Fax +41 61 306 12 34 E-Mail karger@karger.ch www.karger.com Stress Dev Neurosci 2009;31:285–292 DOI: 10.1159/000216539 Prenatal Stress and Neurodevelopment of the Child: Focus on the HPA Axis and Role of the Placenta K. O’Donnell a T.G. O’Connor b V. Glover a a Institute of Reproductive and Developmental Biology, Imperial College London, London, UK; b Department of Psychiatry, University of Rochester Medical Center, Rochester, N.Y., USA Prenatal Stress or Anxiety Predicts Neurodevelopmental Outcomes in the Child There is good evidence from several independent pro- spective studies that maternal stress, anxiety or depres- sion during pregnancy is associated with several types of adverse neurodevelopmental outcomes in the child. Out- comes linked so far with prenatal stress or anxiety in- clude autism, schizophrenia, emotional/behavioral prob- lems, and reduced cognitive abilities especially with lan- guage development. Although we still lack conclusive causal evidence, the number of studies showing effects is now sizeable; furthermore, the consistency with the ex- perimental animal evidence makes it a powerful model for translational research on how early stress exposure may have long-term effects. We briefly review key com- monalities and discrepancies in the human studies and then consider the possible mechanisms. The range of prenatal maternal stressors that predict child outcomes is quite wide and includes minor stresses such as daily hassles, more severe traumas, and symp- toms and disorders of anxiety and depression (table 1). The type and degree of stress may differ for different out- comes. For example, the increased risk for schizophrenia was associated with the very severe stress of the death of a close relative during pregnancy [1] . There may be a dose-dependent effect where certain neurodevelopmen- Key Words Prenatal stress  Neurodevelopment  Cortisol  Placenta  11- HSD2  Fetal programming Abstract Recent human studies have shown that a wide variety of pre- natal stressors, from anxiety and partner relationship prob- lems, to natural disasters, increase the risk for a diverse range of adverse neurodevelopmental outcomes in the child. These include impaired cognitive development and behavioral problems, autism and schizophrenia. However, many questions remain about the underlying processes. Much of the research, based on animal studies, has focussed on the maternal HPA axis, with mixed results. Maternal stress or anxiety during pregnancy has been found to be weakly associated with raised maternal cortisol, if at all. The placen- ta may be a more promising programming vector, because it controls fetal exposure to the maternal environment. Animal studies indicate that prenatal stress can affect the activity of the placental barrier enzyme 11- HSD2, which metabolises cortisol. We review the evidence for a similar mechanism in humans and how maternal stress may cause other changes in the placenta which affect fetal neurodevel- opment. Copyright © 2009 S. Karger AG, Basel Received: December 15, 2008 Accepted after revision: January 9, 2009 Published online: June 17, 2009 V. Glover Institute of Reproductive and Developmental Biology, Imperial College London Hammersmith Campus, Du Cane Road London W12 0NN (UK) Tel. +44 207 594 2136, Fax +44 207 594 2138, E-Mail v.glover@imperial.ac.uk © 2009 S. Karger AG, Basel 0378–5866/09/0314–0285$26.00/0 Accessible online at: www.karger.com/dne