Azithromycin in early infancy and pyloric stenosis

Use of oral erythromycin in infants is associated with infantile hypertrophic pyloric stenosis (IHPS). The risk with azithromycin remains unknown. We evaluated the association between exposure to oral azithromycin and erythromycin and subsequent development of IHPS.

A retrospective cohort study of children born between 2001 and 2012 was performed utilizing the military health system database. Infants prescribed either oral erythromycin or azithromycin as outpatients in the first 90 days of life were evaluated for development of IHPS. Specific diagnostic and procedural codes were used to identify cases of IHPS.

A total of 2466 of 1 074 236 children in the study period developed IHPS. Azithromycin exposure in the first 14 days of life demonstrated an increased risk of IHPS (adjusted odds ratio [aOR], 8.26; 95% confidence interval [CI], 2.62-26.0); exposure between 15 and 42 days had an aOR of 2.98 (95% CI, 1.24-7.20). An association between erythromycin and IHPS was also confirmed. Exposure to erythromycin in the first 14 days of life had an aOR of 13.3 (95% CI, 6.80-25.9), and 15 to 42 days of life, aOR 4.10 (95% CI, 1.69-9.91). There was no association with either macrolide between 43 and 90 days of life.

Ingestion of oral azithromycin and erythromycin places young infants at increased risk of developing IHPS. This association is strongest if the exposure occurred in the first 2 weeks of life, but persists although to a lesser degree in children between 2 and 6 weeks of age.