Infantile hemangiomas don’t have a single confirmed cause, but researchers have identified a combination of biological triggers that explain why these blood vessel growths appear. About 4 to 5 percent of infants develop one, making hemangiomas the most common tumor of infancy. They arise from an abnormal burst of blood vessel growth in the skin, likely set in motion by oxygen-starved tissue, displaced placental cells, and hormonal influences during fetal development or shortly after birth.
The Placental Cell Theory
One of the most compelling explanations centers on the placenta. Hemangioma cells share a striking molecular fingerprint with cells found in the core of placental structures called chorionic villi. Both cell types produce the same pregnancy-related hormones, and hemangiomas are the only tumors outside the placenta that test positive for a specific glucose transport protein called GLUT1. In a study of 143 hemangiomas, 97 percent showed strong GLUT1 positivity, while none of 66 vascular malformations, 20 pyogenic granulomas, or 7 granulation tissue samples showed any trace of it.
The theory is that small clusters of placental cells break free and travel through the fetal bloodstream, lodging in the skin or other tissues. Because fetal circulation includes natural shunts that route blood from the right side of the heart directly to the left, these stray cells can reach virtually any organ. Once embedded, they lie dormant until something triggers rapid growth after birth. This also explains an otherwise puzzling observation: chorionic villus sampling, a prenatal procedure that physically disrupts placental tissue, increases the risk of hemangiomas, presumably because the procedure dislodges more cells into fetal circulation.
How Low Oxygen Fuels the Growth
Even if displaced placental cells are the seed, the soil matters too. Localized oxygen deprivation in tissue appears to be the main trigger that switches hemangioma cells from dormant to rapidly dividing. When tissue is starved of oxygen, cells ramp up production of a master switch protein called HIF-1α. In proliferating hemangiomas, roughly 96 percent of cell nuclei tested positive for HIF-1α, compared to only about 15 percent in hemangiomas that were already shrinking. That’s a dramatic difference, and it points directly to oxygen deprivation as the engine of growth.
Once HIF-1α is activated, it triggers a cascade. The oxygen-starved cells release signaling molecules that recruit stem cells from the bone marrow to the site, where they begin building new blood vessels at an abnormal pace. One of the key signals is VEGF-A, a potent growth factor for blood vessels. This isn’t a gentle process. It produces the raised, bright red mass that parents typically notice in the first weeks of life.
Estrogen Amplifies the Effect
Estrogen plays a measurable role in accelerating hemangioma growth. In laboratory experiments, combining low-oxygen conditions with estrogen produced a nearly 100 percent increase in hemangioma cell proliferation compared to cells grown in normal oxygen without estrogen. Estrogen also stimulates hemangioma stem cells to produce more VEGF-A, which in turn drives even more blood vessel formation. This synergy between oxygen deprivation and estrogen helps explain why hemangiomas are more common in girls, though the difference between sexes is smaller than once believed. Recent studies put the female-to-male ratio closer to 53:47 rather than the 3:1 ratio quoted in older textbooks.
Known Risk Factors
Low birth weight is the single strongest predictor. A prospective study published in The Journal of Pediatrics found that for every 500-gram decrease in birth weight (roughly one pound), the risk of developing a hemangioma increased by 40 percent. This relationship held even after accounting for other variables, which makes biological sense: smaller babies are more likely to have experienced tissue-level oxygen deprivation, the very trigger that activates the growth cascade.
Other established risk factors include:
- Prematurity: closely linked to low birth weight and associated oxygen stress
- Caucasian race: hemangiomas occur at higher rates in white infants
- Multiple gestations: twins and triplets face higher risk, likely due to lower average birth weight
- Progesterone treatments during pregnancy
- Family history: though most cases are sporadic with no hereditary pattern
Why No Single Gene Has Been Found
Despite decades of searching, researchers have not identified a consistent genetic mutation responsible for infantile hemangiomas. This stands in sharp contrast to other vascular tumors and malformations, where specific gene mutations have been pinpointed over the past 25 years. Studies of identical twins have confirmed that most hemangiomas occur without a hereditary component, since one twin can develop a hemangioma while the other does not. The current thinking is that epigenetic changes, modifications to how genes are read rather than changes to the DNA code itself, are more likely involved. This fits with the placental embolism theory: the cause may not be a broken gene but rather a normal placental cell ending up in the wrong place at the wrong time.
Growth Phases and Natural Resolution
Hemangiomas follow a remarkably predictable life cycle. The rapid growth phase begins in the first four weeks of life and is most intense during the first four to six months. Most hemangiomas have completed their expansion by around four months of age, though growth can continue at a slower pace through the end of the first year.
After that, hemangiomas gradually shrink on their own in a process called involution. Half of all hemangiomas resolve by age 5, and 70 percent by age 7. The remainder may take an additional three to five years to fully disappear. Many leave behind no trace, though larger or deeper hemangiomas can leave residual loose skin, a faint mark, or small visible blood vessels.
When Treatment Is Needed
Because most hemangiomas resolve without intervention, many are simply monitored. Treatment becomes necessary when a hemangioma threatens vision (near the eye), airway (in the throat), or causes persistent ulceration and bleeding. Hemangiomas on the face, especially large ones over 5 centimeters, sometimes signal a condition called PHACE syndrome, which involves brain, heart, and eye abnormalities that need separate evaluation.
The standard first-line treatment is an oral beta-blocker, which works by constricting the abnormal blood vessels and slowing growth. Treatment typically starts at a low dose and is gradually increased over two weeks, then maintained for about six months. This approach has largely replaced older treatments like steroids and surgery for problematic hemangiomas, and most infants tolerate it well. The medication is given as a liquid twice daily, spaced at least nine hours apart, and parents are typically asked to monitor for signs of low blood sugar or slow heart rate during the early adjustment period.
Hemangiomas That Look Similar but Aren’t
Congenital hemangiomas are fully formed at birth, unlike infantile hemangiomas which appear in the first few weeks and then grow. Despite looking similar, congenital hemangiomas are biologically distinct: they test negative for GLUT1 and carry different genetic mutations. The distinction matters because congenital hemangiomas follow a different course and don’t respond to the same treatments. If a vascular birthmark is already fully developed at delivery, it’s worth having it evaluated to determine which type it is, since the management and outlook differ significantly.