Accepted for Publication: August 18, 2021.
Published Online: November 8, 2021. doi:10.1001/jamapediatrics.2021.4565
Correction: This article was corrected on January 31, 2022, to change mg/kg/d to mg/kg per day.
Open Access: This is an open access article distributed under the terms of the CC-BY License. © 2021 Pope E et al. JAMA Pediatrics.
Corresponding Author: Elena Pope, MD, MSc, Division of Pediatric Dermatology, The Hospital for Sick Children, University of Toronto, 555 University Ave, Toronto, ON M5J 1X8, Canada (firstname.lastname@example.org).
Author Contributions: Drs Pope and Ma had full access to all of the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis.
Concept and design: Pope, Lara-Corrales.
Acquisition, analysis, or interpretation of data: All authors.
Drafting of the manuscript: Pope.
Critical revision of the manuscript for important intellectual content: All authors.
Statistical analysis: Pope, Lara-Corrales, Ma.
Obtained funding: Pope.
Administrative, technical, or material support: Pope, Lara-Corrales.
Supervision: Pope, Lara-Corrales.
Conflict of Interest Disclosures: Dr Pope reports serving as an advisory board member for Boeringher Ingelheim, Novartis, Sanofi Genzyme, and Timber outside the submitted work. Dr Lara-Corrales reports personal fees from Pierre Fabre during the conduct of the study as well as personal fees from Amgen, Ipsen, Novartis, Pfizer, and Sanofi Genzyme and grants from AbbVie, Clementia, Mayne Pharma, and Sanofi Genzyme outside the submitted work. Dr Kanigsberg reports personal fees from Pierre Fabre advisory committee outside the submitted work. Dr Drolet reports grants from Venthera and personal fees from Venthera outside the submitted work and has a patent for PCT/US2020/034270 issued for a new topical treatment of infantile hemangioma. No other disclosures were reported.
Funding/Support: This study was supported by Physician Services Inc, Ontario, Canada.
Role of the Funder/Sponsor: The funder had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.
Data Sharing Statement: See Supplement 3.
Additional Contributions: We thank Hanna Fadzeyedeva, SickKids research coordinator; Harini Balasundaram and Nicole Travis, Children’s Hospital of Eastern Ontario research coordinators; Michelle Lee, Jackie Su, and Melanie Audette, the clinic nurses who contributed to patient monitoring and photography; and George Tomlinson for his help with statistical interpretation. The research coordinators were compensated for their contributions; other individuals were not. Finally, we thank the families who agreed to allow their children to participate in the study.
A , Butschek
R , Tom
et al. Prospective study of infantile hemangiomas: incidence, clinical characteristics and association with placental anomalies. Br J Dermatol
. 2014;170:907-913 doi:10.1111/bjd.12804PubMedGoogle ScholarCrossref
DW , Hebert
AA . Benign cutaneous vascular tumors of infancy: when to worry, what to do. Arch Dermatol
. 2000;136(7):905-914. PubMedGoogle ScholarCrossref
IJ , Haggstrom
AN , Drolet
et al. Infantile hemangiomas: current knowledge, future directions. Proceedings of a research workshop on infantile hemangiomas, April 7-9, 2005, Bethesda, Maryland, USA. Pediatr Dermatol
. 2005;22(5):383-406. doi:10.1111/j.1525-1470.2005.00102.xPubMedGoogle ScholarCrossref
C , Dumas de la Roque
E , Hubiche
T , Boralevi
F , Thambo
J-B , Taïeb
A . Propranolol for severe hemangiomas of infancy. N Engl J Med
. 2008;358(24):2649-2651. PubMedGoogle ScholarCrossref
C , Hoeger
P , Mazereeuw-Hautier
et al. A randomized, controlled trial of oral propranolol in infantile hemangioma. N Engl J Med
. 2015;372(8):735-746. PubMedGoogle ScholarCrossref
FN , Weeke
PE , Tfelt-Hansen
P , Tfelt-Hansen
J ; ESCAPE‐NET. Pharmacokinetic variability of beta-adrenergic blocking agents used in cardiology. Pharmacol Res Perspect
. 2019;7(4):e00496. PubMedGoogle Scholar
A , Pope
E . Propranolol and central nervous system function: potential implications for paediatric patients with infantile haemangiomas. Br J Dermatol
. 2015;172(1):13-23. PubMedGoogle ScholarCrossref
RC , Brogden
RN , Pakes
GE , Speight
TM , Avery
GS . Nadolol: a review of its pharmacological properties and therapeutic efficacy in hypertension and angina pectoris. Drugs
. 1980;20(1):1-23. PubMedGoogle ScholarCrossref
J , Cruickshank
JM . Beta-blockers and central nervous system side effects. Pharmacol Ther
. 1990;46(2):163-197. PubMedGoogle ScholarCrossref
M , Peterson
K . Drug Class Review on Beta Adrenergic Blockers. Oregon Health & Science University; 2005.
