Intrauterine Growth Retardation is a Risk Factor for Anthracycline Toxicity

Pediatr Hematol Oncol. 2021 Aug;38(5):497-503. doi: 10.1080/08880018.2021.1897717. Epub 2021 Mar 15.


Background: Anthracycline chemotherapy is used to treat a variety of cancers. However, late cardiac effects of anthracycline chemotherapy, such as subclinical left ventricular dilatation and/or dysfunction, have been observed in more than half of long-term survivors of childhood cancers. A major risk factor for anthracycline cardiotoxicity is intrauterine growth restriction (IUGR). We assessed the significance of IUGR as an important risk factor for late cardiotoxic effects of anthracycline therapy in asymptomatic long-term survivors of childhood cancers.

Materials and methods: The study included 61 survivors of childhood cancers. Cardiac functions were prospectively studied using both conventional and non-conventional echocardiographic methods (two-dimensional speckle tracking echocardiography) after completion of the treatment. The patients were divided into two groups based on their birth weights: Group 1 (patients with IUGR) and Group 2 (patients with normal birth weight).

Results: Conventional echocardiography revealed a similar and normal range of left ventricle systolic and diastolic functions in both groups. However, global longitudinal and circumferential strain values demonstrated subclinical left ventricular systolic dysfunction in both groups as compared with normal reference strain values. Furthermore, Group 1 patients had significantly lower global longitudinal and circumferential strain and strain rate values than those in Group 2 patients.

Conclusion: Asymptomatic long-term survivors of childhood cancers with a history of IUGR may have an increased risk of anthracycline cardiotoxicity due to the low content of mitochondrial DNA (mtDNA). IUGR is a risk factor for late anthracycline cardiotoxicity.

Keywords: Anthracycline; intrauterine growth retardation; toxicity.

MeSH terms

  • Adolescent
  • Adult
  • Anthracyclines / adverse effects*
  • Antineoplastic Agents / adverse effects*
  • Birth Weight
  • Cancer Survivors
  • Cardiotoxicity / etiology*
  • Cardiotoxins / adverse effects
  • Child
  • Cross-Sectional Studies
  • Fetal Growth Retardation* / etiology
  • Humans
  • Neoplasms / drug therapy*
  • Prospective Studies
  • Risk Factors
  • Young Adult


  • Anthracyclines
  • Antineoplastic Agents
  • Cardiotoxins