Association between exposure to macrolides and the development of infantile hypertrophic pyloric stenosis: a systematic review and meta-analysis
Macrolides are bacteriostatic antibiotics with a broad spectrum of activity against Gram-positive bacteria. The aim of this study was to systematically review and meta-analyze the association between infantile hypertrophic pyloric stenosis (IHPS) and macrolides. Nine databases were searched systematically for studies with information on the association between macrolides and IHPS. We combined findings using random effects models. Our study revealed 18 articles investigating the association between macrolides and IHPS. There was a significant association between the development of IHPS and erythromycin (2.38, 1.06–5.39). The association was strong when erythromycin was used during the first 2 weeks of life (8.14, 4.29–15.45). During breastfeeding, use of macrolides showed no significant association with IHPS in infants (0.96, 0.61–1.53). IHPS was not associated with erythromycin (1.11, 0.9–1.36) or macrolides use during pregnancy (1.15, 0.98–1.36).
What is known?
• Erythromycin intake in the first 2 weeks of life is associated with an increased risk of pyloric stenosis.
What is New?
• There is currently no evidence of significant association between macrolides use during pregnancy or breastfeeding and pyloric stenosis.
KeywordsErythromycin Macrolides Systematic review Meta-analysis Hypertrophic pyloric stenosis Infancy Chemotherapy
Global Health Library
infantile hypertrophic pyloric stenosis
National Institute of Health
New York Academy of Medicine
System for Information on Grey Literature in Europe
Virtual Health Library
World Health Organization
MA was responsible for the idea and study design. MA, MG, AWA, TTLH, DTVD, and NTH determined the inclusion and exclusion criteria. MA, MGK, SG, SSE, MG, AWA, TTLH, and DTVD screened the articles and extracted the data. M.G.K. and N.T.H. analyzed the data and interpreted it. All authors reviewed the paper and approved the final manuscript.
This study was conducted in part at the Joint Usage/Research Center on Tropical Disease, Institute of Tropical Medicine, Nagasaki University.
Compliance with ethical standards
Conflict of interest
The authors declare that they have no conflict of interest.
- 5.Centers for Disease Control Prevention (1999) Hypertrophic pyloric stenosis in infants following pertussis prophylaxis with erythromycin--Knoxville, Tennessee, 1999. MMWR Morb Mortal Wkly Rep 48:1117Google Scholar
- 14.Friedman DS, Curtis CR, Schauer SL, Salvi S, Klapholz H, Treadwell T, Wortzman J, Bisgard KM, Lett SM (2004) Surveillance for transmission and antibiotic adverse events among neonates and adults exposed to a healthcare worker with pertussis. Infect Control Hosp Epidemiol 25:967–973CrossRefGoogle Scholar
- 25.Kowalewski M, Schulze V, Berti S, Waksman R, Kubica J, Kołodziejczak M, Buffon A, Suryapranata H, Gurbel PA, Kelm M, Pawliszak W, Anisimowicz L, Navarese EP (2015) Complete revascularisation in ST-elevation myocardial infarction and multivessel disease: meta-analysis of randomised controlled trials. Heart 101:1309–1317CrossRefGoogle Scholar
- 27.Liberati A, Altman DG, Tetzlaff J, Mulrow C, Gøtzsche PC, Ioannidis JP, Clarke M, Devereaux PJ, Kleijnen J, Moher D (2009) The PRISMA statement for reporting systematic reviews and meta-analyses of studies that evaluate health care interventions: explanation and elaboration. Ann Intern Med 151:W-65–W-94CrossRefGoogle Scholar
- 28.Lin KJ, Mitchell AA, Yau W-P, Louik C, Hernández-Díaz S (2013) Safety of macrolides during pregnancy. Am J Obstet Gynecol 208:221. e221–221. e228Google Scholar
- 33.McGuire JM, Bunch R, Anderson R, Boaz H, Flynn E, Powell H, Smith J (1952) Ilotycin, a new antibiotic. Antibiot Chemother 2:281–283Google Scholar
- 35.Mohammadizadeh M, Ghazinour M, Iranpour R (2010) Efficacy of prophylactic oral erythromycin to improve enteral feeding tolerance in preterm infants: a randomised controlled study. Singap Med J 51:952Google Scholar
- 38.National Institutes of Health (2014) National Blood Lung and Heart Insititute. Quality assessment of controlled intervention studies. 2014. Avaliable: http://www.nhlbi.nih.gov/health-pro/guidelines/in-develop/cardiovascular-risk-reduction/tools/rct
- 39.National Institutes of Health (2014) Quality assessment tool for observational cohort and cross-sectional studies. National Heart, Lung, and Blood Institute Avaliable from: www nhlbi nih gov/health-pro/guidelines/in-develop/cardiovascular-risk-reduction/tools/cohort [Accessed November 5, 2015]Google Scholar
- 41.Nguyen AV, Thanh LV, Kamel MG, Abdelrahman SAM, El-Mekawy M, Mokhtar MA, Ali AA, Hoang NNN, Vuong NL, Abd-Elhay FA, Omer OA, Mohamed AA, Hirayama K, Huy NT (2017) Optimal percutaneous coronary intervention in patients with ST-elevation myocardial infarction and multivessel disease: an updated, large-scale systematic review and meta-analysis. Int J Cardiol 244:67–76CrossRefGoogle Scholar