AV , Chidambaram
B . Efficacy and safety of intravenous and oral nadolol for supraventricular tachycardia in children. J Am Coll Cardiol
. 1992;19(3):630-635. PubMedGoogle ScholarCrossref
DF , Ozbayrak
KR , Benjamin
S , Ma
Y , Fletcher
KE . A pilot study of nadolol for overt aggression in developmentally delayed individuals. J Am Acad Child Adolesc Psychiatry
. 1997;36(6):826-834. PubMedGoogle ScholarCrossref
J , Brannick
LJ , Vukovich
RA , Shaw
JM , Willard
DA . Metabolic studies in patients with nadolol: oral and intravenous administration. J Clin Pharmacol
. 1977;17(5-6):300-307. PubMedGoogle ScholarCrossref
E , Chakkittakandiyil
A , Lara-Corrales
I , Maki
E , Weinstein
M . Expanding the therapeutic repertoire of infantile haemangiomas: cohort-blinded study of oral nadolol compared with propranolol. Br J Dermatol
. 2013;168(1):222-224. PubMedGoogle ScholarCrossref
SR , van Oosterhout
M , de Laat
PC , van Rosmalen
J , Madern
GC , Oranje
AP . Scoring the therapeutic effects of oral propranolol for infantile hemangioma: a prospective study comparing the hemangioma activity score (HAS) with the hemangioma severity scale (HSS). J Am Acad Dermatol
. 2015;73(2):258-263. PubMedGoogle ScholarCrossref
AN , Beaumont
JL , Lai
et al. Measuring the severity of infantile hemangiomas: instrument development and reliability. Arch Dermatol
. 2012;148(2):197-202. PubMedGoogle ScholarCrossref
HK , Sibbald
C , Garcia Romero
MT , Pope
E . Oral nadolol for the treatment of infantile hemangiomas: a single-institution retrospective cohort study. Pediatr Dermatol
. 2015;32(5):690-695. PubMedGoogle ScholarCrossref
E , Dembowska-Baginska
B , Przewratil
et al. Efficacy of propranolol between 6 and 12 months of age in high-risk infantile hemangioma. Pediatrics
. 2018;142(3):e20173866. PubMedGoogle Scholar
E , Glover
M , Irvine
et al. Propranolol in the treatment of infantile haemangiomas: lessons from the European Propranolol In the Treatment of Complicated Haemangiomas (PITCH) taskforce survey. Br J Dermatol
. 2016;174(3):594-601. PubMedGoogle ScholarCrossref
M , Adams
S , Wargon
O . A randomized controlled trial of propranolol for infantile hemangiomas. Pediatrics
. 2011;128(2):e259-e266. PubMedGoogle ScholarCrossref
C , Boccara
O , Degrugillier-Chopinet
et al. Safety of oral propranolol for the treatment of infantile hemangioma: a systematic review. Pediatrics
. 2016;138(4):e20160353. PubMedGoogle Scholar
S , Saddi
V , Teng
et al. Propranolol’s effects on the sleep of infants with hemangiomas: a prospective pilot study. Pediatr Dermatol
. 2021;38(2):371-377. PubMedGoogle ScholarCrossref
J , Narváez-Moreno
B , de la Torre-García
et al. Oral nadolol for children with infantile hemangiomas and sleep disturbances with oral propranolol. Pediatr Dermatol
. 2015;32(6):853-857. PubMedGoogle ScholarCrossref
BA , Frommelt
PC , Chamlin
et al. Initiation and use of propranolol for infantile hemangioma: report of a consensus conference. Pediatrics
. 2013;131(1):128-140. PubMedGoogle ScholarCrossref
X , Yang
K , Li
H , Huo
R . Propranolol treatment for infantile hemangiomas: short-term adverse effects and follow-up to age two. Biomed Res Int
. 2019;2019:2728952. PubMedGoogle Scholar