Oral propranolol is the first-line therapy for infantile hemangioma (IH), but its mechanism of action remains unclear. The aim of this study was to evaluate the change in serum vascular endothelial growth factor (VEGF) levels in patients with IH who underwent propranolol treatment. The study included 22 patients with IH receiving propranolol treatment. At three time points-before treatment and 1 and 3 months after treatment-blood samples were examined by enzyme-linked immunosorbent assay for serum VEGF expression. The mean serum VEGF concentration in children with proliferative hemangiomas was 395.0 ± 176.7 pg/mL, approximately twice as high as in patients with venous malformations (mean 170.7 pg/mL) and in healthy controls (204.8 pg/mL, p = 0.006). After 1 month of propranolol treatment, the level had fallen 21.6% (p = 0.003), although the downward trend was less obvious after 3 months of treatment (18.0%, p = 0.63). VEGF expression correlated significantly with the lesion size (correlation coefficient [R] = 0.43, p = 0.046), whereas no correlation was observed with age (R = 0.13, p = 0.56). Serum VEGF levels were higher in patients with IH and fell after 1 month of oral propranolol treatment. Similar results, although less pronounced, were found after 3 months of treatment. Lesion volume and serum level of VEGF were significantly correlated.

Infantile hemangioma (IH) is the most common benign tumor occurring during childhood. We hypothesized that, in addition to already known risk factors, such as female sex, prematurity, and low birthweight (LBW), antenatal vaginal bleeding and progesterone therapy would be highly associated with IH. We randomly selected 650 individuals with IH and matched them with 650 children of the same age and nationality without IH. Trained investigators used a standardized questionnaire to collect data from both groups, including demographic, prenatal, and perinatal characteristics. Prematurity (p < .001, odds ratio [OR] = 2.22, 95% confidence interval [CI] = 1.44-3.41), LBW (p < .001, OR = 3.10, 95% CI = 1.87-5.16) and female sex (p < .001, OR = 2.06, 95% CI = 1.65-2.58) were significantly associated with IH. Maternal vaginal bleeding during the first trimester was shown to be an independent risk factor according to logistic regression analyses (p < .001, OR = 1.6, 95% CI = 1.36-1.91), which was most evident in those receiving progesterone therapy to prevent miscarriage (p < .001, OR = 2.11, 95% CI = 1.77-2.51). Subgroup analyses revealed that the effect was more pronounced in female than in male infants (OR = 2.82, 95% CI = 2.39-3.34). In addition to the known relationships, the present study identified a close relationship between maternal vaginal bleeding and progesterone therapy during early pregnancy and IH. Twins appeared to have a higher incidence of IH than singletons.