
But the authors note that subgroup analyses did find some elevated risks in specific populations. For example, children born to women exposed to cephalosporin antibiotics during pregnancy had a moderately increased risk of Crohn’s disease. In the early infancy cohort, there was an increased risk of Hashimoto’s thyroiditis in boys exposed to antibiotics.
The authors say further research is needed to explore these associations in greater detail.
“While the potential benefits of antibiotic treatment in managing infections during pregnancy or early infancy likely outweigh the minimal risk of autoimmune outcomes, our findings also highlight the need for cautious and clinically appropriate antibiotic use during these critical developmental periods, particularly in specific subgroups,” they concluded.