Infantile hypertrophic pyloric stenosis after pertussis prophylaxis with erythromycin: a case review and cohort study

Background In February, 1999, a local US health department identified a cluster of pertussis cases among neonates born at a community hospital and recommended oral erythromycin for post-exposure prophylaxis for about 200 neonates born at that hospital between Feb 1 and Feb 24, 1999, We investigated a cluster of seven cases of infantile hypertrophic pyloric stenosis (IHPS) that occurred the following month among the neonates who had received erythromycin. Methods We obtained a masked, independent review of the IHPS ultrasonography diagnoses, calculated the monthly IHPS incidence, and compared index and historical (1998-99) IHPS cases with respect to several characteristics including erythromycin exposure. We used a retrospective cohort of infants born in January and February, 1999, to investigate further erythromycin exposure and development of IHPS. Findings An independent review confirmed the ultrasonographic diagnoses of all seven index IHPS cases. All index cases versus none of the historical IHPS cases had been given erythromycin for pertussis prophylaxis. The IHPS rate for infants born in the hospital in February, 1999, was 323 per 1000 liveborn infants, representing nearly a seven-fold increase over 1997-98 (relative risk 6.8 [95% CI 3.0-15.7]). Among infants born in January and February, 1999, erythromycin was associated with IHPS (absolute risk 4.5%, relative risk infinity [1.7-infinity]). Interpretation Neonates receiving oral erythromycin may have an increased risk of IHPS. The risks and benefits of erythromycin for neonatal pertussis prophylaxis should be re-evaluated, and caution should be used in defining risk groups for prophylaxis.