The stress of chronic hypoxia in fetal growth restriction: Some physiological considerations

Lawrence D. Longo, Ravi Goyal

Research output: Chapter in Book/Report/Conference proceedingChapter

2 Scopus citations


Fetal growth restriction (FGR), defined as 10th percentile or less of estimated fetal weight, is a complication of 7 to 10% of pregnancies in the USA and throughout the world. Strikingly, the relation of FGR to chronic hypoxia is complex and poorly understood. Development of the normal embryo has been shown to occur in a state of relative hypoxia. Nonetheless, beyond a certain degree of physiological adjustment, hypoxia is associated with a number of factors inimical to cell growth and function. In response to prolonged or long-term hypoxemia (LTH), a number of compensatory changes transpire in many organ systems and tissues to maintain homeostasis. These result in what has been called intrauterine growth restriction, small for gestational age infants, and more recently fetal growth restriction. The FGR phenomenon, which with the use of contemporary ultrasonography can become evident during the mid-to late-second trimester, is accompanied by a host of specific responses in essentially every tissue and organ system that has been studied. For instance, in the cardiovascular system secondary to a decrease in myocardial cell contractile function, the heart shows a decrease in cardiac output. In turn, the cerebrovasculature demonstrates a number of significant changes including decreased vascular resistance to maintain cerebral blood flow (CBF) at near normal sea levels values. To effect changes in tone, the cerebral arteries undergo a number of other changes in receptor density and functions. For instance, the function of alpha1 adrenergic receptor subtypes, potassium channel function, and a host of other endocrinologic, metabolic, and neurobiologic changes occur. A key element of these responses includes fundamental changes in structure and function of the placenta of the FGR infant. The results emphasize the role of hypoxemia in modulating a number of signal transduction mechanisms, including those for protein synthesis, in the various organs and tissues to affect a mosaic of cellular and molecular responses. These specifically highlight the implications of these changes for development and the genesis of disease in the adult. Of critical relevance, our challenge is to move beyond phenomenology to gain an understanding of the fundamental cellular and molecular changes and the mechanisms by which hypoxia and/or other stress result in FGR. In addition, we need to understand how we can prevent the lifelong consequences with a panoply of diseases in adult life.

Original languageEnglish (US)
Title of host publicationStress and Developmental Programming of Health and Disease
Subtitle of host publicationBeyond Phenomenology
PublisherNova Science Publishers, Inc.
Number of pages37
ISBN (Electronic)9781634633703
ISBN (Print)9781633218369
StatePublished - Oct 1 2014
Externally publishedYes


  • Cardiac
  • Cerebrovascular
  • Development
  • Long-term hypoxia

ASJC Scopus subject areas

  • General Medicine


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