Pediatric Neurology
Volume 38, Issue 3 , Pages 163-176, March 2008

Fetal Mechanisms in Neurodevelopmental Disorders

  • Susan L. Connors, MD

      Affiliations

    • Department of Neurology and Developmental Medicine, Kennedy Krieger Institute, Baltimore, Maryland
  • ,
  • Pat Levitt, PhD

      Affiliations

    • Vanderbilt Kennedy Center for Research on Human Development and Department of Pharmacology, Vanderbilt University, Nashville, Tennessee
  • ,
  • Stephen G. Matthews, PhD

      Affiliations

    • Departments of Physiology, Obstetrics and Gynecology, and Medicine, University of Toronto, Toronto, Ontario, Canada
  • ,
  • Theodore A. Slotkin, PhD

      Affiliations

    • Department of Pharmacology and Cancer Biology, Duke University Medical Center, Durham, North Carolina
  • ,
  • Michael V. Johnston, MD

      Affiliations

    • Department of Neurology and Developmental Medicine, Kennedy Krieger Institute, Baltimore, Maryland
    • Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, Maryland.
  • ,
  • Hannah C. Kinney, MD

      Affiliations

    • Department of Pathology, Children’s Hospital Boston and Harvard Medical School, Boston, Massachusetts
  • ,
  • William G. Johnson, MD

      Affiliations

    • Department of Neurology, University of Medicine and Dentistry of New Jersey-Robert Wood Johnson Medical School, Piscataway, New Jersey
  • ,
  • Rosa M. Dailey, BA

      Affiliations

    • Fetal Physiology Foundation, Baltimore, Maryland
  • ,
  • Andrew W. Zimmerman, MD

      Affiliations

    • Department of Neurology and Developmental Medicine, Kennedy Krieger Institute, Baltimore, Maryland
    • Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, Maryland.
    • Corresponding Author InformationCommunications should be addressed to: Dr. Zimmerman; Department of Neurology and Developmental Medicine, Kennedy Krieger Institute; 707 North Broadway; Baltimore, MD 21205.

Received 30 August 2007; accepted 29 October 2007.

Normal development of the central nervous system depends on complex, dynamic mechanisms with multiple spatial and temporal components during gestation. Neurodevelopmental disorders may originate during fetal life from genetic as well as intrauterine and extrauterine factors that affect the fetal-maternal environment. Fetal neurodevelopment depends on cell programs, developmental trajectories, synaptic plasticity, and oligodendrocyte maturation, which are variously modifiable by factors such as stress and endocrine disruption, exposure to pesticides such as chlorpyrifos and to drugs such as terbutaline, maternal teratogenic alleles, and premature birth. Current research illustrates how altered fetal mechanisms may affect long-term physiological and behavioral functions of the central nervous system more significantly than they affect its form, and these effects may be transgenerational. This research emphasizes the diversity of such prenatal mechanisms and the need to expand our understanding of how, when altered, they may lead to disordered development, the signs of which may not appear until long after birth.

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PII: S0887-8994(07)00542-5

doi:10.1016/j.pediatrneurol.2007.10.009

Pediatric Neurology
Volume 38, Issue 3 , Pages 163-176, March 2008