Oral azithromycin or erythromycin use may increase risk for infantile hypertrophic pyloric stenosis (IHPS), particularly with exposure in the first 2 weeks of life, according to findings from a retrospective cohort study published online February 16 and in the March issue of Pediatrics.

"Exposure to oral erythromycin in the first few weeks of life has been associated with the development of pyloric stenosis," write Matthew D. Eberly, MD, from the Department of Pediatrics, F. Edward Hebert School of Medicine, Uniformed Services University of the Health Sciences, Bethesda, Maryland, and colleagues. "Although azithromycin has become an acceptable alternative, little is known on whether this medication increases the risk of pyloric stenosis."

Using the military health system database, the investigators identified a cohort of 1,074,236 children born between 2001 and 2012, including 2466 children who developed IHPS, as determined from diagnostic and procedural codes. The overall rate for IHPS was 2.29 cases per 1000 live births.

However, the risk for IHPS increased eightfold with azithromycin exposure in the first 14 days of life (adjusted odds ratio [aOR], 8.26; 95% confidence interval [CI], 2.62 - 26.0). Exposure between 15 and 42 days tripled the risk (aOR, 2.98; 95% CI, 1.24 - 7.20).

The investigators also confirmed the previously observed association between erythromycin and IHPS, with 13-fold increased risk for exposure to erythromycin in the first 14 days of life (aOR, 13.3; 95% CI, 6.80 - 25.9) and fourfold increased risk for exposure to erythromycin at 15 to 42 days of life (aOR, 4.10; 95% CI, 1.69 - 9.91).

All eight infants exposed to azithromycin who developed IHPS were boys, as were 14 of the 17 infants exposed to erythromycin who developed IHPS.

Exposure to erythromycin or azithromycin between 43 and 90 days of life was not associated with increased risk for IHPS.

"Exposure to oral azithromycin in the newborn period increases the risk of developing pyloric stenosis," the authors write. "Although this risk is highest if the exposure occurred in the first 2 weeks of life, the risk extends out to 6 weeks of age."

The authors note several limitations, including the study's retrospective design, reliance on International Classification of Diseases, Ninth Revision, Clinical Modification, coding, and lack of data on factors associated with antibiotic prescription.

Azithromycin, similar to erythromycin, is a motilin receptor agonist, which stimulates migrating motor complexes in the stomach. It causes long-lasting facilitation of cholinergic activity and stimulates antral activity.

"In an era when an increasing number of young infants are being considered for pertussis prophylaxis, practitioners must carefully weigh the risks and benefits when prescribing azithromycin, particularly to male infants in the first few weeks of life," the study authors conclude. "These infants should be monitored for signs and symptoms of pyloric stenosis for 6 weeks after treatment with azithromycin."

The authors have disclosed no relevant financial relationships.

Pediatrics. 2015;135:483-488. Abstract