Cortical hyperostosis: a complication of prolonged prostaglandin infusion in infants awaiting cardiac transplantation

Pediatrics. 1994 Mar;93(3):417-20.


Background: Infants awaiting heart transplantation for congenital heart disease frequently require prostaglandin E1 (PGE1) infusion for prolonged periods. As a result, complications of prolonged PGE1 infusion, such as cortical hyperostosis, are being encountered more commonly.

Objective: To determine the incidence and severity of cortical hyperostosis in newborns requiring prolonged PGE1 infusion.

Methods: Chest radiographs of 86 infants receiving PGE1 infusion awaiting heart transplantation were reviewed. The chest radiographs were graded for the severity of cortical hyperostosis (no bony changes, minimal hyperostosis, or severe hyperostosis). Duration of PGE1 infusion, total PGE1 dose, and highest alkaline phosphatase were recorded for each patient. Infants were arbitrarily divided into three groups according to the duration of PGE1 infusion (< 30 days, 30 to 60 days, > 60 days).

Results: Fifty-three of the 86 infants (62%) had radiologic evidence of cortical hyperostosis. Forty-two of 80 infants (53%) had elevated alkaline phosphatase. The percentage of infants with hyperostosis increased with increasing duration of PGE1 infusion (42% at < 30 days; 87% at 30 to 60 days; 100% at > 60 days). The incidence and severity of cortical hyperostosis were related (by Kruskal-Wallis) to the duration of PGE1 infusion (P < .0001) and the total dose of PGE1 received (P < .0001). The highest alkaline phosphatase levels were observed in infants with the most severe grades of hyperostosis (P < .0001). The percentage of infants with elevated alkaline phosphatase increased with greater severity of hyperostosis (26% of infants with no bony changes, 59% with minimal changes, and 85% with severe changes). Two infants had symptomatic bone tenderness or swelling mimicking osteomyelitis.

Conclusion: It is concluded that cortical hyperostosis is a frequent, often asymptomatic, side effect of prolonged PGE1 infusion that should be evaluated in any infant on long-term PGE1 therapy. When symptoms occur in infants awaiting transplantation, osteomyelitis must be excluded rapidly to avoid an unnecessary delay in transplantation.

MeSH terms

  • Alprostadil / administration & dosage
  • Alprostadil / adverse effects*
  • Clavicle / diagnostic imaging
  • Dose-Response Relationship, Drug
  • Heart Transplantation
  • Humans
  • Humerus / diagnostic imaging
  • Hyperostosis / chemically induced*
  • Hyperostosis / diagnostic imaging
  • Infant, Newborn
  • Radiography
  • Time Factors


  • Alprostadil