European Journal of Pediatrics

, Volume 178, Issue 3, pp 301–314 | Cite as

Association between exposure to macrolides and the development of infantile hypertrophic pyloric stenosis: a systematic review and meta-analysis

  • Mohammed Abdellatif
  • Sherief Ghozy
  • Mohamed Gomaa Kamel
  • Sameh Samir Elawady
  • Mohamed Mohy Eldeen Ghorab
  • Andrew Wassef Attia
  • Truong Thi Le Huyen
  • Diep Trong Vien Duy
  • Kenji Hirayama
  • Nguyen Tien HuyEmail author
Original Article


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).

Conclusions: There is an association between erythromycin use during infancy and developing IHPS in infants. However, no significant association was found between macrolides use during pregnancy or breastfeeding. Additional large studies are needed to further evaluate potential association with macrolide use.

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.


Erythromycin Macrolides Systematic review Meta-analysis Hypertrophic pyloric stenosis Infancy Chemotherapy 



confidence interval


Global Health Library


infantile hypertrophic pyloric stenosis


National Institute of Health


New York Academy of Medicine


odds ratio


rate ratio


standard deviation


System for Information on Grey Literature in Europe


Virtual Health Library


World Health Organization


Authors’ contributions

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.

Informed consent

Not Applicable.

Supplementary material

431_2018_3287_MOESM1_ESM.docx (1.7 mb)
ESM 1 (DOCX 1789 kb)


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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  • Mohammed Abdellatif
    • 1
    • 2
  • Sherief Ghozy
    • 2
    • 3
  • Mohamed Gomaa Kamel
    • 2
    • 4
  • Sameh Samir Elawady
    • 2
    • 5
  • Mohamed Mohy Eldeen Ghorab
    • 2
    • 6
  • Andrew Wassef Attia
    • 2
    • 7
  • Truong Thi Le Huyen
    • 2
    • 8
  • Diep Trong Vien Duy
    • 2
    • 8
  • Kenji Hirayama
    • 9
  • Nguyen Tien Huy
    • 10
    • 11
    Email author
  1. 1.Neonatal Intensive Care UnitAl-Adan hospital, Ministry of HealthHadiyaKuwait
  2. 2.Online Research Club (
  3. 3.Neurosurgery DepartmentEl Sheikh Zayed Specialized HospitalGizaEgypt
  4. 4.Faculty of MedicineMinia UniversityMiniaEgypt
  5. 5.Faculty of MedicineTanta UniversityTantaEgypt
  6. 6.Faculty of MedicineAlexandria UniversityAlexandriaEgypt
  7. 7.Ain Shams University HospitalCairoEgypt
  8. 8.University of Medicine and PharmacyHo Chi Minh CityVietnam
  9. 9.Department of Immunogenetics, Institute of Tropical Medicine (NEKKEN), Leading Graduate School Program, and Graduate School of Biomedical SciencesNagasaki UniversityNagasakiJapan
  10. 10.Evidence Based Medicine Research Group & Faculty of Applied SciencesTon Duc Thang UniversityHo Chi Minh CityVietnam
  11. 11.Department of Clinical Product Development, Institute of Tropical Medicine (NEKKEN), Leading Graduate School Program, and Graduate School of Biomedical SciencesNagasaki UniversityNagasakiJapan

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