The Potential of Gene Therapy as a Treatment Strategy for Intra-uterine Growth Restriction

  • Mounira Habli
  • Timothy M. Crombleholme


Intra-uterine growth restriction (IUGR) is a major cause of perinatal morbidity and mortality. Growth-restricted fetuses are also at higher risk for developing diabetes, obesity, hypertension, coronary artery disease, and dyslipidemia later in adult life. Placental insufficiency, or abnormal placental vascular development or function, accounts for up to two-thirds of IUGR. Despite the relatively high prevalence of IUGR and the frequent perinatal morbidity and mortality and the potential for serious long-term sequelae, there is still no effective treatment for IUGR due to placental insufficiency. However, placental gene therapy that aims to overexpress transgene to compensate for deficient native gene expression in placenta tissues is a potential new therapeutic strategy. Placental gene therapy has numerous advantages including gene transfer to discarded tissue at the end of gestation, avoidance of fetal and maternal gene transfer, high level of transgene levels in target cells in placenta for duration of pregnancy, and the potential for long-term reprogramming of the fetal metabolic response to prevent long-term sequelae of IUGR. There are, however, a number of obstacles to be overcome before clinical translation of placental gene transfer can be considered as short- and long-term safety, efficacy, potential of germ line gene transfer, and insertional mutagenesis. In this chapter we review the etiologies of IUGR, management and treatment options, and the potential for gene therapy as treatment strategy.


Fetal Growth Fetal Growth Restriction Insertional Mutagenesis Placental Insufficiency Placenta Growth Factor 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.



Adeno-associated virus vectors


Adeno virus vectors






Basic fibroblast growth factor


Coxsackie–adenovirus receptor


Insulin-like growth factor-binding proteins


Hepatocyte growth factor


Simplex virus


Insulin-like growth factor


Insulin-like growth factor receptor


Intra-uterine growth restriction


Platelet-derived growth factor B


Placental insufficiency


Placenta growth factor


Vascular endothelial growth factor-121


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© Springer Science+Business Media, LLC 2012

Authors and Affiliations

  1. 1.Division of Pediatric General, Thoracic and Fetal SurgeryThe Fetal Care Center of Cincinnati, Cincinnati Children’s Hospital Medical Center, University HospitalCincinnatiUSA

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