Oral propranolol for infantile haemangioma may be associated with transient gross motor delay

Mahon, Caroline; Heron, G. A.; Perkins, Deborah; Drage, A.; Wargon, Orli

doi:10.1111/bjd.16334

Cited by 10 publications

(3 citation statements)

References 7 publications

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“…As propranolol is a lipophilic molecule, its use in infants raised the question of its ability to passively cross the blood-brain barrier (BBB) and directly activate adrenoreceptors on neuronal cells, and to subsequently impact the neurologic development of the child. Even if many reports have documented that propranolol treatment during infancy does not alter further brain development when compared to child and adolescents from the general population examined several years after cessation of treatment (Moyakine et al, 2016, 2017; Gonzalez-Llorente et al, 2017; Mahon et al, 2018), other beta-blockers with hydrophilic properties have been here or there introduced in the treatment of infantile hemangiomas. The most commonly used molecules are nadolol and atenolol, which display hydrophilic properties and are therefore suggested to be unable to cross the BBB (Neil-Dwyer et al, 1981; Dahlof and Dimenas, 1990) and thus potentially decrease the risk to induce deleterious central effects (de Graaf et al, 2013; Pope et al, 2013; Tasani et al, 2017; Alexopoulos et al, 2018).…”

Section: Introductionmentioning

confidence: 99%

Central Effects of Beta-Blockers May Be Due to Nitric Oxide and Hydrogen Peroxide Release Independently of Their Ability to Cross the Blood-Brain Barrier

et al. 2019

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Propranolol is the first-line treatment for infants suffering from infantile hemangioma. Recently, some authors raised the question of potential neurologic side effects of propranolol due to its lipophilic nature and thus its ability to passively cross the blood-brain barrier (BBB) and accumulate into the brain. Hydrophilic beta-blockers, such as atenolol and nadolol, where therefore introduced in clinical practice. In addition to their classical mode of action in the brain, circulating factors may modulate the release of reactive oxygen/nitrogen species (ROS/RNS) from endothelial cells that compose the BBB without entering the brain. Due to their high capacity to diffuse across membranes, ROS/RNS can reach neurons and modify their activity. The aim of this study was to investigate other mechanisms of actions in which these molecules may display a central effect without actually crossing the BBB. We first performed an oral treatment in mice to measure the accumulation of propranolol, atenolol and nadolol in different brain regions in vivo. We then evaluated the ability of these molecules to induce the release of nitric oxide (NO) and hydrogen peroxide (H2O2) ex vivo in the hypothalamus. As expected, propranolol is able to cross the BBB and is found in brain tissue in higher amounts than atenolol and nadolol. However, all of these beta-blockers are able to induce the secretion of signaling molecules (i.e., NO and/or H2O2) in the hypothalamus, independently of their ability to cross the BBB, deciphering a new potential deleterious impact of hydrophilic beta-blockers in the brain.

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Section: Introductionmentioning

confidence: 99%

Central Effects of Beta-Blockers May Be Due to Nitric Oxide and Hydrogen Peroxide Release Independently of Their Ability to Cross the Blood-Brain Barrier

et al. 2019

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“…Among them, central nervous system-related adverse events may influence brain development in young infants. 4 Compared to propranolol, atenolol has similar efficacy and fewer adverse events in the treatment of infantile hemangioma. 5 For safety reasons, we chose atenolol to treat KHE.…”

Section: First Report Of Oral Atenolol For Treatment Of Kaposiform He...mentioning

confidence: 99%

First report of oral atenolol for treatment of kaposiform hemangioendothelioma, a viable alternative to propranolol

et al. 2022

The Journal of Dermatology

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“…Einschränkend ist anzumerken, dass nur reifgeborene Säuglinge in die Studie einbezogen wurden und somit über Frühgeborene keine Aussage getroffen werden kann. Mehrere Untersuchungen zur Frage von Propranolol-Langzeiteffekten auf die spätere psychomotorische und kognitive Entwicklung behandelter Kinder zeigten außer einer leichten transienten Verzögerung der motorischen Entwicklung in einer Studie [5] erfreulicherweise unauffällige Ergebnisse. In Anbetracht der geringen Zahl aussagekräftiger Studien zu dieser Thematik ist sorgloser Dauerschlaf der Behandler jedoch fehl am Platz.…”

Section: Transfer In Die Praxis Von Prof Dr Henning Hamm (Würzburg)unclassified

Schlaf‘, Kindlein, schlaf‘: Schlafverhalten von Säuglingen unter Propranolol-Therapie

Hamm¹

2021

Kompass Dermatol

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Sleep problems are frequently reported in infants treated with propranolol for infantile hemangiomas, possibly serving as a marker for a negative impact on central nervous system function. In this cohort study, we objectively investigate the sleep behavior of infants with infantile hemangiomas on propranolol compared to a healthy, untreated control group. Sleep of propranolol-treated infants and controls was investigated using ankle actigraphy and a 24-h diary for 7–10 days at ages 3 and 6 months. The main outcome measures were the Number of Nighttime Awakenings and Sleep Efficiency. The main secondary outcome measures included 24-hour Total Sleep, daytime sleep behavior, and parent-rated infant sleep quality and behavioral development based on the Brief Infant Sleep Questionnaire (BISQ) and the age-appropriate Ages-and-Stages Questionnaire (ASQ), respectively. Fifty-four term-born infants were included in each cohort. No group difference in any investigated parameter was seen at age 3 months. At age 6 months, the propranolol group exhibited a decrease in Sleep Efficiency and a trend towards an increased Number of Nighttime Awakenings compared to the control group. Treated infants at 6 months also had shorter daytime waking periods. 24-hour Total Sleep was unaffected by propranolol. No negative impact of propranolol on subjective sleep quality and behavioral development was noted. Conclusion: Propranolol exerts a measurable yet mild impact on objectively assessed infants’ sleep measures. Behavioral developmental scores were unaffected. Our results support propranolol as first-line therapy for complicated infantile hemangiomas. What is Known: •Sleep disorders are frequently reported in infants with infantile hemangiomas treated with propranolol and often lead to treatment discontinuation. • Investigations of the sleep pattern in this patient group using objective measures are lacking. What is New: • The sleep pattern of propranolol-treated infants is assessed using actigraphy and a 24-h sleep diary and compared to healthy, untreated controls. • Propranolol leads to a decreased sleep efficiency at night and an increased demand of daytime sleep, yet effects are mild overall.

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Oral propranolol for infantile haemangioma may be associated with transient gross motor delay

Cited by 10 publications

References 7 publications

Central Effects of Beta-Blockers May Be Due to Nitric Oxide and Hydrogen Peroxide Release Independently of Their Ability to Cross the Blood-Brain Barrier

Central Effects of Beta-Blockers May Be Due to Nitric Oxide and Hydrogen Peroxide Release Independently of Their Ability to Cross the Blood-Brain Barrier

First report of oral atenolol for treatment of kaposiform hemangioendothelioma, a viable alternative to propranolol

Schlaf‘, Kindlein, schlaf‘: Schlafverhalten von Säuglingen unter Propranolol-Therapie

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