Long-term neurocognitive functioning of children treated with propranolol or atenolol for infantile hemangioma

Mireille M. Hermans, André B. Rietman, Renske Schappin, Peter C.J. de Laat, Elodie J. Mendels, Johannes M.P.J. Breur, Hester R. Langeveld, Saskia N. de Wildt, Corstiaan C. Breugem, Marlies de Graaf, Martine F. Raphael, Suzanne G.M.A. Pasmans*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

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The purpose of this study was to compare long-term neurocognitive functioning (working memory, processing speed, and attention) between children who had been treated with either propranolol or atenolol for infantile hemangioma during infancy. All eligible children (n = 158) aged 6 years or older and treated with propranolol or atenolol as infants were invited to participate in this two-center cross-sectional study. The primary outcome was the Wechsler Intelligence Scale for Children-V Cognitive Proficiency Index (CPI), a measure of working memory, processing speed, and attention. Secondary outcomes were general intelligence, auditory, visuospatial, and narrative memory, as well as executive functioning and sleep. A total of 105 children, of whom 36 had been treated with propranolol (age 6.0–11.8 years, follow-up time 1.6–9.7 years, 19% male) and 69 had been treated with atenolol (age 6.9–9.7 years, follow-up time 4.5–8.4 years, 19% male), were analyzed. The CPI and other neurocognitive outcomes did not differ between the propranolol and atenolol groups and were in line with general population test norms. Post hoc analyses revealed lower CPI scores for males, both compared to participating females (10.3 IQ points, medium effect size) and compared to matched test norms (12.4 IQ points, medium effect size). Conclusions: Long-term neurocognitive functioning did not differ between children treated with propranolol and those treated with atenolol for IH. Overall, propranolol and atenolol appear to be safe treatments for IH regarding long-term neurocognitive functioning. The substantially lower CPI scores in males warrant further investigation. Trial registration: Netherlands Trial Register, NL7703 https://www.trialregister.nl/trial/7703 What is Known:• Infants with infantile hemangioma are effectively treated with propranolol or atenolol.• Parents and professionals are concerned about long-term neurocognitive effects.What is New:• No long-term (≥ 6 years) differences in neurocognitive functioning were found between children treated with propranolol or atenolol.• Males treated with beta-blockers had substantially lower IQ scores than treated females and males from the general population, which is a matter of concern and should be considered when evaluating the risk/benefit ratio in less severe forms of infantile hemangioma.

Original languageEnglish
Pages (from-to)757-767
Number of pages11
JournalEuropean Journal of Pediatrics
Issue number2
Early online date7 Dec 2022
Publication statusPublished - Feb 2023

Bibliographical note

This investigator-initiated study was carried out with an unrestricted grant provided by Pierre Fabre Dermatologie.

Publisher Copyright:
© 2022, The Author(s).

Funding Information:
This project is part of the ERN-SKIN-Mosaic group and ERN-VASCERN. The authors would like to thank Aviël Ragamin, Ilja van Stuivenberg, and Emma Jonge Poerink for their contribution to this research project. The authors wish to thank Wichor Bramer from the Erasmus MC Medical Library for developing and updating the search strategies. We thank Ko Hagoort for editorial assistance.

Publisher Copyright:
© 2022, The Author(s).


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