Published online June 2, 2008
PEDIATRICS Vol. 121 No. 6 June 2008, pp. 1251-1252 (doi:10.1542/peds.2007-2418)
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COMMENTARY

Corticosteroid Treatment for Problematic Infantile Hemangioma: Evidence Does Not Support an Increased Risk for Cerebral Palsy

Arin K. Greene, MD, MMSc

Vascular Anomalies Center and Department of Plastic Surgery, Children's Hospital Boston, Harvard Medical School, Boston, Massachusetts

Abbreviations: VLBW, very low birth weight

Many practitioners are hesitant to give corticosteroids to preterm infants because of data suggesting that corticosteroids may increase the child's risk for cerebral palsy; however, randomized, prospective trials and meta-analyses have shown that only dexamethasone administered within 96 hours after birth to very low birth weight infants (VLBW; <1250 g) increases the frequency of cerebral palsy.1–3 Corticosteroids' effect on neurodevelopment depends on the (1) age of the infant, (2) timing of administration, and (3) type of corticosteroid.

In contrast to VLBW infants, corticosteroids that are given to older preterm infants does not affect neurodevelopment.4,5 Even in VLBW children, dexamethasone started after 1 week of age is not associated with cerebral palsy.3,6,7 In fact, dexamethasone given after 2 weeks of age may improve neurodevelopment in these high-risk infants.8 Compared with dexamethasone, early treatment of VLBW infants with other types of corticosteroid (hydrocortisone, methylprednisolone) does not cause cognitive impairment and reduces the rate of cystic periventricular leukomalacia, a risk factor for cerebral palsy.9–11

Corticosteroid treatment of hemangioma has not been shown to cause cerebral palsy and differs from the therapy of bronchopulmonary dysplasia (BPD). First, oral prednisone, not intravenous dexamethasone, generally is used. Second, corticosteroid treatment of hemangioma is initiated at an older age, compared with patients with BPD. Infants with BPD receive pharmacotherapy between 12 hours and 3 weeks postnatally, whereas the average age and weight of a child who is treated for problematic hemangioma is 3 months and 5.7 kg, respectively.5,12,13 Hemangioma usually is not diagnosed until after 2 weeks of age, and postnatal growth often is necessary before a tumor can be identified as problematic. Thus, even in the event that a hemangioma is found to be troublesome in a premature child, several weeks usually will have passed since birth until the time therapy is initiated.

Although the timing, duration, and type of corticosteroid differs between patients who are treated for hemangioma and those for BPD, drug dosage is approximately equivalent. Prednisone for hemangioma is well accepted: 2 to 3 mg/kg per day is administered daily for 1 to 2 months, then tapered over weeks to months.4,12 Corticosteroid treatment of BPD is more variable: 2.5 to 5.0 mg/kg per day (prednisone-equivalent dosage) of dexamethasone, hydrocortisone, or methylprednisolone is administered for 10 to 42 days. It is interesting that longer dexamethasone treatment (42 days) of VLBW infants with BPD improves neurocognitive outcome, compared with 18 days of treatment.8

Complications of systemic corticosteroid for the management of problematic hemangioma have been studied, and no adverse effects on neurodevelopment have been found.4,5,12,14,15 Short-term morbidity includes cushingoid face (71%); personality change (29%); gastric irritation (21%); hirsutism (13%); cutaneous fungal infection (6%); and a decreased gain in head circumference (13%), height (35%), or weight (43%).4,15 These adverse effects resolve after the completion of therapy. For example, 1 study showed that >90% of children returned to their pretreatment growth curve for height by 24 months of age. The risk for a temporary decrease in height gain fell to 12% for patients who were given prednisone after 3 months of age and for a course of <6 months.4 Serious adverse effects of corticosteroid treatment for infantile hemangioma, such as Pneumocystis carinii pneumonia, are rare.16

The distinction between corticosteroid administration for infantile hemangioma and BPD is important because prednisone is the most effective treatment for a problematic hemangioma. Although most hemangiomas proliferate and involute without sequelae, ~10% require intervention for distortion, destruction, obstruction, ulceration, or life-threatening complications.17 Prednisone effectively regresses or stabilizes the growth of hemangioma in 84% of children, regardless of the location of the tumor.12,13 Small, well-localized lesions have an equal response rate with intralesional corticosteroid injection.18

Withholding prednisone from a premature infant with a problematic hemangioma for fear of compromising neurodevelopment places the child at risk for complications of the tumor. The infant also may experience additional morbidity if an intervention other than corticosteroid therapy is chosen. For example, interferon {alpha}-2a or {alpha}-2b has a long onset of action and can cause neurologic complications (spastic diplegia), particularly in infants.19–21 Vincristine may lead to transient loss of deep tendon reflexes, abdominal pain, and intravenous line complications.22 Operative excision of a proliferating hemangioma can cause major blood loss, injury to vital structures, and even death.23,24

Although current evidence suggests that corticosteroid treatment of infantile hemangioma does not cause cerebral palsy, prospective studies are needed to confirm this observation. In addition, when treating a child with a problematic hemangioma, the risks of systemic corticosteroid therapy must be weighed against its benefits, particularly in younger infants.


   FOOTNOTES
 
Accepted Sep 27, 2007.

Address correspondence to Arin K. Greene, MD, MMSc, Children's Hospital Boston, 300 Longwood Ave, Boston, MA 02115. E-mail: arin.greene{at}childrens.harvard.edu

The author has indicated he has no financial relationships relevant to this article to disclose.

Opinions expressed in these commentaries are those of the author and not necessarily those of the American Academy of Pediatrics or its Committees.


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PEDIATRICS (ISSN 1098-4275). ©2008 by the American Academy of Pediatrics

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