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Maternal Proinflammatory Processes and Fetal Neurodevelopment: Integrating Clinical and Preclinical Research Approaches and Identifying Knowledge Gaps That Warrant Future Collaboration

  • Melissa D. Bauman
    Correspondence
    Address correspondence to Melissa D. Bauman, Ph.D.
    Affiliations
    Department of Psychiatry and Behavioral Sciences, University of California, Davis

    The MIND Institute, University of California, Davis

    California National Primate Research Center, University of California, Davis
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  • Claudia Buss
    Correspondence
    Claudia Buss, Ph.D.
    Affiliations
    Development, Health and Disease Research Program, University of California, Irvine, School of Medicine, Irvine, California

    Department of Pediatrics, University of California, Irvine, School of Medicine, Irvine, California

    Department of Medical Psychology, Charité – Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany
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      Epidemiological and clinical evidence has identified a diverse range of gestational conditions, such as obesity, poor diet, psychosocial stress, and exposure to environmental toxins as well as infection, that are associated with an increased risk of offspring neurodevelopmental disorders. Maternal inflammation is common among these various conditions, raising the possibility that exposure to chronic or acute inflammatory processes during gestation may trigger changes in fetal neurodevelopment (
      • Yockey L.J.
      • Iwasaki A.
      Interferons and proinflammatory cytokines in pregnancy and fetal development.
      ). In the context of the ongoing COVID-19 pandemic, pregnant women are among the vulnerable populations that require specific protection against infection owing to the potential negative consequences that infection may have on the mother during this already challenged physiological state and on fetal development. Despite the lack of vertical viral transfer to the fetus, a COVID-19 infection during pregnancy may alter fetal (neuro)development as a consequence of an induced maternal and placental immune response that may alter the intrauterine milieu. It is important to emphasize that not all pregnancies are equally susceptible to inflammatory insults. For example, although exposure to viral or bacterial infections during pregnancy is associated with an increased risk of offspring neurodevelopmental disorders, most women are exposed to some form of infection during pregnancy, and the vast majority of exposed offspring will not experience significant neurodevelopmental changes (
      • Meyer U.
      Neurodevelopmental resilience and susceptibility to maternal immune activation.
      ). However, for a subset of pregnancies, inflammatory processes associated with a COVID-19 infection, but also with other clinical and subclinical conditions, such as obesity, stress, and infection, may serve as a “disease primer” for exposed offspring. Such differential susceptibility in the context of increased maternal inflammation during pregnancy highlights the critical and currently unmet need to understand factors that determine risk and resilience and to develop evidence-based guidelines to mitigate the impact of various inflammatory processes during pregnancy.
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