Infantile hemangiomas are vascular tumors, most of which grow gradually within the first month of life and then slowly subside over the next few years, usually causing some skin lesions. However, the diagnosis and treatment of neonatal hemangiomas is still in its early stages. Recently, Prof. Goelz published a review on the latest advances in the diagnosis and treatment of hemangiomas in preterm infants, detailing the clinical diagnosis and treatment strategies for this disease. Lin Xiaoqing, Department of Dermatology, Minnan Branch, The First Affiliated Hospital of Fujian Medical University Definition Infantile hemangioma (IH) is composed of proliferating hemangiomas. Infants and young children are born without hemangiomas and undergo a characteristic period of rapid growth during the first 5-9 months of life, with 5-8 weeks of particularly rapid growth. By the time the hemangioma completes its growth after 5 years, there is a period of slow regression or remodeling, accompanied by skin lesions such as skin atrophy, scarring, anatomical disruption, large patches of adipose fibrous tissue, and in some cases capillary dilatation. According to Professors Mulliken and Glowatzki, the key to the definition of hemangiomas in infants and children is to distinguish between hemangiomas and vascular malformations. The majority of hemangiomas in infants and children are limited in 67% of cases, 13% are segmental, 17% are indeterminate, and 4% are multifocal. Infantile hemangiomas can also be categorized as superficial, mixed, and deep, which are differentiated based on the distribution on the body surface as well as the anatomical depth of infiltration. Recent immunohistochemical studies have shown that glucose transporter protein 1 can specifically differentiate infantile hemangiomas from other vascular tumors or birthmarks (especially congenital hemangiomas). The differential diagnosis of infantile hemangiomas also includes congenital hemangiomas (rapidly regressing congenital hemangiomas and non-regressing congenital hemangiomas), Kaposiform hemangioendotheliomas, tufted hemangiomas, suppurative hemangiomas, and multifocal endothelial sarcomas of the lymphatic vessels. Epidemiology The incidence of infantile hemangiomas may be higher in preterm infants than in term infants, but exact incidence data are still unknown. The incidence of infantile hemangiomas increases with decreasing gestational age (GA) and birth weight, ranging from 1-4% of term infants to 23% of preterm infants with birth weights less than 1,000 g. Females are predominantly affected, and Caucasians are more likely to be affected than other ethnic groups. Facial involvement appears to be uncommon in preterm infants. Indications for Treatment There is currently a high incidence of infantile hemangiomas among premature infants, but except for one small study, there are no specific studies on this high-risk group. In this study, researchers used nitrogen cryotherapy (NCCT) to treat hemangiomas. Based on the current situation, the treatment of preterm infants can only rely on the experience of term infants. A document from the Cochrane Library shows that as of March 2011 there were only four randomized controlled trials (RCTs) on the treatment of hemangiomas in infants and young children, and the evidence for treatment from these RCTs is too narrow. In infants and young children, hemangiomas carry the risk of being life-threatening or leading to impaired body function, as well as the development of ulcers. These risks are typically found on the face, scalp, neck, hands, feet, and the anogenital region, which is prone to friction. Hemangiomas can grow rapidly as well as lead to acute or chronic skin lesions, all of which may require treatment. Since hemangiomas have a characteristic period of rapid growth between the 5th and 8th month of life, treatment must be initiated before this age, and in 2008, the use of beta-blockers lowered the standard of care for hemangiomas, with fewer side effects and better outcomes. It has been reported that the application of beta-blockers is increasing and the use of steroids is decreasing. Treatment The application of propranolol to infantile hemangiomas has revolutionized the pharmacological treatment of hemangiomas, with Professor Labrèze stating that propranolol can dramatically shrink hemangiomas. If it were available for systemic treatment, most experts would use it as a first-line drug. For localized treatment, another beta-blocker, timolol maleate 0.5%, could also be used as a first-line drug. Traditional medications reported after 2008 for the treatment of hemangiomas include corticosteroids, interferon-alpha, and vincristine, which are generally used as second- or third-line medications, primarily because of their side effects, some of which can lead to spastic diplegia and other neurologic abnormalities. Other treatments include cryotherapy, laser and surgical therapies, and topical and intra-lesional medications. Treatment Options for Preterm Infants Local treatments for hemangiomas in preterm infants currently include cryotherapy, laser therapy, and the application of timolol maleate. Systemic therapies include propranolol and second line drugs – corticosteroids (prednisolone), these treatment options are currently available. Cryotherapy There is only one prospective controlled study using liquid nitrogen cryotherapy (-196 degrees Celsius for 2-6 seconds). The subjects in this article all had infantile hemangiomas less than 10 mm in diameter and the children were less than 34 weeks of gestational age. Liquid nitrogen cryotherapy induced rapid tumor regression and also had cosmetic effects. On the downside, the endpoints of this trial were not well established, with the longest follow-up being only 2 years, and the side effect: mild scarring. Data from other centers on liquid nitrogen cryotherapy show better results with less scarring and are currently recommended in German treatment guidelines. It is fast, easy to perform, well tolerated, inexpensive, can be performed at the bedside, and most importantly has few systemic side effects. The only drawback is that this treatment is only suitable for children with superficial hemangiomas smaller than 10 mm. Laser therapy There are no reports on laser therapy in preterm infants. However, there is a randomized controlled trial on the treatment of hemangiomas in young children, and the results showed that when children were treated at the age of 1 week, laser therapy did not offer much advantage. Now, due to the lack of sufficient data, it is also less clear whether this modality is recommended for preterm infants. Propranolol Therapy In the past 6 years, 6 randomized controlled trial articles have been published, 1 of which the trial was terminated due to serious complications in the steroid group. Combined use of prednisolone and propranolol has been reported to be no better than propranolol alone. Propranolol and atenolol have similar efficacy, but atenolol has fewer side effects, which may be related to atenolol’s higher beta-1 receptor selectivity. The use of oral propranolol has been reported to be more effective than local and intra-lesional applications. However, none of the above 1 article is related to the treatment of preterm infants. a randomized controlled trial that recruited and concluded in May 2014 stated that the use of propranolol 3 mg/(kg?d) for 24 weeks results in better cosmetic outcomes. Additionally, there are a large number of reports on the assessment of propranolol’s effectiveness. One systematic review indicated that the mean treatment-effective response to propranolol was 98%, with side effects including: sleep alterations (e.g., insomnia, nightmares, agitation, and sleep disturbances), cyanosis of the hands and feet, hypotension, bradycardia, hypoglycemia, and respiratory- and gastrointestinal-related symptoms. After cessation of treatment, rebound growth of the lesions occurred in 17% of the children. In another systematic review and meta-analysis comparing propranolol and corticosteroids, 97.3% of children in the propranolol group and 71% of children in the corticosteroid group had improved symptoms. However, neither of these reports addressed the treatment of preterm infants. In one case report, nine very low-birth-weight children were treated with propranolol 2-3 mg/(kg?d), and no side effects or growth disturbances were observed in these children. In summary, there is still a paucity of data on the treatment of hemangiomas in preterm infants and young children, with insufficient data on treatment in the first week of life as well as in those who have reached the equivalent age of full-term infants. Long-term outcomes regarding neurocognitive aspects are also insufficient. Therefore, systemic application of propranolol as well as vasoactive drugs in immature infants and children should be given adequate attention.