Dose, Timing, and Type of Infant Antibiotic Use and the Risk of Childhood Asthma

Abstract

Background: Aspects of infant antibiotic exposure and its association with asthma development have been variably explored. We aimed to evaluate comprehensively and simultaneously the impact of dose, timing, and type of infant antibiotic use on the risk of childhood asthma.

Methods: Singleton, term-birth, non-low-birth-weight, and otherwise healthy children enrolled in the Tennessee Medicaid Program were included. Infant antibiotic use and childhood asthma diagnosis were ascertained from prescription fills and healthcare encounter claims. We examined the association using multivariable logistic regression models.

Results: Among 152 622 children, 79% had at least 1 antibiotic prescription fill during infancy. Infant antibiotic use was associated with increased odds of childhood asthma in a dose-dependent manner, with a 20% increase in odds (adjusted odds ratio [aOR], 1.20 [95% confidence interval {CI}, 1.19-1.20]) for each additional antibiotic prescription filled. This significant dose-dependent relationship persisted after additionally controlling for timing and type of the antibiotics. Infants who had broad-spectrum-only antibiotic fills had increased odds of developing asthma compared with infants who had narrow-spectrum-only fills (aOR, 1.10 [95% CI, 1.05-1.19]). There was no significant association between timing, formulation, anaerobic coverage, and class of antibiotics and childhood asthma.

Conclusions: We found a consistent dose-dependent association between antibiotic prescription fills during infancy and subsequent development of childhood asthma. Our study adds important insights into specific aspects of infant antibiotic exposure. Clinical decision making regarding antibiotic stewardship and prevention of adverse effects should be critically assessed prior to use during infancy.

Keywords: childhood asthma; clinical decision making; dose-response relationship; drug utilization; infant antibiotics.

Figure 1.

Infant antibiotic use is associated with an increased odds of childhood asthma in a dose-dependent manner (N = 152 622). The predicted probability was calculated using a multivariable logistic regression model adjusting for maternal smoking during pregnancy, maternal age at delivery, maternal education level, marital status, residence, gestational age at delivery, mode of delivery, number of living siblings at home, birth weight, infant race, infant sex, birth year, and birth month.

Figure 2.

Timing in month at the first antibiotic fill is associated with an increased odds of childhood asthma compared with infants who had no antibiotics filled during infancy (reference group) (N = 152 622). Adjusted odds ratios were calculated using a multivariable logistic regression model adjusting for maternal smoking during pregnancy, maternal age at delivery, maternal education level, marital status, residence, gestational age at delivery, mode of delivery, number of living siblings at home, birth weight, infant race, infant sex, birth year, birth month, and total number of prescription fills during infancy. Horizontal lines denote 95% confidence intervals. The number (%) of children in each group is given to the right of these lines.

Figure 3.

Infant antibiotic use is associated with an increased odds of childhood asthma in a dose-dependent manner in every severity level of bronchiolitis healthcare encounters infants experienced during their first year of life (N = 152 622; P value for interaction effect = .006). The predicted probability was calculated using a multivariable logistic regression model adjusting for maternal smoking during pregnancy, maternal age at delivery, maternal education level, marital status, residence, gestational age at delivery, mode of delivery, number of living siblings at home, birth weight, infant race, infant sex, birth year, and birth month.

Figure 4.

Infant antibiotic use is associated with an increased odds of childhood asthma in a dose-dependent manner in children of mothers with (n = 3884) and without (n = 83 264) maternal asthma. The predicted probability was calculated using a multivariable logistic regression model adjusting for number of prenatal antibiotic prescription fills, maternal smoking during pregnancy, maternal age at delivery, maternal education level, marital status, residence, gestational age at delivery, mode of delivery, number of living siblings at home, birth weight, infant race, infant sex, birth year, and birth month.