Antibiotic use among Dutch pregnant woman and the development of toddler asthma: the influence of confounding
Recent studies have reported an increased risk for the development of asthma in children after prenatal exposure to antibiotics, notably during third trimester, but associations could have been influenced by unmeasured confounders. We aimed to assess the association between antibiotic use during pregnancy and the development of toddler asthma with a confounding minimizing crossover (case-sibling) and a case-control design.
METHODS:
Using a linked mother-infant subset of the University Groningen prescription database IADB.nl we conducted a crossover study in which 1,228 children with asthma were compared to their own siblings without asthma. In addition we applied a traditional matched case-control study to gain more insights in the potential of confounding influences. Maternal exposure was defined as ≥1 day of supply of systemic antibiotics during pregnancy. Children were considered to have asthma if they received ≥3 prescriptions for anti-asthma medication within a year before the fifth birthday. Conditional logistic regression was used to estimate crude and adjusted odds ratios(aOR). Sensitivity analyses were performed to estimate the potential influence of unobserved time-varying confounders.
RESULTS:
The crossover analysis showed no increased risk for the development of toddler asthma if antibiotics were used anytime during pregnancy (aOR 1.06 95% CI (0.85-1.32)). In the case-control study the use of antibiotics anytime during pregnancy was associated with an aOR of 1.46 (95% CI 1.34-1.59). The crossover analysis yielded only a significant increased risk for the development of asthma if mothers had used antibiotics during third trimester (aOR 1.37 95% CI (1.02-1.83)).
CONCLUSIONS:
Prenatal exposure to antibiotics in the third trimester of pregnancy appeared associated with an increased risk of childhood asthma. This association did not appear to be influenced by time-invariant confounders such as genetic predisposition. However the influence of time-variant confounders, such as disease severity, cannot be ruled out.