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Imbalance of Fetal Growth Factor Levels in Congenital Heart Disease Pathology: A Systematic Review

Yazdan Ghandi1, Samira Zakeri Shahvari2, Negar Poor Ahmadian3

  • 1Department of Pediatrics, School of Medicine, Arak University of Medical Sciences, Arak, Iran.

Birth Defects Research
|December 9, 2025
PubMed

Insights

Vascular Endothelial Growth Factor (VEGF) and Hypoxia-Inducible Factor (HIF) increases during fetal development are key to congenital heart disorder (CHD) pathology. Their regulation is crucial for heart development, diagnosis, and pathology.

Area of Science:

  • Cardiovascular Research
  • Developmental Biology
  • Medical Genetics

Background:

  • Vascular Endothelial Growth Factor (VEGF) is vital for cell proliferation, blood vessel growth, and angiogenesis.
  • Altered VEGF levels are linked to the pathology of structural disorders like Congenital Heart Disease (CHD).
  • This study systematically reviews VEGF's influence on congenital heart disorders.

Purpose of the Study:

  • To assess the role of VEGF in the pathology of cardiovascular structural disorders.
  • To investigate the therapeutic and diagnostic effects of VEGF.
  • To identify related factors influenced by VEGF.

Main Methods:

  • Systematic review adhering to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) criteria.
  • Literature search conducted across Web of Science, PubMed, and Scopus databases (2014-2024).
  • Analysis focused on VEGF's role in cardiovascular pathology, therapeutic/diagnostic potential, and related factors.

Main Results:

  • Twenty-two studies were included. VEGF dysfunction is implicated in Tetralogy of Fallot (TOF).
  • VEGF contributes to abnormal heart tube elongation and disproportionate cardiovascular tissue growth during fetal development.
  • Increased Hypoxia-Inducible Factor (HIF) correlates with VEGF activity, preceding fetal heart development. HIF levels are elevated in children with cyanotic and acyanotic CHD, particularly complex cases.

Conclusions:

  • Elevated VEGF and HIF during fetal heart development are primary drivers of CHD pathology.
  • Post-heart completion, VEGF and HIF aid in heart tissue regeneration.
  • Regulating fetal VEGF and HIF levels is critical for CHD diagnosis and understanding its pathology.
Abstract

Keywords:
congenital heart diseasediagnosishypoxia‐inducible factorsystematic reviewtreatmentvascular endothelial growth factor

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