Table 1 Erythromycin and infantile hypertrophic pyloric stenosis.
| Author, country, year | Study group | Study type (level of evidence) | Outcome | Key results | Comments |
|---|---|---|---|---|---|
| Sanfillipo, USA, 19761 | 963 live births at Naval Hospital, Great Lakes, between November 1972 and October 1973. All the infants with confirmed pyloric stenosis during this period were identified | Retrospective cohort study (level IIb) | Association between erythromycin use and development of pyloric stenosis | Five of six infants with operative confirmed pyloric stenosis received erythromycin estolate at a dose of 40 mg/kg/day for superficial skin infections between 8 and 17 days of life | Small sample size |
| Retrospective study | |||||
| No controls | |||||
| Detailed discussion of all the cases was reported | |||||
| No specific information was given on the prevalence of erythromycin use among infants who did not develop IHPS | |||||
| Honein USA, 19992 | 282 infants born in Jan– Feb 1999 at a community hospital | Retrospective cohort study and case review (level IIb) | Association between erythromycin use and development of pyloric stenosis | Absolute risk of IHPS was 5.1% for infants who took erythromycin for 8–14 days and 10% for infants who took it for 15–21 days | A blinded independent review of ultrasonography scans of the seven IHPS cases identified at surgery, and seven negative ultrasonography scans of the pylorus from the same hospital during the same period was obtained to validate the diagnosis. |
| Risk did not differ by erythromycin preparation (ethylsuccinate or estolate) | |||||
| 157 of those were given erythromycin as post pertusis exposure prophylaxis whereas 125 were not given erythromycin | The seven index cases were younger at the time erythromycin started (median 5 days) than the unaffected infants exposed to erythromycin (median 13 days, mean 14.1 days) | All of the seven index cases with IHPS were compared with historical IHPS cases at the two hospitals in the region at which pyloromyotomies were performed | |||
| Mahon Indianapolis, USA, 20013 | 14 876 Infants born at an urban hospital from June 1993 through December 1999. Infants who died in first 3 months of life and infants who did not receive care within the study network were excluded from the study. A total of 469 infants were prescribed systemic erythromycin, 124 erythromycin ophthalmic ointment and 3346 mothers were prescribed systemic erythromycin | Retrospective cohort (level IIb) | Association between erythromycin use and development of pyloric stenosis | Infants who were prescribed systemic erythromycin had increased risk of IHPS with the highest risk in the first 2 weeks of life (relative risk = 10.51, 95% CI 4.48 to 24.66) | Retrospective study |
| Prescriptions of longer periods of treatment (>14 days ) were associated with higher risk (p<0.05) | Decent sample size | ||||
| Erythromycin ophthalmic ointment use was not associated with increased risk of IHPS. | No specific information was obtained to assess the compliance with the treatment | ||||
| There were inconclusive data related to the association between maternal use of macrolides within 10 weeks of delivery and IHPS | |||||
| Cooper et al, USA, 20024 | Medicaid or TennCare (Tennessee's program for Medicaid enrolees and uninsured individuals) births in Tennessee from 1985 to 1997 (314 029 infants) | Retrospective cohort study (level IIb) | Association between erythromycin use and development of pyloric stenosis | Very early exposure to erythromycin (between 3 and 13 days of life) was associated with nearly eightfold increased risk of pyloric stenosis (adjusted incidence rate, 7.88; 95% CI 1.97 to 31.57). | Retrospective study |
| All the infants with a diagnosis of pylorics stenosis at hospital discharge and an associated surgical procedure were identified. | Decent sample size | ||||
| Exposure to erythromycin or other antibiotics between 3 and 90 days of life was identified from prescription files | Exposure to erythromycin before 90 days of life was associated with a twofold increase risk of pyloric stenosis (adjusted rate ratio, 2.05; 95% CI 1.06 to 3.97) | Infants included in Honein et al's study2 were not included | |||
| Among 314 029 infants enrolled in Medicaid, 804 (2.6/100 infants) met the criteria for pyloric stenosis | No increased risk of pyloric stenosis was seen in infants exposed to antibiotics other than erythromycin | ||||
| Sorensen et al, Denmark, 20035 | All women who had live or still births after 28 weeks of gestation between 1991 and 2000 in the Danish county of North Jutland | Population‐based cohort study (level IIb) | Association between erythromycin use and development of pyloric stenosis | The use of macrolides during breast feeding increases the risk of IHPS | No specific information was obtained to assess compliance with treatment |
| Data on drug exposure and IHPS on all of them was obtained from National Health Service, Danish Birth Registry and hospital discharge registry | The odds ratio for IHPS varied between 2.3 and 3 according to different periods of postnatal exposure, and after stratification for sex, they were 10.3 (95% CI 1.2 – 92.3) for girls and 2.0 (95% CI 0.5 –8.4) for boys. | Insufficient power | |||
| A total of 1166 pregnant women were prescribed macrolides from birth to 90 days postnatally. 41 778 women who were not prescribed erythromycin acted as control | Discharge diagnosis in the database used in the study are not entirely accurate, the proportion of misclassified cases in the used database is 5–15%. | ||||
| Patole S et al, Australia, 20056 | A total of seven studies looking at the use of erythromycin as a prokinetic agent in preterm neonates involving 359 preterm neonates (<37 weeks). | Systemic review (level Ia) | Primary outcome: time taken to reach full enteral feeds.Secondary outcome: Erythromycin‐related adverse side effects such as hypertrophic pyloric stenosis. | The issue of erythromycin‐related adverse effects cannot be considered adequately given the small sample size and insufficient data on long‐term follow‐up. | In three of the seven studies, erythromycin was used at a higher dose (>12 mg/kg/6–8 h). In the remaining four studies, it was used at a low dose (3–12 mg/kg/day). |
| None of the infants from available data developed hypertrophic pyloric stenosis |
IHPS, infantile hypertrophic pyloric stenosis.