This was a retrospective, observational clinical study involving 74 infants. All infants were recruited from the Outpatient of Oncological Department of Oral and Maxillofacial Surgery, the First Affiliated Hospital of Xinjiang Medical University, China, between January 2018 and May 2019. The protocol of study was approved by the Ethics Committee, Stomatology School of Xinjiang Medical University, The First Affiliated Hospital of Xinjiang Medical University (approval no. K202007-03), and the informed consents were signed by all the guardians. All data generated or analysed during this study are included in this published article.
Eligible subjects were infants aged younger than 12 months. The inclusion criteria were as followed: a. infants suffered from superficial hemangiomas who had not accepted any previous treatment; b. the diagnosis was confirmed by the criteria of International Society for the Study of Vascular Anomalies (ISSVA).27 The following as exclusion criteria were: a. infants had other types of vascular anomalies besides superficial hemangiomas; b. the general condition was unhealthy which amalgamated with fever, hypotension, atrioventricular block, bradycardia, pneumonia, bronchial asthma or diarrhea; c. infants had contraindications of betaxolol hydrochloride; d. during the clinical treatment, infants took β-agonist, or received medication other than β-blockers.
All infants met the selective criteria of study were assigned into three groups according to their age: a. 0-3 months; b. 3-6 months; c. 6-9 months. The general characteristics of infants, particularly the description of their hemangiomas, are shown in Table 1. Prior to treatment, the admitted infants well-received relevant examinations completely, which consisted of ultrasonography, electrocardiogram, blood routine examination, blood glucose concentration, serum potassium concentration and test of hepatic and renal function, in order to evaluate vital signs as well as recognize contraindications. Infants of this analysis only accepted betaxolol hydrochloride as topical administration apart from any other therapies. Specific therapeutic regimen was as followed: sterile gauze soaked fully of 0.25% betaxolol hydrochloride ophthalmic suspension (catalog nr. 111820, content 5ml: 12.5mg, S.A. ALCON-COUVREUR N.V.) was applied to cover hemangioma lesion three times per day (every six to eight hours); the dosage kept 30-40 μl/cm2 on surface and each time lasted 5-15 minutes (depending on the thickness of hemangioma and the reaction to treatment); preventing drugs infiltrating into eye or reproductive tract.
Parents were required to closely monitor the changes of complexion, heart and respiration rate after each local medication. Especially, the heart rates of pre- and post treatment, rest-activity and sleep-wake should be recorded. Once they had lower heartbeats than the normal minimum (neonate 120 /min, infant 100 /min), the drug must be stopped immediately. In case of ulceration appeared, it was necessary to avoid topical drugs on the wound. The whole process sustained for six months. Through each subsequent visit monthly, the same doctor took a standardized digital photograph and emphasized on checking heart rate (HR) and blood pressure (BP). Last but not least, in line with the extent of IHs regression, withdrawal of topical betaxolol was assessed. What should be recommended was that, gradual reduction or proper decrease the frequency of use until final discontinuing, so as to avoid drug withdrawal symptom. Every patient needed to be followed up for half a year after the treatment.
Based on clinical photographs, the efficacy of topical betaxolol hydrochloride was estimated by visual analog scale (VAS) at the onset, during and in the end of treatment separately. VAS for color (VAS-C) and for size, tension and thickness (VAS-STT), with scores ranging from -100 to 100, were assessed outcome measures. Among them, -100, 0, and 100 respectively signified doubling in size, no change, and complete healing for VAS-SEV, whilst doubling in intensity of color, no change, and complete absence of discoloration contrasted by the surrounding skin. Therapeutic response was graded into four levels: 1. class I, excellent (scores ranging from 76-100); 2. class II, good (scores ranging from 51-75); 3. class III, moderate (scores ranging from 26-50); 4. class IV, poor (scores < 25). Classes I and II were regarded as effective cases.20,28-30 A panel of three specialists independently recorded the outcomes, and any discrepancies among them were resolved by discussion.
Statistical analysis of all data was performed by Statistical Package for Natural Science (IBM SPSS version 22.0, New York, USA) and expressed as mean ± standard deviation (SD). Kruskal-Wallis H test was applied to contrast the clinical responses for the differences across three age groups. The multi-factor analysis of variance (MANOVA) followed by multivariate analysis was employed to detect the difference between the two kinds of VAS scores among the age groups at three time points after topical treatment. Tukey HSD test was used for calculating the distinction of BP and HR between every time point and baseline point separately. For the sake of comparison, P < 0.05 was considered statistically significant. GraphPad Prism software version 6.0 (Graph Pad Software Inc., San Diego, California, USA) was performed for plotting values. Adobe Photoshop version CC 16.0 (Adobe Systems Software Ireland Ltd, San Jose, California, USA) was for drawing diagrammatic sketch.